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THE     BASIS     OF 

SYMPTOMS 

THE  PRINCIPLES  OF  CLINICAL  PATHOLOGY 


BY 

DR.  LUDOLPH  KREHL 

ORDINARY  PROFESSOR  AND  DIRECTOR  OF  THE  MEDICAL  CLINIC  IN  HBIDBLBBRG 

AUTHORIZED    TRANSLATION    FROM 
THE  SEVENTH  GERMAN  EDITION  BY 

ARTHUR  FREDERIC  BEIFELD,  PH.B.,  M.D. 

INSTRUCTOR  IN  MEDICINE,  NORTHWESTERN  UNIVERSITY  MEDICAL  SCHOOL,  CHICAGO 

WITH  AN  INTRODUCTION  BY 

A.  W.  HEWLETT,  M.D. 

PROFESSOR  OF  INTERNAL  MEDICINE,  UNIVERSITY  OF  MICHIGAN,  ANN  ARBOR 


THIRD  AMERICAN  EDITION 


PHILADELPHIA  AND  LONDON 
J.  B.  LIPPINCOTT  COMPANY 


Copyright,  1905 
by  j.  b.  lippincott  company 

Copyright,  1907 
by  j.  b.  lippincott  company 

Copyright,  1916 
bt  j.  b.  lippincott  company 


Electrotyped  and  Printed  by  J.  B.  Lippincott  Company 
The  Washington  Square  Press,  Philadelphia,  U.  S.  A. 


r 


TRANSLATOR'S  PREFACE  TO  THE  THIRD 
AMERICAN  EDITION 

The  translation  into  English  of  Professor  Krehl's  "  Patholo- 
gische  Physiologic  "  is  closely  identified  with  the  name  of  Dr. 
Hewlett,  who  prepared  the  first  two  American  editions  of  this 
work  from  the  third  and  fourth  German  editions,  respectively. 
It  is  with  Dr.  Hewlett's  permission  that  I  am  offering  to  the 
profession  a  third  American  edition  based  upon  the  seventh 
edition  of  the  Grcrman.  Dr.  Hewlett  has  also  placed  at  my 
disposal  whatever  of  his  I  have  found  available — a  privilege  I 
have  freely  used  and  for  which  I  take  great  pleasure  in  acknowl- 
edging my  indebtedness.  The  title  of  the  earlier  translations, 
Clinical  Pathology,  derived  from  the  first  German  edition,  has 
been  continued,  as  a  subtitle,  in  this  volume,  the  new  title,  The 
Basis  of  Symptoms,  having  been  selected  to  convey  the  immediate 
relation  of  the  contents  to  clinical  medicine. 

Noteworthy  advances  have  been  recorded  in  the  medical 
sciences  since  the  publication  of  the  second  American  edition. 
Thus,  the  last  German  edition  in  its  growth  reflects  in  particular 
the  newer  studies  devoted  to  the  cardiac  arrhythmias;  to  the 
leukaemias  and  pseudoleuksemias ;  to  such  phases  of  infection  and 
immunity  as  anaphylaxis,  complement  fixation  and  chemotherapy; 
to  the  phenomena  of  gastric  secretion  and  motility;  to  the  renal 
functional  tests  and  the  role  of  the  incoagulable  nitrogen;  and, 
finally,  to  the  glands  of  internal  secretion,  to  gout,  diabetes,  fever, 
etc.  In  addition,  there  has  been  included  a  new  chapter  on 
"  Constitutional  Diseases  and  Diatheses," 

The  last  few  years  have  been  significant  also  for  the  part 
which  American  science  has  contributed.  There  is  scarcely  a 
field  in  which  cisatlantic  workers  are  not  creditably  represented; 
while  along  many  lines  they  are  pioneers.  I  have  made  an  effort 
to  take  cognizance  of  this  fact,  and  have  inserted  many  notes 
indicative  of  the  same. 

Particular  attention  has  been  devoted  to  the  literature.  Many 
of  the  older,  and  classical,  German  references  have  been  omitted 

iii 


iv  TRANSLATOR'S  PREFACE 

and  replaced  by  more  recent  studies,  particularly  when  the  latter 
are  in  the  nature  of  collective  monographs.  The  numerous 
American  studies  referred  to  in  the  text  and  footnotes  contain, 
as  a  rule,  comprehensive  bibliographies. 

Professor  Krehl's  appended  note  on  the  cardiac  arrhythmias 
(referred  to  in  his  Preface)  has  been  incorporated  into  the  main 
body  of  the  text. 

The  translation  though  not  a  literal  one,  does  not  depart  in  any 
essential  way  from  the  original  text,  and  embodies,  it  is  hoped,  the 
spirit  of  the  latter.  I  have  allowed  myself  the  privilege  of  certain 
condensations  and  slight  rearrangements — all  with  the  view  of 
rendering  the  material  more  serviceable  to  the  readers  for  whom 
it  is  intended.  Editorial  notes — several  of  which  are  taken  from 
the  earlier  American  editions — ^are  included  in  parentheses. 

It  is  with  keen  pleasure,  finally,  that  I  acknowledge  my  debt 
to  Dr.  R.  G.  Hoskins,  Professor  of  Physiology  in  the  North- 
western University  Medical  School,  for  his  constant  stimulus  and 
many  suggestions;  and  to  Messrs.  J.  B.  Lippincott  Co.  for  their 
cooperation  throughout  the  preparation  of  the  volume. 

Arthur  F.  Beifeld. 
Chicago,  1916. 


AUTHOR'S  PREFACE  TO  THE  SEVENTH 
GERMAN  EDITION 

With  a  greater  trepidation  than  ever,  I  commit  this  revision 
to  the  profession.  In  every  department  of  pathological  physiology 
there  are  diligent  workers  and  the  literature  has  grown  immeas- 
urably. My  assistants,  with  whom  it  has  been  my  pleasure  to 
work,  as  well  as  Professor  Schwenckenbecher,  of  Frankfurt,  and 
Professor  Morawitz,  of  Freiburg,  have  •  rendered  me  abundant 
aid,  without  which  I  should  have  found  it  quite  impossible,  even 
in  small  measure,  to  do  justice  to  the  wealth  of  material.  De- 
spite this,  I  cannot  say,  with  any  degree  of  certainty,  that  I  am 
cognizant  even  of  the  more  important  work  from  German  sources ; 
while  of  foreign  literature  I  have  given  only  suggestions. 

I  am  deeply  sensible  of  my  shortcomings,  and  I  have  seriously 
asked  myself  if  the  time  has  not  arrived  for  a  collaborative  treat- 
ment of  the  contents  of  this  volume;  for  it  has  attained  a  scope, 
which,  unassisted,  I  can  no  longer  hope  to  present  evenly.  There 
is  not  a  chapter,  indeed,  which  my  colleagues  could  not  have 
presented  more  ably. 

Pathological  physiology  concerns  the  student,  the  teacher  and 
the  clinician.  In  our  profession  it  is  linked  with  the  best  we  have 
in  us,  predicating  thought  and  study  and  the  desire  to  understand. 
I  do  not  say  that  the  speculative  mind  is  essential  to  the  proper 
conduct  of  medical  practice;  for  success  at  the  bedside  is  pre- 
eminently and  fittingly  the  fruit  of  a  full  and  cumulative  experi- 
ence. To  him  indeed,  who  would  advise  mankind,  experience  is 
all-important,  but  if  this  be  the  measure  of  his  content,  it  is 
well.    Let  him  pursue  his  way. 

Our  profession  embraces  something  larger  and  finer,  how- 
ever; it  is  like  a  faith  whose  God  may  be  judged  from  the  charac- 
ter of  him  who  worships.  Thus  to  many  comes  the  impulse  to 
devote  themselves  with  fervor  to  something  purer,  higher  and 
less  tangible;  to  ponder  how  the  wondrous  processes  of  life 
unfold  themselves  in  the  sick;  to  understand  how  disease  arises 
out  of  health;  to  be  a  nature  philosopher. 

The  tendency  to  speculate  is  deeply  rooted  in  us  of  German 


vi  AUTHOR'S  PREFACE 

blood;  to  seize  with  winged  thought  what  only  calm,  painstaking 
study  can  elaborate  and  acquire.  We  like  to  construct  in  thought 
edifices  that  can  be  erected  only  upon  the  foundation  stones  fur- 
nished by  the  more  suitable  and  exact  methods  of  the  laboratory. 
And  for  each  of  us  to  have  his  own  pathology  still  plays  a  prom- 
inent and,  in  my  opinion,  a  not  desirable  role. 

To  curb  this  tendency  and  to  foster  a  more  definite  leaning 
upon  the  biological  sciences  in  general,  is  the  desire  of  this  volume 
and  its  purpose.  Its  justification  lies  perhaps  in  the  attempt  to 
correlate  the  functions  of  the  different  organs  on  a  uniform  bio- 
logical basis ;  for  despite  their  individuality,  they  are  efficient  only 
as  parts  of  the  larger  whole.  And  to-day,  more  than  ever,  we 
are  agreed  that  he  who  will  understand  disease  must  see  clearly 
the  interrelationship  of  all  the  organs — must  consider  the  unit  only 
in  its  bearing  upon  the  ensemble. 

For  reasons  beyond  my  control  the  publication  of  this  book 
has  been  considerably  delayed,  so  that  when  concluded,  I  would 
fain  have  made  a  number  of  alterations.  This  being  impossible, 
I  have  appended  a  few  notes  on  the  cardiac  arrhythmias. 

References  to  the  literature  have  been  given  with  every  pos- 
sible care,  yet  I  fear  that  many  errors  in  volume  and  page  citation 
have  crept  in.  L.  Krehl. 


CONTENTS 

PAGE 

Foreword,  by  A.  W.  Hewlett,  M.  D xi 

Descriptive  Note,  by  Professor  William  Osler xiii 

Introduction xv 

CHAPTER  I 
The  Circulation i 

The  Importance  of  the  Circulation;  The  Puknonary,  or  Lesser  Circula- 
tion; The  Systemic,  or  Greater,  Circtilation. 

The  Heart:  The  Adaptability  of  the  Heart;  Hypertrophy  of  the  Heart; 
Valvular  Disease  of  the  Heart;  The  Etiology  of  Valviilar  Disease;  Mus- 
cular InsuflSciency;  Aortic  Insufficiency;  Aortic  Stenosis;  Mitral  Steno- 
sis; Mitral  Insufficiency;  Valvular  Lesions  of  the  Right  Side;  Combined 
V^vular  Lesions;  Hypertrophy  of  the  Right  Ventricle;  Hypertrophy  of 
the  Left  Ventricle;  Hypertrophy  of  Both  Ventricles;  Cardiac  Changes 
in  Renal  Disease;  The  "Athlete's  Heart";  The  "Beer-Heart";  The 
Heart  in  Pregnancy;  The  Ability  of  the  Heart  to  Hypertrophy;  Con- 
centric and  Eccentric  Hypertrophy;  The  Inefficiencies  of  a  Compensated 
Circulation;  Myocardial  Changes  in  Hypertrophied  Hearts;  Causes  of 
Broken  Compensation  in  Hypertrophied  Hearts;  Causes  of  Primary 
Insufficiency  of  the  Heart  Muscle;  Results  of  Cardiac  Weakness;  Dis- 
turbances of  the  Heart-Rate;  Tachycardia;  Bradycardia;  Disturbances 
of  the  Cardiac  Rhythm;  Extrasystoles;  Perpetual  Arrhythmia;  Pulsus 
Altemans — Hemisystoles;  Heart-Block;  Causes  of  Arrhythmia;  The 
Cardiac  Impulse;  The  Heart-Sotmds;  Cardiac  Murmurs;  Palpitation; 
Cardiac  Dyspnoea;  Cardiac  Pain. 

The  Arteries:  The  Arterial  Blood-Pressure;  Systolic  and  Diastolic 
Pressures — The  Pulse-Pressure;  Physiological  Variations  in  Blood-Pres- 
sure; Pathologically  Increased  Blood-Pressure;  Pathological  Diminution 
in  Blood-Pressure. 

The  Veins:  Venous  Stasis;  Venous  Murmurs. 

The  Circtilation  of  the  Lymph:  CEdema;  Composition  of  Exudates;  Chy- 
lous and  Chyliform  Ascites;  Pulmonary  CEdema. 

CHAPTER  II 
The  Blood 102 

General  Considerations. 

Ancemia:   Anaemia  from  Hemorrhage;  General  Considerations  Relative 

to  Chronic  Anaemias ;  Chlorosis ;  Secondary  Anaemias ;  Pernicious  Anaemia ; 

Haemoglobinaemia;   Paroxysmal   Hsemoglobinuria ;  Other  Causes  which 

Injure  the  Red  Blood-Corpuscles;  Systemic  Effects  of  Rapid  Destruction 

of  Red  Blood-Corpuscles. 

The  White  Blood- Corpuscles:  Physiological  Leucocytoses;  Pathological 

Leucocytoses;  Leucopaenia;  Leukaemia  and  Pseudoleukaemia. 

Plasma  and  Serum — The  Total  Quantity  of  Blood:  Coagulation;  The 

Blood-Serum;  Salts  of  the  Serum;  Hydraemia;  Polycythaemia;  Plethora. 

CHAPTER  III 
Infection  and  Immunity 151 

Portals  of  Entry;  The  Factors  Determining  the  Character  of  an  Infec- 
tion; Mixed  and  Secondary  Infections;  Varieties  of  Immunity;  The 
Factors  Concerned  in  Immunity:  (a)  General  Considerations;  (b) 
Complement  and  Amboceptor;  (c)  The  Side-Chain  Theory;  The  Haemo- 
lytic  Action  of  Alien  Plasmas;  Aiititoxins;  Precipitation  and  Precipitins; 
Complement  Fixation — The  Wassermann  Reaction;  Agglutination  and 
Agglutinins ;  The  Relation  of  Antitoxins  and  Bacteriolysins  to  Immunity ; 
Anaphylaxis — Serum  Disease;  Phagocytosis  and  Immimity;  Bacillus 
Carriers;  Chemotherapy — Salvarsan;  Autoinfection;  Conclusions. 

vii 


viii  CONTENTS 

CHAPTER  IV 

PAGB 

Respiration 197 

External  Respiration:  Means  for  Removing  Harmful  Material  from 
the  Air-Passages;  Stenosis  of  the  Air-Passages;  Bronchial  Asthma; 
Paralysis  of  the  Respiratory  Muscles;  Loss  of  Pulmonary  Elasticity — 
Emphysema;  Respiratory  Changes  of  Nervous  Origin — Cheyne-Stokes 
Breathing;  Pleural  Effusions — Pneumothorax;  Atelectasis;  The  Effects 
of  an  Obliteration  of  the  Air-Spaces;  The  Effects  of  Atmospheric 
Pressure;  Inhalation  of  Poisonous  Gases;  The  Effects  of  Anaemia ;  The 
Effects  of  Circulatory  Changes;  Respiratory  Compensation;  Asphyxia. 
Internal  Respiration:  Respiratory  Sensations. 

CHAPTER  V 
Digestion 229 

Mouth  and  CEsophagus:  Stomatitis ;  The  Saliva ;  Diminished  Secretion 
of  Saliva;  Ptyalism;  Composition  and  Reaction  of  Saliva;  Swallowing; 
(Esophageal  Stenosis;  Pressure  Diverticula;  Primary  Dilatation  of  the 
CEsophagus. 

The  Stomach:  The  Disturbances  of  Gastric  Secretion;  Hypersecretion 
of  Gastric  Juice ;  Hyperacidity — Ulcer  of  the  Stomach ;  Effects  of  Hyper- 
secretion and  Hyperacidity;  Subaddity  and  Anacidity;  Bacterial  Action 
in  the  Stomach. 

Disturbances  of  Gastric  Motility:  Increased  Peristalsis  and  Increased 
Gastric  Motihty;  Motor  Insufficiency  and  Gastric  Dilatation;  Causes 
of  Dilatation;  Effects  of  Motor  Insufficiency ;  Belching  and  Vomiting; 
Sensations  Arising  from  the  Stomach. 

Disturbances  in  the  Secretion  of  Bile:  Gall-Stones;  Exclusion  of  Bile 
from  the  Intestines;  Jaundice;  Effects  of  Javmdice;  Other  Hepatic 
Toxaemias. 

Pancreatic  Juice:    Fat  Necroses. 

The  Processes  in  the  Intestines:  The  Effect  of  Poisons  upon  the 
Intestines;  Abnormal  Bacterial  Processes  within  the  Gastit>-Intestinal 
Tract;  The  Pathology  of  Absorption;  Disturbances  in  the  Intestinal 
Movements;  Diarrhoea;  Nervous  Diarrhoeas;  Diarrhoeas  in  General 
Diseases;  Diarrhoeas  of  Intestinal  Origin;  Constipation;  Causes  of 
Constipation;  Effects  of  Constipation;  Intestinal  Obstruction ;  Stran- 
gulation; Meteorism;  Abnormal  Intestinal  Sensations. 

CHAPTER  VI 

Nutrition  and  Metabolism 304 

Quantitative  Variations  in  the  Metabolism  of  Proteids  and  Fats:  Caloric 
Needs  of  the  Body;  Proteid  Needs  of  the  Body;  Inanition; 
Effects  of  an  Oversupply  of  Food;  Disturbances  in  Fat  Metabolism; 
Pathological  Acctimulations  of  Fat ;  Pathological  Changes  in  the  Metab- 
olism of  Proteids;  Pathological  Destruction  of  Proteid  Material;  The 
Metabolism  in  Thyroid  Disease. 

Qualitative  Changes  in  Meiabolism:  Autolysis;  Formation  and  Excretion 
of  Ammonia;  Production  of  Organic  Acids;  Diabetic  and  Other  Toxic 
Comas;  Relation  Between  Hepatic  Disease  and  the  Excretion  of 
Ammonia;  Alkaptonuria;  Cystinuria;  The  Adrenals — ^Addison's 
Disease — Epinephrin. 

CHAPTER  VII 

Disturbances  of  Carbohydrate  Metabolism.    Diabetes 343 

Alimentary  Glycosuria;  Phlorhizin  Glycosviria;  Renal  Diabetes;  Epi- 
nephrin Glycosuria;  Transient  Glycosurias. 

Diabetes  Mellitus:  Mild  and  Severe  Diabetes — Derivation  of  Sugar 
from  Proteids  and  Fats;  The  Glycogenic  Function  of  the  Liver  in 
Diabetes;  The  Consumption  of  Sugar  in  Diabetes;  The  Etiology  of 
Diabetes;  Effects  of  Diabetes  upon  the  Body;  Theory  of  Diabetes. 


CONTENTS  ix 

PAGE 

CHAPTER  VIII 
The  Metabolism  of  the  Purin  Bodies.    Gout ^ .  364 

Gout;  Uric  Acid  in  the  Blood;  Uric  Acid  in  the  Urine;  The  Cause  of 
the  Local  Deposits  of  Urates, 

CHAPTER  IX 
Constitutional  Diseases  and  Diatheses 372 

CHAPTER  X 

Fever 381 

Variations  in  the  Clinical  Picture  of  Fever;  The  Causes  of  Fever;  The 
Relation  of  the  Nervous  System  to  Fever;  The  Normal  Regulation  of 
the  Body  Temperature;  Heat-Stroke;  Heat  Regulation  in  Fever;  Heat 
Production  in  Fever;  Heat  Losses  in  Fever;  Metabolism  in  Fever;  The 
Cause  of  the  High  Temperature  in  Fever;  The  Site  of  Heat  Production; 
The  Heat-Regulatory  Mechanism  in  Fever;  Nutrition  in  Fever;  Water 
Retention  in  Fever;  The  Significance  of  Fever;  The  Temperature  in 
Collapse;  Subnormal  Temperature, 

CHAPTER  XI 
The  Secretion  of  Urine 413 

The  Effect  of  an  Increased  Flow  of  Blood  through  the  Kidneys; 
Diabetes  Insipidus;  The  Effect  of  a  Diminished  Flow  of  Blood 
through  the  Kidneys;  The  Effect  of  an  Obstruction  to  the  Escape 
of  Urine;  The  Effect  of  Lesions  of  the  Secreting  Membranes; 
Albuminuria;  Orthotic  Albuminuria;  The  General  Causes  of  Albu- 
minuria; Albuminuria  from  Circulatory  Disturbances  of  the  Kidneys; 
Toxic  Albiuninurias;  The  Varieties  of  Proteids  in  the  Urine;  The  Amount 
of  Albumin  Excreted;  Casts;  The  Effect  of  Changes  in  the  Composition 
of  the  Blood;  The  Localization  of  Functional  Disturbances;  The  Effect 
of  Disturbances  of  the  Urinary  Secretion  upon  the  Body;  Uraemia. 
The  Urinary  Passages:  Urinary  Calculi;  The  Symptoms  of  Urinary 
Calcvili;  The  Origin  of  Pain  in  tJae  Urinary  Passages. 

CHAPTER  XII 

The  Nervous  System 441 

Disturbances  of  the  Circulation;  The  Cerebrospinal  Lymphatic  System; 
Increased  Cerebral  Pressure ;  Cerebral  Concussion ;  Cerebral  Hemorrhage 
and  Embolism;  Disturbances  of  Motility;  Disturbances  of  Coordination; 
The  Effect  of  the  Reflexes  upon  Motion;  Nervous  Disturbances  of  Urina- 
tion and  Defecation ;  Pathological  Alterations  in  the  Reflexes ;  Strychnin 
Poisoning  and  Tetanus;  Contractures;  Motor  Irritative  Symptoms;  Dis- 
turbances of  Sensation;  The  Cutaneous  Sensations;  Orientation  of  our 
Bodies  in  Space;  Dizziness;  Hyperalgesia;  Irritative  Sensory  Symptoms; 
The  Influence  of  the  Nervous  System  upon  Tissue  Nutrition ;  The  Effect 
of  Separating  a  Nerve-Fibre  from  its  Cell;  Nutritional  Disturbances  in 
the  Muscles;  Changes  in  the  Electrical  Irritability  of  Muscles;  Atrophy 
from  Cerebral  Lesions;  Muscular  Atrophy  from  Diseases  of  Joints;  Mus- 
cular Dystrophies;  Nutritional  Disturbances  in  the  Bones  and  Joints; 
Influence  of  Nervous  Diseases  upon  the  Skin;  Herpes  Zoster. 


FOREWORD 

The  remarkable  development  of  pathologic  anatomy  during 
the  past  century  was  reflected  in  the  clinical  medicine  of  the  time. 
Physical  diagnosis  reached  its  present  plane  of  accuracy,  the 
ability  to  predict  the  anatomic  changes  found  at  autopsy  became 
the  goal  of  certain  clinical  schools,  and  therapeutic  nihilism  be- 
came the  order  of  the  day  since  it  was  obvious  that  no  medicine 
could  have  changed  most  of  the  alterations  in  structure  that  were 
found  at  autopsy.  Modern  surgery  has  indeed  been  able  to  cut 
many  a  Gordian  knot  prescribed  by  anatomic  change ;  but  modem 
medicine,  though  still  directly  dependent  upon  pathologic  anatomy 
for  the  interpretation  of  many  clinical  syndromes,  has  turned  its 
main  path  of  development  into  other  channels. 

Anatomic  changes  do  harm  by  interfering  with  certain  func- 
tions of  the  body,  but  functional  alterations  may  also  be  present 
without  evident  alterations  of  structure.  The  symptoms  for 
which  a  patient  seeks  relief  are  all  due  to  changes  in  function. 
Even  when  the  physician  cannot  remove  the  anatomic  cause  of  the 
disease,  he  may  yet  be  able  to  alter  the  bodily  functions  in  such  a 
way  as  to  relieve  symptoms  or  other  disease  manifestations. 

The  functional  outlook  on  disease  requires  from  the  physician 
that  he  think  not  in  terms  of  diseased  structure  alone  but  also  in 
terms  of  diseased  physiology.  The  science  of  abnormal  physiology 
is  at  present  passing  through  a  period  of  rapid  development.  It 
has  been  zealously  studied  in  recent  years  by  physiologists,  experi- 
mental pathologists,  biochemists,  immunologists  and  by  clinicians 
themselves.  Modern  pharmacology  devotes  itself  mainly  to  the 
effect  of  drugs  upon  physiological  processes.  The  bearing  of  this 
new  knowledge  upon  the  interpretation  of  clinical  pictures  and  its 
application  in  the  treatment  of  disease  are  to  my  mind  the  most 
important  problems  that  lie  before  the  modern  clinical  school. 

In  his  book  on  Pathologische  Physiologic,  Ludolf  Krehl  has 
sought  to  interpret  the  various  pictures  observed  in  the  clinic 
from  the  stand-point  of  disturbed  physiology.  That  his  work 
has  met  with  wide  approval  is  evident  from  the  fact  that  it  has 
passed  through  eight  Grcrman  editions  and  that  it  has  been  trans- 

xi 


xii  FOREWORD 

lated  into  a  number  of  languages.  The  writer  of  this  note  is 
responsible  for  the  first  and  second  American  editions,  and  it  was 
with  great  pleasure  that  he  learned  of  Dr.  Bcif eld's  willingness 
to  undertake  a  new  American  translation.  To  this  new  trans- 
lation he  wishes  all  success,  not  alone  because  such  a  work  de- 
serves success  in  itself  but  because  success  would  indicate  that 
our  profession  is  taking  an  interest  in  the  fundamental  principles 
that  underlie  the  modern  development  of  internal  medicine. 

A.  W.  Hewlett. 
January,  191 6. 


DESCRIPTIVE  NOTE 

Knowing  its  worth,  I  very  gladly  agreed  to  write  a  brief 
introductory  preface  to  an  American  edition  of  Professor  Krehl's 
well-known  work.  Not  that  it  needs  any  words  of  commendation. 
A  successful  book  in  Germany,  it  has  already  been  translated  into 
several  languages,  and  has  long  since  passed  beyond  the  probation 
stage;  but  a  few  words  from  me  may  serve  to  introduce  it  to 
the  English-speaking  profession.  Those  of  us  who  were  brought 
up  on  Williams's  "  Principles  of  Medicine "  recall  the  pleasure 
and  the  profit  derived  from  it,  mingled  now  with  the  regret  that 
we  have  no  work  of  the  same  character  to  place  in  the  hands  of 
our  senior  students.  This  want  Professor  Krehl's  book  will 
supply.  Herter's  "  Lectures  on  Chemical  Pathology  "  cover  part 
of  the  ground,  and  Cohnheim's  well-known  "  Lectures  on  General 
Pathology"  is  somewhat  similar.  In  Professor  Krehl's  work 
disease  is  studied  as  a  perversion  of  physiological  function,  and 
the  title  "  Clinical  Pathology  "  expresses  well  the  attempt  which 
is  made  in  it  to  fill  the  gap  between  empirical  and  scientific  medi- 
cine. The  facts  presented  are  derived  in  part  from  studies  upon 
patients,  and  in  part  from  experiments  upon  animals,  designed 
to  explain  clinical  problems.  The  author  has  had  the  advantage 
of  prolonged  laboratory  training,  to  which  has  been  added  that 
accurate  knowledge  of  disease  to  be  had  only  by  years  of  study 
and  teaching  in  the  wards.  For  such  a  work  as  this  there  is  at 
the  present  time  great  need.  Every  few  years  the  laboratories 
seem  to  run  ahead  of  the  clinics,  and  it  takes  time  before  the  facts 
of  the  one  are  fully  appreciated  by  the  other.  In  the  complexity 
of  the  problems,  sometimes  in  the  fascination  of  the  scientific  side, 
we  are  apt  to  lose  sight  of  the  practical  application  to  diagnosis 
and  to  treatment  of  the  facts  obtained  in  the  laboratories.  The 
surgeons  have  invaded  the  medical  wards  with  great  advantage  to 
our  patients,  and  in  many  diseases  to  the  great  improvement  of 
the  art  of  diagnosis.  How  helpful  it  would  be  if  clinicians  had 
always  at  hand  skilled  physiologists,  pathologists,  and  chemists 
to  apply  their  most  advanced  technic  to  clinical  problems,  and  not 
the  technic  alone,  but  the  biological  and  chemical  principles  upon 

ziii 


»Y  DESCRIPTIVE  NOTE 

which  medicine  as  an  exact  natural  science  is  founded.  Prin- 
ciples, as  Plato  reminds  us,  require  constant  revision  and  con- 
sideration; and  this  book,  representing  a  revision  to  date  of  the 
"Principles  of  Clinical  Pathology,"  will  be  most  helpftd  to  all 
students  and  teachers  who  wish  to  know  the  scientific  basis  of 
our  art. 
(From  the  Second  Edition.)  WiLLIAM  OSLER. 


INTRODUCTION 

The  different  chapters  of  this  volume  are  concerned  with  a 
consideration  of  the  behavior  of  correlated  organs  under  the 
influence  of  a  particular  disturbance  of  function.  Intended  as 
supplementary  to  texts  on  physiology  and  special  pathological 
anatomy,  the  attempt  is  not  made  to  cover  what  properly  be- 
longs to  those  fields.  The  arrangement  of  material  is  that  con- 
ventional in  the  study  of  pathology  in  the  German  universities. 

Conventional,  too,  is  the  treatment  of  the  material — in  part 
an  anatomical,  and  in  part  a  physiological  consideration  of  dis- 
turbances in  associated  organs  and  functions.  In  this  I  am  fol- 
lowing also  the  current  method  of  considering  purely  physiologi- 
cal processes.  This  clear,  dispassionate,  and  to  him  who  would 
know  the  phenomena  of  life,  one  might  say  sober,  plan  is  a 
product  of  the  newly  arisen  physiology  of  the  last  century.  The 
new  era  was  inaugurated  with  a  mechanistic  notion  of  the  physical 
and  chemical  workings  of  the  individual  organs.  Therein  lay  the 
tremendous  advance  of  that  transitional  period — a  change  from 
the  speculative  to  the  empirical  treatment  of  the  subject. 

Pathology  underwent  a  like  alteration;  dyscrasias  and  dia- 
theses were  displaced  by  clearly  defined  organ-changes.  This 
was  the  expression  of  the  Virchow  teaching,  which  associated 
each  disease  with  a  local  pathology  and  acknowledged  no  general- 
ized conditions.  The  pathological  point  of  view,  therefore,  did 
not  differ  in  any  way  from  the  physiological.  But  the  lessons 
learned  at  the  autopsy  table  fall  far  short  of  what  we  must  know 
to  understand  the  processes  of  life.  In  the  failure  to  recognize 
this  lay  the  weakness  and  the  narrowness  of  that  intense  period. 

What  we  have  contributed  to  normal  and  pathological  physiol- 
ogy in  the  effort  to  understand  the  life  of  the  organs  consists 
chiefly  in  the  employment  of  more  exact  methods  and  in  the 
recourse  to  physics  and  chemistry.  How  can  the  circulation  be 
regarded  other  than  from  a  mechanical  point  of  view,  or  the 
digestion  other  than  from  the  chemical  or  physico-chemical? 

Pathology,  in  part  then,  is  indeed  only  the  normal  under 
peculiar  conditions,  called  morbid.  The  fault  may  reside  in  a 
constitutionally  defective  organ-correlation  which  leads  to  a  dis- 


xvi  INTRODUCTION 

turbance  of  function  even  under  the  ordinary  conditions  of  life 
(endogenous  causes)  ;  or  noxious  factors  may  arise  outside  the 
body  (exogenous  causes).  Illustrative  of  the  former  is  a  congeni- 
tally  weak  heart  muscle,  and,  of  the  latter,  a  mitral  regurgitation 
on  an  infectious  basis.  In  neither  case  can  the  owner  of  such  a 
heart  compete  in  muscular  efifort  with  normal  men  of  his  age  and 
strength.  In  both,  the  circulation  goes  on  under  morbid  in- 
fluences, which  can  be  studied  and  understood  only  from  the  point 
of  view  of  physics,  just  as  in  normal  conditions. 

This  is  the  guiding  principle  in  the  majority  of  processes 
dealt  with  by  this  volume.  Disease  is  synonymous  with  a  per- 
verted function  of  cells,  organs  and  organ-complexes.  The  cell 
is  altered  both  in  structure  and  in  composition,  or  it  is  disturbed 
by  nervous  or  chemical  influences  (hormones).  The  result  in 
the  average  case  is  a  functional  deviation  from  the  normal,  and 
a  limitation  in  vitality  and  efficiency. 

An  exhaustive  treatment  of  our  subject  would  demand  not 
only  a  consideration  of  disordered  cell  function,  but  of  the  nature 
of  its  physical,  chemical  and  morphological  changes.  In  only  a 
small  minority  of  morbid  conditions,  however,  has  our  knowl- 
edge progressed  to  that  degree.  In  one  case  we  know  the  function 
that  is  disturbed  and  the  anatomical  substratum;  in  another 
chiefly  the  chemical  anomaly,  and  in  a  third  we  are  familiar 
merely  with  certain  functional  abnormalities,  the  morphological 
or  chemical  basis  of  which  are  still  dark. 

Our  knowledge  of  morbid  processes  depends  primarily  upon 
the  stage  of  development  of  methods  for  their  investigation.  As 
this  varies  considerably  in  different  disorders,  our  acquaintance 
with  the  pathology  of  individual  organs  is  not  uniform.  This 
reflects  the  stamp  of  dominant  personalities  upon  the  lines  of 
investigation  pursued  by  their  contemporaries.  Controversies 
as  to  the  proper  point  of  view — whether  functional,  chemical  or 
morphological — to  be  taken  in  the  interpretation  of  the  manifes- 
tations of  disease  have  been,  and  to  some  extent  still  are,  preva- 
lent. The  barrenness  of  such  discussion  is  obvious,  for  these 
different  aspects  are  closely  bound  together,  granting  that  upon 
certain  conditions  a  particular  line  of  reasoning  throws  more  light 
than  another.  Even  so,  under  any  circumstances,  for  a  final 
judgment  as  to  any  pathological  state,  the  problem  must  be  viewed 
from  every  aspect. 


mXRODUCTION  xvu 

Under  pathological  processes  are  included  two  essentially  dif- 
ferent types  of  events.  The  first  is  directly  dependent  upon  the 
morbid  factor  itself;  thus  in  sublimate  nephritis,  the  injury  to  the 
renal  epithelium  may  be  looked  upon  as  the  immediate  result  of 
the  passage  through  the  kidneys  of  mercury  in  combination.  The 
second  type  is  exemplified  in  the  dilatation  of  the  left  ventricle 
in  aortic  insufficiency — an  event  produced  by  the  response  of  the 
organism  to  the  valvular  defect.  Such  a  reaction  represents  an 
effort  toward  healing  and  is  per  se  not  pathological.  In  both  a 
theoretical  and  a  practical  way  these  two  types  are  diametrically 
opposed.  Our  effort,  therefore,  must  be  to  place  each  manifes- 
tation of  disease  in  one  or  the  other  of  these  categories,  for  such  a 
distinction  is  of  great  importance  in  therapy.  In  practice,  indeed, 
the  tendency  is  to  individualize  too  little. 

In  my  opinion,  then,  there  is  but  one  correct  way  to  study  the 
majority  of  morbid  processes  and  the  functional  disorders  of  the 
organs  which  produce  them,  and  that  is  by  a  comprehensive  com- 
parison of  physical  and  chemical  anomalies  in  disease  with  con- 
ditions as  we  know  them  in  health. 

The  scope  of  theoretical  pathology  is  no  more  limited  by  a 
consideration  of  the  disturbances  that  pertain  to  it  than  is  that 
of  the  normal  life  processes  by  the  study  of  the  functions  of  the 
different  organ-systems.  The  coordinate  workings  of  the  organs, 
their  place  in  the  scheme  of  the  whole — and  through  this  their 
efficiency — the  structural  and  chemical  building  of  the  body  from 
a  single  cell,  the  wonderful  problems  of  heredity,  adaptation, 
growth  and  death,  the  preservation  of  the  characteristics  of  the 
species  and  the  relation  of  mind  to  matter — these  are  questions 
which  cannot  be  ignored  if  one  wishes  really  to  understand  life. 
Each  has  its  pathological  aspect,  and  each  is  wonderful  in  itself. 
Some  of  these  questions  are  touched  upon  in  texts  of  general 
pathology.  But  the  remainder  await  the  worker  who  shall  corre- 
late our  present  knowledge. 

These  are  all  problems  naturally  of  pathological  physiology — ■ 
problems  which  cannot  be  regarded  as  solved  until  their  every 
phase  shall  have  been  illuminated.  The  desideratum  includes  the 
most  comprehensive  and  difficult  problems.  In  part  they  cannot 
even  be  systematized,  because  as  yet  we  have  penetrated  too  little 
into  the  fundamentals  of  normal  biology.  Even  the  general 
principles  which  we  must  adduce  in  the  solution  of  these  problems 


xviii  INTRODUCTION 

are  not,  in  all  respects,  clear.  To  attempt  to  solve  them  purely 
on  a  physical  or  chemical  basis  would  be  to  build  on  false  premises. 
A  something,  not  unlike  the  long  forgotten  vitalistic  doctrine,  is 
manifest  here,  though  it  is  a  vitalism  of  a  totally  different  charac- 
ter from  that  applicable  to  the  consideration  of  organ  disturb- 
ances. 

But  to  what  purpose  all  this  here?  To  ask  pardon  because  a 
pathological  physiology  begins  with  the  circulation,  and  because 
in  place  of  a  well-rounded  presentation  only  a  picture  here  and 
there  can  be  offered.  And  also  to  explain  why  the  subdivisions 
of  our  subject  fall  into  the  well-worn  tracks.  We  must  dismem- 
ber the  processes  occurring  in  each  sick  individual  in  order  to 
group  them  for  convenience  of  classification  under  disorders  of 
particular  organs.  But  in  the  living  person,  as  the  physician  sees 
him,  things  are  quite  different ;  for  at  the  bedside  we  must  deter- 
mine how  a  disturbance  of  the  coordinate  action  of  the  different 
organs  affects  the  individual  as  a  whole. 


THE  BASIS  OF  SYMPTOMS 

CHAPTER  I 
THE  CIRCULATION 

The  Importance  of  the  Circulation. — ^The  circulation  is  of 
fundamental  importance  to  the  body.  It  is  not,  of  course,  true, 
as  was  formerly  believed,  that  the  functions  of  the  individual 
organs  depend  primarily  upon  the  amount  of  material  that  they 
receive  from  the  blood.  Without  doubt  their  activities  depend 
rather  upon  the  condition  of  the  parenchyma  cells  and  upon  the 
stimuli  which  these  receive  from  hormones  and  from  the  nervous 
system.  Yet  it  is  certain  that  in  warm-blooded  animals,  at  least, 
a  sufficient  supply  of  oxygen,  salts  and  food  materials  to  the 
tissues  is  a  necessary  requisite  for  a  normal  course  of  life.  Dis- 
turbances of  the  circulation  are,  therefore,  of  great  importance, 
and  the  more  complex  the  organ  affected,  the  more  serious  are 
the  results  of  such  disturbances. 

The  Pulmonary,  or  Lesser,  Circulation. — A  disordered  con- 
dition of  the  circulatory  system  may  have  its  origin  either  in 
the  pump  which  propels  the  blood  or  in  the  tubes  through  which 
the  blood  flows.  The  right  ventricle  drives  venous  blood  at  a 
comparatively  low  pressure  through  the  pulmonary  vessels,  which 
form  a  system  of  short  tubes  whose  combined  area  of  cross- 
section  is  very  great.  Through  the  walls  of  the  capillaries,  the 
interchange  of  gases  between  the  blood  and  the  air  in  the  lungs 
occurs;  and  since  this  interchange  takes  place  quite  rapidly,  the 
pulmonary  system  of  a  large  number  of  short  tubes  seems  best 
adapted  to  the  purpose.  The  vessels  play  a  relatively  subordinate 
part  in  controlling  the  circulation  in  the  lungs,  for  the  pulmonary 
arteries  possess  little,  if  any,  tone.^  So  far  as  we  know,  the 
different  parts  of  the  lungs  are  functionally  equal,  and  there 
would  seem  to  be  no  necessity  for  a  variation  in  the  blood-supply 
to  different  pulmonary  areas,  though  theoretically  it  might  be 
highly  desirable  in  morbid  conditions  of  the  lungs.  During  a 
period  of  rest,  when  only  a  slight  interchange  of  gases  is  neces- 
sary, the  rate  of  blood-flow  in  the  lungs  is  comparatively  slow ; 
but  during  exercise,  when  larger  amounts  of  gases  must  be  inter- 

1 
V 


2  THE  BASIS  OF  SYMPTOMS 

changed,  a  great  quantity  of  blood  is  propelled  through  the  lungs. 
The  increased  respiratory  movements  assist  the  action  of  the  heart 
in  maintaining  this  more  rapid  circulation. 

The  Systemic,  or  Greater,  Circulation. — The  relations  are 
quite  different  in  the  greater  circulation.  Here  a  higher  blood- 
pressure  prevails  at  the  outset,  its  height  depending  upon  the  con- 
tractile strength  of  the  left  ventricle,  and  upon  the  size  of  the 
smaller  arteries.  Variable  amounts  of  blood  may  be  made  to  pass 
through  different  organs  without  any  alteration  of  the  general 
arterial  pressure,  for,  as  the  resistance  to  the  flow  through  one 
organ  is  lessened,  the  resistance  through  another  may  be  corre- 
spondingly increased.  Such  a  mechanism  is  of  the  greatest  ser- 
vice, for  here  all  parts  are  not  of  equal  functional  value  as  they 
are  in  the  case  of  the  lungs,  and  it  may  be  necessary  to  furnish 
one  organ  with  a  rich  supply  of  blood  at  one  time,  and  then  later 
to  do  the  same  for  another.  The  activity  of  the  muscle-fibres 
of  the  smaller  arteries  regulates  the  distribution  of  the  blood 
without  at  the  same  time  necessarily  altering  the  general  blood- 
pressure.  Indeed,  this  latter  must  not  sink  below  a  certain  point 
if  the  brain  and  eye  are  to  perform  their  functions  properly. 

The  flow  of  blood  in  the  veins  is  caused  in  part  by  the  slight 
blood-pressure  transmitted  through  the  capillaries  from  the  arte- 
ries and  in  part  by  other  forces.  Among  the  latter  are  the  suction 
exerted  by  the  heart  and  the  thoracic  cavity,  as  well  as  the  pump- 
ing effect  produced  by  the  varying  pressure  of  the  muscles  and 
fasciae  upon  those  veins  that  are  provided  with  valves. 

The  Heart 

The  Adaptability  of  the  Heart. — Any  of  the  various 
parts  of  the  cardiovascular  apparatus  may  be  diseased  without 
necessarily  disturbing  the  general  circulation.  This  is  due  to 
the  fact  that  this  apparatus,  like  so  many  others  in  the  animal 
body,  possesses  a  compensatory  mechanism.  The  compensatory 
mechanism  for  pathological  processes  does  not  differ,  however, 
from  that  which  a  healthy  man  possesses  and  uses  in  order  to 
meet  the  varying  physiological  demands  made  upon  the  circu- 
lation. 

The  amount  o  f  work  which  the  heart  performs^ 
may  be  approximately  estimated  if  we  know  the  volume  of 
blood  delivered  at  each  systole,  the  velocity  imparted  to  this 


THE  CIRCULATION  8 

blood,  the  peripheral  resistance  and  the  number  of  heart-beats 
in  a  unit  of  time.  In  other  words,  it  depends  upon  the  size  of 
the  ventricular  cavity  in  diastole,  the  number  and  intensity  of 
the  ventricular  contractions  and  the  degree  of  constriction  of  the 
hlood-vessels.  The  latter,  in  the  lesser  circulation,  depends  pri- 
marily upon  the  condition  of  the  lungs ;  whereas,  in  the  greater 
circulation,  it  depends  upon  the  condition  of  the  smooth  muscle- 
fibres  of  the  arteries  and  upon  the  vasomotor  nerves  which  supply 
them. 

During  the  life  of  a  healthy  individual,  the  blood  flows  at 
varying  rates  of  speed — rapidly  when  the  cells  need  much  oxygen 
or  food  material,  slowly  when  this  need  is  small.  As  stated  above, 
it  is  possible  that  the  blood  supply  to  an  organ,  or  possibly  to 
several  organs,  should  vary  greatly  without  affecting  the  general 
blood-flow.  This  is  brought  about  by  a  contraction  in  one  set  of 
vessels,  compensating  for  a  dilatation  in  another  set.  Yet  this 
compensation  cannot  meet  all  emergencies  on  account  of  the  lim- 
ited quantity  of  blood  in  the  body.  When  large  amounts  of  blood 
are  needed  in  several  parts  of  the  body  at  the  same  time,  they  can 
be  furnished  only  by  increasing  the  velocity  of  the  general  blood- 
stream. 

We  might  think  that  propelling  a  larger  amount  of 
blood  would  not  necessarily  increase  the  work  of  the  heart,  for, 
as  the  volume  of  blood  increased,  the  general  blood-pressure 
might  be  so  decreased  that  the  two  would  counterbalance  each 
other.  As  a  matter  of  fact,  however,  this  does  not  occur,  and, 
indeed,  could  not  occur,  on  account  of  the  relations  that  exist 
between  the  amount  of  blood  propelled,  the  general  pressure  and 
the  rate  of  flow.  For  example,  if  an  extra  supply  of  blood  to  the 
body  were  necessary,  a  diminution  in  the  general  arterial  pressure 
would  so  reduce  the  difference  in  pressure  between  the  arteries 
and  the  veins  that  the  rate  of  flow  in  the  capillaries  would  be 
insufficient  to  keep  the  heart  supplied  with  fresh  blood.  Thus 
it  is  that  any  great  increase  in  the  rate  of  flow  is  incompatible 
with  a  lessened  arterial  pressure,  and  that  consequently  such  an 
increased  flow  necessarily  entails  more  work  for  the  heart. 

The  work  of  the  heart  may  be  increased  in 
another  way,  viz.,  by  increasing  the  periph- 
eral resistance.  The  latter  varies  frequently  and  consider- 
ably even  in  health,  for  we  know  that  the  irritation  of  numerous 


4  THE  BASIS  OF  SYMPTOMS 

sensory  nerves  will  call  forth  contractions  of  the  smaller 
arteries  and  therewith  increased  resistance.  It  is  theoretically 
possible  that  this  increased  resistance  should  be  overcome  without 
additional  work  for  the  heart,  provided  that  as  the  resistance  is 
increased,  the  amount  of  blood  delivered  is  correspondingly  de- 
creased. Such  a  condition,  however,  would  slow  the  circulation 
to  such  an  extent  that  the  body  could  not  perform  its  functions 
properly;  and,  as  a  matter  of  fact,  it  does  not  occur.  We  may 
say,  therefore,  that  any  marked  increase  in  the  peripheral  resis- 
tance necessitates  more  work  for  the  heart. 

The  heart  is,  as  amatter  of  fact,  thebestmotor 
known  to  man.  It  performs  equally  well  the  small 
amount  of  work  necessary  when  a  man  is  at  complete  rest,  and 
the  large  amount  called  forth  by  great  exertion.  It  possesses, 
therefore,  the  power  of  adapting  itself  to  the  varying  demands 
made  upon  it.  Not  every  man's  heart  is  capable  of  the  most 
extreme  exertion,  and  "a  tailor  in  a  large  city  could  hardly 
furnish  the  circulation  necessary  for  the  ascent  of  the  Matter- 
horn."  The  weight  of  the  muscular  tissue  of  the  heart — and 
with  this  its  capabilities — ^bears  a  certain  relation  to  the  weight 
of  the  skeletal  muscles.  The  tailor  is  unable  to  ascend  the  moun- 
tain mainly  because  his  general  musculature  is  weak.  If  this  be 
improved  by  training,  the  heart  also  increases  in  its  capabilities, 
and  usually  at  a  more  rapid  rate.  Indeed,  a  healthy 
heart  rarely  fails  in  any  effort.  It  possesses  extreme 
adaptability,  and,  what  is  of  greater  importance,  the  adapta- 
tion occurs  precisely  at  the  time  when  most 
needed.  To  this  fact  the  body  owes  its  remarkable  capa- 
city for  work.  For  example,  when  a  ventricle  in  diastole 
becomes  unusually  filled  (even  up  to  six  times  its  customary 
capacity),^  the  next  systole,  though  it  may  not  drive  out  all  the 
blood,  propels  at  least  several  times  the  ordinary  quantity.  Fur- 
thermore, if  the  arterial  resistance  be  suddenly  increased,  it  is 
as  promptly  overcome  by  the  succeeding  ventricular  contractions. 
There  is  no  time  lost  in  experimentation:  the  demand  and  the 
accompHshment  occur  together.*  This  wonderful  adap- 
tability of  the  heart  expresses  itself  both  in  its 
powers  of  dilatation  and  of  contraction.  Thus  in 
d  i  a  s  t  o  1  e  the  ventricles  will  readily  expand  and  take  up  greater 
amounts  of  blood  without  a  corresponding  increase  in  their  ten- 


THE  CIRCULATION  £ 

sion.  Only  a  slight  pressure  is  necessary  to  distend  the  heart 
after  the  first  short  period  of  suction  is  passed.^  When  the 
ventricle  is  nearly  filled,  however,  the  tension  rapidly  increases. 
The  same  occurs  even  though  much  larger  amounts  of  blood  must 
flow  into  the  heart  during  each  diastole.  The  elasticity  of  the 
heart-muscle,  which  governs  the  resistance  to  the  inflowing  blood, 
must,  therefore,  vary  with  the  amount  of  fluid  that  is  to  enter. 
By  means  of  this  variation  it  is  possible  for  the  ventricle  to 
receive  very  different  amounts  of  blood  within  the  same  period  of 
time. 

The  contractility  of  the  heart  likewise  bears  a 
certain  relation  to  the  amount  of  blood  to  be  propelled:  it  also 
accommodates  itself  to  the  increased  demand.  The  ventricle  is 
able,  therefore,  to  expel  almost  completely  much  more  blood  than 
usual,  and  this  even  against  greatly  increased  resistance. 

This  remarkable  adaptability  is  usually  regarded  as  a  func- 
tion of  the  muscle  itself  f  for  the  ventricular  apex  possesses  the 
above  properties  to  precisely  the  same  degree  as  does  the  intact 
organ.''^  To  those  who  regard  the  few  nerve  fibres  and  ganglion 
cells  in  the  apex  as  possessing  not  only  conducting  but  other 
higher  powers,  this  view  may  be  unsatisfactory.  At  any  rate, 
the  actual  cause  of  the  accommodation  is  no  better 
understood  than  is  that  of  the  automatic  beat  of  the  heart;  while 
additional  complexities  have  been  introduced  by  the  important 
studies  on  the  structure  of  the  conduction  system. 

So  far  as  we  know,  the  heart  uses  all  its  muscle-fibres  at  each 
contraction.  The  increasedwork,  therefore,  is  accom- 
plished not  by  calling  new  fibres  into  play,  but 
by  causing  the  old  to  contract  more  quickly  and 
more  energetically.  How  is  this  brought  about?  In 
a  skeletal  muscle,  poisoned  by  curare,  the  strength  of  the  con- 
traction depends  not  only  upon  the  stimulus  but  upon  the  weight 
to  be  lifted.  If  we  ascribe  similar  properties  to  the  heart  muscle, 
we  are  led  to  the  conclusion  that  the  amount  of  distention  directly 
regulates  the  force  of  the  subsequent  contraction,  v.  Frey 
rightly  remarks  that  the  response  occurs  too  quickly  to  be  a  reflex 
act.  "  It  frequently  happens  that  the  heart  does  not  feel  the  in- 
creased resistance  until  the  beginning  of  systole.  It  is  then  too 
late  for  a  reflex  adjustment,  and,  if  it  waited  for  that,  the  next 
contraction  would  be  abortive.    Experience,  however,  shows  that 


«  THE  BASIS  OF  SYMPTOMS 

this  is  not  the  case ;  indeed,  the  contractions  which  follow  immedi- 
ately after  an  increased  call  upon  the  heart  are,  as  a  rule,  unusually 
powerful." 

Although  the  nervous  system  is  not  necessary  for  this 
adaptation,  yet  it  would  seem  that  in  many  cases  both  the 
elasticity  and  the  contractility  may  be  increased 
by  nervous  influences.  Kauders®  has  performed  a  re- 
markable series  of  experiments,  in  which  he  has  shown  that  an 
increased  resistance,  produced  by  an  irritation  of  a  sensory  nerve 
— the  sciatic,  for  example — is  better  overcome  by  the  left  ven- 
tricle than  the  same  degree  of  resistance  produced  by  direct  com- 
pression of  the  aorta.  In  the  latter  case,  the  left  ventricle  failed 
to  do  its  work,  and  the  pressure  in  the  left  auricle  increased; 
whereas  in  the  former,  the  work  was  not  only  well  done,  but  the 
auricular  pressure  was  even  diminished.  The  left  ventricle 
worked  here  to  better  purpose,  probably  because  it  was  favored 
by  nervous  influences  from  the  medulla. 

As  has  been  shown  above,  when  the  peripheral  resistance  is 
increased,  or  when  there  is  a  demand  for  a  greater  blood  supply, 
the  heart  can  meet  the  new  requirements  only  by  doing  more 
work.  The  slightly  lengthened  systole,  which  may  occur  under 
these  circumstances,  and  which  amounts  to  not  more  than  from 
twenty  to  thirty  per  cent.,  does  not  lessen  the  work  sufficiently 
to  compensate  for  the  other  factors. 

The  heart's  capacity  for  work  is  indeed  very  great.  Even 
though,  experimentally,  the  amount  of  blood  in  the  ventricles 
during  diastole  be  increased  sixfold,  they  are  able  to  empty  them- 
selves almost  completely;  and  a  doubling  of  the  arterial  pressure 
does  not  cause  serious  embarrassment.  Yet,  on  the  other  hand, 
an  increase  in  the  heart's  activities  is  not  with- 
out its  disadvantages.  For,  in  the  first  place,  the  in- 
creased work  is  made  possible  only  by  increasing  the  chemical 
decompositions  in  its  muscle;  and,  in  the  second,  an  excessive 
rise  in  arterial  pressure  is  by  no  means  without  danger,  especially 
if  the  blood-vessels  are  not  perfectly  healthy. 

H3rpertrophy  of  the  Heart. — Frequent  and  marked  increase 
in  the  work  of  the  heart  leads  to  secondary  changes.  In 
this  respect,  so  far  as  we  know,  the  heart  acts  precisely  like  a 
striated  muscle.  Continued  exertion  leads  to  its  enlargement, 
owing  to  the  increase  in  size  and  number  of  its  muscle-fibres. 


THE  CIRCULATION  7 

It  then  reaches  a  new  equilibrium  and  is  able  to  accomplish  with- 
out effort  tasks  that  formerly  called  its  reserve  force  into  play. 
Bauer  designates  this  as  a  "strengthening  of  the 
h  e  a  r  t .  "  ^  When  an  increased  effort  is  demanded  of  it,  the 
work  is  divided  among  more  numerous  and  stronger  fibres,  and 
it  is  therefore  more  easily  performed.  The  extreme  limits  of 
accommodation  have  also  become  greater,  for  we  may  assume 
that  the  stronger  hypertrophied  muscle  possesses  a  greater  re- 
serve force  than  the  former  weak  muscle;  and  experience  seems 
to  bear  out  this  assumption. 

If  the  weight  of  the  heart  muscle  depends  upon  the  amount 
of  work  done,  we  should  expect  that  the  weight  would  vary  in 
different  individuals.^ °  In  the  numerous  and  careful  observa- 
tions of  W.  Miiller^^  and  of  Hirsch,^^  such  a  variation  has  been 
demonstrated,  there  being  a  definite  ratio  between  the 
weight  of  the  heart  and  the  total  weight  of  liv- 
ing body  tissue,  though  this  is  not  always  the  case,  espe- 
cially in  youth. ^^  We  have  no  method  of  directly  determining 
the  amount  of  work  that  has  been  performed  by  a  heart.  Perhaps 
it  would  be  of  value  to  know  the  work  done  by  the  body  as  a 
whole,  although  different  sorts  of  work  affect  the  circulation 
differently.  It  is  also  difficult  to  determine  the  total  weight  of 
living  tissue  in  a  body,  or  even  that  of  the  muscular  system,  which 
is  of  special  importance.  Thus  far,  statistics  have  dealt  with  the 
relation  that  exists  between  the  weight  of  the  heart  and  the  total 
body  weight;  and  although  the  latter  introduces  inaccuracies  on 
account  of  the  varying  amount  of  fat  and  the  presence  of  oedema, 
nevertheless  the  figures  from  a  large  amount  of  material  have 
shown  that  the  ratio  between  the  weight  of  the  heart  and  that 
of  the  body  varies  only  within  narrow  limits,  from  which  Hirsch 
concludes  that  the  activity  and  weight  of  the  body  musculature 
exercise  a  determining  influence  upon  the  weight  of  the  heart. 

If  this  ratio  of  the  weight  of  the  heart  to  the 
body  weight  be  increased,  we  speak  of  an  hyper- 
trophy of  the  heart.  Although  such  an  hypertrophy  may 
arise  from  a  variety  of  causes,  it  is  questionable  whether  it  ever 
results  from  prolonged  exertion  alone.  We  know  that  severe 
muscular  exertion  increases  the  weight  of  the  heart,  for  the 
amount  of  the  blood  to  be  propelled  is  much  greater  than  normal 


8  THE  BASIS  OF  SYMPTOMS 

and  the  arterial  pressure  is  not  diminished,  but  is  usually  in- 
creased.^^ Under  these  circumstances,  the  heart  necessarily  be- 
comes larger,  but  this  increase  in  size  is  usually  not  out  of  pro- 
portion to  the  accompanying  increase  in  the  skeletal  musculature. 
In  other  words,  the  relation  existing  between  the  heart-muscle 
and  the  skeletal  muscle  is  undisturbed,  and  in  this  sense  no  hyper- 
trophy arises.  We  possess  no  very  exact  anatomical  observations 
on  the  size  of  the  heart  under  such  conditions.  Clinical  exam- 
ination, however,  usually  fails  to  show  any  hypertrophy.  Yet 
some  observations  speak  in  favor  of  the  view  that  hypertrophy 
without  weakness  may  result  from  prolonged  over-exertion ;  and 
the  orthodiagraphic  method  of  examination  bears  out  this  concep- 
tion.*'* Race-horses  possess  relatively  large  hearts,  prolonged 
exertion  increases  the  weight  of  young  dogs'  hearts  to  a  rela- 
tively greater  extent  than  it  increases  the  weight  of  their  muscles,*® 
and  skee-runners  of  Denmark,  who  were  apparently  healthy,  have 
been  shown  in  several  instances  to  have  hypertrophy  of  the  left 
ventricle.  We  may  say,  nevertheless,  that  a  relative  increase  in 
the  weight  of  the  heart  as  a  result  of  over-exertion  is  a  great 
rarity,  and  that  when  it  occurs  it  is  usually  due  to  pathological 
changes  in  the  muscle.  We  shall  return  to  this  subject  in  speaking 
of  heart  hypertrophy. 

The  specialized  muscle  fibres  forming  the 
cardiac  conduction  system  do  not  participate  in  the 
hypertrophy  of  the  ordinary  heart-muscle. 

Valvular  Disease  of  the  Heart. — ^As  has  been  said,  the  heart 
possesses  the  power  of  adjusting  itself  to  varying  circulatory 
conditions  which  would  otherwise  interfere  seriously  with  the 
supply  of  blood  to  the  body.  It  exercises  this  power  not  only 
to  meet  the  varying  demands  made  upon  it  during  health,  but  to 
compensate  for  the  destructive  processes  wrought  by  disease. 

The  function  of  the  valves  of  the  heart ^'^  is  to 
direct  the  current  of  blood  in  the  proper  direction.  In  order  to 
prevent  leaks,  the  valves  must  be  intact,  they  must  be  properly 
controlled  by  the  papillary  muscles  and  the  chordae  tendinese,  while 
the  openings  which  they  close  must  be  reduced  in  size  by  the  con- 
traction of  the  surrounding  ring  of  muscle — a  most  important 
factor.  The  orifices  of  the  heart  become  much  smaller  during 
systole,  at  which  time  they  may  be  readily  closed ;  whereas  during 
diastole  they  are  relatively  too  large  for  the  valves. 


THE  CIRCULATION  9 

The  Etiology  o£  Valvular  Disease. — Diseases  of  the  valve 
segments  may  be  produced  by  micro-organisms  or  their 
toxins.^^  Acute  articular  rheumatism  and  the  septic  diseases 
are  the  most  frequent  causes ;  next  to  these  we  may  name  typhoid 
fever,  scarlet  fever,  variola,  chorea  and  gonorrhoea.  Indeed  any 
infectious  disease  may  injure  the  heart  valves  and  the  heart  muscle 
as  well. 

The  bacteria  most  frequently  found  in  acute 
endocarditis  are  the  streptococci,  staphylococci  and  pneumococci, 
although  other  organisms,  as  the  gonococci,  are  occasion? lly  pres- 
ent. In  a  number  of  instances,  as  in  gonorrhoeal  endocarditis,  the 
heart  is  simply  one  localizing  point  of  a  general  infection.  In 
other  cases,  as  in  the  acute  exanthemata,  the  heart  complications 
are  to  be  regarded  as  the  result  of  secondary  infections.  The 
original  disease  prepares  the  ground  for  the  invasion  of  the  organ- 
isms which  attack  the  heart  valves. 

Not  infrequently,  however,  no  bacteria  are 
found  in  the  endocardial  vegetations.  It  is  pos- 
sible in  such  instances  that  organisms  have  been  present,  but  that 
they  have  died  out,  or,  on  the  other  hand,  that  the  condition  may 
have  been  produced  not  by  the  local  action  of  micro-organisms, 
but  by  toxins  generated  in  some  other  part  of  the  body.  No 
micro-organisms  are  found,  as  a  rule,  in  the  endocarditides  compli- 
cating carcinoma,  tuberculosis  or  nephritis.  Not  infrequently 
none  has  been  found  in  the  rheumatic  endocarditis,  though  from 
other  cases  of  this  disease  various  bacteria  have  been  isolated. 
The  real  cause  of  the  heart  complications  of  rheumatism  is  of 
considerable  interest,  for  rheumatism  is  analogous  in  many  ways 
to  an  infection  with  pyogenic  cocci  ^^  (seep.  153). 

Infections  may  attack  different  parts  of  the  heart,  certain  ones 
showing  a  tendency  to  localize  on  the  valves,  others  to  involve 
more  especially  the  myocardium.  The  injury  to  the  valves  begins 
with  a  degeneration  of  the  endothelium,  quickly  followed  by  a 
deposit  of  blood-platelets  and  by  thrombi.  The  tissue  reaction 
comes  later,  and  is  more  marked  when  the  auriculoventricular 
valves  are  affected  than  when  the  semilunar  valves  are  diseased. 

It  is  not  our  purpose  to  discuss  the  different  anatomical  and 
clinical  forms  of  endocarditis.  Suffice  it  to  say  that  by  ulceration 
and  shrinkage  the  valves  may  be  shortened  or  perforated,  and 
that  by  adhesions  along  their  margins  the  orifices  may  be  nar- 


10  THE  BASIS  OF  SYMPTOMS 

rowed.  Furthermore,  owing  to  a  concomitant  myocardial  affec- 
tion, the  orifices  may  not  be  properly  closed  during  systole,  or  the 
auriculoventricular  valves  may  not  be  efficiently  controlled  by  the 
chordae  tendineae.  These  latter  factors  are  of  no  little  importance. 
For  example,  when  at  autopsy  we  see  only  a  slight  marginal  affec- 
tion of  the  mitral  leaflets,  whereas  during  life  there  had  been  a 
decided  functional  insufficiency,  we  must  regard  the  complicating 
myocarditis  rather  than  the  valve  lesion  as  the  cause  of  the  dis- 
turbances in  functions.  No  one  who  understands  the  closure 
of  the  auriculoventricular  orifices  can  believe  that  such  a  minimal 
affection  of  the  valve  could  possibly  be  the  sole  cause  of  a  serious 
insufficiency.  It  is  an  interesting  fact  that  the  endocarditides 
complicating  ulcerating  carcinomata  and  tuberculosis  are  much 
less  frequently  diagnosed  than  are  those  complicating  rheuma- 
tism. Since  a  myocarditis  is  usually  absent  in  these  cases,  the 
muscular  rings  contract  well  during  systole,  and  the  heart  is  less 
likely  to  be  rendered  insufficient  from  the  valvular  affection. 

Chronic  endarteritis  is  another  important 
factor  in  the  production  of  valvular  disease. 
This  usually  spreads  from  the  aorta  to  the  valves,  though  it  may 
arise  primarily  in  the  intima  of  the  valvular  vessels.  The 
great  significance  of  syphilitic  processes  at  the 
root  of  the  aorta  in  the  causation  of  aortic  insufficiency  is 
fully  recognized  to-day .2*^ 

Finally,  the  insufficiency  may  develop  because  the  valves  or 
chordae  tendinae  are  torn  during  very  severe  exertion,  as  the  result 
of  a  great  rise  in  intracardiac  pressure — a  very  uncommon  acci- 
dental 

The  large  thrombi  which  are  sometimes  found  in  the  left 
auricle  may  hinder  the  flow  of  blood,  and  even  produce  the  symp- 
toms of  a  mitral  stenosis.  The  clinical  signs  and  symptoms  so 
produced  are  not  as  yet  well  understood. 

The  effects  of  valvular  lesions  may  show  them- 
selves in  two  different  ways — either  the  orifices  are  not  properly 
closed  when  they  should  be  (insufficiency),  or  they  can- 
not be  opened  widely  enough  to  allow  the  blood  to  pass  through 
freely  (stenosis).  Whether,  in  a  given  case,  the  one  or  the 
other  occurs — or,  as  frequently  happens,  both  occur  together — 
depends  upon  the  nature  of  the  anatomical  changes  present. 

The  seat  of  the  disease  is  in  part  dependent 


THE  CIRCULATION  11 

upon  the  causative  factor.  Arteriosclerotic 
lesions  most  frequently  affect  the  left  semilunar  valves  on 
account  of  their  proximity  to  the  aorta.  As  a  rule,  a  fresh 
endocarditis  will  produce  an  insufficiency  and  not  a  sten- 
osis. The  valvular  vegetations  in  conjunction  with  the  diseased 
heart  muscle  render  the  closure  of  the  valves  imperfect;  whereas 
in  order  to  produce  a  stenosis,  a  chronic  inflammation  with  ulti- 
mate adhesions  between  the  valve  leaflets  is  necessary.  The 
grade  of  insufficiency,  or  of  stenosis,  i.e.,  the 
amount  of  blood  which  in  the  former  case  flows  back,  and  in 
the  latter  is  hindered  from  passing  through  the  orifice,  is  deter- 
mined partly  by  the  condition  of  the  heart  muscle  and  partly  by 
the  anatomical  changes  in  the  valves. 

Muscular  Insufficiency. — We  have  already  mentioned  the 
great  importance  of  a  proper  constriction  of  the  valvular  orifices 
during  systole  by  the  surrounding  ring  of  muscular  tissue.  A 
faulty  constriction  may  entail  serious  consequences,  and  the  so- 
called  muscular  insufficiencies  are  much  more  common  than  is 
generally  supposed. ^^  They  occur  most  frequently  as  a  result 
of  myocardial  disease;  and,  in  chronic  myocarditis,  especially, 
they  may  lead  to  precisely  the  same  disturbances  of  function  as 
does  a  shortening  of  the  valve  segments.  Indeed,  the  diagnosis 
between  the  two  is  often  extraordinarily  difficult;  and  many  re- 
ported instances  of  "  healed  valvular  disease "  are  doubtless 
merely  improved  cases  of  myocarditis  with  muscular  insufficiency. 

Muscular  insufficiencies  occur  much  more 
frequently  at  the  auriculoventricular  orifices 
than  at  thesemilunar  openings.  At  the  mitral  orifice 
they  are  usually  due  to  a  faulty  contraction  of  the  surrounding 
ring  of  muscle,  or  possibly  at  times  to  a  lack  of  control  of  the 
valve  segments  by  the  papillary  muscles  and  chordae  tendineae. 
On  the  right  side  of  the  heart  the  contraction  of  the  ventricle, 
as  a  whole,  is  usually  at  fault.  According  to  v.  Jiirgensen,  the 
slow  contraction  of  the  fatigued  muscle  may  also  interfere  with 
the  closure  of  the  valves.  The  term  relative  insuffi- 
ciency has  been  used  for  the  condition  in  which  the  orifice  is 
so  widened  that  the  valves  are  no  longer  able  to  close  it.  Al- 
though this  stretching  of  the  opening  may,  indeed,  occur,  we  must 
insist  that,  after  all,  the  essential  factor  is  not  the  dilatation  of 
the  ring,  but  the  faulty  constriction  during  systole. 


12  THE  BASIS  OF  SYMPTOMS 

A  relative  insufficiency  of  the  valves  at  the  entrance  to  the 
aorta  is  much  less  common.  At  times  it  is  due  to  an  insufficient 
development  of  the  muscle  just  beneath  the  semilunar  valves; 
or  it  may  originate  in  a  dilatation  of  the  fibrous  ring  at  the  begin- 
ning of  the  aorta. 

Aortic  Insufficiency. — It  is  now  necessary  to  point  out  how 
the  various  valvular  lesions  affect  the  distribution  of  the  blood 
in  the  body,  and  how  the  heart  accommodates  itself  to  the  new 
conditions  arising  from  the  valvular  defects. 

When  there  is  an  insufficiency  of  the  aortic  valves,  a  part  of 
the  blood  that  is  thrown  into  the  aorta  by  the  contraction  of  the 
left  ventricle  is  returned  into  that  cavity  during  diastole.  The 
amount  that  flows  back  is  determined  by  the  size  of  the 
pathological  opening  left  by  the  improper  closure  of  the  valves, 
by  the  difference  between  the  pressure  in  the  aorta  and  that 
in  the  ventricle,  and  by  the  duration  of  diastole.  An  increased 
heart-rate,  which  shortens  more  especially  the  diastolic  period, 
should  be  of  advantage  in  aortic  insufficiency,  since  it  lessens  the 
amount  of  the  leak  backward.^^  CHnically,  a  rapid  heart  action 
is  not  infrequently  found  associated  with  this  lesion,  but  we  are 
ignorant  of  its  cause.  The  walls  of  the  ventricle  are  very  flabby 
during  diastole,  so  that  they  are  easily  stretched  by  the  stream 
of  blood  flowing  in  under  high  pressure  from  the  aorta.  This 
leads  to  a  dilatation  of  the  ventricular  cavity,  the  amount  of 
dilatation  depending  upon  the  quantity  of  blood  which  flows  back 
and  upon  the  degree  of  elasticity  of  the  muscle  wall.  In  early 
diastole  the  ventricular  wall  is  particularly  flabby,  but  as  the 
filling  proceeds,  it  becomes  more  tense,  while  toward  the  end  of 
diastole  the  tension  increases  rapidly.  By  thus  increasing  the 
resistance  to  the  inflowing  blood  the  ventricle  can  protect  itself 
against  overdistention.^^  We  have  already  seen  that  this  re- 
sistance varies  normally  with  the  varying  amounts  of  blood  which 
must  be  delivered,  and  that  the  ventricular  wall  becomes  more 
distensible  whenever  larger  quantities  of  blood  must  be  propelled 
(p.  5).  The  abnormal  filling  of  the  ventricle  in  aortic  insuffi- 
ciency may  or  may  not  act  as  a  hindrance  to  the  entrance  of  blood 
from  the  auricle.  Whether  the  one  or  the  other  occurs  depends 
mainly  upon  this  variation  in  the  elasticity  of  the  ventricular 
musculature.  If  distention  and  elasticity  go  hand 
in  hand  in  order  to  accommodate  the  extra  amount  of  blood. 


THE  CIRCULATION  IS 

it  is  possible  that  the  auricle  will  empty  itself  as  usual  and  that 
there  will  be  no  disturbance  in  the  flow  of  blood  from  the  lungs. 
Such  cases  do  occur,  and  have  been  observed  both  clinically  and 
experimentally. 

On  the  other  hand,  many  patients  with  aortic  in- 
sufficiency show  symptoms  referable  to  a  dam- 
ming back  of  blood  into  the  lungs.  Their  dyspnoea 
and  the  marked  accentuation  of  the  pulmonic  second  sound  are  in- 
dicative of  increased  pressure  in  the  pulmonary  circulation.  It 
is  easy  to  understand  how  this  might  be  brought  about  by  an 
uncomplicated  aortic  regurgitation;  it  is  only  necessary  for  the 
tension  of  the  ventricular  wall  to  increase  before  all  the  blood 
from  the  lungs  has  entered  the  ventricle.  This  would  hinder  the 
entrance  of  blood  from  the  auricle  and  would  tend  to  produce  a 
pulmonary  congestion.  Furthermore,  the  suction  of  blood  from 
the  lungs  due  to  the  expansion  of  the  ventricle  in  early  diastole 
may  also  be  diminished  owing  to  the  stream  entering  from  the 
aorta.  We  have  both  clinical  and  experimental  evidence  that 
under  such  circumstances  a  pure  aortic  regurgitation  may  cause 
a  stasis  of  blood  in  the  lungs.^^ 

In  spite  of  its  increased  contents,  the  left  ventricle  in  aortic 
regurgitation  empties  itself  in  about  the  same  length  of  time  as 
does  the  normal  ventricle,  although  according  to  recent  observa- 
tions ^^  it  may  not  empty  itself  so  completely.  For  there  is  evi- 
dence that  the  blood  is  not  usually  entirely  expelled  during  systole 
if  the  ventricular  cavity  be  greatly  dilated.  This  fact,  however, 
is  really  of  no  great  importance  in  the  matter  under  consideration, 
for  so  long  as  the  ventricular  muscle  is  efficient,  the  residue  of 
blood  left  in  the  cavity  at  the  end  of  systole  is  insignificant  com- 
pared with  that  which  streams  back  from  the  aorta  during  diastole. 

In  a  series  of  classical  experiments,  Rosenbach^^  has  shown 
that  after  artificially  puncturing  the  aortic  valves  of  a  dog,  all 
the  symptoms  of  an  insufficiency  occur  without  any  marked 
lowering  of  the  mean  arterial  pressure.  This  experiment  has 
been  frequently  repeated,  but  with  varying  results.  In  rabbits, 
the  mean  pressure  is  usually  lowered  as  a  result  of  the  operation, 
whereas  in  dogs  it  may  remain  normal,  be  lowered  or  even  be 
raised.  These  variable  results  probably  depend,  in  the  first  place, 
upon  the  strength  of  the  heart,  and,  in  the  second  place,  upon  the 
severity  of  the  lesion.    The  rabbit's  weak  heart  cannot  so  readily 


14  THE  BASIS  OF  SYMPTOMS 

compensate  for  the  injury,  and  its  blood-pressure  sinks.  The 
dog's  stronger  heart  readily  overcomes  a  slight  injury  (e.g., 
puncture  of  the  valve  by  a  rod)  ;  whereas  a  more  serious  one 
(e.g.,  tearing  off  a  valve)  results  in  a  lowered  mean  blood-pressure. 
It  is  possible  that  nervous  reflexes  may  play  some  part  in  main- 
taining the  blood-pressure  in  these  cases,  especially  when  the 
injury  to  the  valves  is  sudden.  The  principal  factor,  however, 
is  undoubtedly  the  accommodation  of  the  heart-muscle  itself. 

In  man,  moderate  and  severe  cases  of  aortic 
insufficiency  are  generally  associated  with  a 
very  considerable  pulse-pressure,  evidenced  by  an 
augmented  systolic  and  a  diminished  diastolic  pressure. ^^ 

All  our  experience  goes  to  prove  that  a  muscle  will  hyper- 
trophy if  it  does  an  increased  amount  of  work  over  a  long  period 
of  time.  We  should  expect  the  same  rule  to  apply  to  individual 
parts  of  the  heart,  especially  since  their  work  is  not  limited  to 
eight  or  ten  hours  a  day,  but  is  continuous,  day  and  night.  The 
work  of  the  left  ventricle  is  increased  in  aortic 
insufficiency,  for  it  must  propel  not  only  the  blood  which 
enters  from  the  auricle,  but,  in  addition,  that  which  leaks  back 
from  the  aorta  during  each  diastole.  The  total  amount  expelled 
is  therefore  increased,  while  the  pressure  against  which  it  is 
expelled  is  but  little  changed.  Practical  observations  have  shown 
that  in  aortic  insufficiency  there  is  always  an 
hypertrophy  of  the  left  ventricle  with  a  dilata- 
tion of  its  cavity.  The  cavity  is  dilated  on  account  of 
the  abnormal  amount  of  blood  which  it  must  accommodate,  and 
the  walls  hypertrophy  because  of  the  extra  work  thrown  upon 
them.  If  the  conditions  for  an  increased  pressure  in  the  left 
auricle,  as  described  above  (p.  13),  are  present,  then  its  work  and 
the  work  of  the  right  ventricle  are  also  increased,  and  hyper- 
trophy of  these  two  parts  of  the  heart  results. 

Unfortunately  we  possess  no  exact  anatomical  data  concern- 
ing these  last  points.  The  thickness  of  the  heart  wall  at  autopsy 
is  greatly  influenced  by  the  condition  of  the  heart  when  it  stopped 
beating,  whether  it  was  in  systole  or  diastole,  so  that  we  cannot 
judge  from  such  measurements  as  to  whether  such  slight  hyper- 
trophy as  would  occur  in  the  left  auricle  and  the  right  ventricle 
in  cases  of  aortic  insufficiency  was  present  or  not.     Perhaps  the 


THE  CIRCULATION  15 

employment  of  W.  Miiller's  ^®  method  will  throw  more  light  on 
the  subject. 

It  is  often  erroneously  stated  that  every  aortic  insufficiency 
is  accompanied  by  a  considerable,  and  easily  demonstrable,  en- 
largement of  the  left  ventricle.  When  the  muscle  is  efficient,  the 
degree  of  dilatation  and  hypertrophy  is  directly  dependent  upon 
the  amount  of  blood  which  regurgitates  from  the  aorta.  If  a 
third  or  fourth  of  the  volume  driven  out  leaks  back,  it  is  possible 
that  the  lesion  can  readily  be  diagnosed  clinically  from  the  charac- 
teristic murmur,  but  that  the  hypertrophy  and  dilatation  of  the 
left  ventricle  will  be  so  slight  as  to  elude  the  ordinary  methods 
of  physical  examination. 

Aortic  Stenosis. — In  stenosis  of  the  aortic  orifice  the  flow 
of  blood  from  the  left  ventricle  into  the  aorta  is  impeded.  It  is 
probable  that  even  under  physiological  conditions  this  orifice  is 
not  round  and  large  during  systole,  but  that  it  is  encroached  upon 
by  the  contraction  of  the  muscle  which  surrounds  it  and  which 
is  an  extension  upward  of  the  ventricular  musculature.  The 
blood  flows  smoothly  up  to  the  contracted  portion  and  then  out 
into  the  wider  aorta.  Under  ordinary  conditions,  the  delicate 
semilunar  valves  are  easily  thrust  aside.  If,  on  account  of  dis- 
ease, they  become  stiff  and  rigid,  they  hinder  the  escape  of  blood 
more  or  less.  The  ventricle  must,  therefore,  work  against  a 
greater  resistance.  The  prolongation  of  the  ventricular  systole, 
which  may  be  from  seven  to  thirty  per  cent.^^  longer  than  normal, 
is  by  no  means  proportionate  to  the  increased  resistance.  The 
lesion,  therefore,  causes  a  greater  amount  of  work  to  be  thrown 
on  the  left  ventricle.  As  a  result  of  this  extra  work,  we 
always  find  an  hypertrophied  left  ventricle  in 
cases  of  aortic  stenosis.  At  first,  there  is  no  dilatation 
of  its  cavity,  and  the  auricle,  lungs  and  right  heart  are  entirely 
unaffected.  A  dilatation  will  occur  only  when  the  heart 
muscle  can  no  longer  accomplish  the  additional  work,  either 
because  the  obstruction  has  become  too  great,  or  because  the 
muscle  itself  is  weakened. 

Mitral  Stenosis. — Lesions  at  the  mitral  orifice  produce  more 
complicated  conditions  than  do  those  at  the  aortic,  because  they 
lead  to  changes  in  the  lungs  and  in  the  right  heart. 

In  mitral  stenosis  ^^  there  is  a  hindrance  to  the  flow  of  blood 
from   the   left   auricle   into   the   left   ventricle.     When   the 


16  THE  BASIS  OF  SYMPTOMS 

auricle  contracts,  it  must  overcome  a  greater  re- 
sistance, and  this  additional  work  leads  to  an 
hypertrophy  of  its  musculature..  On  account  of  the 
thin  walls,  however,  its  capacity  for  increased  work  is  very  lim- 
ited, so  that  a  dilatation  occurs  much  earlier  than  in  the 
case  of  the  ventricle.  An  important  factor  contributing  to  this 
dilatation  is  the  increased  pressure  which  prevails  in  the  pul- 
monary veins.  At  each  systole  of  the  auricle,  an  unusual  pro- 
fHDrtion  of  its  contents  is  forced  back  into  the  pulmonary  veins 
owing  to  the  obstruction  in  front  at  the  mitral  orifice.  During 
diastole,  therefore,  the  blood  from  the  lungs  enters  the  auricle 
with  more  than  ordinary  force,  the  diastolic  pressure  in  the 
auricle  is  increased,  and,  owing  to  the  diminished  muscular  tonus 
during  this  period,  the  cavity  becomes  dilated. 

The  abnormal  pressure  in  the  pulmonary  veins  is  transmitted 
through  the  short  and  relatively  wide  capillaries  of  the  lungs  to 
the  pulmonary  artery.  Everything  now  depends  upon  the  be- 
havior of  the  right  ventricle,  which  is  placed  in  much  the  same 
position  as  is  the  left  ventricle  in  a  case  of  aortic  stenosis.  The 
pressure  in  the  pulmonary  artery  must  be  maintained  at  a  higher 
level  than  usual,  in  order  to  conserve  the  difference  in  pressure 
between  the  artery  and  vein,  and,  in  turn,  the  flow  of  blood 
through  the  lungs.  We  recognize  this  increased  pul- 
monary pressure,  clinically,  by  the  accentua- 
tion of  the  pulmonic  second  sound.  The  extra 
work  necessitated  by  this  high  pressure  is  thrown  upon 
the  right  ventricle  and  leads  to  its  hypertrophy. 

The  effect  of  mitral  stenosis  upon  the  left 
ventricle ^2  depends  entirely  upon  the  amount  of  blood  that 
the  latter  receives.  When  the  stenosis  is  slight  and  the  right 
heart  maintains  the  necessary  pressure  in  the  pulmonary  system, 
the  left  ventricle  is  not  affected,  for  it  receives  its  customary- 
supply  of  blood.  If,  however,  the  right  heart  cannot  compensate 
for  the  obstruction  present,  then  the  left  ventricle  is  not  filled  to 
the  normal  amount,  its  work  is  diminished  and  its  muscle  atro- 
phies. This  reasoning  has  been  confirmed  by  the  findings  at 
autopsy.  In  pure  mitral  stenosis,  the  left  ven- 
tricle is  either  normal  or  atrophied.  If  at  times 
an  hypertrophy  of  the  left  ventricle  has  been  found,  it  is  to  be 
attributed  to  an  associated  mitral  insufficiency  of  simultaneous 


THE  CIRCULATION  17 

or  previous  origin.  The  two  lesions  are  very  frequently  com- 
bined, and  this  naturally  modifies  the  resulting  anatomical  changes. 

Mitral  Insufficiency. — The  conditions  present  in  mitral  in- 
sufficiency are  very  similar  to  those  in  mitral  stenosis.  A  part 
of  the  contents  of  the  left  ventricle  is  thrown  back  into  the  auricle 
during  systole,  and  the  degree  of  insufficiency  may  be  measured 
by  the  amount  of  blood  which  takes  this  backward  course.  The 
lungs  and  the  right  heart  are  affected  precisely  as  in  the  case  of 
mitral  stenosis.  The  left  auricle  becomes  dilated 
and  hypertrophied,  and  the  blood-pressure  in  the  pul- 
monary system  is  raised.  The  work  of  the  right  ven- 
tricle is  increased  by  the  heightened  pulmonary  pressure ; 
whereas  it  tends  to  be  lessened  by  the  diminished  amount  of  blood 
that  comes  to  it,  and  consequently  by  the  lessened  systolic  output. 
Ordinarily  the  effect  of  the  increased  pulmonic  pressure  pre- 
dominates, and  we  find  an  accentuated  pulmonic  sec- 
ond sound  and  at  autopsy  an  hypertrophied  right 
ventricle.  Sometimes  these  are  not  present,  and  we  may 
then  assume  that  the  left  auricle  dilates  at  each  ventricular  con- 
traction to  receive  the  regurgitated  blood  and  that  it  empties  itself 
during  its  systole,  thereby  compensating  in  a  measure  for  the 
mitral  defect.  Such  favorable  conditions  could  only  occur  in  the 
milder  grades  of  insufficiency.^^ 

During  diastole  the  blood  flows  into  the  left  ventricle  with 
unusual  force,  owing  to  the  increased  pressure  in  the  auricle  and 
the  pulmonary  veins.  There  is  also  more  blood  to  flow  in  on 
account  of  the  overfilling  of  the  left  auricle  and  the  pulmonary 
system  with  regurgitated  blood.  A  certain  amount  of  blood, 
varying  according  to  the  grade  of  insufficiency,  moves  back  and 
forth  at  each  beat  between  the  left  ventricle  on  the  one  hand, 
and  the  left  auricle  and  pulmonary  blood-vessels  on  the  other. 
The  ventricle,  therefore,  pumps  more  blood  than  usual,  which 
we  have  no  reason  to  believe  that  it  does  against  a  lessened  re- 
sistance, for  the  mitral  leak  is  hardly  large  enough  to  bring  that 
about.  The  increased  work  performed  by  the  left 
ventricle  leads  to  its  hypertrophy,  a  condition 
always  present  in  mitral  insufficiency.^*  The  ventricular 
cavityalsobecomesdilated  owing  to  the  larger  quantity 
of  blood  which  it  receives  during  diastole.  Thus,  hypertrophy 
and  dilatation  of  the  left  ventricle  go  hand  in  hand.     This  com- 

2 


18  THE  BASIS  OF  SYMPTOMS 

bination  is  of  advantage  not  only  in  propelling  the  blood,  but 
probably  also  in  withdrawing  it  from  the  auricle  and  from  the 
lungs  during  diastole. 

Valvular  Lesions  of  the  Right  Side  of  the  Heart. — Valvu- 
lar lesions  of  the  right  side  of  the  heart  give  rise  to  second- 
ary changes  very  similar  to  those  which  take  place  on  the  left  side 
under  corresponding  conditions.  We  must  remember,  however, 
that  the  musculature  of  the  right  ventricle  is  relatively  weak,  and 
that  it  is  not  capable  of  the  same  degree  of  accommodation  as  is 
that  of  the  left  ventricle ;  furthermore,  that  there  is  no  powerful 
ventricle  directly  behind  the  tricuspid  orifice  to  compensate  for  its 
disabilities.  Valvular  lesions  of  the  right  side  of 
the  heart  are  characterized  by  the  fact  that  they 
develop  almost  exclusively  during  the  fetal 
period.  Although  the  tricuspid  valve  is  but  rarely  the  seat 
of  a  verrucous  inflammation  in  later  life,  a  relative  insufficiency 
of  the  tricuspid  orifice  is  no  uncommon  sequel  to  valvular  disease 
of  the  left  heart.^^  Disease  of  the  pulmonary  valve,  developing 
during  adult  life,  is  a  great  rarity. 

During  fetal  life,  micro-organisms  in  the  blood-stream  usually 
injure  the  valves  of  the  right  side  of  the  heart,  whereas  in  extra- 
uterine life  those  of  the  left  side  are  the  ones  which  are  more 
frequently  affected.  One  is  tempted  to  explain  this  remarkable 
fact  by  the  relative  amounts  of  work  done  by  the  two  sides  or 
by  the  influence  of  the  aerated  blood,  since  in  fetal  life  it  is  the 
right  side  which  receives  the  oxygenated  blood.  We  have  no 
proof,  however,  for  either  of  these  two  hypotheses.  A  fetal 
endocarditis  is  not  uncommonly  associated  with 
congenital  malformations,  such  as  septum  de- 
fects, transposition  of  the  arteries  or  persist- 
ence of  the  ductus  Botalli.^^  Possibly  the  malforma- 
tions are  primary  and  tend  to  diminish  the  resistance  of  the  endo- 
cardium to  infectious  agents.  This  hypothesis  would  at  least 
be  the  most  natural  explanation  of  their  almost  exclusive  pre- 
dilection for  the  right  heart.  The  most  important  of  the  con- 
genital heart  lesions  is  pulmonary  stenosis.  This  anomaly,  which 
may  be  situated  in  the  neighborhood  of  the  valves,  or  at  the 
conus  arteriosus,  leads  to  hypertrophy  of  the  right  ventricle  pre- 
cisely as  does  an  aortic  stenosis  to  hypertrophy  of  the  left.  Of 
the  purely  developmental  anomalies  only  defects  in  the  ventricular 


THE  CIRCULATION  19 

septum  are  frequent;  in  these  a  systolic  murmur  is  heard  over 
the  sternum  and  occasionally  over  both  lungs.  Ordinarily  they 
cause  no  circulatory  disturbances. 

Combined  Valvular  Lesions. — The  effects  of  valvular  dis- 
ease may  be  best  studied  when  there  is  a  simple  stenosis  or  in- 
sufficiency of  a  single  valve,  and  when  no  complications  are  pres- 
ent. Yet  such  simple  cases  are  rare.  In  the  right  heart  we  fre- 
quently find  associated  defects  in  development;  in  the  left  heart, 
combinations  of  several  valvular  lesions.  Pure  mitral  insufficiency 
is  comparatively  frequent,  but  uncomplicated  cases  of  mitral  sten- 
osis, or  of  aortic  insufficiency  or  of  aortic  stenosis,  are  much  rarer 
than  are  the  combinations  of  mitral  insufficiency  with 
mitral  stenosis,  aortic  insuffiency  with  aortic 
stenosis  or  aortic  insufficiency  with  double 
mitral  disease.  The  aortic  semilunar  valves  are  closely  ad- 
jacent to  the  aortic  segment  of  the  mitral  valve,  and  when  the 
latter  is  diseased  the  former  are  also  frequently  affected. 

The  effect  of  a  combination  of  valvular 
lesions  is  the  resultant  of  the  effects  of  the  individual  lesions. 
They  may  even  tend  to  neutralize  each  other  so  that  the  com- 
bination is  less  harmful  than  are  the  individual  lesions.  For 
example,  the  dilatation  of  the  left  ventricle  resulting  from  aortic 
insufficiency  may  be  lessened  by  an  associated  aortic  stenosis ;  and 
although  both  mitral  insufficiency  and  mitral  stenosis  act  similarly 
in  damming  the  blood  back  into  the  lungs,  they  tend  to  neutralize 
each  other  so  far  as  their  effect  upon  the  left  ventricle  is  con- 
cerned. Indeed,  we  may  say  in  general  that  the  stenosis  which 
so  often  follows  a  valvular  insufficiency  may  be  of  advantage  in 
that  it  limits  the  amount  of  blood  which  regurgitates.  Caution  is 
indicated,  however,  in  deciding  this  question  in  the  individual 
case,  for  other  factors,  especially  the  condition  of  the  heart- 
muscle,  are  often  of  paramount  importance. 

Hypertrophy  of  the  Right  Ventricle. — The  work  of  the 
right  ventricle  is  directly  dependent  upon  the  condition  of  the 
pulmonary  circulation.  Anything  that  increases  the 
pressure  in  the  pulmonary  vessels  increases  the 
resistance  against  which  the  right  ventricle 
must  force  the  blood.  We  have  seen  an  illustration  of 
this  in  the  case  of  mitral  valve  disease.  Similar  effects  may 
result  from  a  weakened  left  ventricle  which  cannot  com- 


20  THE  BASIS  OF  SYMPTOMS 

pletely  empty  itself  during  systole.  Its  power  of  suction  in 
early  diastole  is  also  diminished,  for  this  power  depends  upon  the 
elastic  rebound  after  a  powerful  contraction,^^  or  possibly  upon 
an  active  process  in  the  muscle-fibres  themselves.^^  The  unex- 
pelled  blood  in  the  ventricle  and  the  lessened  suction  hinder  the 
entrance  of  blood  from  the  lungs,  raise  the  pressure  in  the  pul- 
monary circulation,  and  so  increase  the  work  of  the  right  ventricle. 
We  have  seen  that  the  left  ventricle  can  alter  its  elasticity  under 
certain  circumstances,  enabling  it  to  hold  a  larger  amount  of  blood 
in  each  diastole,  and  the  question  naturally  arises,  "Why  does 
not  the  weakened  ventricle  do  this  instead  of  damming  the  blood 
back  into  the  lungs?"  The  reason  seems  to  be  that  the  muscle 
tissue  is  so  diseased  that  its  elasticity  as  well  as  its  contractility 
is  diminished. 

Primary  disturbances  of  the  circulation  in 
the  lungs  may  likewise  affect  the  right  heart. 
We  know  that  the  resistance  to  the  blood-flow  in  the  pulmonary 
vessels  is  normally  very  slight.  Though  large  vascular  areas, 
even  up  to  three-quarters  of  the  total,  may  be  thrown  out  of  func- 
tion, a  sufficient  amount  of  blood  may  still  be  sent  through  to  the 
left  ventricle.^^  The  right  heart  simply  propels  the  blood  through 
the  remaining  pulmonary  vessels  with  a  greater  velocity.  The 
open  vessels  are,  indeed,  dilated,  but  not  sufficiently  to  compen- 
sate for  the  others  thrown  out  of  function,  so  that  the  pressure 
in  the  pulmonary  artery  rises.  The  dilatation  of  the  vessels  re- 
maining open  is  quite  different  from  that  which  takes  place  under 
corresponding  circumstances  in  the  greater  circulation.  In  the 
latter,  when  a  vessel  is  closed,  the  general  pressure  does  not  neces- 
sarily rise,  because  vasomotor  influences  may  produce  a  com- 
pensatory vascular  dilatation  in  other  parts  of  the  body;  in  the 
lungs,  the  resulting  dilatation  is  purely  passive,  and  is  due  to  the 
increase  of  pressure  in  the  pulmonary  artery  caused  by  the  ob- 
struction in  one  of  its  branches.  This  increased  pressure  necessi- 
tates an  increase  in  the  amoimt  of  work  done  by  the  right 
ventricle,  which  will  be  greater  or  less  in  any  given  case,  depend- 
ing upon  the  number  and  dilatability  of  the  pulmonary  vessels 
remaining  open.  In  case  the  increased  work  persists  for  some 
time,  hypertrophy  of  the  right  ventricle  will  ensue. 

For  this  reason  the  right  ventricle  becomes  hypertrophied  as 
a  result  of  sclerosis  of  the  pulmonary  artery  (a  rare 


THE  CIRCULATION  21 

condition)  ;  also  in  those  more  frequent  pulmonary  diseases  which 
lead  to  destruction  or  compression  of  the  vessels,  such  as  cir- 
rhosis of  the  lungs  from  various  causes,  chronic  pneu- 
monia, pulmonary  emphysema  and  thoracic  de- 
formities.^® Long-continued  bronchitis  is  often 
described  as  a  cause  of  hypertrophy  of  the  right  ventricle,  and 
especially  as  a  cause  of  the  enlarged  right  heart  found  in  children 
who  are  subjects  of  this  disease.  It  is  difficult  to  say  whether 
the  bronchial  inflammation  directly  increases  blood  pressure  or 
whether  the  continual  coughing  gives  rise  to  the  hypertrophy  of 
the  right  ventricle  by  its  effect  on  the  intrathoracic  pressure. 

It  has  often  been  asserted  that  we  have  in  tuberculosis 
an  exception  to  the  general  rule  that  chronic  pulmonary  disease 
leads  to  hypertrophy  of  the  right  ventricle.  To  account  for  this 
supposed  exception,  numerous  explanations  have  been  offered,  one 
of  which  is  to  the  effect  that  the  total  quantity  of  blood  is 
diminished  in  this  disease.  We  now  know,  however,  that  tuber- 
culosis is  no  exception  to  the  general  rule.  Anatomical  investi- 
gations*^ have  shown  that,  in  proportion  to  the  body  weight, 
the  weight  of  the  right  ventricle  is  increased  in  a  large  proportion 
of  those  who  die  of  consumption.  Clinical  evidence  supports 
the  same  view,  for  it  is  not  uncommon  to  find  an  accentuation  of 
the  pulmonic  second  sound  in  tuberculous  patients.  Nor  from 
the  orthodiagraphic  method  ^^  cain  any  other  conclusion  be  drawn. 
To  what  extent  individuals  of  the  tuberculous  habitus  are  en- 
dowed with  especially  small  hearts,  and  what  bearing  the  latter 
have  on  the  development  of  the  disease,  are  questions  that  cannot 
be  entered  into  in  this  place.* ^ 

Extensive  pleuritic  adhesions  may  also  lead  to  an 
hypertrophy  of  the  right  ventricle.  Their  interference  with  the 
movements  of  the  lungs  doubtless  deprives  the  pulmonary  circu- 
lation of  the  assistance  in  the  aspiration  of  the  blood  usually 
derived  from  these  movements,  so  that  additional  work  is  thrown 
on  the  right  ventricle. 

Hypertrophy  of  the  Left  Ventricle. — .The  work  of  the 
left  ventricle  is  made  greater  by  any  increase 
in  the  resistance  to  the  flow  of  blood  through  the 
peripheral  arteries.  A  temporary  increase  in  resistance 
arising  from  vasomotor  influences  is  not  an  uncommon  physio- 
logical occurrence. 


22  THE  BASIS  OF  SYMPTOMS 

Of  considerable  importance  as  a  cause  of  permanent  increase 
in  the  arterial  pressure  are  certain  forms  of  arterioscle- 
rosis.^^ When  the  elasticity  of  the  arteries  is  diminished, 
they  offer  a  greater  resistance  to  dilating  forces ;  but  once  having 
been  dilated  they  do  not  so  easily  recover  their  original  size. 
Various  opposing  factors  must,  therefore,  be  considered.  The 
rigidity  of  certain  areas  may  be  neutralized  by  dilatation  of  other 
areas.  There  is  also  a  tendency  for  the  affected  vessels  to  become 
permanently  dilated.  The  precise  effect  of  these  various  opposing 
factors  can  only  be  determined  by  experimental  investigations. 

As  a  matter  of  fact,  hypertrophy  of  the  left  ventricle  develops 
in  only  a  small  proportion  of  patients  with  uncomplicated  arterio- 
sclerosis. Those  types  accompanied  by  hyperten- 
sion are  the  ones  which  regularly  exhibit  such  an 
hypertrophy.  It  is  present,  therefore,  especially  in  cases  of 
sclerosis  of  the  first  part  of  the  aorta  and  in 
extensive  sclerosis  of  the  splanchnic  vessels. 
The  splanchnic  arteries  are  of  such  paramount  importance  in 
controlling  the  peripheral  resistance  that  when  they  are  dis- 
eased it  is  difficult  or  impossible  to  attain  compensation  by  a 
dilatation  of  other  vascular  areas.  Other  uncomplicated  cases 
of  arteriosclerosis  rarely  show  any  marked  degree  of  heart  hyper- 
trophy. The  frequency  of  hypertension  in  arteriosclerosis  is  still 
undetermined.  Besides  the  paramount  influence  of  the  localiza- 
tion of  the  process,  as  noted  above,  there  are  other  factors,  such 
as  the  social  status,  mode  of  living  and  perhaps  race,  that  play 
a  role.'*^  Hypertension  is  distinctly  more  common  in  the  well- 
to-do. 

Various  complications  often  render  it  ex- 
tremely difficult  to  estimate  the  effect  of 
arteriosclerosis  upon  the  heart.  The  same  cause  that 
induces  the  disease  of  the  arterial  walls  may  also  independently 
act  upon  the  heart  muscle.  As  examples  of  such  causes,  we  may 
name  the  excessive  use  of  alcoholic  drinks,  of  coffee 
and  of  tobacco,  severe  and  continued  exertion, 
infectious  diseases,  and,  above  all,  syphilis.  Then, 
too,  arteriosclerosis  itself  may  lead  to  degeneration  of  the  heart 
muscle  owing  to  an  involvement  of  the  coronary  arteries.  Final^, 
an  associated  chronic  nephritis  may  produce  an  hyper- 
trophy of  the  heart.     We  thus  see  how  extremely  difficult  it  is, 


THE  CIRCULATION  23 

in  the  individual  case,  to  determine  whether  the  arteriosclerosis 
is  the  direct  cause  of  the  heart  hypertrophy  or  whether  the  latter 
is  due  to  some  associated  condition. 

Another  important  question  revolves  about 
the  point  as  to  whether  arteriosclerotic  hyper- 
tension is  due  to  the  anatomical  changes  in  the 
vessel-walls,  or  to  an  augmented  vascular  tonus, 
as  is  the  case  in  the  nephritides.  (Indicative  of  the 
latter  hypothesis  is  the  reported  therapeutic  efficacy,  in  some  cases, 
of  papaverin,  the  action  of  which,  as  pointed  out  by  Pal,^^  is  to 
cause  a  relaxation  of  smooth  muscle.  Excellent  results  have  been 
recorded  in  cases  of  uraemia  due  to  vascular  spasm,  e.g.,  in  scarla- 
tinal nephritis,  as  contrasted  with  the  type  founded  on  extensive 
anatomical  changes  in  the  renal  vessels. — Ed.)  In  any  event, 
the  determining  moment  will  reside  in  the  involvement  of  the 
root  of  the  aorta,  or  of  a  large  number  of  smaller  vessels.  An- 
gina pectoris  and  intermittent  claudication  are  classical  examples 
of  conditions  in  which  vessel  spasm  plays  an  important  part. 
(And  papaverin  has  likewise  been  found  of  great  value  in  the 
former.  Experimentally,  the  drug  causes  a  dilatation  of  the 
coronary  arteries.*''^ — Ed.  ) 

The  left-sided  hypertrophy  accompanying 
aneurism  of  the  aorta ^^  is  to  be  ascribed  to  some  complicat- 
ing condition.  It  is  difficult  to  see  how  a  dilatation  of  the  vessel 
would  increase  the  work  of  the  heart,  and,  as  a  matter  of  fact,  we 
do  see  patients  with  aneurisms  in  whom  there  is  no  enlargement 
of  the  left  ventricle.  When  the  latter  occurs,  we  can  usually 
ascribe  it  to  the  arteriosclerosis — generally  luetic — present,  or  to 
an  associated  aortic  insufficiency.  Interesting  in  this  connection 
are  the  observations*^  indicating  that  hypertrophy  of  the  left 
ventricle  and  an  increase  in  the  elastic  elements  in  the  aorta  may 
follow  the  inhibition  of  regulating  influences  via  the  depressor 
nerves. 

Hypertrophy  of  the  left  ventricle  may  result  from  that  rare 
condition,  congenital  stenosis  of  the  aorta. ^^  Such  a  narrowing 
would  increase  the  work  of  the  heart  by  offering  a  greater  resist- 
ance to  the  blood-flow.  In  this  anomaly,  the  hypertrophy  may 
not  develop  until  late  in  life.  If  such  be  the  case,  we  may  assume 
that  the  stenosis  produced  but  little  effect  so  long  as  there  were 
no  great  demands  upon  the  heart,  but  that  the  hindrance  made 


24  THE  BASIS  OF  SYMPTOMS 

itself  felt  when  a  more  active  circulation  was  rendered  necessary 
by  the  exertions  of  later  life. 

Severe  dyspnoea  causes  a  marked  rise  in  blood-pressure,  and 
it  has  long  been  a  question  whether  moderate  dyspnoea  continued 
over  a  long  period  of  time  may  not  give  rise  to  hypertrophy  of  the 
left  ventricle.  From  recent  observations,^^  we  know  that  persons 
with  chronic  dyspnoea  do  show  an  unusually  high  arterial 
pressure,  and  there  is  reason  to  believe  that  this  may  ulti- 
mately produce  an  hypertrophy  of  the  left  ven- 
tricle. 

Hypertrophy  of  Both  Ventricles. — Hypertrophy  of  both 
ventricles  is  produced  by  causes  that  increase  the  work  of  both. 
Pericardial  adhesions  with  mediastinitis  are 
usually  reckoned  among  such  causes;  and  it  is  easily  conceivable 
that  these  conditions  might  throw  extra  work  upon  the  heart, 
which  must  now  move  surrounding  structures,  even  the  chest  wall, 
with  each  contraction.  As  a  matter  of  fact,  we  frequently  find 
heart  hypertrophy  associated  with  chronic  pericarditis.  It  is 
questionable,  however,  whether  any  causal  relation  exists  between 
the  two,  for  in  some  cases  no  hypertrophy  is  present,  and,  indeed, 
the  heart  may  be  atrophied.  Since  pericarditis  is  often  associated 
with  disease  of  the  heart  muscle,  the  cases  that  show  hypertrophy 
should  be  studied  with  especial  regard  to  the  effect  which  these 
myocardial  changes  may  have  had  in  the  production  of  the  hyper- 
trophy. 

It  is  theoretically  possible  that  an  increase  in  the  num- 
ber of  beats  per  minute  might  lead  to  hypertrophy  of 
the  heart.  Such  an  increased  heart-rate  is  seen  in  nervous  people, 
especially  in  association  with  hyperthyroidism  or  sexual  excesses. 
In  our  opinion,  a  more  powerful  heart-beat,  sensed  by 
the  patient  as  a  palpitation,  is  another  important  cause  of  heart 
hypertrophy,  even  in  the  absence  of  an  accelerated  beat.  It  has 
been  shown,  furthermore,  that  in  hyperthyroidism  the  blood- 
pressure  is  frequently  above  the  normal,  due  apparently  to  an 
excitation  of  the  vasomotor  system."^  The  conditions  necessary 
to  produce  an  hypertrophy  are,  therefore,  present,  and  as  a  matter 
of  fact,  it  is  not  uncommon  to  find  enlargement  of  the  heart 
accompanying  thyreotoxic  states.  It  is  probable,  never- 
theless, that  this  hypertrophy  is  due  not  so  much  to  the  rapid  and 
forcible  heart-beat  as  to  the  direct  action  of  toxic  substances. 


THE  CIRCULATION  25 

Tobacco,  especially  in  the  form  of  heavy  cigars  and  when 
burned  in  short-stemmed  pipes,  is  also  said  to  cause  heart  hyper- 
trophy.   The  action  is,  undoubtedly,  toxic  in  nature. 

Cardiac  Changes  in  Renal  Disease. — The  influence  of  renal 
changes  upon  the  heart  presents  a  problem  of  considerable  diffi- 
culty.^^ In  the  majority  of  cases  of  acute  and  chronic  Bright's 
disease,  there  is  an  increased  blood-pressure  which,  if  of  more 
than  four  weeks'  duration,  leads  to  hypertrophy  of  the  heart. 
The  left  ventricle  is  first  affected,  and  though  ana- 
tomical studies  would  indicate  that  there  is  a  frequent  coordinate 
involvement  of  both  the  left  and  right  ventricles,  it  is  clear  from 
the  studies  of  Hirsch^*  that  the  former  is  the  primary.  Indeed, 
as  Passler^^  has  shown,  the  right  heart  hypertrophies 
only  after  the  left  has  become  insufficient,  the 
conditions  being  in  nowise  different,  therefore,  from  those  obtain- 
ing in  valvular  disease  of  the  left  heart. 

Accordingly,  the  increased  demands  made  upon 
the  left  ventricle  must  be  the  starting  point  of  all 
inquiries  into  the  origin  of  nephritic  heart  hy- 
pertrophy. Thus,  we  have  a  clear-cut  and  valuable  analogy  in 
the  hypertrophy  incident  to  arteriosclerosis.  The  first  point  to 
be  determined  is  whether  the  type  of  the  nephritis  pres- 
ent governs  the  development  of  increased  arterial  pressure  and  of 
hypertrophy.  The  latter  are,  in  my  opinion,  regularly  absent  in 
those  nephritides  due  to  toxic  disturbance  of  the  epithelial  cells, 
as  in  arsenic,  mercury  and  phosphorus  poisoning,  and  also  in  the 
group  following  the  acute  infections  (diphtheria,  typhoid  fever, 
sepsis).  In  scarlatinal  nephritis,  hypertrophy  is  of  variable 
occurrence;  and  in  the  s®-called  acute  primary  form,  it  is  also 
occasionally  observed.  These  primary  types,  incidentally,  will  be 
diagnosed  less  frequently  as  we  become  better  equipped  to  recog- 
nize that  they  are  often  secondary  to  latent  infections. 

Among  the  chronic  nephritides,  the  contracted  kid- 
ney is  most  often  associated  with  heart  enlarge- 
ment ;  in  this  form,  indeed,  the  hypertrophy  attains  its  high- 
est grade.  Yet  there  are  typical  examples  of  granular  atrophy 
of  the  kidney  in  which  both  the  arterial  tension  and  the  size  of 
the  heart  are  normal.^®  In  the  so-called  chronic  interstitial  and 
chronic  parenchymatous  types,  hypertension  is  also  frequent, 
though  in  the  latter  it  is  often  absent — indeed,  in  the  majority  of 


26  THE  BASIS  OF  SYMPTOMS 

cases  according  to  some  observers.^^  Pure  amyloid  kidney  leads 
to  no  heart  changes.  Conditions  such  as  renal  stone  and  tumors 
of  the  lower  abdomen,  causing  pressure  upon  both  ureters  and 
leading  to  chronic  hydronephrosis  may  also  be  followed  by  hyper- 
trophy according  to  Cohnheim;  yet  this  is  surely  an  infrequent 
event.  (Chronic  infections  of  the  renal  pelves,  even  though  en- 
tailing no  obstruction  to  the  flow  of  urine,  not  infrequently  lead 
to  changes  in  the  size  of  the  left  ventricle  and  in  the  arterial 
tension  as  pronounced  as  those  seen  in  granular  kidneys;  and 
they  may  likewise  terminate  in  uraemia.  The  differential  diag- 
nosis in  such  cases  may  be  exceedingly  difficult. — Ed.  ) 

It  is  evident,  therefore,  that  there  is  no  constant  re- 
lation between  the  type  of  nephritis  and  the 
occurrence  of  hypertrophy,  though  an  enlargement  of 
the  heart  is  most  frequent  and  most  pronounced  in  cases  of  gen- 
uine contracted  kidney.  Nor  is  there  a  definite  relationship  ex- 
isting between  the  localization  of  the  renal  process  and  the  appear- 
ance of  circulatory  changes,  for  the  particular  tendency  of  glome- 
rulonephritis in  this  direction  has  not  been  proved. ^^  Indeed,  I 
am  almost  inclined  to  agree  with  those  who  believe  that  nephritis, 
as  an  anatomical  process,  has  no  effect  upon  the  heart  and  blood- 
pressure,  and  that  the  latter  suffer  changes  only  as  a  result  of 
functional  disturbances  initiated  by  the  nephritis. 

The  theory  that  the  rise  of  blood-pressure  is 
due  to  an  augmented  viscosity  of  the  blood ^®  is 
scarcely  tenable,  for  though  the  work  of  the  heart  would 
thereby  be  increased,  the  blood-pressure  would  be  kept  at  its 
normal  level  by  a  compensatory  regulation  of  vascular  tone.  And, 
furthermore,  observations  indicate  that  the  viscosity  of  nephritic 
blood  does  not  differ  from  that  of  the  normal. 

A  general  decrease  in  the  calibre  of  the  blood- 
vessels would  explai-n  everything,  for  even  a  slight 
diminution,  either  in  all  the  vessels  or  in  the  more  important 
vascular  areas,  would  greatly  increase  the  work  of  the  heart,  since 
this  varies  inversely  as  the  fourth  power  of  the  diameter  of  the 
combined  vessels.  Such  a  change  in  diameter,  if  present,  must 
take  place  within  a  short  space  of  time,  as  in  acute  nephritis,  and 
must  last  for  years,  as  occurs  in  chronic  interstitial  nephritis.  A 
permanent  narrowing  of  this  sort  might  be  due  to  disease  of  the 
smaller  arteries,  itself  either  secondary  to  the  nephritis  or  co- 


THE  CIRCULATION  «7 

ordinate  with  it.  The  latter  conception  is  the  more  reasonable, 
because  it  is  scarcely  likely  that  the  noxious  element  leading  to 
heart  hypertrophy  in  renal  disease  confines  its  action  to  the  kid- 
neys alone.  This  subject  will  be  considered  again  under  nephritic 
oedema  (p.  92). 

That  the  cardiac  hypertrophy  and  the  hyper- 
tension observed  in  nephritis  are  due  to  changes 
in  the  peripheral  blood-vessels  is  a  classic  con- 
ception and  one  based  on  considerable  evidence.^"  Thus, 
well-defined  arteriosclerosis  is  frequently  associated  with 
contracted  kidney;  further,  the  arteriocapiUary  fi- 
brosis of  Gull  and  Sutton  occurs  in  granular  kidney;  and  in 
a  number  of  nephritides,  acute  inflammatory  changes 
in  the  vessels  have  been  noted.  Jores,  in  a  comprehensive 
and  careful  study,  noted  the  frequency  and  extensiveness  of 
changes  in  the  small  vessels  both  of  the  kidneys  and  of  other 
organs.  These  changes  may  augment  the  work  of  the  heart, 
and  raise  the  arterial  tension  in  a  purely  mechanical  way  by  in- 
creasing the  peripheral  resistance ;  but,  in  addition,  the  origin  and 
persistence  of  the  high  tension  point  with  great  probability  to 
an  altered  functional  condition  of  the  vessels.*^ 
That  vascular  disease  leads  to  an  irritable  vasomotor  condition 
has  already  been  noted  in  connection  with  atheromatous  heart 
hypertrophy  (p.  22). 

On  the  other  hand,  the  origin  and  nature  of  the 
increased  arterial  pressure  in  renal  disease 
point  with  certainty  to  an  altered  functional 
condition  of  the  vessels.  The  hypertension  develops 
early  in  acute  nephritis,  and  during  the  course  of  acute  and 
chronic  nephritides,  the  blood-pressure  is  subject  to  sudden  and 
excessive  variations.  It  readily  rises  as  a  result  of  excitement, 
exertion,  abundant  mixed  food,  and,  most  of  all,  as  a  result  of 
impending  uraemia.  It  is  lowered  by  a  quiet  life  and  a  careful 
diet,  e.g.,  milk.  In  all  renal  diseases  associated  with  high  blood- 
pressure,  we  frequently  encounter  considerable  variations:  of 
pressure  for  which  no  cause  is  apparent. 

It  seems  to  me  that  these  facts  can  only  be  ex- 
plained by  assuming  a  contracted  state  of  the 
smaller  arteries  which  is  liable  to  sudden  and 
excessive  variations.     One  might   naturally   object   to 


28  THE  BASIS  OF  SYMPTOMS 

the  assumption  of  a  continued  arterial  spasm  which  lasts  for 
years.  This  is  not  what  is  here  assumed,  however.  It  is  well 
known  that  the  arteries  are  normally  maintained  in  a  condition 
of  partial  contraction  and  that  this  so-called  tonus  is  largely  regu- 
lated through  the  nervous  system,  perhaps  through  an  intermediate 
and  continuous  epinephrin  action  (see  p.  336).  It  seems  to  me 
most  probable  that  this  normal  tonus  is  increased  in  nephritis,  and 
that  this  causes  the  cardiovascular  symptoms  of  this  disease. 

Thus  we  may  say  that  in  association  with  nephritis  there  arise 
conditions  favoring  an  increase  in  vasomotor  tone.  It  is  not 
unlikely  that  it  is  brought  about  by  a  pressor  action  exerted  by 
the  toxic  materials  that  are  retained.  Possibly  on  this  basis  is 
to  be  explained  the  beneficial  effect  in  high  tension  cases  of  a 
milk  diet,  in  that  it  throws  no  added  strain  upon  the  already 
overburdened  kidneys,  thus  enabling  them  to  excrete  the  uraemic 
toxins.  Our  ignorance  of  the  nature  of  these  poisonous  end- 
products  is  no  proof  that  chemical  processes  are  not  at  work  in 
the  production  of  high  tension.  Indeed,  we  are  not  as  yet  en- 
tirely informed  as  to  the  substances  which  are  excreted  by  the 
glomeruli. 

French  observers  have  called  attention  to  the  possibility  of 
the  coexistence  of  nephritis  and  disease  of  the 
suprarenal  glands,  or  other  portions  of  the  chromaffin 
system.  In  the  light  of  our  present  knowledge  of  the  hyperten- 
sive action  of  epinephrin,  there  is  no  theoretical  objection  to  this 
hypothesis;  on  the  other  hand,  the  epinephrin  content  of  the  blood 
has  not  been  found  increased  in  nephritis.^^  As  to  the  interesting 
observation  that  the  kidney  tissues  themselves  contain  substances 
which  raise  the  arterial  pressure,  little  can  at  present  be  said.*^ 
In  an  examination  of  diseased  kidneys,  for  instance,  the  amount 
of  such  pressor  substances  was  found  not  abnormally  large;  nor 
is  the  presence  of  pressor  bodies  peculiar  to  the  kidneys. 

The  foregoing  discussion  of  the  etiology  of  the  cardiovascular 
changes  in  nephritis  leads  naturally  to  a  consideration  of  their 
possible  significance.  The  increase  in  the  normal  vas- 
cular tonus  is  apparently  of  benefit  in  the 
secretion  of  urine,  for  the  filtration  processes  in  the 
glomeruli  demand  a  certain  capillary  pressure  and  a  certain  capil- 
lary flow.  If  the  glomerular  surface  be  diminished,  then  less 
blood  would  come  in  contact  with  the  glomerular  epithelium  and 


THE  CIRCULATION  29 

less  urine  would  be  secreted.  An  Increased  arterial  pressure  with 
an  increased  glomerular  flow  will  cause  an  increased  secretion 
from  the  healthy  glomeruli  and  possibly  from  the  diseased  ones  as 
well.  The  increased  arterial  pressure  then  becomes  advantageous 
to  the  kidneys.  At  the  same  time,  as  we  shall  see  (p.  34),  it 
may  be  a  source  of  danger  to  other  parts  of  the  body. 

We  may  sum  up  what  we  have  said  concerning  the  factors 
concerned  in  the  causation  of  nephritic  hypertrophy  of  the  left 
ventricle  by  regarding  the  matter  from  a  different,  and,  in  my 
opinion,  better- founded  point  of  view.  Mention  has  been  made 
of  the  fact  that  nephritis  as  such  need  have  no  effect  upon  the 
circulation;  that  the  majority  of  nephroses  are  unaccompanied 
by  circulatory  changes;  and  that  in  nephritides  associated  with 
hypertension,  arterial  changes  are  always  present.  On  the  other 
hand,  we  meet  with  cases  showing  similar  arterial  changes,  accom- 
panied by  an  increased  blood-pressure  and  by  an  enlargement  of 
the  heart,  clinically  indistinguishable  from  that  occurring  in  granu- 
lar atrophy  of  the  kidney,  but  in  which  the  kidneys  are  quite 
normal;  or,  if  definitely  diseased,  the  type  of  the  affection  is 
obscure  (see  under  Hypertension,  p.  84).  I  am  more  and  more 
convinced  that  these  cases,  which  unquestionably  are  more  fre- 
quent than  is  the  genuine  contracted  kidney,  cannot  fundamen- 
tally be  distinguished  from  the  latter;  and  in  this  view  I  am 
upheld  by  many.^*  It  is  an  error,  in  my  opinion,  to  emphasize 
the  renal  changes  present  in  such  cases.  On  the  strength  of 
the  investigation  of  Jores,  we  are  justified,  I  believe,  I n 
attributing  the  heart  hypertrophy  and  arterial 
hypertension  of  most,  if  not  all,  cases  of  neph- 
ritis, of  arteriosclerosis,  of  the  so-called 
essential  hypertension  and  of  syphilitic  hyper- 
tension, to  the  concomitant  action  of  vessel- 
wall  disease  and  fu  n  c  t  i  o  n  a  1  vascular  dis- 
turbances. This,  however,  does  not  solve  the  genetic  rela- 
tion between  the  arterial  and  renal  changes.  I  believe  that  we 
have  to  do  with  a  more  or  less  generalized  process  affecting  the 
kidneys  and  vessels,  equally  and  simultaneously. 

The  "Athlete's  Heart."— As  has  been  previously  stated, 
severe  muscular  exertion  ordinarily  increases  the  weight  of  the 
heart  in  the  same  ratio  as  It  increases  the  weight  of  the  general 
musculature.     It  is  frequently  assumed,  however,  that  hyper- 


30  THE  BASIS  OF  SYMPTOMS 

trophy  of  the  heart  may  result  from  prolonged  muscular  exer- 
tion. Such  a  relative  increase  in  the  heart's  weight  does  perhaps 
occur  in  individual  cases  in  the  absence  of  any  impairment  of 
function,  but  this  is  certainly  exceptional  (see  p.  8).  When 
over-activity  affects  the  heart,  it  usually  does  so  by  causing  a 
primary  weakness  of  the  muscle ;  yet  here  again  it  may  frequently 
be  questioned  whether  this  weakening  should  not  be  attributed 
to  some  other  associated  causal  agent,  such  as  the  excessive  use  of 
alcoholic  liquors,  arteriosclerosis  or  renal  disease.  Further  obser- 
vations upon  these  questions  are,  therefore,  necessary. 

The  recent  orthodiagraphic  observations^^  relative  to  a 
diminution  in  the  size  of  the  heart  following 
severe  muscular  exertion  are  subject  to  two  possible 
interpretations,  vis.,  that  a  functionally  efficient  organ  empties 
itself  more  completely  in  systole  than  under  normal  conditions, 
or  that  the  rapid  heart  action  does  not  allow  a  proper  diastolic 
filling  of  the  chambers  and  that  the  reduced  orthodiagraphic 
figure,  therefore,  is  an  evidence  of  beginning  myocardial  insuffi- 
ciency. 

The  "  Beer-Heart." — It  is  not  uncommon  to  find  weak  hearts 
with  an  hypertrophy  of  the  muscle  and  a  dilatation  of  the  cavi- 
ties in  men  who  have  been  accustomed  to  drinking  very  large 
quantities  of  beer.  Such  hearts  are  most  frequently  seen  in 
Munich,  and  may  show  extreme  grades  of  hypertrophy.  Excessive 
wine-drinkers  ocasionally  suffer  from  a  similar  condition,  whereas 
drinkers  of  more  concentrated  alcoholic  liquors  are  only  very 
rarely  affected  in  this  way ;  they  tend  to  develop  cardiac  weakness 
unassociated  with  hypertrophy.  In  many  beer-drinkers  no  other 
etiological  factor  is  present  except  the  immoderate  use  of  beer. 
The  majority,  however,  do  very  heavy  work,  and  consume  large 
quantities  of  food  in  addition  to  their  beer. 

That  the  kidneys,  or  at  least  the  blood-vessels, 
are  concerned  in  this  type  of  hypertrophy  seems 
likely  from  the  observation  of  F.  Miiller^®  that  the  majority  of 
beer-drinkers  exhibit  a  more  or  less  marked  increase  in  blood- 
pressure.  The  entire  question,  therefore,  must  be  elaborated  again. 
Perhaps  the  conditions  here  are  similar  to  those  underlying 
cyanotic  induration  of  the  kidney. 

The  cause  of  the  enlargement  of  the  heart  in  beer-drinkers 
has  been  ascribed  by  some  to  an  increase  in  the  total  amount  of 


THE  CIRCULATION  81 

blood,  a  genuine  plethora.  Autopsy  studies  apparently  give 
substance  to  this  hypothesis.  Experiments  have  been  made  to 
show  the  effect  of  such  a  plethora  upon  the  heart.^^  In  rabbits 
in  which  a  genuine  polycythaemic  plethora  was  produced  and 
maintained  for  several  months  by  injections  of  an  homologous 
blood,  the  weight  of  the  heart  was  found  not  increased.  Accord- 
ingly, the  work  of  the  heart  could  not  have  been  augmented.  For 
our  purpose,  these  experiments  lack  the  accessory  factor  residing  in 
the  alcohol. 

Personally,  I  have  observed  these  heart  changes  in  brewers, 
laborers  and  students  who  drank  immoderately,  and  who  also 
did  heavy  work,  or  took  violent  exercise.  A  number  of  such 
people  certainly  did  not  give  the  impression  of  being  "  full- 
blooded."  It  seems  to  me  that  the  combination  of  beer-drinking 
with  heavy  work  was  responsible  for  the  heart  condition;  and 
indeed  I  gained  the  impression  that  both  the  dilatation  and  the 
hypertrophy  tended  to  disappear  if  the  patient  changed  his  manner 
of  living. 

Gourmands  may  at  times  acquire  a  similar  heart  condition, 
probably  from  the  large  amounts  of  food  and  wine,  the  heavy 
smoking  and  the  not  infrequent  sexual  excesses.  In  such  cases  the 
picture  is  often  complicated  by  arteriosclerosis  and  nephritis,  and 
myocardial  weakness  is  generally  prominent.  Incidentally,  we 
may  observe  that  the  injurious  action  of  tobacco  upon  the  vessels 
is  now  a  well-recognized  fact.  ' 

The  Heart  in  Pregnancy. — It  has  been  frequently  asserted, 
especially  by  French  observers,  that  there  is  an  enlargement  of 
the  heart  during  pregnancy.  As  a  matter  of  fact,  in  pregnancy, 
as  in  other  conditions  associated  with  a  high  position  of  the 
diaphragm,  the  area  of  cardiac  dulness  is  enlarged  because  the 
heart  approaches  the  chest  wall.  The  truth  is  that  pregnancy 
exercises  no  effect  on  the  heart  other  than  that  which  could  be 
explained  by  the  general  increase  in  the  weight  of  the  body.®® 

The  Ability  of  the  Heart  to  Hypertrophy.— It  may  be  asked, 
What  conditions  influence  the  power  of  the  heart  to  hyper- 
trophy ?  We  may  mention  three  factors.  In  the  first  place,  there 
is  the  rapidity  with  which  the  new  demands  are 
made  on  the  heart.  If,  as  usually  occurs,  the  work  is 
gradually  increased,  the  heart  has  time  to  hypertrophy  gradually 
and  to  attain  ultimately  an  enormous  size  and  greatly  increased 


82  THE  BASIS  OF  SYMPTOMS 

working  capacity.  In  the  second  place,  the  degree  of  hypertrophy  is 
influenced  by  the  amount  of  new  work  required.  The 
more  work  the  heart  does,  the  greater  is  the  resulting  hypertrophy. 
As  has  been  said,  an  enormous  increase  in  work  may  be  accom- 
plished, provided  the  new  demands  are  gradually  increased.  Yet 
even  sudden  calls  upon  the  healthy  heart  are  well  responded  to  up 
to  a  certain  limit.  We  can  give  no  definite  figures  for  this  limit 
in  man,  but  we  know  from  clinical  experience  that  it  is  not  a 
low  one.  Experimentally,  it  has  been  shown  that  the  heart  of 
a  healthy  dog  is  able  to  pump  six  times  the  customary  quantity 
of  blood,  and  to  overcome  three  times  the  usual  blood-pressure. 

The  third  and  most  important  factor  that  influences  the  heart's 
capacity  to  hypertrophy  is  the  condition  of  the  cardiac 
muscle.  Without  a  healthy  muscle,  the  heart  cannot  accom- 
modate itself  to  an  increase  in  work.  The  general  nutrition  of 
the  body  is  of  comparatively  little  significance,  for  Tangl^^  has 
shown  that  even  in  the  most  emaciated  animals  hypertrophy  of 
the  left  ventricle  will  develop  after  an  artificial  valvular  lesion. 
We  have  no  right,  therefore,  to  attribute  a  lack  of  hypertrophy 
to  the  poor  general  nutrition  of  the  patient.  It  is  to  be  attributed 
solely  to  the  fact  that  there  has  been  no  increase  in  the  work  of 
the  heart,  which,  in  our  opinion,  is  the  case  in  amyloid  kidney. 
When  additional  work  is  required  of  the  heart,  there  are  only  two 
possibilities — either  it  responds  and  hypertrophies,  or  it  weakens. 
It  is,  of  course,  probable  that  when  the  body  is  well  nourished  the 
heart  is  better  able  to  respond  and  is  less  likely  to  weaken.  We 
may  mention  here  that  in  childhood  the  heart  possesses  far  greater 
powers  of  adaptation  than  in  later  life,  and  that  it  is  then  able 
to  compensate  to  a  very  marked  degree. 

Concentric  and  Eccentric  Hypertrophy. — ^The  heart  hyper- 
trophies discussed  thus  far  may  be  divided  into  two  general 
classes,  according  to  the  size  of  the  ventricular  cavities.  When 
the  muscle  increases  with  no  enlargement  of  the  cavity,  we  speak 
of  a  simple  (concentric)  hypertrophy.  On  the  con- 
trary, the  size  of  the  cavity  may  also  increase,  and  such  a  con- 
dition is  called  an  eccentric  hypertrophy.  This  division 
is  applicable  only  to  hearts  which  are  properly  compensated.  As 
soon  as  this  fails,  dilatation  of  a  totally  different  nature  occurs, 
which  shall  be  discussed  later. 

The  ventricular  cavity  must  become  dilated  during  diastole 


THE  CIRCULATION  38 

whenever  it  is  necessary  to  pump  more  blood  at  each  beat. 
Whether  the  cavity  is  also  dilated  in  systole,  or  not,  depends  upon 
the  completeness  with  which  the  ventricle  empties  itself.  Experi- 
mental evidence  would  lead  us  to  the  belief  that  an  incomplete 
expulsion  of  the  blood  is  by  no  means  infrequent.  In  heart- 
failure  this  is  the  rule;  but  even  when  the  heart  is  maintaining 
a  good  circulation  it  does  not  empty  itself  completely  when  very 
large  amounts  of  blood  must  be  propelled,  or  when  the  resistance 
is  much  increased.  Yet  hypertrophy  may  occur  even  in  a  ven- 
tricle which  does  not  empty  itself  completely,  so  long  as  the  work 
of  the  heart  is  increased  and  the  myocardium  is  responsive. 

The  Inefficiencies  of  a  Compensated  Circulation. — The  hyper- 
trophy which  enables  the  heart  to  carry  on  the  circulation  under 
pathological  conditions  is  spoken  of  as  a  compensatory  hyper- 
trophy. This  does  not  mean  that  the  new  circulatory  mechanism 
is  just  as  effective  as  the  old.  According  to  the  view  of  Romberg 
and  of  the  author,  however,  the  power  of  the  hypertrophied  heart 
muscle  to  accommodate  itself  to  further  new  demands  is  equal 
to  that  of  the  intact  muscle. 

Martins  and  Aschoff,'^^  on  the  contrary,  regard  the  reserve 
power  of  such  a  heart  as  inferior  to  that  of  the  normal  organ, 
and  explain  thus  the  ease  with  which  the  owners  become  fatigued. 
Yet  we  know  that  it  is  not  uncommon  for  individuals  with  hyper- 
trophied hearts  to  perform  as  much  physical  work  as  the  healthy. 
And,  as  Romberg  has  shown,  animals  with  aortic  insufficiency 
are  able  to  meet  demands  upon  their  heart  muscle  in  a  way  that 
would  indicate  that  the  myocardial  reserve  force  is  equally  as 
great  as  that  of  a  non-hypertrophied  organ.''* 

Hypertrophy,  therefore,  may  be  regarded  as 
of  great  advantage  to  the  heart  in  these  cases, 
for  it  not  only  enables  the  latter  to  accommodate 
itself  to  additional  burdens,  but  also,  within 
certain  limits,  makes  possible  the  maintenance 
of  the  circulation  at  practically  the  same  effi- 
cient level  as  in  health. 

In  the  foregoing  discussion  we  have  taken  the  ground  that 
hypertrophy  in  all  cases  represents  the  response  of  the  cardiac 
muscle  to  increased  work.  The  views  of  earlier  writers  differed 
from  this;  thus  Buhl  ascribed  the  hypertrophy  in  nephritis  to 
inflammatory  changes  in  the  myocardium.  And  even  Albrecht'^^ 
s 


84  THE  BASIS  OF  SYMPTOMS 

regards  hypertrophy  as  the  first  stage  of  a  progressive  myocar- 
ditis, and  to  the  latter  and  the  accompanying  degenerative  changes 
he  ascribes  the  eventual  weakening  of  the  heart.  I  am  free  to 
admit  that  this  conception  of  an  inflammatory  hyperplasia  offers 
an  attractive  solution  of  certain  types  of  hypertrophy  not  ex- 
plainable on  a  mechanical  basis.  The  proof  that  this  is  the  case, 
however,  is  lacking. 

And  yet,  as  has  been  stated,  a  compensatory  en- 
largement of  the  heart  cannot  restore  the  circu- 
lation to  a  normal  condition,  and  for  many  reasons. 
In  the  first  place,  the  blood-pressure  in  the  pulmonary  system 
must  frequently  be  maintained  at  a  higher  level  than  usual,  as 
happens  in  many  diseases  of  the  left  heart  and  of  the  lungs 
(see  p.  19).  If  the  high  pressure  in  the  pulmonary  circulation 
continues  for  any  length  of  time,  the  connective  tissue  of  the 
lungs  increases  and  small  quantities  of  blood  are  extravasated. 
The  resulting  pigment  is  taken  up  by  the  alveolar  epithelial  cells, 
and  if  these  appear  in  the  sputum,  they  are  diagnostic  of 
chronic  passive  hypersemia  of  the  lungs  (heart- 
failure  cells).  The  increased  pressure  in  the  pulmonary 
system,  if  at  all  marked,  unquestionably  interferes  with 
breathing. '^^  The  tissues  of  a  lung  that  is  the  seat  of  chronic 
passive  hyperaemia  also  seem  to  suffer  in  their  nutrition  and  in 
their  resistance  to  infection.  At  least,  such  patients  are  very 
susceptible  to  bronchitis,  so  that  it  seems  as  if  the  lungs 
had  become  less  able  to  resist  organisms  that  may  have  entered 
through  the  upper  air-passages.  And,  in  addition,  atypical 
pneumonias  are  not  infrequently  seen.'^* 

Lesions  of  the  right  side  of  the  heart  not  infrequently  lead 
to  stasis  in  the  veins  of  the  general  circulation. 
Since  the  same  condition  is  produced  by  any  weakness  of  the 
right  ventricle,  it  will  be  considered  in  that  connection. 

All  patients  with  continuously  high  arterial  pressure  are  in 
danger  of  the  rupture  of  an  artery,  which  is  espe- 
cially true  if  the  walls  of  the  arteries  are  already  weakened.  The 
immediate  cause  of  the  hemorrhage  is  usually  some  act  which 
itself  produces  a  further  rise  in  pressure,  such  as  excitement, 
violent  exertion,  coitus  and  straining  at  stool.  In  patients  with 
arteriosclerosis  or  granular  kidney,  such  acts  are  not  infrequently 
followed  by  hemorrhages  into  the  brain  or  retina. 


THE  CIRCULATION  85 

As  IS  well  known,  the  characteristic  pulse  of  aortic  insuffi- 
ciency is  one  of  great  excursion.  It  bounds  up  against  the  pal- 
pating finger,  and  as  suddenly  recedes.  It  may  be  transmitted 
to  the  capillaries,  producing  a  visible  capillary  pulse.  Such  a 
pulse  is  not  without  its  effect  upon  the  arterial  wall.  The  rapid 
and  excessive  distention  may  result  ultimately  in  a  stretching  of 
the  artery,  so  that  vasomotor  influences  are  no  longer  able  to 
reduce  it  to  its  former  size.  The  amount  of  blood  in  the  body 
is  limited,  and,  since  the  dilated  arteries  contain  more  than  nor- 
mally, there  may  thus  result  an  inadequate  filling  of 
the  rest  of  the  vascular  system. '^^  This  is  perhaps  the 
explanation  of  the  poor  circulation  sometimes  seen  in  cases  of 
aortic  insufficiency  in  which  there  is  no  weakening  of  the  left 
ventricle. 

Still  another  effect  of  an  enlarged  heart  must  be  mentioned, 
viz.,  the  space  taken  up  in  the  chest  cavity  and  the  resultant 
compression  of  the  other  intrathoracic  organs. 

The  foregoing  considerations  relative  to  hypertrophied  hearts 
are  applicable  to  the  individual  case  in  variable  degree,  depending 
upon  what  part  of  the  heart  has  undergone  hypertrophy,  and 
upon  the  cause  of  the  latter.  Certain  valvular  lesions,  there- 
fore, are  less  unfavorable  than  others ;  thus  an  aortic  insufficiency 
of  moderate  grade  or  a  combined  aortic  lesion  tend  to  be  less 
injurious  in  their  effects  than  do  certain  mitral  affections,  in 
that  the  former  involve  the  pulmonary  circulation  to  a  lesser 
degree. 

We  have  dealt  thus  far  with  the  heart's  condition  so  long  as 
the  body  is  at  rest.  If  patients  with  heart  disease  exercise,  the 
work  of  the  heart  is  at  times  enormously  increased.  Thus  we 
see  that  although  the  hypertrophy  of  the  heart  may  compensate 
for  the  valvular  lesion  in  certain  particulars,  it  cannot  restore  the 
circulatory  conditions  to  their  normal  state. 

Myocardial  Changes  in  H^jrpertrcphied  Hearts. — ^And  yet  the 
chief  source  of  difficulty  with  an  hypertrophied  heart  does 
not  lie  in  any  of  the  factors  thus  far  mentioned,  but  rather  in 
the  condition  of  the  muscle  itself.  We  have  enlarged  upon  the 
fact  that  a  healthy  hypertrophied  muscle  possesses  capabilities 
not  differing  from  those  of  the  normal  muscle.  The  hyper- 
trophied heart  muscle  and  the  enlarged  biceps  of  the  athlete  are 
comparable  in  some  cases,  but,  unfortunately,  it  is  not  so  in  the 


86  THE  BASIS  OF  SYMPTOMS 

majority  of  instances.  For  the  very  causes  which  lead 
to  hypertrophy  of  the  heart  often,  at  the  same 
time,  produce  pathological  changes  in  the  myo- 
cardium. It  will  be  recalled  how  frequently  the  infectious 
diseases  give  rise  to  valvular  lesions  and  consequently  to  heart 
hypertrophy.  In  such  infections  the  myocardium  is  almost  in- 
variably diseased,  and  often  to  a  greater  degree  than  the  endo- 
cardium. These  diseases,  and  especially  acute  articular  rheuma- 
tism, cause  degenerations  of  the  muscle  fibres,  interstitial  myo- 
cardial inflammations  and  diseases  of  the  arteries.  It  is  indis- 
putable that  these  disturb  the  functions  of  the  heart  muscle  most 
seriously. '^^  Such  a  disturbance  may  take  the  form  of  an  acute 
dilatation — which  is  not  of  a  compensatory  nature,  due  to  the 
necessity  for  an  increased  supply  of  blood — ^but  which  results 
from  the  incomplete  contractions  of  the  heart-muscle.  The  dila- 
tation of  the  right  ventricle  in  the  early  stages  of  a  mitral  lesion 
is  usually  of  this  nature.  Chronic  myocardial  changes  are  like- 
wise of  great  importance  in  the  subsequent  course  of  a  valvular 
disease. 

Though  observers  are  not  agreed  as  to  the  frequency  of  well- 
marked  myocardial  changes  in  valvular  affairs — Aschoff,  for  ex- 
ample, believing  that  the  significance  of  such  changes  is  greatly 
overestimated'^^ — yet  clinical  experience  has  shown  that  the  effi- 
ciency of  the  heart-muscle  plays  a  very  important  part  in  the 
maintenance  of  the  circulatory  equilibrium.  But  as  our  present 
knowledge  of  the  anatomical  alterations  in  the  myocardium  is 
insufficient  to  explain  its  functional  disturbances,  there  has  sprung 
up,  very  naturally,  considerable  speculation  relative  to  muscular 
injuries  which  have  escaped  our  notice.  Looking  at  the  problem 
in  the  broadest  way,  we  can  say  that  even  the  infectious  myocar- 
dial lesions  are  evidence  simply  of  the  action  of  some  harmful 
chemical  influence.  And  as  the  extent  of  a  myocardial  process 
cannot  be  taken  as  the  measure  of  the  diminished  capabilities  of 
the  heart,  I  must  admit  that  some  cases  of  insufiiciency  are  insus- 
ceptible of  explanation  on  the  basis  of  the  anatomical  changes 
present. 

We  may  sum  up  then  as  follows:  The  insuffi- 
ciencies of  many  valvular  hypertrophies  are 
due  to  a  damaged  heart  muscle,  itself  in  certain 
cases  the  result  of  inflammatory  processes.   The 


THE  CIRCULATION  37 

latter  may  vary  both  in  location  and  intensity,  and  bear  no  definite 
relation  to  the  kind  or  age  of  the  valvular  lesion.  It  adds  an 
uncertainty  to  the  prognosis  of  valvular  disease  which  must 
always  be  taken  into  account.  The  progressive  character  of  the 
processes  in  question  is  another  source  of  uncertainty.  On  the 
one  hand,  the  endocarditis  may  gradually  progress  and  lead  to 
more  and  more  extensive  alterations  in  the  valves ;  while,  on  the 
other  hand,  the  heart  muscle  may  gradually  weaken  so  that  it 
becomes  less  and  less  able  to  respond  to  the  increased  calls  made 
upon  it.     A  most  unhappy  combination ! 

The  weakness  of  the  hypertrophied  heart 
muscle  in  valvular  conditions,  apparently  not  of 
infectious  origin,  is  less  easily  explained.  Hyper- 
trophy of  the  right  ventricle  often  arises  from  diseases 
of  the  lungs.  The  progressive  character  of  the  pulmonary 
disease  may  gradually  throw  an  overwhelming  burden  upon  the 
right  ventricle.  In  other  cases,  however,  no  such  explanation 
is  possible,  and  we  are  entirely  ignorant  of  the  reason  why  the 
hypertrophied  ventricle  weakens. 

So  far  as  the  left  ventricle  is  concerned,  the  relations 
are  comparatively  simple  when  the  hypertrophy  is  consequent 
to  arteriosclerosis,  for  it  is  well  known  that  the  coronary  arteries 
are  frequently  involved  in  this  process  and  that  coronary  sclerosis 
leads  to  most  serious  disturbances  in  the  nutrition  of  the  heart 
muscle. 

The  hypertrophied  hearts  of  patients  with 
nephritis  are  often  singularly  free  from  signs  of  weakness. 
Many  patients  with  granular  kidneys  maintain  a  good  circulation 
for  years,  and  only  in  the  last  stages  of  the  disease  do  they  de- 
velop signs  of  cardiac  weakness  and  of  uraemia.  Albrecht^^ 
has  recently  shown  that  in  such  cases  disease  of  the  myocardium, 
sufficient  to  account  for  all  symptoms,  is  present. 

It  is  extremely  difficult  to  explain  the  cardiac  weak- 
ness that  develops  as  a  result  of  the  abuse  of  beer 
and  wine,  and  also  of  excessive  physical  exer- 
tion. In  a  number  of  these  cases,  the  extensive  fatty  degenera- 
tion and  the  fresh  inflammatory  processes  are  sufficient  to  account 
for  all  the  symptoms;  but  no  satisfactory  explanation  can  be 
given  of  those  cases  in  which  there  is  cardiac  weakness  without 


38  THE  BASIS  OF  SYMPTOMS 

demonstrable  signs  of  disease  in  the  myocardium.  Further  stud- 
ies are  necessary  to  throw  light  on  such  conditions. 

We  can  now  understand  how  it  is  that  in  many  instances 
the  hypertrophied  heart  is  less  efficient  than  the  normal  organ. 
Hypertrophy  itself  does  not  necessarily  entail  any  weakness. 
Theoretically,  the  hypertrophied  organ  possesses  the  same  reserve 
force  as  the  healthy  one.  Such  favorable  hypertrophies  are,  in- 
deed, observed,  but  unfortunately  they  are  rare.  In  the  majority 
of  cases  the  cause  which  induces  the  hypertrophy  also  damages  the 
capabilities  of  the  muscle.  The  heart  is  so  injured  that  it  cannot 
properly  respond  to  an  emergency  at  the  very  time  when  its  power 
to  do  so  is  most  needed. 

For  this  reason,  many  hypertrophied  hearts  are  unable  to 
meet  any  additional  call  made  upon  them.  They  tire  much  more 
readily  than  the  normal  organ,  and  when  once  tired  they  do  not 
recover  so  quickly;  indeed,  a  serious  or  even  irreparable  damage 
may  result.  On  this  account,  the  patient  with  heart  disease  is 
repeatedly  warned  of  the  dangers  of  over-exertion.  On  this 
account,  also,  women  who  have  heart  disease  often  do  badly  during 
a  confinement. 

Causes  of  Broken  Compensation  in  H)T)ertrophied  Hearts. — 
If  a  heart  becomes  unable  to  meet  the  increased  demands 
that  are  made  upon  it,  we  speak  of  a  break  in  compen- 
sation. This  failure  in  compensation  may  be  brought  about  in 
several  ways.  In  the  first  place,  what  is  ordinarily  a 
moderate  call  upon  the  heart  may  be  an  excessive 
one  in  certain  forms  of  disease.  Or,  it  is  conceiv- 
able that  inflammatory  processes  at  work  in  the  heart 
muscle  interfere  with,  or  even  render  impossible,  its  recovery; 
for  in  a  functionally  impaired  tissue,  morbid  processes  find  a 
good  soil  for  extension. 

It  frequently  happens  that  a  break  in  compensation  occurs 
even  though  the  patient  has  taken  great  care  not  to  exert  him- 
self. Such  a  break  in  compensation  may  improve,  and  even  be 
recovered  from ;  but,  on  the  other  hand,  it  may  lead  to  permanent 
insufficiency  or  death.  The  prognosis  is  decidedly  better  when 
the  compensation  of  the  right  ventricle  is  alone  at  fault;  and  the 
breaks  in  compensation  which  occur  in  mitral  disease  are  decidedly 
more  favorable  than  those  which  develop  in  a  heart  in  which  the 


THE  CIRCULATION  89 

left  or  both  ventricles  are  hypertrophled  as  a  result  of  continued, 
severe  exertion,  arteriosclerosis  or  active  valve  disease. 

In  a  certain  proportion  of  the  cases  in  which  such  a  decom- 
pensation occurs,  apparently  spontaneously,  it  is  to  be  attributed 
to  a  fresh  infectious  process  involving  the  heart  muscle.  A 
second  attack  of  acute  articular  rheumatism,  a  pneumonia  or  a 
tonsillitis  may  in  this  manner  be  the  immediate  cause.  It  seems 
as  if  the  hypertrophled  heart  muscle  formed  a  locus  minoris  re- 
sistentice  to  the  infecting  organisms  or  to  their  toxins. 

In  another  group  of  cases  the  apparently 
spontaneous  break  in  compensation  is  due  to 
the  progressive  character  of  the  process  that 
caused  the  hypertrophy.  The  demands  upon  the  heart 
are  gradually  increased  to  such  an  extent  that  they  cannot  be 
carried  out.  Among  such  progressive  processes  are  to  be  reck- 
oned many  valvular  lesions,  pulmonary  cirrhosis  and  emphysema, 
arteriosclerosis,  chronic  nephritis  and  the  excessive  use  of  beer; 
in  a  word,  they  include  the  majority  of  all  the  causes  of  heart 
hypertrophy. 

Finally,  the  break  may  occur,  not  from  any  increase  in  the 
demands  upon  the  hypertrophled  heart,  but  from  a  pro- 
gressive weakening  of  the  muscle  through  myo- 
cardial disease,  which  renders  the  heart  unable  to  do  even 
its  normal  quota  of  work.  This  form  of  cardiac  weakness  will 
be  more  fully  considered  below. 

In  a  certain,  though  relatively  small,  number  of  the  cases, 
therefore,  we  are  familiar  with  the  causes  of  transitory  and  per- 
manent disturbances  in  compensation.  In  particular,  we  are 
ignorant  as  to  the  factors  concerned  in  the  majority  of  those 
more  or  less  rapid  decompensations  occurring  in  hypertrophled 
hearts  and  which  recover  upon  the  proper  administration  of 
digitalis  (see  also  Auricular  Fibrillation,  p.  65). 

The  active  principles  of  this  drug  stimulate  both- the  myocar- 
dium and  the  cardiac  vessels  to  more  efficient  contractions.*^^  To 
be  efficacious,  therefore,  digitalis  must  encounter  a  myocar- 
dium which  is  still  responsive.  Herein  lies  the  great  prognostic 
value  of  the  preparation.  Though  of  little  apparent  service  in 
the  fresh  inflammatory  cardiac  lesions,  it  is  eminently  successful 
in  many  of  the  classical  decompensations.  Whether  the  action 
of  digitalis  is  physical,  counteracting  abnormal  swelling  of  the 


40  THE  BASIS  OF  SYMPTOMS 

muscle  fibres,  or  chemical,  restoring  an  altered  sodium  chlorid 
balance,  are  questions  requiring  further  elaboration. 

It  is  a  noteworthy  fact  that  in  the  stage  of  broken  compen- 
sation the  arterial  blood-pressure  is  often,  and  according  to  some 
observers,  always  increased  ^°  (Hochdruckstauung, 
Sahli).  To  explain  this  we  must  fall  back  upon  Traube's  hy- 
pothesis, viz.,  that  vasomotor  irritability  is  responsible  (see  also 

p.  85). 

Causes  of  Primary  Insufficiency  of  the  Heart  Muscle. — Some 

of  the  causes  that  lead  to  a  primary  weakness  of  the  heart 

muscle  have  already  been  mentioned  in  the  last  section.     The 

others  may   affect  either  hypertrophied   or   non-hypertrophied 

hearts.®^ 

Of  first  importance  among  such  causes  are  those  which 
interfere  with  the  blood-supply  to  the  cardiac 
muscle,  such  as  thrombosis,  emboHsm  and  sclerosis  of  the 
coronary  arteries.  The  heart  is  exceedingly  sensitive  to  changes 
in  its  blood-supply.®^  Though  the  heart  of  a  healthy  rabbit  has 
been  shown  capable  of  withstanding  an  interrupted  blood-supply 
for  a  period  of  six  minutes,®^  yet  any  prolonged  ischaemia  is  as 
badly  borne  by  the  heart  as  by  any  other  organ.  Hence  the  im- 
portance of  Eppinger's®*  observation  that  the  vessel  diameter 
in  hypertrophic  and  insufficient  hearts  is  diminished.  If  a  large 
portion  of  its  wall  be  suddenly  deprived  of  its  nourishment,  the 
organ  stops  beating.  This  has  been  observed  clinically  when 
an  embolus  has  lodged  in  a  coronary  artery,  and  it 
has  been  demonstrated  experimentally  by  ligating  one  of  the 
circumflex  vessels.  In  other  cases,  where  the  damage  is  less 
extensive,  the  muscle  wall  may  degenerate  and  rupture,  leading 
to  a  fatal  hemorrhage  within  the  pericardial  sac. 

The  effect  of  occlusion  of  a  smaller  branch  of  a 
coronary  artery  is  variable.  The  usual  consequence  is  a 
weakening  of  the  affected  ventricle,  a  fall  in  pressure  in  the  effer- 
ent arterial  trunks,  and  a  rise  in  venous  pressure.  In  some  in- 
stances the  patient  experiences  a  sensation  of  oppression  or  of 
severe  pain  in  the  precordium,  which  may  or  may  not  herald  a 
fatal  termination.  Arrhythmia  is  usually  present,  and  the  rate  is  at 
first  slow  and  later  accelerated.  The  heart  may  stop  in  fibrillary 
twitchings,  a  condition  in  which  the  different  muscle  fibres  con- 
tract  incoordinately    and    therefore    uselessly.      Porter®^    has 


THE  CIRCULATION  41 

shown  that  it  is  possible  to  tie  even  large  coronary  branches 
without  causing  the  death  of  the  animal.  Correspondingly, 
patients  have  been  observed  at  autopsy  who  have  apparently  re- 
covered from  extensive  infarctions  of  the  heart  muscle.  There 
is  a  slight  anastomosis  among  the  branches  of  the  coronary  arte- 
ries, so  that  these  can  no  longer  be  considered  end-arteries  in  the 
strictest  sense  of  the  term.  The  anastomosis,  however,  is  insuffi- 
cient to  establish  a  collateral  circulation  if  an  area  of  any  magni- 
tude has  been  deprived  of  its  regular  blood-supply.  An  area 
so  affected  undergoes  anaemic  necrosis.  In  general,  therefore, 
we  may  say  that  the  occlusion  of  a  coronary  vessel  of  any  magni- 
tude is  a  matter  of  serious  import. 

Marked  general  anaemia  also  injures  the 
heart,  either  by  causing  degeneration  of  its  muscle-fibres,  or 
by  lowering  their  nutrition  in  some  other,  less  obvious  manner. 
General  bodily  malnutrition  exercises  a  similar  un- 
favorable influence  upon  the  strength  of  the  cardiac  muscle,  espe- 
cially if  the  latter  is  otherwise  subnormal,  though  symptoms  are 
lacking.  It  is  comparatively  unimportant  whether  the  malnutri- 
tion arise  from  poor  food,  gastro-intestinal  disease  or  infectious 
processe^^^  In  regard  to  infectious  diseases,  however, 
we  must  remember  that  they  may  injure  the  heart  in  a  variety 
of  other  ways,  as  by  causing  myocarditis,  or  through  the  direct 
action  of  their  toxins.  The  symptoms  which  arise  under  these 
circumstances  are  irregularities  of  rhythm  and,  especially,  those 
disturbances  referable  to  a  diminution  in  the  heart's  capacity  for 
work. 

A  fresh  inflammation  of  the  heart,  whether  of 
the  endocardium,  myocardium  or  pericardium,  is  injurious  to 
the  heart's  activities.  In  many  cases  there  results  an  actual  loss 
of  contractile  tissue.  As  we  have  already  mentioned,  such  changes 
not  infrequently  affect  hearts  which  are  already  hypertrophied. 
They  also  occur,  however,  in  previously  normal  hearts,  espe- 
cially from  the  general  infectious  diseases,  such  as  acute  articular 
rheumatism,  diphtheria,  typhoid  fever  and  scarlet  fever.  Such 
an  infectious  myocarditis  may  develop  at  the  height  of  the  dis- 
ease, or  it  may  not  develop  until  some  weeks  after  the  fever  has 
disappeared,  as  happens  especially  after  diphtheria  and  typhoid 
fever.®"^ 

Significant,  in  addition  to  the  severity  and 


42  THE  BASIS  OF  SYMPTOMS 

the  extent  of  the  myocardial  changes,  is  their 
location.  Attention  has  already  been  drawn  to  the  fact  that 
a  small  lesion  situated  in  an  important  area  may  entail  more 
serious  consequences  than  a  larger  one  located  elsewhere.  The 
discovery  of  the  cardiac  conduction  path,  made  up 
of  a  specialized  muscular  tissue  and  of  relatively  limited  extent, 
has  taught  us  the  location  of  such  important  areas.  The  litera- 
ture is  rich  in  observations  concerning  anatomical  changes  in 
the  various  parts  of  this  system,  which  originates  in  the  Keith- 
Flack  node,  at  the  mouths  of  the  great  veins,  and  which  traverses 
the  auricle  to  the  node  of  Tawara,  whence  it  is  distributed  by  the 
bundle  of  His  and  its  two  main  trunks  with  their  ramifications  to 
all  parts  of  the  ventricular  walls.  In  a  way,  this  peculiar  muscle 
path  possesses  a  pathology  of  its  own.®^  It  takes  no  part  either 
in  the  hypertrophy  or  in  the  atrophy  of  the  remainder  of  the 
myocardium ;  and  it  is  endowed  with  an  independent  blood-supply. 
Furthermore,  it  may  independently  be  the  site  of  fatty  and  in- 
flammatory changes  and  of  tumor  growths.  The  significance  of 
these  isolated  changes  in  the  causation  of  sudden  death  (heart- 
block)  is  still  a  matter  of  controversy.*^ 

( Lewis ®^  has  reviewed  about  fifty  cases  of  clinical  heart- 
block,  in  none  of  which  did  a  histological  examination  of  the 
His  bundle  and  its  branches  fail  to  reveal  pathological  changes. 
On  the  other  hand,  no  case  is  on  record  of  a  complete  destruction 
of  the  bundle  in  which  just  prior  to  death  conduction  was  normal. 
Yet  the  presence  of  any  lesion  of  the  bundle  short  of  a  complete 
break  in  continuity  served  in  no  way  as  an  index  of  the  functional 
disturbances  that  may  have  been  present  intra  vitam.  In  some 
instances,  with  extensive  structural  changes  in  the  bundle,  or  in 
one  or  both  main  trunks,  the  degree  of  clinical  dissociation  may 
have  been  slight  or  transitory;  while  in  others  with  complete 
dissociation,  the  bundle  changes  were  less  in  evidence  than  in 
hearts  exhibiting  no  clinical  manifestations  at  all. — Ed.) 

In  other  respects,  what  has  been  said  concerning  the  remainder 
of  the  cardiac  muscle,  applies  equally  well  to  this  specialized 
system. 

Numerous  poisons  may  depress  the  activities  of  the  heart, 
in  some  instances  after  a  primary  stimulation,  as  occurs  with 
digitalis  and  muscarin.  It  is  possible  that  similar  poisons  are 
generated  in  the  metabolism  of  the  body.     We  know  of  at  least 


THE  CIRCULATION  48 

one  disease  in  which  the  heart  changes  are  probably  due  to  such 
a  cause,  viz.,  hyperthyroidism.^^  There  is  here  an  in- 
crease in  the  rate  and  in  the  force  of  the  heart's  contractions.  In 
many  cases,  an  hypertrophy  of  both  ventricles  develops,  and  not 
a  few  of  the  patients  die  with  the  signs  of  a  cardiac  insufficiency. 
At  autopsy  hypertrophy  and  dilatation  of  the  heart  are  present, 
but  no  characteristic  changes  are  found  in  the  cardiac  muscle.®* 
Since  the  blood-pressure  in  these  cases  is  not  always  higher  than 
normal,  we  might  attribute  the  hypertrophy  to  the  more  rapid 
and  forcible  heart  action,  whether  produced  by  nervous  or  toxic 
influences.®^  It  is  possible  that  the  cardiac  disturbances  of  cer- 
tain individuals  with  struma  may  be  due  to  an  associated  tracheal 
stenosis.  But  such  a  factor  must  be  distinctly  subordinate  to  the 
toxic  action  of  the  glandular  secretion.®^ 

The  toxins  produced  by  bacteria  may  likewise 
injure  the  strength  of  the  cardiac  muscle.  This  has  been  proved 
beyond  question  in  the  case  of  diphtheria  toxin,®^  and  is  prob- 
ably equally  true  of  others. 

It  is  difficult  to  say  to  what  extent  degenerations  of 
thecardiacmuscle  injure  the  activities  of  the  heart.  Where 
they  are  very  extensive,  there  can  be  no  doubt  that  they  cause 
serious  disturbances.  When,  for  example,  in  phosphorus  poison- 
ing, the  ether  extract  amounts  to  twenty-six  per  cent,  of  the  dried 
muscle,  instead  of  the  normal  eleven  per  cent.,  and  when  micro- 
scopic examination  shows  that  nearly  every  fibre  is  filled  with  fat 
droplets,  a  diminished  capacity  for  work  is  to  be  expected.  We 
are  not  yet  able,  however,  to  estimate  the  effect  of  the  slight  and 
of  the  moderate  grades  of  fatty  or  of  hyalin  degener- 
ation. It  is  customary  to  attribute  cardiac  weakness  to  these 
conditions.  Yet  we  know  that  the  degenerations  may  be  found 
in  apparently  strong  as  well  as  in  weak  hearts.®®  Furthermore, 
it  is  possible  that  the  cause  of  the  fatty  degeneration  may  itself 
independently  weaken  the  cardiac  muscle.  Brown  atrophy 
has  hardly  any  clinical  significance;  and  we  are  not  yet  able  to 
say  what  functional  effect  is  produced  by  fragmentation 
of  the  cardiac  muscle. 

The  so-called  fatty  heart ^'^  remains  to  be  considered. 
This  term  has  been  applied  to  two  separate  conditions — fatty 
degeneration  of  the  muscle  fibres,  and  excessive  fatty  infiltration 
into  the  interstitial  tissue.     The  two  affections  have  apparently 


44  THE  BASIS  OF  SYMPTOMS 

nothing  to  do  with  each  other;  and  fatty  degeneration  rarely 
occurs  to  any  marked  degree  in  hearts  which  are  the  seat  of  fatty 
infiltration.  The  latter  are  usually  associated  with  a  general 
lipomatosis,  and  it  is  to  them  that  the  term  fatty  heart  is  more 
commonly  applied.  It  is  uncertain  how  much  this  excessive  fat 
about  the  muscle-cells  injures  their  functional  activity.  The  mus- 
cular tissue  is  often  surprisingly  reduced  in  such  hearts,  prob- 
ably from  the  pressure  of  the  fat;  possibly,  however,  because 
the  atrophy  of  the  muscle  is  primary,  the  infiltration  of  the  fat 
secondary  {cf.  progressive  muscular  dystrophy).  The  disturb- 
ances of  fimction  in  such  hearts  are  probably  due  to  the  small 
amount  of  cardiac  muscle  present,  relative  to  the  total  body 
weight.  In  other  cases  coronary  sclerosis  or  an  overindulgence 
in  wine  or  beer  constitutes  the  cause  of  the  cardiac  weakness. 

Finally,  there  is  a  group  of  cases  exhibiting  weakness  of 
the  heart  which  falls  into  the  class  of  so-called  functional 
disturbances.  Such  a  term  simply  means  that  at  present 
we  are  ignorant  as  to  the  cause  of  these  disturbances.  The  num- 
ber of  cases  included  in  this  group  will  progressively  diminish 
as  our  knowledge  increases.  At  the  present  time  we  must  place 
in  this  category  many  of  those  cases  of  hypertrophy  in  which  the 
demands  so  increase  that  the  heart  is  no  longer  able  to  meet 
them,  as  well  as  many  cases  of  heart  weakness  resulting  from 
disturbances  of  the  general  nutrition.  Many  of  the  apparent  ner- 
vous derangements  must  likewise  be  placed  in  this  group. 

Fatigue  of  the  heart  is  just  as  little  understood  as  is 
fatigue  of  the  skeletal  muscles.  We  speak  of  fatigue  when  the 
strength  of  a  muscle  diminishes  as  the  result  of  exercise,  and  is 
recovered  after  a  period  of  rest.  If  the  heart  be  diseased,  it  is 
fatigued  by  a  smaller  amount  of  work  than  is  the  normal  organ, 
and  not  infrequently  it  recovers  slowly  or  not  at  all. 

If  sudden  excessive  demands  be  made  upon  a  normal  heart, 
it  usually  becomes  fatigued,  and  after  a  rest  it  recovers.  There 
have  been  cases  described,  however,  in  which  a  heart,  as  the  result 
of  a  brief  but  excessive  amount  of  work,  was  said  to  have  been 
permanently  injured,  or,  indeed,  to  have  given  out  entirely. 
This  has  been  looked  upon  as  due  to  an  excessive  dilatation  of 
the  heart.®^  We  know  that  such  an  acute  dilatation, 
with  an  arrest  in  diastole,  may  be  produced  in  animals  by 
greatly  increasing  the  resistance  against  which  the  heart  must 


THE  CmCUTATION  45 

pump.  The  possibility  that  a  similar  result  may  occur  in  man 
from  excessive  exertion  cannot  be  denied  absolutely.  Yet  the 
probabilities  are  entirely  against  this  view.  In  the  reported  cases 
of  heart-failure  following  exertion,  too  little  attention  has  been 
paid  to  the  condition  of  the  heart  muscle,  which  has,  in  most 
instances,  been  previously  damaged. 

There  is  no  doubt  that  the  diseased  heart  is  not  only  easily 
fatigued,  but  that  it  is  especially  liable  to  become  overdistended. 
When  a  convalescent  from  typhoid  fever  or  diphtheria  drops 
dead  after  some  unusual  exertion,  it  is  usually  from  this  cause. 
It  is  probable  that  fatigue  or  acute  dilatation  of  a  slightly  damaged 
heart  frequently  occurs  without  recognition;  and  there  always 
exists  the  danger  that  too  much  will  be  demanded  of  such  a 
weakened  heart. 

The  influence  of  the  nervous  system  upon  the 
heart  remains  to  be  considered.^^  It  is  theoretically  possible 
that  gross  or  microscopical  lesions  of  the  central  nervous  system 
should  exercise  an  unfavorable  influence  upon  the  heart's  activi- 
ties because  they  injure  the  centres  which  regulate  the  organ,  yet 
we  have  at  present  no  direct  evidence  to  prove  that  an  injurious 
effect  is  actually  produced  in  this  way. 

The  central  nervous  system  does  in  certain  cases  influence  the 
heart  unfavorably,  but  it  is  through  so-called  psychic  in- 
fluences, which  are  of  quite  a  different  nature.  It  is  well 
known  that  sorrow,  worry  and  care  may  affect  the  heart,  not  only 
in  its  rhythm,  but  in  its  strength.  ^°^  This  is  frequently  observed 
in  those  suffering  from  heart  disease,  but  it  may  occur  also  in 
healthy  individuals.  Indeed,  the  depression  of  the  heart's  activi- 
ties may  be  so  extreme  as  to  terminate  fatally.  ^^^  Neurasthenics 
frequently  suffer  from  distressing  cardiac  sensations,  from  irregu- 
larity of  the  heart's  action  and  even  from  cardiac  weakness.**'^ 
This  last,  however,  is  not  common,  and  it  is  more  frequently  a 
part  of  a  general  muscular  weakness. 

(In  certain  forms  of  heart-block,  however,  vagus  in- 
fluences seem  to  play  an  important  role  in  cardiac  function. 
According  to  Lewis, ^°^  the  vagus  action  in  these  cases  is  merely 
that  of  bringing  into  being,  or  intensifying  the  existing  clinical 
manifestations,  of  an  anatomical  disturbance  of  the  His  bundle. 
The  action  of  the  vagus  is  observed  also  in  the  so-called  sinus 
arrhythmias. — Ed.  ) 


46  THE  BASIS  OF  SYMPTOMS 

Many  are  inclined  to  refer  various  disturbances  of  the  heart's 
function  to  disease  of  the  nervous  mechanism  situated  within  the 
heart  itself,  but  we  are  without  any  exact  knowledge  on  this 
subject. 

Cardiac  weakness  is  ordinarily  regarded  as  a  weakness  in 
the  contractile  power  of  the  heart.  Yet  disturbances  in  the  dila- 
tation of  the  heart  might  almost  equally  well  lead  to  serious 
consequences,  for  diastole  is  not  merely  a  passive  process.  There 
is  probably  an  active  dilatation  at  the  beginning  of  diastole,^^* 
and  toward  the  end  there  is  a  rapid  increase  in  the  tension  of  the 
muscular  wall  which  limits  the  degree  of  filling  of  the  ventricle. 
If  these  acts  are  improperly  performed,  serious  alterations  in  the 
circulation  would  result ;  the  effects  of  such  disturbances  will  per- 
haps play  an  important  part  in  the  heart  pathology  of  the  future. 
At  present,  however,  we  are  quite  ignorant  of  their  practical 
significance,  though  Brauer  is  of  the  opinion  that  certain  of  the 
manifestations  of  an  adhesive  mediastino-pericarditis  and  the 
gallop  rhythm  of  contracted  kidney  are  due  to  some  such  disturb- 
ance in  the  dilatation  of  the  heart. 

Results  of  Cardiac  Weakness. — In  the  consideration  of  the 
effects  of  cardiac  weakness  upon  the  circulation,  it  is  immaterial 
whether  the  heart  is  primarily  weakened  so  that  it  is  unable  to  fulfil 
the  ordinary  demands  of  the  circulation,  or  whether  the  demands 
are  so  increased  that  they  become  excessive. 

Even  the  healthy  ventricle  does  not  expel  the  blood  com- 
pletely when  increased  quantities  must  be  pumped  with  each  con- 
traction. If  the  auricle  weakens,  it  soon  ceases  to 
contract,  especially  if  it  be  distended.  This  has  been  observed 
experimentally  and  chnically.^^'  If  the  ventricle  be 
weakened,  it  does  not  contract  so  completely  as  does  the 
normal  one,  and  a  smaller  amount  of  blood  than  usual  is  expelled 
at  a  reduced  speed.  The  aorta  is  less  completely  filled,  and  the 
arterial  pressure  sinks.  The  flow  of  blood  into  the  ventricle  is 
impeded,  for  not  only  is  there  less  available  space  in  the  ventricle 
owing  to  the  incomplete  expulsion  of  blood,  but  the  suction  of 
early  diastole  is  also  probably  weakened.  The  result  is  that  the 
veins  become  distended,  and  the  venous  pressure  increases. 

The  effects  are  best  studied  in  those  cases  in 
which  both  ventricles  are  equally  or  nearly 
equally  affected,  which  is,  indeed,  the  commonest  form 


THE  CIRCULATION  47 

of  cardiac  weakness.  The  insufficiency  of  the  left  ventricle  lowers 
the  systemic  arterial  pressure,  while  the  insufficiency  of  the  right 
ventricle  increases  the  pressure  in  the  systemic  veins.  The  dif- 
ference in  pressure  between  the  veins  and  arteries,  therefore,  is 
less  than  it  is  normally,  and  consequently  the  rate  of  flow  in  the 
capillaries  is  lessened.  At  the  same  time,  the  distribution  of 
blood  is  affected,  for  the  arteries  contain  less,  the  veins  more, 
blood  than  normal.  Thus  the  result  of  a  weakening  of  both  ven- 
tricles upon  the  greater  circulation  is  a  diminished  arterial 
pressure,  an  increased  venous  pressure,  a  diminution  in  the  rate 
of  blood-flow  and  an  overfilling  of  the  veins  with  blood.  Some- 
what similar  conditions  result  in  the  pulmonary  circulation;  in 
the  final  analysis,  the  amount  of  blood  in  the  latter  will  depend 
upon  whether  the  right  heart  or  the  left  is  the  weaker. 

If  only  one  ventricle  be  weakened,  or,  as  is 
more  frequently  the  case,  if  one  be  decidedly  weaker  than  the 
other,  then  the  effects  are  quite  different.  Let  us  first  consider 
the  consequences  of  a  weakened  left  ventricle.  This 
leads  to  a  lower  pressure  in  the  systemic  arteries  and  consequently 
to  a  slower  rate  of  flow  in  the  capillaries.  The  venous  pressure 
in  the  pulmonary  system  is  increased,  and  this  leads  to  increased 
pressure  in  the  pulmonary  arteries,  which  necessitates  more  work 
for  the  right  ventricle,  as  we  have  already  explained  (p.  19). 
Although  the  flow  of  blood  through  the  lungs  is  maintained  as 
well  or  nearly  as  well  as  before,  yet  the  pulmonary  vessels  are 
overfilled  and  this  is  not  without  its  effect  ufKDn  the  interchange 
of  gases  in  the  lungs  (p.  34).  Furthermore,  these  pulmonary 
changes  react  upon  the  general  circulation,  for  the  intrathoracic 
pressure  is  increased,  and  this  lessens  the  aspiration  of  the  blood 
from  the  great  veins.  In  this  manner  an  uncomplicated  weakness 
of  the  left  ventricle  may  cause  stasis  in  the  veins  of  the  general 
circulation.  In  practice,  such  a  stasis  is  greatly  favored  by  the 
fact  that  nearly  every  case  of  weakness  of  the  left  ventricle  is 
associated  with  more  or  less  weakness  of  the  right. 

It  may  be  asked  whether  it  is  possible  for  the  right  ventricle 
to  pump  its  regular  quota  of  blood  if  the  left  is  only  pumping 
a  part  of  what  it  should.  Such  a  condition  would  ultimately  lead 
to  an  accumulation  of  all  the  blood  of  the  body  in  the  lungs.  If 
life  is  to  be  maintained,  a  stationary  period  must  develop  in  which 
both  ventricles  pump  equal  amounts  of  blood.     But  during  the 


48  THE  BASIS  OF  SYMPTOMS 

time  that  it  is  developing,  there  is  a  gradual  accumulation  of  blood 
in  the  lungs,  so  that  in  the  fully  developed  condition  there  is  an 
abnormal  distribution  of  blood,  more  being  in  the  lungs  and  less 
in  the  general  circulation,  even  though  both  ventricles  are  now 
pumping  equal  amounts. 

If  the  right  ventricle  is  insufficient,  less  blood 
is  sent  into  the  pulmonary  arteries,  the  pulmonary  pressure  falls, 
and  the  rate  of  flow  in  the  lungs  is  diminished.  Less  blood  is 
taken  from  the  great  veins  of  the  general  circulation,  these  be- 
come swollen,  and  all  the  organs,  especially  the  liver,  become 
hypersemic  from  the  venous  congestion.  The  blood-flow  in  the 
general  circulation  is  retarded,  chiefly  because  the  left  ventricle 
cannot  pump  more  blood  than  is  furnished  to  it  by  the  weakened 
right  ventricle. 

As  a  matter  of  fact,  cases  in  which  one  ventricle 
alone  is  weakened  are  extremely  rare.  Most  in- 
jurious agents  affect  both  sides  of  the  heart.  Diseases  of 
the  lungs,  however,  affect  chiefly  the  right 
heart,  while  arteriosclerosis  and  aortic  insuffi- 
ciency lead  to  disease  of  the  left.  In  these  con- 
ditions, therefore,  we  are  most  likely  to  see  pathological  pictures 
corresponding  to  those  just  described  as  characteristic  of  weak- 
ness of  only  one  ventricle.  In  all  cases,  the  blood  flow  is  retarded 
and  there  is  labored  breathing  on  account  of  the  lessened  amount 
of  blood  which  traverses  the  lung  in  a  unit  of  time.  The  dis- 
turbances of  breathing  are  greater  when  the  left  ventricle  is 
weakened,  because  this  causes  in  addition  a  passive  hyperaemia 
of  the  lungs ;  whereas  when  insufficiency  of  the  right  heart  exists 
alone,  the  blood  tends  to  collect  in  the  systemic  veins  without 
producing  a  pulmonary  congestion. 

Of  the  harmful  effects  resulting  from  car- 
diac weakness,  the  most  serious  is  unquestionably  the 
slowing  of  the  blood-current;  next  to  this  is  the 
change  in  blood-pressure.  We  are  accustomed  to  re- 
gard the  latter  as  the  more  important,  perhaps  because  estima- 
tions of  the  blood-pressure  are  made  with  comparative  ease. 
Yet,  in  the  last  analysis,  the  rate  of  blood-flow  is  of  greater 
importance.  This  rate  is,  of  course,  largely  dependent  upon  the 
arterial  pressure,  owing  to  the  narrow  range  within  which  the 
venous  pressure  varies.     (No  deductions  as  to  the  rate  of 


THE  CIRCULATION  49 

blood-flow  can  be  made  from  the  systolic  arterial  pressure 
alone,  for  with  the  same  pressure  the  flow  may  vary  enormously, 
depending  upon  the  amount  of  resistance  which  it  encounters  in 
the  smaller  arterioles — ^the  so-called  diastolic  pressure.  The  ease 
and  the  comparative  accuracy  with  which  the  latter  can  now  be 
estimated  have  led  to  numerous  studies  relative  to  its  significance. 
As  an  index  of  circulatory  conditions,  the  diastolic  pressure  is 
not  subordinate  in  importance  to  the  systolic;  and  possibly  it  is 
greater.  This  subject  will  be  referred  to  again. — Ed.)  Nor 
can  we  say  that  the  higher  the  arterial  pressure  the  more  favorable 
the  condition,  for  a  diminution  under  certain  conditions  is  of 
distinct  advantage,  and  a  great  increase  brings  with  it  certain 
dangers.  On  the  other  hand,  the  lowering  of  pressure  must  not 
be  excessive,  for  a  certain  arterial  pressure  is  absolutely  necessary 
to  maintain  the  rate  of  blood-flow  essential  for  the  proper  per- 
formance of  the  functions  of  the  body. 

Disturbances  of  the  heart's  strength  lead  to  its  enlargement 
through  a  dilatation  of  its  cavities.  The  weakened  ventricle  is 
unable  to  empty  itself  as  completely  as  does  the  healthy  one,  and 
a  certain  amount  of  blood  is  left  in  it  at  the  end  of  each  systole. 
In  diastole,  likewise,  it  contains  more  blood  than  normal.  There 
is,  therefore,  a  dilatation  of  the  ventricular  cavity,  and  physical 
examination  demonstrates  an  enlargement  of  the  area  of  cardiac 
dulness.  This  dilatation  ofstasis  must  be  sharply 
distinguished  from  the  compensatory  dilatation 
which  we  have  already  described  in  connection  with  certain  val- 
vular lesions.  The  latter  are  hardly  pathological,  for  they  are 
necessary  in  the  accommodation  of  the  heart  to  the  new  circu- 
latory conditions.  Only  by  a  compensatory  dilatation  of  this 
sort  is  the  heart  enabled  to  maintain  a  proper  circulation  in 
such  valvular  affections  as  aortic  insufficiency  (see  p.  12).  The 
dilatation  which  we  are  here  considering  is  not  of  a  compensatory 
nature,  and  it  occurs  only  when  the  heart  is  unable  to  do  its  work. 
Although  the  normal  heart  does  not  empty  itself  completely  when 
very  large  amounts  of  blood  must  be  propelled,  yet  it  soon  regains 
its  usual  condition  after  the  extraordinary  demands  have  passed. 
In  a  case  of  pathological  dilatation,  however,  a  complete  systole 
never  occurs,  and  the  cardiac  chambers  are  constantly  overfilled. 

This  dilatation  of  a  weakened  heart  may  arise 
from  many  causes.    A  heart  may  be  unable  to  maintain  the  cir- 

4 


50  THE  BASIS  OF  SYMPTOMS 

culation  even  when  the  body  is  at  rest,  in  which  case  it  is  in  a  state 
of  continual  dilatation.  On  the  other  hand,  the  insufficiency  may 
develop  only  when  some  extraordinary  demands  are  made  upon 
the  heart;  in  this  case  the  dilatation  is  temporary.  Hypertro- 
phied  hearts  are  especially  susceptible  to  dilatation.  They  may 
maintain  the  circulation  for  years,  in  spite  of  the  extra  work 
necessary,  but  finally  injurious  influences  weaken  the  muscle,  or 
the  work  to  be  performed  gradually  increases  beyond  the  capacity 
of  the  heart,  and  dilatation  follows.  Frequently,  hypertrophy 
and  dilatation  develop  together.  This  occurs  when,  at  the  same 
time,  increased  work  is  necessary  and  injurious  influences  act 
on  the  cardiac  muscle.  The  ultimate  outcome  of  such  a  case  de- 
pends upon  the  relation  between  these  two  factors.  If  the  hyper- 
trophy be  in  excess,  the  prognosis  is  comparatively  good,  whereas 
if  the  dilatation  preponderate  it  is  comparatively  bad.  A  dilated 
heart  may  gradually  strengthen  and  hypertrophy,  so  that  it  will 
accommodate  itself  to  the  increased  amount  of  work  necessary. 

One  effect  of  the  poor  circulation  is  a  de- 
ficient supply  of  oxygen  to,  and  an  imperfect 
removal  of  carbon  dioxide  from,  the  tissues.  The 
lessened  blood-flow  in  the  lungs  also  diminishes  the  interchange  of 
gases  there.  The  patient  feels  that  he  needs  more  air.  The  lack 
of  oxygen  and  especially  the  presence  of  carbonic  acid  gas  in 
the  blood  stimulate  certain  cells  of  the  medulla  oblongata,  and 
this  stimulation  causes  more  frequent  and  deeper  respirations. 
( See  Dyspnoea,  in  the  chapter  on  Respiration. )  The  increase  in 
respiratory  movements  may  partly  compensate  for  the  slower 
blood-flow,  but  it  does  not  do  so  wholly.  An  added  unfavorable 
factor  in  these  cases  is  the  marked  predisposition  to  bronchitis 
and  pneumonia. 

The  stasis  of  blood  in  the  veins  of  the  general 
circulation  is  very  apparent.  The  superficial  veins 
are  enlarged  and  tortuous,  and  many,  not  before  visible,  appear. 
The  poorly  aerated  blood  gives  a  bluish  tinge  to  the  skin,  which  is 
usually  most  marked  in  the  nose,  ears,  cheeks,  fingers  and  toes, 
probably  on  account  of  the  relative  coolness  of  these  parts. 

The  highest  grade  of  cyanosis  without  a  correspondingly 
great  cardiac  insufficiency  is  seen  in  congenital  defects  of  the 
right  heart  (morbus  cseruleus).  The  fingers  acquire  a 
characteristic  club-shape,   owing  to  nutritional  changes  in  the 


THE  CIRCULATION  51 

bones,  and  these,  with  the  broad,  dark-blue  finger-nails,  present  a 
very  characteristic  appearance.  It  is  difficult  to  give  an  adequate 
explanation  of  this  cyanosis  of  congenital  heart  disease.  A  num- 
ber of  factors  probably  combine  to  bring  it  about.  In  the  first 
place,  owing  to  the  inability  of  the  right  ventricle  to  compensate 
completely  for  the  defect,  there  results  an  insufficient  aeration  of 
the  blood  and  a  stasis — the  latter  being  evident  from  the  tortuosity 
of  the  veins  of  the  skin  and  of  the  ocular  fundi.  In  the  second 
place,  a  defect  in  the  ventricular  septum,  so  commonly  associated 
with  congenital  lesions,  allows  the  arterial  and  the  venous  blood 
to  mix.  Finally,  the  well-known  increase  in  the  number  of  red 
blood-corpuEcles  in  a  unit-volume  is  probably  an  important  factor, 
which  may  account  for  certain  cases  of  cyanosis  that  cannot  be 
explained  in  any  other  manner. 

The  venous  hyperaemia  causes  a  swelling  of 
distensible  organs.  The  kidneys  become  enlarged  and 
dark  blue,  and  their  secretion  is  altered  in  a  characteristic  man- 
ner. The  liver  becomes  swollen,  hard  and  tense,  producing  a 
distressing  feeling  of  pressure  in  the  abdomen,  or,  indeed,  actual 
pain.  The  plasma  escapes  from  the  capillaries  into  the  subcu- 
taneous tissues,  causing  oedema ;  and  transudation  into  the  serous 
cavities  may  also  take  place. 

If  the  veins  are  much  swollen,  they  frequently 
exhibit  pulsations  synchronous  with  phases  of 
the  heart-beat  in  addition  to  those  of  respira- 
tory origin.  These  pulsations ^*°  are  most  marked  in  the 
jugulars,  but  they  may  be  present  in  the  veins  of  the  upper  ex- 
tremity or  of  the  chest  wall.  We  distinguish  two  types  of 
venous  pulsation.  The  first  is  due  to  an  insufficiency  of 
the  valves  of  the  afifected  veins,  which  allows  the  pulsations  nor- 
mally present  in  the  superior  vena  cava  to  be  conducted  to  the 
peripheral  veins.  Such  a  normal  or  negative  venous 
pulse  arises  from  a  hindrance  to  the  venous  flow  of  blood 
caused  by  each  contraction  of  the  right  auricle.  The  vein  is 
most  distended  during  auricular  systole  just  before  the  contrac- 
tion of  the  ventricle.  Tricuspid  insufficiency  produces  a  venous 
pulse  of  a  totally  different  character.  Here,  the  vein  is  distended 
by  the  blood  which  regurgitates  from  the  right  ventricle  through 
an  insufficient  tricuspid  valve,  and  the  greatest  distention  occurs 
synchronously  with  or  just  after  the  ventricular  systole.     This  is 


52  THE  BASIS  OF  SYMPTOMS 

called  a  pathological,  or  positive,  venous  pulsa- 
tion. Without  the  aid  of  accurate  tracings,  it  is  often  ex- 
tremely difficult  to  determine  which  form  of  pulsation  is  present, 
owing  to  the  irregular  heart  action  and  to  the  dyspnoea. 

A  positive  venous  pulse,  though  especially  character- 
istic of  tricuspid  insufficiency,  occurs  also  in  that  type  of  car- 
diac arrhythmia  known  as  perpetual  irregularity 
(arrhythmia  perpetua),  which  is  dependent  upon  a  dis- 
turbance of  the  rhythmic  beat  of  the  auricles.  The  musculature 
of  the  latter  either  shows  no  evidence  of  contractions,  or  is  in 
a  state  of  fibrillation  (see  p.  66).  The  venous  pulse,  therefore, 
fails  to  portray  the  oscillation  due  to  the  contraction  of  the 
auricle,  while  during  ventricular  systole  there  exists  a  pronounced 
hindrance  to  the  flow  of  blood  from  the  great  veins.  The  result- 
ing systolic  wave  in  the  venous  pulse  is  naturally  not  so  marked 
as  in  the  case  of  tricuspid  insufficiency.  A  pathological  venous 
pulsation  may  occur  also  when  extrasystoles  arise  in  the  junc- 
tional tissues  (atrio-ventricular  extrasystoles), 
and  occasionally  in  paroxysmal  tachycardia  (see  p.  56). 

( Mackenzie  ^^''^  formerly  was  of  the  opinion  that  auricular 
fibrillation  was  due  to  the  fact  that  the  inception  of  cardiac  rhythm 
was  transferred  from  its  normal  position — the  sinus  node — to  the 
auriculoventricular  node  of  Aschoff-Tawara.  He  applied  to  this 
condition,  therefore,  the  term  nodal  rhythm,  explaining  in  this 
way  the  apparent  synchronous  contractions  of  the  ventricle  and 
auricle,  and  the  positive  venous  pulse.  This  conception  of  the 
nature  of  auricular  fibrillation  has  been  completely  disproved  by 
electrocardiographic  studies,  and  is  no  longer  held  even  by  Mac- 
kenzie.— Ed.  ) 

Disturbances  of  the  Heart-Rate. — Disturbances  of  the  rate 
of  the  heart  may  be  due  to  a  weakening  of  the  organ,  or  may 
be  independent  of  a  diminution  in  its  strength.  The  heart- 
rate  varies  greatly  even  in  health.  ^^^  It  usually  becomes  slower 
with  age,  although  in  extreme  old  age  it  may  again  become  more 
rapid.  It  is  interesting  to  note  that  at  this  age  the  vagus  tone 
is  slight,  or  may  be  completely  absent.^*^®  There  are  also  great 
individual  variations  in  the  heart-rate ;  while  some  have  a  normal 
rate  of  fifty-six  to  sixty-eight  per  minute,  others  have  a  pulse-rate 
of  seventy  to  eighty.  As  a  rule,  the  rate  is  more  rapid  in  women 
than  in  men.     It  is  not  our  intention  to  name  all  those  influences 


THE  CIRCULATION  58 

which  affect  the  rate  of  a  normal  heart.  The  mode  of  action  of 
many  is  easily  understood,  whereas  others  have  not  yet  been 
explained. 

Physiological  studies ^*°  have  demonstrated  that  the  con- 
traction of  the  heart  is  initiated  by  a  periodic 
stimulation  of  the  fibres  situated  at  the  en- 
trance of  the  great  veins  into  the  auricles.  The 
impulse  traverses  the  auricular  muscle  and  is  propagated  via  the 
bundle  of  His  to  the  ventricles.  The  His  bundle  is  a  part 
of  the  so-called  conduction  path,  a  knowledge  of  which  we  owe 
particularly  to  Aschoff,  Monckeberg  and  their  co-workers."^ 
The  bundle  is  made  up  of  specialized  muscle  fibres  (Purkinje 
fibres).  Immediately  above  the  auriculoventricular  junction 
lies  a  denser  accumulation  of  this  specialized  tissue,  known  as  the 
Aschoff-Tawara  node,  which  is  unquestionably  con- 
cerned in  the  coordination  and  rhythm  of  the  ventricular  beat. 
It  is  interesting  to  note  that  this  node  lies  close  to  the  point 
regarded  by  Kronecker  as  the  cardiac  centre  of  coordination. 

From  the  Tawara  node  run  fibres  of  a  similar  nature  to  all 
parts  of  the  ventricles.  A  disturbance  of  the  main  trunk  of  the 
His  bundle  causes  the  ventricles  to  assume  the  rate  peculiar  to 
the  isolated  ventricle,  i.e.,  about  thirty  to  the  minute;  unquestion- 
ably, however,  the  ventricles  may  have  a  higher  automatic  rate. 

Near  the  entrance  of  the  great  veins  into  the  auricles  lies  a 
similar  mass  of  differentiated  tissue — the  Keith-Flack 
node.  The  evidence  is  still  lacking  to  show  that  this  node  is 
of  particular  significance  in  the  initiation  of  automatic  stimuli 
from  the  sinus  and  auricles. ^^^  i^  t^^  light  of  our  present 
knowledge  it  seems  more  likely  that  all  parts  of  the  auricle  are 
of  equal  weight  in  automatic  rhythm  inauguration.  And,  in  all 
likelihood,  even  the  propagation  of  the  stimuli  through  the  auricle 
is  by  the  ordinary  musculature.^  ^^ 

Though  automatic  stimuli  may  arise  at  any  point  in  the 
myocardium,  as  Engelmann  has  always  emphasized,  those  which 
are  of  auricular  origin  take  precedence  over  the  ventricular  be- 
cause of  their  more  rapid  inception.  On  the  whole,  the  studies 
of  Hering  have  led  me  to  believe  that  we  must  return  to  the  older 
view  of  the  power  of  any  part  of  the  cardiac  muscle  to  originate 
stimuli — a  view  which  has  been  forced  into  the  background  by  the 
prominence  which  has  recently  been  given  to  the  function  of  the 


54  THE  BASIS  OF  SYMPTOMS 

conduction  path.^^*  (Though  observers  are  still  not  entirely  in 
accord  as  to  the  role  of  the  sinus  node  in  the  initia- 
tion of  the  normal  heart-beat,  yet  the  evidence  favor- 
ing this  view  is  considerable.  Thus,  artificial  stimulation  applied 
to  the  sinus  node  produces  v^hat  may  be  called  a  normal  electro- 
cardiogram, whereas  stimuli  applied  elsewhere  cause  atypical  pict- 
ures. And  the  sinus  tissue  has  been  shown  to  be  more  irritable 
than  that  of  the  remainder  of  the  auricle;  while  of  the  two 
auricles,  the  right  begins  to  contract  0.01-0.03  second  before  the 
left.— Ed.) 

The  rhythm  of  a  normal  heart  may  seem  absolutely  regular  to 
an  ordinary  observer,  but  more  exact  methods  have  shown  that 
there  are  distinct  physiological  differences  in  the  duration  of  the 
pulse-waves.  According  to  Engelmann,  the  heart's  action  may 
be  affected  in  various  ways.  There  may  be  variations  not  only 
in  the  regular  initiation  of  stimuli  (chronotropiy),  but  in 
the  ability  of  the  heart  to  respond  to  these  stimuli  (bath- 
m  o  t  r  o  p  y) .  Furthermore,  the  propagation  of  the  stimuli  over 
the  heart  (dromotropy),  as  well  as  the  contractility  of  the 
muscle  (inotropy),  may  be  abnormally  increased  or  dimin- 
ished. The  causes  of  disturbances  of  cardiac  rate  and  rhythm 
may  lie  either  in  the  muscle  itself  or  in  its  nervous  connections.^^^ 
Thus  we  see  how  complicated  are  the  conditions  governing  the 
rate  and  rhythm  of  the  heart,  and  how  difficult  it  must  be  to 
interpret  the  many  clinical  variations. 

Though  we  shall  not  enter  into  the  old  controversy  as  to 
whether  the  heart-beat  is  neurogenic  or  myogenic,^  ^®  it  is  inter- 
esting to  note  that  the  conduction  system  contains  in  addition 
to  differentiated  muscle-fibres,  numerous  ganglion-cells  and  nerve- 
fibres. 

Rapid  Heart  Action  (Tachycardia). — In  certain  conditions, 
the  cause  of  an  abnormally  rapid  heart  action  is  clear.  For 
example,  atropin  and  similar  drugs  frequently  increase 
the  heart-rate  by  paralyzing  the  terminations  of  the  pneumo- 
gastric  nerve,  although  they  can  do  this  only  in  individuals  in 
whom  the  vagus  normally  exerts  an  inhibitory  action  upon  the 
heart.  The  same  effect  may  be  produced  by  pathological 
conditions  of  thevagus  fibres  or  nuclei.  Thus  the 
rapid  heart  action  which  is  so  frequently  observed  at  the  end  of 
meningeal  inflammations  is  due  to  a  vagus  paralysis  following 


THE  CIRCULATION  55 

the  period  of  vagus  stimulation.  Not  infrequently  a  pulse-rate 
of  I  GO  to  1 60  is  observed  in  such  cases,  unassociated  with  any- 
other  cardiovascular  symptoms. 

It  is  more  difficult  to  explain  the  rapid  heart  action  due  to 
exertion,  which  is  so  frequently  seen  in  convalescents,  anae- 
mic individuals  and  in  those  who  have  heart  disease.  It  is  pos- 
sible that  there  is  here  an  increased  irritability  either  of  the  heart 
itself  or  of  its  nervous  connections,  so  that  the  chemical  products 
of  muscular  activity  produce  an  unusual  effect  upon  these  tissues. 

Fever  also  causes  a  rapid  heart  action,  for  the  increased 
temperature  of  the  body  stimulates  both  the  central  endings  of 
the  accelerator  nerves  and  the  heart  muscle  itself.  If  no  other 
disturbing  factors  come  into  play,  the  rate  of  the  heart  increases 
proportionately  to  the  rise  in  temperature.  This  parallelism  be- 
tween the  temperature  and  the  heart-rate  is  missed  in  certain 
infections.  For  example,  in  typhoid  fever  the  pulse  is  relatively 
slow.  With  a  temperature  of  104°  F.  (40°  C),  we  may  have 
a  pulse  of  seventy  or  eighty.  In  scarlet  fever,  on  the  other  hand, 
the  pulse-rate  is  usually  surprisingly  rapid.  In  these  diseases  the 
action  of  toxins  probably  modifies  the  usual  relation  between  the 
temperature  and  the  pulse-rate. 

A  diminution  in  the  arterial  pressure  is  usually 
accompanied  by  an  acceleration  of  the  pulse.  In  many  cases  this 
is  to  be  explained  by  the  fact  that  there  is  a  fall  in  cerebral  pressure, 
which  stimulates  the  central  endings  of  the  accelerator  nerves. 
The  purest  example  of  this  accelerating  action  is  seen  in  the  rapid 
pulse  of  widespread  vasomotor  paralysis  (see  p.  86).  We 
frequently  observe  a  rapid  pulse  in  cases  of  cardiac  weakness  also, 
but  in  such  cases  it  is  uncertain  whether  the  rapid  heart  action  is 
attributable  to  the  heart  disease  itself  or  to  the  fall  in  pressure. 
Experiments  on  animals  would  seem  to  indicate  that  an  uncom- 
plicated cardiac  weakness  leads  to  less  frequent  contractions,  a 
fact  favoring  the  hypothesis  that  the  rapid  action  of  the  weakened 
heart  is  really  due  to  the  stimulation  of  the  accelerator  fibres 
occasioned  by  the  lowering  of  the  blood-pressure. 

In  hyperthyroidism,  the  tachycardia  may  be  contin- 
uous, or  it  may  occur  in  paroxysms.  The  symptoms  of  this  dis- 
ease are  now  attributed  by  many  to  an  excessive  thyroid  metabo- 
lism, and  it  seems  probable  that  the  cardiac  disturbances  are  like- 
wise due  to  this  cause  (see  Chapter  VI).    We  are  ignorant  as 


56  THE  BASIS  OF  SYMPTOMS 

to  which  part  of  the  cardiac  mechanism  is  affected  in  these  cases, 
whether  it  be  the  muscle,  the  cardiac  gangha  or  the  central 
nervous  connections. 

The  tachycardia  of  nervous  people  resembles  that 
occurring  in  hyperthyroidism.  Even  in  healthy  individuals  an 
increased  heart-rate  may  be  induced  by  various  influences,  as 
exercise,  psychic  disturbances  and  indigestion,  but  in  nervous 
people  the  response  to  these  influences  is  excessive.  It  is  pos- 
sible that  the  seat  of  the  increased  irritability  is  located  in  the 
cardiac  muscle,  for  similar  variations  in  rate  are  seen  in  those 
who  suffer  from  disease  of  the  myocardium,  and  in  them  at  least 
there  is  no  reason  to  assume  that  the  condition  is  in  any  way 
dependent  upon  disturbances  of  the  nervous  system. 

A  rapid  heart-rate  may  be  produced  by  disease  of 
various  other  organs  of  the  body,  such  as  the  periph- 
eral nerves  (especially  of  the  left  arm),  the  lungs,  the  liver,  the 
genitals  and  the  gastro-intestinal  canal.  When  the  primary  dis- 
ease is  cured,  the  cardiac  disturbances  disappear.  Apparently 
such  disturbances  are  due  to  reflexes  from  the  diseased  organs, 
a  view  which  is  supported  by  many  facts.  The  patients  are 
usually  neurotic,  the  disturbances  come  and  go  in  perplexing 
succession,  and,  furthermore,  they  usually  arise  from  organs  that 
are  innervated  by  the  vagus.  For  reflexes  apparently  occur  most 
readily  via  nerves  which  carry  both  motor  and  sensory  fibres. 

The  condition  known  as  paroxysmal  tachycardia  H7  is  char- 
acterized by  an  enormously  accelerated  heart-rate,  which  begins 
suddenly,  lasts  a  short  time  and  ceases  as  suddenly  as  it  began. 
It  may  affect  individuals  with  apparently  normal  hearts,  or  it 
may  occur  in  those  suffering  from  some  definite  cardiac  disease. 
The  duration  of  the  attack  may  be  minutes,  hours,  days  or  even 
weeks.  The  pulse-rate  usually  ranges  between  1 50  and  300 
per  minute.  The  heart  rhythm  is  regular  and  the  sounds 
dear.  The  difference  between  the  quality  of  the  first  and  that  of 
the  second  sound  tends  to  disappear  (embrydcardia),  a 
common  phenomenon  in  any  great  acceleration  of  the  cardiac  rate. 
The  pulse  is  small;  oftentimes  it  cannot  be  counted.  The 
blood-pressure  is  usually  low,  probably,  because  the 
shortness  of  diastole  does  not  allow  time  for  a  complete  filling 
of  the  ventricle.  Wenckebach  *  ^^  has  called  attention  to  the  fact 
that  because  of  this  short  diastole,  an  auricular  systole  may  coin- 


THE  CIRCULATION  57 

cide  with  the  ventricular  contraction  of  the  preceding  heart  cycle, 
thus  obstructing  the  venous  inflow,  and  accounting  in  all  proba- 
bility for  the  venous  stasis,  A  ventricular  venous 
pulse  may  also  be  present  (see  p.  52).  The  patient  may  or  may 
not  suffer  from  dyspnoea.  The  jugular  veins  are  always  swollen 
and  usually  exhibit  marked  pulsations.  Other  signs  of  venous 
stasis,  such  as  swelling  of  the  liver,  albuminuria  and  even 
oedema,  may  develop. 

Occasionally,  even  at  the  beginning  of  an  attack,  the  heart 
is  found  to  be  enlarged;  at  times,  however,  it  may  be  found 
smaller  than  normal.  The  apex  beat  is  generally  feeble,  though 
the  entire  precordium  may  show  a  lively  systolic  quivering.  Im- 
mediately after  the  attack  the  heart  returns  to  its  former  size. 
Nevertheless,  we  have  no  right  to  consider  this  dilatation  as  the 
cause  of  the  paroxysm,  for  it  has  been  found  absent  in  some  cases, 
by  the  most  careful  observers.  In  my  opinion,  dilatation  in  these 
cases  is  an  evidence  merely  of  cardiac  weakness. 

An  acute  distention  of  the  lungs  has  also  been 
noted  in  certain  cases  at  the  onset  of  the  attack,  and  the  respiratory 
movements  of  the  borders  of  the  lungs  have  been  diminished. 
To  what  extent  these  changes  affect  the  heart  is  not  definitely 
known. 

Subjective  symptoms  are  always  present.  During  the 
paroxysm  nearly  all  patients  feel  weak  and  faint,  most  of  them 
suffer  from  dyspnoea,  and  some  experience  the  sense  of  impending 
death.  As  a  rule,  the  symptoms  begin  and  end  suddenly,  fre- 
quently with  peculiar  sensations  in  the  precordium;  yet  in  some 
cases  it  is  almost  certain  that  the  paroxysm  may  begin  or  end 
gradually. 

During  the  interval  between  attacks  the  heart  is  often  normal, 
so  far  as  can  be  determined  by  physical  examination.  We  should, 
however,  be  very  cautious  in  our  judgment  of  such  cases,  for  it 
is  difficult  to  exclude  a  coronary  sclerosis,  and  many  sufferers 
from  this  form  of  tachycardia  are  the  subjects  of  easily  recognized 
heart  lesions. 

The  individual  attack  may  begin  spontaneously,  or 
it  may  be  precipitated  by  some  unusual  exertion,  by  excitement  or 
by  gastro-intestinal  disturbances.  These  same  causes  normally 
lead  to  an  acceleration  of  the  heart's  action,  and  it  may  be  some- 


58  THE  BASIS  OF  SYMPTOMS 

what  difficult  to  determine  in  the  individual  case  whether  the 
attack  is  really  one  of  paroxysmal  tachycardia  or  not. 

We  are  still  unacquainted  both  with  the  nature  of  paroxysmal 
tachycardia  and  with  the  cause  of  the  individual  attack.  That 
nervous  factors  are  of  importance  is  evidenced  by  the  fact  that  in 
certain  cases  pressure  upon  the  vagus  will  end  a  paroxysm. 
(Pressure  upon  the  vagus  other  than  manual  will  also  at  times 
abort  an  attack;  thus  a  similar  effect  may  be  produced  by  the 
swallowing  of  liquids  with  the  head  tilted  far  back  (Herz),  or  by 
swallowing  unchewed  pieces  of  bread.^^^ — Ed.)  The  etiol- 
ogy is  unquestionably  not  a  uniform  one;  in  some  cases  the 
central  nervous  system  seems  to  be  at  fault,  psychic  influences 
apparently  precipitating  the  attack;  while  in  others  the  disease 
appears  to  be  of  local  nervous  origin. 

(Though  there  is  a  distinct  nervous  element  in  a  great  many 
cases  of  paroxysmal  tachycardia,  we  are  in  a  position  to  say,  on 
the  basis  of  electrocardiographic  studies,  that  the  condition  is 
not,  as  was  formerly  believed,  merely  a  neurosis.  Many,  if 
not  most,  cases  represent  a  displacement  of 
automatic  impulse  production  from  the  normal 
place — the  sino-auricular  node,  the  "pace- 
maker" of  the  heart — to  other  parts  of  the  myo- 
cardium. This  new  point  of  origin  is  oftenest,  it  would 
seem,  in  the  auricles,  though  very  rarely  it  may  reside  in  the 
ventricles  or  in  the  junctional  tissues. — Ed.) 

It  is  likely  that  no  single  explanation  will  suffice  for  all  cases.*  ^^ 
Possibly  in  some,  the  basis  is  extrasystolic,  because  the  paroxysm 
often  seems  to  be  precipitated  by  nervous  influences  and  because 
the  latter  in  turn  frequently  give  rise  to  extrasystoles.  Accord- 
ing to  A.  Hoffmann,  cases  exhibiting  an  exact  doubling  of  the 
normal  rate  suggest  an  extrasystolic  character.  Another  theory 
is  that  the  sinus  node  is  unduly  irritable.  Or  it  is  conceivable  that 
this  node  normally  initiates  more  stimuli  than  are  represented 
by  heart-beats ;  whereas  in  the  tachycardial  paroxysm  each  auto- 
matic stimulus  is  followed  by  an  actual  beat.  (Sinus  tachycardias 
usually  begin  and  end  gradually  and  are  precipitated  by  excitement 
or  over-exertion.  They  are  observed  as  a  rule  in  neurotic  individ- 
uals, in  whom  insignificant  causes  are  likely  to  increase  the  cardiac 
rate  enormously.  Alcohol,  nicotin,  bacterial  toxins  and  fever  may 
also  be  causative  factors.     In  this  type  the  pulse  rhythm  is  normal, 


THE  CIRCULATION  59 

and  the  electrocardiogram  gives  evidence  that  the  contraction 
wave  arises  homogenetically,  i.e.,  in  the  Keith-Flack  node. — Ed.) 

Many  unusual  types  of  paroxysmal  tachycardia  have  been  re- 
corded, such  as  exact  doubling  and  quadrupling  of  the  normal  rate ; 
while  occasionally  early  in  the  attack  a  mid-wave  is  seen  in  the 
pulse-tracing,  in  which  case  it  may  be  difficult  to  determine  whether 
we  are  dealing  with  pulsus  altemans  or  with  a  pulsus  pseudo- 
alternans. 

We  shall  return  to  this  subject  in  our  consideration  of  the 
cardiac  arrhythmias  (p.  62). 

The  effect  of  an  acceleration  of  the  heart- 
rate  upon  the  circulation  is  variable.  It  may  lead  in  the 
first  place  to  an  increased  blood-flow ;  but,  on  the  other  hand,  the 
shortening  of  diastole  may  cause  an  insufficient  filling  of  the  ven- 
tricles, with  a  consequent  retardation  of  the  circulation.  Thus, 
experimental  stimulation  of  the  accelerator  nerve  produces  more 
rapid  and  powerful  cardiac  contractions  and  an  improvement  of 
the  circulation,  whereas  even  the  moderate  acceleration  caused  by 
a  vagus  paralysis  may  lead  to  a  slowing  of  the  blood-current.  A 
tachycardia  may,  therefore,  affect  the  circulation  of  a  patient  in 
various  ways,  and  numerous  other  factors  must  be  considered  in 
the  individual  case. 

Slow  Heart  Action  (Bradycardia). — A  slow  heart-rate 
may  be  due,  in  the  first  place,  to  a  stimulation  of  the 
vagus  nerve.  We  have  an  example  of  such  an  action  in 
the  slow  pulse  of  asphyxia,  in  which  the  venous  blood  power- 
fully stimulates  the  central  endings  of  the  pneumogastric  nerve. 
This  tends  in  a  certain  degree  to  counteract  the  great  rise  in 
blood-pressure  produced  by  the  simultaneous  constriction  of  the 
splanchnic  vessels. 

The  central  terminations  of  the  vagus  are  also  stimulated  by 
any  rise  in  the  general  arterial  p  res  sure. ^^^  The 
high  blood-pressure  in  acute  nephritis,  for  example,  nearly  always 
causes  a  slowing  of  the  pulse.  If  the  pressure  rises  gradually, 
however,  and  if  it  remains  high  for  a  long  time,  as  happens  in 
chronic  nephritis  and  in  some  cases  of  arteriosclerosis,  there  is 
usually  no  reduction  of  the  pulse-rate. 

A  rise  in  cerebral  pressure  will  likewise  stimulate 
the  vagus,  and  we  always  find  a  slow  pulse  in  those  conditions 
which  lead  to  a  rapid  increase  of  pressure  in  the  cranial  cavity, 


60  THE  BASIS  OF  SYMPTOMS 

such  as  intracranial  hemorrhages  and  extensive  meningitis.  In 
such  cases  the  vagus  pulse  is  of  great  diagnostic  significance. 
Even  the  gradual  increase  in  the  cerebral  pressure  that  results 
from  a  brain  tumor  not  infrequently  causes  a  slow  pulse. 

Changes  in  the  medulla,  particularly  in  the  region 
of  the  nucleus  of  the  pneumogastric  nerve,  may  lead  to  a  marked 
slowing  of  the  pulse  and  also  to  syncopal  attacks.  The  similarity 
of  this  picture  to  that  of  complete  heart-block  has  led  some  to 
refer  the  latter  to  such  changes  in  the  medulla.  ^^^  This  has  no 
scientific  basis,  however. 

The  vagus  may  also  be  stimulated  reflexly. 
The  slow  pulse  observed  at  the  onset  of  vomiting  is  caused  in  this 
manner ;  here  the  blood-pressure  is  probably  lowered.  This  stimu- 
lation is  usually  due  to  a  reflex  from  the  stomach,  although  the 
vagus  centre  may  be  directly  affected,  as  happens  in  the  vomiting 
from  increased  cerebral  pressure,  or  from  the  action  of  such  drugs 
as  apomorphin.  Clinically,  a  reflex  vagus  pulse  is  frequently  seen 
in  the  acute  dyspepsias  of  children,  in  peritonitis,  in  strangulation 
of  the  intestines  and  in  chronic  constipation.  In  these  cases  there 
is  often  an  associated  arrhythmia. 

Bradycardia  may  be  produced  by  the  direct  action  of 
certain  poisons,  as,  for  example,  muscarin  and  the  bile 
salts.^^  In  the  early  stages  of  catarrhal  jaundice,  there  is 
always  a  slowing  of  the  heart-rate,  and  often  irregularities  of 
rhythm.  In  the  chronic  jaundice  accompanying  diseases  of  the 
liver  itself,  and  in  those  associated  with  infectious  diseases,  the 
bradycardia  is  often  absent,  probably  because  smaller  amounts  of 
bile  salts  are  manufactured,  or  because  other  factors  influence 
the  heart.  Even  in  the  marked  jaundice  of  chronic  obstruction 
of  the  common  duct  by  stone  or  by  tumor,  there  is  frequently 
no  slowing  of  the  pulse.  This  is  probably  due  to  a  diminished 
production  of  the  bile  salts;  or  possibly  the  body  becomes  accus- 
tomed to  their  presence.  Experimental  investigations  have  shown 
that  the  bile  salts  act  both  upon  the  central  and  the  peripheral 
terminations  of  the  vag^s,  as  well  as  upon  the  cardiac  muscle 
itself,  particularly  in  the  region  of  the  sinus  node.  In  catarrhal 
icterus,  we  cannot  say  at  present  which  action  is  the  most  im- 
portant. The  hypothetical  uraemia  poison  likewise 
slows  the  heart-rate,  but  we  are  ignorant  of  the  manner  in  which 
it  acts. 


THE  CIRCULATION  61 

In  all  cases  of  continued  vagus  irritation  the  slowing  of  the 
pulse  is  only  of  moderate  grade,  rarely  going  below  44  to  48  per 
minute.  The  irregular  pulse  so  frequently  observed  in  these  con- 
ditions well  corresponds  with  the  results  of  experimental  stimu- 
lation of  the  nerve. 

All  varieties  of  bradycardia,  other  than  those  caused  by  vagus 
stimulation,  are  difficult  to  explain.  A  slow  pulse  may  be  present 
in  neurotic  individuals,  but  we  are  unable  to  say  whether  the 
immediate  cause  lies  in  some  alteration  in  the  nervous  system, 
or  in  some  changes  in  the  heart  muscle. 

There  is  a  group  of  bradycardias  caused  by 
changes  in  the  heart  itself.  An  increase  in  intra- 
cardiac pressure  will  cause  a  slowing  of  the  heart-rate,  as  may 
be  observed  in  cases  of  aortic  stenosis  and  also,  in  certain  in- 
stances, as  a  result  of  unusual,  excessive  exertion.  In  such  cases 
the  bradycardia  is  advantageous  for  it  tends  to  lessen  the  work 
of  the  heart. 

The  bradycardias  which  follow  infectious  diseases 
are  likewise  due  to  changes  in  the  heart.  They  are  analogous 
to  the  subnormal  temperature  which  is  so  frequently  present  under 
like  conditions.  The  slowing  of  the  pulse  is  most  marked  after 
pneumonia  and  typhoid  fever.  The  injection  of  atropin  does  not 
stop  the  bradycardias  of  this  type,  nor  may  it  affect  them  at  all. 
Since  atropin  paralyzes  the  vagus  terminals,  and  since  the  paralysis 
of  these  terminals  does  not  materially  affect  the  bradycardias 
under  consideration,  it  must  be  inferred  that  they  are  due  to 
changes  in  the  cardiac  muscle.  Many  would  attribute  this  slowing 
of  the  heart  to  fatigue  of  the  muscle,  for  there  is  usually  an 
increased  cardiac  action  during  infectious  diseases.  It  seems 
more  probable,  however,  that  post- febrile  bradycardia  is  really 
an  expression  of  cardiac  weakness.  We  know  that  the  weakened 
heart  not  infrequently  contracts  at  a  slower  rate  than  normal. 
We  also  know  that  other  signs  of  weakness  are  frequently  present 
during  convalescence,  and  that  a  cardiac  insufficiency  is  especially 
prone  to  develop  at  this  time. 

The  bradycardias  which  appear  at  the  height  of  infectious 
diseases,  especially  that  ominous  slowing  of  the  pulse  during 
the  course  of  diphtheria,  are  doubtless  to  be  referred  to  changes 
in  the  cardiac  muscle  itself.  Before  they  can  be  accurately  classi- 
fied, however,  it  will  be  necessary  to  determine  their  exact  relation 


62  THE  BASIS  OF  SYMPTOMS 

to  the  various  degenerations  in  the  heart  muscle  which  occur  in 
these  diseases.  Anatomical  changes  in  the  myocardium  may,  as 
is  well  known,  lead  to  a  marked  slowing  of  the  pulse.  This  is 
seen  in  both  acute  and  chronic  myocarditis,  as  well  as  in  the 
changes  which  follow  diseases  of  the  coronary  arteries.  A  defi- 
nite opinion  as  to  how  the  bradycardia  is  produced  in  these  con- 
ditions cannot  be  expressed  without  further  observations  based  on 
the  newer  methods  of  study.  Thus  we  must  determine  in  how 
many  of  these  cases  the  auricles  and  ventricles  are  beating  inde- 
pendently, due  to  an  interruption  in  the  bundle  of  His.  For  there 
is  little  doubt  that  the  latter  is  often  afifected  along  with  the  non- 
specialized  cardiac  muscle.  This  form  will  be  considered  imder 
the  arrhythmias  (p.  6y). 

The  bradycardia  of  the  puerperium^^  is  probably 
due  to  the  decrease  in  the  work  of  the  heart  which  follows  the 
delivery  of  the  child,  though  an  augmented  vagus  tonus  must 
be  considered  in  some  cases. 

We  have  already  mentioned  some  of  the  effects  of  a 
slow  heart  action  upon  the  circulation.  The  heart 
is  enabled  to  recover  itself  during  the  lengthened  diastolic  pause, 
and  its  work  is,  to  a  certain  extent,  diminished.  The  velocity  of 
the  blood-current  is  lessened,  yet  this  may  be  very  slight  if  the 
slowing  of  the  heart  is  only  moderate  in  degree.  If  the  brady- 
cardia be  due  to  vagus  irritation,  the  individual  contractions  are 
not  only  less  frequent,  but  they  are  less  forcible,  and  the  current 
may  be  slowed  considerably.  Whenever  the  bradycardia  is  ex- 
treme, the  velocity  of  the  blood-stream  and  the  arterial  pressure 
are  always  markedly  diminished.  Such  patients  cannot  exert 
themselves  without  dyspncea,  and  even  when  at  rest  they  may 
suffer  from  syncopal  attacks. 

Disturbances  of  the  Cardiac  Rh5rthm. — We  have  already 
outhned  the  normal  mechanism  of  the  heart-beat  (p.  53),  a 
knowledge  of  which  is  essential  to  an  understanding  of  the  cardiac 
arrhythmias.  Here  our  concern  is  only  with  those  anomalies  of 
the  beat  which  are  indicative  of  alterations  in  cardiac  rhythm. ^^^ 
Though  the  arterial  pulse,  in  rhythm  and  in  frequency,  corre- 
sponds for  the  most  part  to  the  heart-beat,  this  is  not  always 
the  cause,  for,  on  the  one  hand,  the  latter  is  not  infrequently  too 
feeble  to  evoke  an  arterial  pulse,  and,  on  the  other,  because  of  the 
unequal  time  consumed  by  strong  and  weak  beats  in  reaching 


THE  CIRCULATION  08 

the  periphery,  the  pauses  in  the  arterial  pulse  may  be  considerably 
longer  than  those  between  the  corresponding  heart-beats. 

Extrasystoles  (Premature  Contractions). — One  of  the  com- 
monest causes  of  cardiac  arrhythmia  is  the  occurrence  of 
extrasystoles,  i.e.,  contractions  accompanying  or  superimposed 
upon  the  usual  rhythm  (pararrhythmia).  The  essential 
feature  of  this  type  is  an  irritable  myocardium  which  initiates  a 
premature  contraction.  Arterial  hypertension  is  prob- 
ably an  important  factor  in  some  cases,  for  high  blood-pressure 
by  greatly  increasing  the  tension  of  the  muscle  thereby  renders  it 
more  irritable.  Under  these  circumstances,  only  a  slight  added 
stimulus  is  needed  to  provoke  the  extra  beat.  In  other  cases, 
primary  changes  in  the  myocardium  are  at  fault. 
Nervous  reflexes,  via  the  vagus,  for  instance,  are  very  prone  to 
excite  premature  contractions,  though  this  has  not  been  experi- 
mentally verified  by  direct  stimulation  of  nerve  trunks. 

Extrasystoles  may  arise  at  various  points  in 
the  heart- muscle — in  the  auricles,  in  the  ven- 
tricles and  in  the  sino-auricular  and  auriculo- 
ventricular  nodes.  The  premature  contraction  generally 
follows  closely  upon  a  normal  one.  It  is  inferior  to  the  latter  in 
strength,  partly  because  of  the  short  diastole  and  partly  because 
it  falls  into  the  so-called  refractory  period  of  the  heart 
when  the  irritability  of  the  latter  is  below  normal.  Obviously  the 
shorter  the  pause  between  a  normal  beat  and  extrasystole,  the 
weaker  is  the  extra  beat. 

Following  a  ventricular  extrasystole,  with  a  pulse 
of  average  rate,  the  next  normal  systole  drops  out,  because  the 
stimulus  which  should  produce  it  arises  in  the  refractory  period. 
The  second  normal  systole,  however,  occurs  in  its  proper  place; 
and  the  interval  between  the  normal  beat  before  and  after  the 
extrasystole  is  exactly  twice  that  between  two  normal  successive 
contractions  ("preservation  of  the  physiological 
stimulus  interval,"  Engelmann).  If,  however,  the 
rate  is  abnormally  slow,  the  correspondingly  prolonged  diastole 
allows  of  a  full  compensatory  pause  after  the  premature  con- 
traction, in  which  case  the  next  auricular  beat  is  likewise  followed 
by  a  ventricular  contraction  (interpolated  extrasystole). 

The  rhythm  of  the  auricles  is  ordinarily  not  affected  by  ven- 
tricular extrasystoles,  though  occasionally  the  latter  produce  sec- 


64  THE  BASIS  OF  SYMPTOMS 

ondary,  retrograde  contractions  in  the  auricles.  The  form  of  the 
auricular  wave  in  such  cases  will  depend  upon  the  irritability  of  its 
muscle  at  the  moment. 

Auricular  extrasystoles  exert  a  variable  influence 
upon  the  above-mentioned  physiological  interval  between  stimuli, 
i.e.,  the  compensatory  pause,  depending  upon  whether  the  extra 
beat  originates  nearer  the  venous  or  nearer  the  ventricular  border 
of  the  auricle.  Premature  beats  initiated  in  the  sino-auricular 
node  itself  give  rise  to  a  complete  compensatory  pause,  probably 
because  the  succeeding  normal  stimulus  produces  no  contraction. 
Hence,  the  next  auricular  systole  to  appear  falls  approximately 
in  its  appointed  place.  The  compensatory  pause  is  incomplete, 
however,  according  to  most  observers,  if  the  extra  stimulus  orig- 
inates at  a  distance  from  the  Keith-Flack  node. 

Not  infrequently,  the  extra  stimulus  affects  the  auricle  and 
ventricle  simultaneously,  producing  the  so-called  auriculo- 
ventricular  €xtra systole.  In  this  case,  the  auricles 
and  ventricles  contract  synchronously  (Mackenzie's  nodal 
rhythm),  or  the  ventricle  may  precede  the  auricle.  In  either 
case,  the  interval  between  the  auricular  and  ventricular  systoles 
(the  a-c  interval)  is  shorter  than  normal. 

It  is  obvious  that  manifold  disturbances  of  rhythm  may  be 
caused  by  these  premature  contractions,  depending  upon  their 
point  of  origin  and  their  arrangement,  i.e.,  singly,  or  in  groups 
of  two  (pulsus  bigeminus),  three  (trigeminus),  etc. 
Though  the  study  of  these  conditions  has  brought  with  it  a  great 
advance  in  our  understanding  of  the  arrhythmias,  I  feel  that  the 
tendency  toward  a  subtle  detail  is  overemphasized.  A  greater 
reserve  would  be  well,  in  view  of  the  complexities  present,  the 
meagreness  of  our  present  knowledge  and  the  many  interpre- 
tations possible  in  each  case.  Assurance  often  takes  the  place  of 
exact  knowledge. 

As  to  the  diagnostic  significance  of  the  extrasystolic  arrhyth- 
mias, there  is  likewise  little  known.  They  may  occur  both  in 
cases  of  myocardial  disease  and  in  conditions  of  nervous  origin. 
Subjective  disturbances,  such  as  a  feeling  of  anxiety,  or  an  un- 
pleasant palpitation,  are  often  present,  especially  in  cases  on  an 
apparent  nervous  basis.  On  physical  examination,  a  loud  first 
tone,  similar  to  that  in  mitral  stenosis  and  corresponding  to  the 
premature  beat,  is  often  heard.    On  the  other  hand,  systolic  mur- 


THE  CIRCULATION  d5 

murs  which  may  have  been  present  generally  disappear,  whether 
because  of  the  shortened  systole,  or  because  of  other  intrinsic  dis- 
turbances in  the  mechanism  of  the  heart-beat,  is  not  known. 

Perpetual  Arrhythmia  (Auricular  Fibrillation). — ^To  those 
pulse  irregularities  due  to  a  displacement  of  the  automatic 
stimulus  production  from  its  normal  position  in  the  sinus 
node,  Wenckebach  has  given  the  name  true  arrhythmias 
in  distinction  to  the  extrasystolic  disturbances  in  which  the  abnor- 
mal rhythm  runs  side  by  side  with  the  normal  (pararrhythmias). 
In  the  severe  cases  of  true  arrhythmia  the  original  rhythm  is 
almost  or  entirely  unrecognizable ;  contraction  follows  contraction 
with  bewildering  irregularity,  even  though  the  heart  may  be  fully 
compensated.  In  some  cases  there  is  a  positive  venous 
pulse  similar  to  that  in  tricuspid  insufficiency  (see  p.  52).  The 
oscillation  in  the  jugular  pulse  due  to  auricular  systole  disappears 
as  such  and  is  replaced  by  a  series  of  insignificant  waves.  This 
is  the  condition  known  as  fibrillation  of  the  auricles,  which  forms 
the  basis  of  the  clinical  picture  called  perpetual  arrhythmia,  or 
pulsus  irregularis  perpetua.  Cases  have  been  observed  in  which 
the  auricle  returned  to  its  normal  contraction  modus  after  the 
temporary  disappearance  of  the  fibrillation ^^^  (paroxysmal 
fibrillation). 

The  condition  of  the  auricles  in  this  dis- 
turbance is  still  not  fully  understood;  possibly  it  differs  in 
different  cases.  Observers  have  been  of  various  opinions,  some 
inclining  to  the  belief  that  the  auricular  muscle  is  completely 
paralyzed,  others  that  the  auricles  and  ventricles  contract  syn- 
chronously, and  still  others  that  the  auricular  musculature  is  in 
a  state  of  fibrillation.  Though  polygraphic  and  electrocardio- 
graphic studies  do  not  warrant  a  definite  interpretation  of  the 
phenomenon,  we  can  say  that  the  auricles  are  generally  dilated. ^^^ 

Perpetual  arrhythmia  is  due  either  to  an  anomaly  of  stimulus 
production — a  displacement,  as  noted  above — or  to  a  disturbance 
in  the  conduction  of  the  stimulus  from  the  sinus  node  to  the 
auricles,^  ^^  complicated  by  ventricular  and  perhaps  by  auriculo- 
ventricular  extrasystoles.  This  conception  of  the  origin  of  per- 
petual arrhythmia,  though  resting  in  some  degree  upon  an  ana- 
tomical basis,^^®  must  not  be  accepted  unreservedly,  for,  as 
Aschoff  points  out,  anatomical  changes  may  be  unsafe  localizing 


66  THE  BASIS  OF  SYMPTOMS 

criteria.  Especially  does  the  significance  of  ventricular  extra- 
systoles  in  the  picture  need  further  elucidation. 

(Mention  has  already  been  made  of  the  evolution  of  views  as 
to  the  nature  of  auricular  fibrillation  (p.  52)  ;  how,  at  first, 
owing  to  the  absence  of  the  a-wave  in  the  jugular  tracing  it  was 
assumed  that  the  auricle  was  in  a  state  of  paralysis — a  view  which 
had  to  be  discarded  because  at  autopsy  the  auricle  was  found  to 
be  hypertrophic;  how,  later,  because  of  the  frequently  observed 
ventricular  venous  pulse,  the  idea  was  held  that  auricles  and 
ventricles  contracted  simultaneously  (nodal  rhythm)  ;  and  how, 
finally,  by  means  of  the  electrocardiograph,  it  was  demonstrated 
that  the  auricles  were  not  quiet,  but  were  giving  rise  to  countless 
small  waves,  arising  not  at  the  normal  place,  but  at  innumerable 
points  in  the  auricle. 

Auricular  fibrillation  is  to-day  looked  upon  as  one  of  the 
best-defined  of  the  cardiac  arrhythmias.  Among  its  distinguish- 
ing features  are  its  very  frequent  association  with 
rheumatic  endocarditis,  particularly  with  mi- 
tral stenosis — a  relationship,  indeed,  which  was  noted  long 
before  the  significance  of  perpetual  arrhythmia  was  understood; 
further,  a  ventricular  pulse  which  is  extremely 
irregular  and  usually  rapid  (unless  a  complicating 
heart-block  be  present);  not  infrequently  the  ventricular 
type  of  venous  pulse,  as  already  noted;  and,  finally,  the 
almost  specific  response  to  digitalis. ^^® — Ed.) 

Pulsus  Alternans:  Hemisystoles. — In  the  case  of  two  heart- 
beats occurring  in  quick  succession,  whether  of  extrasystolic 
nature  or  not,  if  the  second  beat  be  too  feeble  to  produce  a  radial 
pulse,  the  possibility  is  present  that  the  phenomenon  is  caused  by 
a  hemisystole,  in  which  the  two  ventricles  contract  alternately,  or 
there  is  an  alternation  between  a  contraction  of  the  entire  beat 
and  that  of  the  right  ventricle.  Such  a  regular  succession  of 
strong  beats  and  weak  beats  has  been  observed  in  animals  whose 
hearts  have  been  injured.  In  this  case  we  must  assume  either 
that  the  contraction-producing  stimuli  are  alternately  weak  and 
strong,  or  that  the  heart  responds  with  imequal  strength  to  the 
same  stimulus,  or  that  regularly  occurring  inotropic  variations 
are  at  work.  A  genuine  pulsus  alternans  is  not  frequent  in  man ; 
indeed  many  observers  ^^^  believe  that  cases  so  diagnosed  are  in 
reality  due  to  extrasystoles  (pulsus  bigeminus).    Electrocardio- 


THE  CIRCULATION  67 

graphic  studies  *^^  have  shown,  however,  that  a  true  pulsus  alter- 
nans  does  occur  in  man,  while  in  animals  it  may  be  produced  by 
the  action  of  certain  poisons.  Pulsus  altemans  may  be  distin- 
guished from  extrasystolic  bigeminy  by  the  fact  that  the  interval 
between  the  complete  and  abortive  systoles  in  the  former  are  gener- 
ally equal.  As  the  alternating  pulse  is  due  in  all  probability  to 
variations  in  the  contractile  power  of  the  heart  it  may  be  taken 
as  evidence  of  cardiac  insufficiency,  and  is  usually  regarded  as 
of  grave  prognosis. 

Heart-Block. — We  have  already  described  the  path  by  which 
stimuli  arising  in  the  sinus  node  are  propagated  over  the  auricle 
to  the  node  of  Tawara  and  thence  via  the  bundle  of  His  to  all 
portions  of  the  ventricles ;  and  we  have  noted  that  clinical  heart- 
block  is  generally,  if  not  always,  associated  with  changes  in  this 
differentiated  muscle-system  (p.  42).  According  to  the  nature  and 
extent  of  the  underlying  anatomical  process,  the  disturbance  in 
conduction  may  be  partial  (partial  heart-block)  or  the  pathway 
may  be  completely  severed  (complete  heart-block). 

In  cases  of  incomplete  block,  the  resulting  manifesta- 
tions are  extremely  variable.  Thus  a  periodic  retardation  in 
conduction  may  cause  a  dropping  out  of  single  ventricular  beats, 
due  to  the  fact  that  the  stimulus  following  the  block  finds  the 
ventricle  still  in  the  refractory  phase.  A  condition  of  this  sort 
may  occur  both  in  toxic  and  inflammatory  injuries  of  the  His 
bundle.  The  greater  the  degree  of  the  injury,  the  greater  is  the 
number  of  ventricular  beats  to  miss.  Vagus  stimulation  also 
has  a  certain  bearing  upon  the  dropping  out  of  beats,  though  the 
modus  operandi  is  not  clear  ^^^  (see  also  p.  45),  Minor  grades 
of  disturbed  conduction  occur  in  various  other  conditions,  espe- 
cially in  the  infectious  diseases  and  after  the  use  of  drugs  such  as 
digitalis. ^^*  In  these  last  types,  the  auriculoventricular  bundle 
is  probably  the  point  of  attack  just  as  in  the  forms  mentioned 
above. 

In  cases  of  complete  dissociation  between  auricles 
and  ventricles,  each  contracts  with  its  own  inherent  rhythm. 
That  of  the  ventricles,  in  man,  is  ordinarily  about  thirty.  Ac- 
cording to  Monckeberg^^^  this  rate  is  probably  found  only  when 
the  main  trunk  of  the  His  bundle  is  interrupted;  whereas  in 
disturbances  in  the  Tawara  node,  the  ventricles  contract  more 
frequently,  though  less  often  than  the  auricles.     Digitalis  seems 


68  THE  BASIS  OF  SYMPTOMS 

capable  of  increasing  the  automatic  ventricular  rate.  (In  incom- 
plete block,  on  the  contrary,  digitalis  is  prone  to  cause  a  complete 
dissociation. — Ed.  ) 

Animal  experiments  have  shown  that  a  partial  heart-block 
can  be  made  complete,  the  ventricles  remaining  motionless  for  a 
brief  period  during  the  transition.  And  in  man,  likewise,  it  has 
frequently  been  noted  that  the  block  may  be  incomplete  at  one 
time  and  complete  at  another. 

The    Adams-Stokes    symptom-complex  1 36     has    its    anatomical 

basis  in  heart-block.  Commonly  arising  in  cases  of  coronary 
sclerosis  and  chronic  myocarditis,  its  distinctive  objective  phe- 
nomenon is  a  marked  bradycardia.  Subjectively,  the  affected  in- 
dividual may  be  aware  of  no  symptoms  not  dependent  upon  the 
underlying  heart  lesion ;  indeed  it  is  noteworthy  that  many  patients 
with  an  extremely  slow  pulse  are  in  nowise  handicapped  as  to 
occupation,  ability  to  move  about,  and  in  general  as  to  the  enjoy- 
ment of  life.  In  characteristic  cases,  however,  there  occur  attacks 
of  unconsciousness,  associated  apnoea  and  epileptiform  convul- 
sions. ( It  is  to  this  type  with  bradycardia,  syncopal  attacks  and 
epileptiform  convulsions  that  the  name  Adams-Stokes  syndrome 
is  generally  applied. — Ed.  ) 

I  am  of  the  opinion  that  in  many  even  of  the  so-called  cardiac 
forms  of  the  disease,  cerebral  changes  play  a  part,  for  a  quite 
similar  picture  may  be  observed,  in  the  complete  absence  of  cardiac 
pathology,  in  cases  of  cerebral  arteriosclerosis.  Nevertheless,  I 
do  not  wish  to  minimize  the  importance  of  the  very  striking  asso- 
ciation of  complete  block  and  these  peculiar  attacks.  Nicolai  has 
recorded  an  interesting  phenomenon  in  an  individual  with  com- 
plete dissociation,  in  whom  exercise  not  only  did  not  accelerate 
the  ventricular  rate,  but,  on  the  contrary,  slowed  it.^^'^  Hoff- 
mann ^^^  has  frequently  observed  an  acceleration  of  the  automatic 
beat  of  the  ventricles  in  cases  of  complete  dissociation. 

There  are  additional  disturbances  of  heart- 
rhythm  dependent  upon  anomalies  in  the  properties  of  heart- 
muscle,  viz.,  conductivity,  contractility,  irritability  and  automatic 
stimulus  production,  which,  according  to  Engelmann,  may  occur 
independently  of  one  another.  To  the  many  experimental  studies 
and  observations  of  Wenckebach  and  Hering  we  are  indebted  for 
a  better  understanding  of  the  manifold  pulse  irregularities  that 
may  arise.     At  this  point,  we  shall  mention  only  the  phenomenon 


THE  CIRCULATION  69 

of  grouped  beats  (Luciani)  which  has  recently  been  ob- 
served clinically  by  Wenckebach.  In  my  opinion,  however,  a 
certain  reserve  is  still  indicated  in  the  interpretation  of  coupled 
beats,  for  there  exists  a  peculiar  innate  tendency  in  this  regard 
in  the  automatically  beating  ventricle,  which  would  explain  some 
of  the  bigeminal  and  polygeminal  pulses  in  heart-block.  In  other 
cases,  as  already  noted,  bigeminy  may  be  due  to  extrasystoles ; 
while  in  still  others  it  is  the  result  of  periodic  disturbances  of 
conduction.  As  Wenckebach  points  out,  therefore,  there  is  much 
included  under  bigeminy  that  belongs  elsewhere. 

Causes  of  Arrhythmia. — Myocardial  disease  is  of 
first  importance  in  the  causation  of  disturbances  of  the  cardiac 
rhythm.  Inflammatory  processes  and  infarcts  resulting  from 
coronary  disease  are  more  frequently  the  anatomical  substrata  of 
such  arrhythmias  than  are  the  parenchymatous  degenerations  of 
the  muscle.  A  diminished  supply  of  blood  to  the 
heart  may  also  lead  to  irregularity  before  the  appearance  of 
serious  myocardial  changes.  As  we  have  previously  noted,  there 
seems  to  be  no  definite  relation  between  the  extent  of  the  myo- 
cardial disease  and  the  degree  of  irregularity.  The  loca- 
tion of  the  process,  however,  is  of  paramount  importance, 
as  is  evident  from  the  results  of  lesions  of  the  His  bundle.  Dis- 
ease of  the  auricular  musculature  is  especially  apt  to  lead  to 
irregularities  in  rhythm,  according  to  many  observers;  yet  our 
knowledge  as  to  the  importance  of  the  auricles,  and  in  particular 
of  that  area  about  the  mouths  of  the  great  veins,  in  its  bearing 
upon  cardiac  arrhythmia  is  still  incomplete. 

Cardiac  irregularity  may  also  occur  without 
any  demonstrable  changes  in  the  myocardium, 
as,  for  example,  in  cases  of  acute  dilatation  of  the  heart  following 
excessive  muscular  exertion.  To  what  extent  nervous  factors 
play  a  role  in  such  disturbances  of  the  rhythm  is  not  known.  The 
etiology  of  the  so-called  nervous  arrhythmias  is  far 
from  clear.  Stimulation  of  the  vagus,  as  we  know,  may  lead 
to  disturbances  of  conduction;  and  extrasystoles  are  especially 
frequent  in  neurotic  individuals  (see  also  p.  64).  Respiratory 
variations  in  the  frequency  of  the  pulse  are  also  particularly 
marked  in  such  individuals.  In  these  cases  the  pulse  is  accelerated 
at  the  beginning  of  inspiration  and  is  retarded  to  such  an  extent 
during  expiration  that  we  can  speak  of  an  actual  irregularity. 


70  THE  BASIS  OF  SYMPTOMS 

(This  is  one  of  the  group  of  so-called  sinus  arrhythmias 
— all  probably  of  vagus  origin — and  which  Mackenzie  has  called 
the  "youthful  type"  of  irregularity. — Ed.) 

Reflexes  may  give  rise  to  irregularities  of  the  heart's 
action,  as  well  as  to  tachycardia  and  bradycardia.  We  know 
that  if  the  endocardium  be  touched  during  the  course  of  an 
experiment,  arrhythmia  results.  How  important  a  part  such 
reflexes  play  in  clinical  pathology  is  imcertain.  Possibly  the 
arrhythmia  of  endocarditis  may  arise  from  such  reflexes;  and 
possibly  the  arrhythmias  sometimes  seen  in  gastro-intestinal  dis- 
eases are  also  of  reflex  nature.  In  both  these  examples,  however, 
there  are  usually  other  factors  present  which  might  produce  an 
irregular  heart  action. 

Arrhythmia  may  be  due  to  the  action  of  poisons,  nota- 
bly of  digitalis,  caffein,  tobacco  and  the  toxins  of  ursemia.  The 
relation  of  digitalis  to  heart-block  has  already  been  considered 
(p.  67).  The  irregular  tobacco  heart  is  well  known.  The 
toxins  of  infectious  diseases,  especially  those  of  typhoid  fever  and 
diphtheria,  may  produce  similar  effects. 

In  chronic  pericarditis  and  mediastinitis  it  is 
possible  for  the  new-formed  connective  tissue  to  compress  the 
aorta  or  the  great  veins  during  inspiration.  This  would  lead  to 
a  diminution  or  disappearance  of  the  pulse  during  inspiration 
(pulsus  paradoxus).^^^  Not  every  pulsus  paradoxus  is 
capable  of  being  explained  in  this  manner.  It  has  been  observed 
in  simple  insufficiency  of  the  heart,  and  esi>ecially  in  association 
with  stenosis  of  the  larger  air-passages,  and  under  such  circum- 
stances the  cause  must  lie  in  the  heart  itself. 

The  Cardiac  Impulse. — If  we  inspect  the  chest  of  a  normal 
individual,  a  periodic  heaving  is  usually  seen  in  the  fifth  inter- 
costal space,  median  to  the  mammary  line.  This  is  called  the 
cardiac  impulse.  It  usually  overlies  the  apex  of  the  left  ventricle, 
which  is  thrust  into  the  intercostal  space  with  each  systole.  Dur- 
ing diastole,  the  heart  is  flaccid  and  tends  to  assume  the  shape 
given  to  it  by  its  suroundings,  but  in  systole  it  becomes  rigid  and 
assumes  its  own  characteristic  form.  This  throws  the  apex 
against  the  chest  wall  and  is  the  principal  factor  in  producing  the 
impulse.  The  main  part  of  the  impulse  occurs  during  the  first 
period  of  systole  at  a  time  when  all  the  valves  are  closed.     The 


THE  CIRCULATION  71 

heaving,  however,  continues  a  short  time  after  the  opening  of 
the  aortic  semilunar  valves. 

Many  factors  may,  therefore,  affect  the  cardiac  impulse,  such 
as  the  position  of  the  apex  within  the  chest  cavity,  the  force  with 
which  the  heart  contracts,  and  the  condition  of  the  chest  wall  and 
the  overlying  border  of  the  left  lung.  Provided  the  latter  do 
not  play  too  disturbing  a  role,  we  may  say  in  general  that  a  power- 
ful systole  will  produce  a  strong  heaving  impulse,  and  a  weak 
systole  will  give  rise  to  a  small  and  soft  impulse.  It  cannot  be 
assumed,  however,  that  an  extensive,  strong  impulse  is  always 
due  to  a  more  powerful  contraction  of  the  heart-muscle. 

A  study  of  the  apex-beat  even  by  the  ordinary  methods  of 
physical  examination  enables  one  to  form  a  rough  estimate  of 
conditions  in  the  heart,  if  he  bears  in  mind  the  various  factors 
which  enter  into  the  formation  of  the  beat  normally,  and  those 
which  cause  a  change  in  its  position,  its  breadth,  its  intensity,  etc. 
Cardiographic  tracings  are  necessary,  however,  to  give 
us  exact  information  about  the  apex-beat,  though  the  value  of 
this  instrumental  method  is  somewhat  impaired  by  the  fact  that 
the  characteristics  of  the  beat  vary  considerably  even  in  healthy 
individuals.  Thus  the  cardiogram  alone  gives  important  infor- 
mation as  to  whether  the  apex-beat  is  formed  by  the  left  ventricle 
or  right  ventricle;  while  combined  with  tracings  taken  from  the 
radial  artery  and  jugular  vein,  the  cardiogram  serves  as  a  valuable 
time-index  of  the  different  phases  of  the  cardiac  cycle.  The  bulk 
of  our  knowledge  of  the  disturbances  of  heart  rhythm  was  gained 
through  the  use  of  such  simultaneous  records  of  the  movements  of 
the  ventricles  and  auricles  (polygram). 

The  Heart-Sounds. — ^The  heart-sounds  may  be  altered  either 
in  their  intensity  or  their  character.  One  of  the  most  important 
of  these  alterations  is  the  increase  in  the  intensity  of 
the  pulmonic  or  the  aortic  second  sound.  This 
accentuation  is  generally  indicative  of  an  abnormally  high  pressure 
in  the  corresponding  artery.  Since  the  pressure  in  the  aorta  is 
normally  more  than  twice  as  great  as  that  in  the  pulmonary 
artery,  one  might  think  that  the  aortic  second  sound  would  be 
normally  much  louder  than  the  pulmonic  second  sound.  Such  is 
not  the  case,  however.  Examination  of  healthy  individuals  shows 
that  there  is  but  little  difference  between  the  second  sounds  in 
either  intensity  or  character.     As  a  rule,  the  pulmonic  second 


72  THE  BASIS  OF  SYMPTOMS 

sound  is  relatively  somewhat  louder  in  childhood,  but  with  advanc- 
ing years  the  relation  gradually  changes  until  in  old  age  the 
aortic  sound  is  usually  the  louder.  This  relative  weakness  of  the 
aortic  second  sound  is  due  in  part,  at  least,  to  differences  in  the 
structure  of  the  aorta  and  the  pulmonary  artery. 

We  have  said  that,  in  general,  an  accentuation  of  a  second 
sound  indicates  an  increase  of  pressure  in  the  corresponding  artery. 
Yet  we  meet  cases  in  which  increased  pressure  is  present  without 
an  accentuation  of  the  corresponding  sound;  and,  conversely, 
accentuation  of  the  second  sound  may  be  present  without  any 
increase  of  pressure.  Other  factors  must  come  into  play.  Of 
these  the  proximity  of  the  vessels  to  the  chest  wall  is  unquestion- 
ably of  importance.  The  physical  condition  of  the  arterial  wall 
also  influences  the  sound  produced,  and  not  infrequently  we 
observe  a  loud,  ringing  aortic  second  sound  in  arteriosclerosis  of 
the  first  part  of  the  aorta,  even  though  there  is  no  increase  of 
blood-pressure. 

Accentuation  of  the  pulmonic  second  sound  is 
caused  by  conditions  which  lead  to  an  increase  of  pressure  in  the 
pulmonary  circulation.  These  conditions,  which  have  already 
been  enumerated  (see  p.  19)  include  mitral  disease,  weakness  of 
the  left  ventricle,  pulmonary  emphysema,  etc.  The  accentuation 
is  ordinarily  associated  with  an  hypertrophy  of  the  right  ventricle, 
for  both  are  caused  by  the  increased  pressure  in  the  pulmonary 
artery. 

Accentuation  of  the  first  sound  is  present  in  many 
cases  of  mitral  stenosis,  in  which  indeed  it  may  be  audible  at 
some  distance  from  the  chest  wall.  The  most  acceptable  explana- 
tion of  this  accentuated  first  sound  is  that  it  is  due  to  a  more 
rapid  systole  of  the  left  ventricle,  occasioned  by  the  abnormally 
small  amount  of  blood  which  this  receives  during  diastole.  The 
same  factors  underlie  the  loud  first  sound  heard  in  rapidly  beating 
hearts.  Quincke  has  described  abortive  contractions  of  the  heart 
which  follow  immediately  upon  normal  ones  in  which  a  good 
filling  of  the  ventricle  was  an  impossibility  and  in  which  the  systole 
was  short.  In  these  the  first  sound  was  often,  but  not  always, 
louder  than  normal.  The  powerful  contraction  of  an  hyper- 
trophied  heart  rarely  produces  a  loud  first  sound,  but  usually  an 
impure  and  mufiled  one.     Weak  and  anaemic  individuals,  indeed. 


THE  CIRCULATION  78 

frequently  show  surprisingly  loud  first  heart-sounds,  due  prob- 
ably to  the  associated  tachycardia. 

In  certain  cases,  a  doubling  of  one  or  other  of  the 
heart-sounds  is  heard,  so  that  three  sounds  may  be  distin- 
guished instead  of  two.  This  is  most  frequently  due  to  a  redu- 
plication of  the  second  sounds,  which  may  sometimes  be  heard 
even  in  healthy  individuals,  more  especially  at  the  height  of  in- 
spiration. It  may  also  be  present  in  various  heart  diseases,  nota- 
bly in  affections  of  the  mitral  valves.  This  reduplication 
of  the  second  sound  is  caused  by  a  non-simultaneous  clos- 
ure of  the  two  sets  of  semilunar  valves.  It  may  be  conceived 
that  the  difference  in  the  time  of  closure  is  due  to  an  unequal 
duration  of  the  right  and  left  ventricular  systoles,  because  one 
ventricle  must  do  more  work  than  the  other.  Such  an  explana- 
tion accounts  very  well  for  the  reduplication  in  mitral  valve  dis- 
ease. Why  it  should  occur  in  normal  individuals,  and  why  it 
should  be  absent  in  cases  where  we  have  reason  to  believe  that  the 
systole  of  one  side  is  lengthened,  is  not  so  readily  understood. 

A  doubling  of  the  second  sound  is  frequently  heard  at  the  apex 
in  cases  of  mitral  stenosis.  In  this  case  the  pause  between  the 
two  second  sounds  is  longer  than  it  usually  is  between  redupli- 
cated sounds.  Possibly  the  extra  tone  is  in  reality  a  rudimentary 
murmur,  or  is  produced  by  the  auricular  contraction. 

Reduplication  of  the  first  sound  is  less  common 
than  reduplication  of  the  second.  In  place  of  a  single  first  sound, 
we  hear  two,  the  second  being,  as  a  rule,  the  louder.  This  is 
considered  ordinarily  to  be  due  to  a  non-simultaneous  contraction 
of  the  two  ventricles,  but  it  must  be  admitted  that  the  explanation 
is  not  beyond  question. 

In  gallop  r  h  y  t  h  m  ^^^  we  likewise  hear  three  heart-sounds 
instead  of  two,  but  the  extra  sound  occurs  at  different  times 
in  different  individuals.  In  some  it  is  heard  shortly  before  the 
first  sound,  being  weaker  and  less  ringing  than  this.  In  such 
cases  it  seems  to  be  produced  by  the  contractions  of  the  auricle. 
"We  know  that  the  auricular  contraction  does  produce  a  tone,  but 
that  in  health  this  so  immediately  precedes  the  ventricular  sound 
that  it  is  merged  into  it  and  only  one  sound  is  heard  for  both 
contractions.  If  a  pause  intervene  between  the  two  contractions, 
we  hear  two  sounds,  and  this  seems  to  be  the  explanation  for  one 
form  of  gallop  rhythm.     In  the  other  form,  the  third  sound  occurs 


74  THE  BASIS  OF  SYMPTOMS 

shortly  after  the  second,  and  it  is  then  associated  with  a  diastolic 
wave  on  the  tracing  from  the  cardiac  impulse.  Its  exact  cause 
is  not  settled,  though  there  is  some  evidence  that  it  is  due  to 
the  ventricular  diastole. ^*^  This  second  form  of  gallop  rhythm 
is  said  to  be  more  serious  than  the  first.  Gallop  rhythm  is  a  sign 
of  cardiac  weakness  and  is  most  frequently  observed  when  an 
hypertrophied  heart  weakens,  above  all  when  the  hypertrophy 
has  been  caused  by  nephritis.  It  may,  however,  result  from 
arteriosclerosis,  myocarditis  or  acute  infectious  diseases. 

The  quality  or  character  of  the  first  sound  may  change,  but 
unfortunately  the  cause  and  the  meaning  of  such  changes  are 
but  little  understood.  A  muffled  or  impure  sound  may 
be  heard  in  the  absence  of  any  anatomical  changes  in  the  valves ; 
but,  on  the  other  hand,  such  an  impure  sound  may  herald  the  onset 
of  a  valvular  lesion.  Many  such  changes  are  perhaps  caused  by 
some  variation  in  the  manner  of  the  muscular  contraction,  or  by 
changes  in  the  tension  of  the  valves. 

The  first  sound  may  be  fainter  than  normal,  even  though  the 
ventricle  is  contracting  powerfully;  on  the  other  hand,  a  faint 
sound  may  be  due  to  a  weakening  of  the  ventricular  contraction. 
I  have  observed  a  disappearance  of  the  first  sound  in  a  case  of 
typhoid  fever  in  which  at  autopsy  no  macroscopical  changes  were 
found  in  the  heart.  In  syncope,  the  heart  sounds  are  often  ex- 
tremely faint;  and  since  the  pulse  is  also  very  weak,  we  must 
assume  that  a  weak  heart  action  is  responsible  for  the  faintness 
of  the  cardiac  sounds. 

Cardiac  Murmurs. — If  the  auriculoventricular  valves  allow 
the  blood  to  flow  back  into  the  auricles  during  systole,  eddies  are 
produced  by  the  mingling  of  this  stream  of  blood  with  the  one 
coming  in  from  the  great  veins.  These  eddies  set  the  valves  and 
heart  wall  in  vibration  very  much  as  the  violinist's  bow  causes 
the  strings  of  the  violin  to  tremble.  Such  vibrations  of  the  valves 
give  rise  to  the  abnormal  heart-sounds  known  as  murmurs.  A 
murmur  of  this  type  assists  us  in  diagnosing  a  regurgitation 
through  the  tricuspid  or  mitral  openings,  as  the  case  may  be. 

If  the  semilunar  valves  are  insufficient,  either  because  they 
are  shrunken,  or  because  the  orifice  is  dilated,  the  murmur  is  pro- 
duced in  diastole,  when  the  blood  streams  from  the  aorta  back 
into  the  ventricle,  and  there  causes  the  eddies  which  set  the  valves 
in  vibration.     The  murmur  may  be  heard  throughout  diastole 


THE  CIRCULATION  75 

or  it  may  be  present  only  in  the  earlier  part,  at  which  time  the 
negative  pressure  caused  by  the  active  dilatation  of  the  ventricle 
most  favors  a  return  flow  from  the  aorta. 

An  obstruction  to  the  flow  of  blood  through  any  of  the  orifices 
of  the  heart  may  also  produce  a  murmur,  and  a  simple  roughening 
of  the  valves  at  the  aortic  orifice  may  do  the  same.  The  murmur 
caused  by  a  stenosis  of  the  mitral  or  of  the  tricuspid  orifices  is 
heard  during  a  part  or  the  whole  of  the  diastole  of  the  ventricles. 
When  it  persists  throughout  this  period  it  is  usually  loudest  at  the 
onset  and  at  the  termination.  The  former  accentuation  is  caused 
by  the  suction  of  the  dilating  ventricle,  the  latter  by  the  auricular 
contraction.  More  frequently  these  murmurs  are  heard  only 
during  a  part  of  the  diastole,  either  at  the  beginning  or  at  the  end. 
The  latter,  called  a  presystolic  murmur,  precedes  and  merges  into 
the  first  heart-sound,  and  is  especially  characteristic  of  mitral 
stenosis. 

The  murmurs  produced  by  a  narrowing  or  roughening  of  the 
semilunar  valves  are  usually  loud  and  rough.  They  occur  at  the 
same  time  that  the  blood  is  passing  from  the  ventricles  into  the 
great  arterial  trunks.  It  is  sometimes  possible  to  demonstrate 
that  they  begin  somewhat  later  than  the  beginning  of  the  cardiac 
impulse,  for  it  must  be  remembered  that  the  first  part  of  this 
impulse  corresponds  to  that  j>eriod  of  the  ventricular  contraction 
during  which  the  intraventricular  pressure  is  being  raised  to  the 
level  of  pressure  which  exists  in  the  great  arterial  trunks.  For 
this  reason  no  blood  is  leaving  the  ventricles  during  the  first 
portion  of  the  cardiac  impulse,  and  consequently  no  murmur  due 
to  an  obstruction  at  the  aortic  orifice  can  be  produced  at  that  time. 

Murmurs  vary  greatly  in  intensity  and  in  tonal  character. 
Not  infrequently  they  are  distinctly  musical,  particularly  when 
systolic.     The  cause  of  these  variations  in  quality  is  not  known. 

In  aortic  stenosis  the  first  sound  may  also  disappear,  not  only 
over  the  aortic  area,  but  at  the  apex  as  well.  The  left  ventricle 
appears  to  contract  without  producing  an  audible  first  sound.  This 
is  probably  due  to  the  gradual  and  prolonged  systole  which  is  so 
characteristic  of  aortic  stenosis.  In  aortic  regurgitation  the  sec- 
ond sound  may  become  very  faint  or  it  may  disappear  entirely. 

Various  opinions  are  held  as  to  the  cause  of  those  murmurs 
which  have  been  variously  designated  as  accidental,  functional 
or  haemic  murmurs.       They  are  usually  systolic  in  time,  and  are 


76  THE  BASIS  OF  SYMPTOMS 

most  intense  in  the  second  intercostal  space  to  the  left  of  the 
sternum  and  at  the  point  of  maximum  cardiac  impulse.  It  is 
quite  certain  that  they  are  not  due  to  an  endocarditis  affecting 
the  mitral  valves.  We  cannot  exclude,  with  equal  certainty,  how- 
ever, the  presence  of  functional  insufficiencies  of  the  auriculo- 
ventricular  orifice.  Indeed,  it  appears  to  me  that  this  is  the 
cause  of  many  of  these  murmurs.  They  are  heard  most  fre- 
quently in  weak  and  anaemic  individuals,  such  as  would  be  most 
liable  to  have  a  weak  cardiac  muscle,  dilatation  of  the  cavities 
of  the  heart,  and  functional  insufficiency  of  the  mitral  and  tricus- 
pid orifices.  We  do  not  mean  to  imply,  however,  that  all  acci- 
dental murmurs  are  thus  caused.  Some,  it  may  be,  are  due  to 
anomalies  in  muscle  contraction,  or  as  Liithje^*^  suggests,  to  a 
physiological  stenosis,  as  it  were,  of  the  pulmonary  artery. 

Palpitation. — Palpitation  of  the  heart  has  been  defined  as  an 
irregular  or  forcible  heart  action  perceptible  to  the  individual 
himself.  In  health,  we  are  not  ordinarily  conscious  of  the  action 
of  our  hearts,  unless  it  is  much  increased  by  exertion  or  by  excite- 
ment. It  seems  probable  that  there  are  sensory  nerves  in  the 
heart  or  in  its  vicinity  which  are  stimulated  under  these  circum- 
stances. Pathological  palpitation  may  be  due  either  to  an  abnor- 
mal heart  action  or  to  an  increased  irritability  of  these  nerves, 
rendering  the  individual  abnormally  sensitive.  Naturally,  both 
causes  may  be  operative  in  the  same  person. 

An  increased  heart  action  does  not  necessarily  produce  the 
sensation  of  palpitation.  This  fact  is  frequently  illustrated  in 
cases  of  valvular  disease,  and  is  perhaps  to  be  explained  on  the 
assumption  that  the  gradual  development  of  the  condition  allows 
the  sensory  nerves  of  the  heart  and  adjacent  structures  to  become 
accustomed  to  the  changed  conditions.  Not  infrequently,  how- 
ever, patients  with  hypertrophy  and  dilatation  of  the  heart  suffer 
from  palpitation,  especially  during  any  exertion.  In  such  cases 
the  heart  is  working  up  to  the  limits  of  its  capabilities,  and  pos- 
sibly the  increased  tension  of  the  cardiac  wall  stimulates  the  sen- 
sory nerves,  and  so  produces  the  feeling  of  palpitation.  This 
would  explain  why  in  stasis  dilatation,  in  which  the  tension  of 
the  muscular  wall  is  reduced,  individuals  often  do  not  complain  of 
palpitation. 

In  yet  other  individuals,  no  definite  connection  between  the 
heart's  action  and  the  palpitation  can  be  discovered.     This  is 


THE  CIRCULATION  77 

especially  true  of  the  form  associated  with  ansemia  and  that  due 
to  certain  poisons,  notably  tobacco,  tea  and  coffee.  In  such  cases 
it  is  possible  that  the  systole  is  modified,  but  it  seems  more  prob- 
able that  the  patient  is  conscious  of  his  heart's  action  merely  be- 
cause of  an  increased  irritability  either  of  the  cardiac  nerves  or 
of  their  centres. 

Cardiac  Dyspnoea. — Shortness  of  breath  is  a  very  frequent 
symptom  of  heart  diseases.  It  is  often  associated  with  a  sensa- 
tion of  oppression  in  the  chest,  or  with  a  general  feeling  of 
anxiety ;  but  it  may  occur  alone.  It  may  vary  greatly  in  degree, 
from  the  slightest  dyspncea  on  exertion  to  the  most  extreme  air- 
hunger,  even  when  at  perfect  rest.  This  s)rmptom  is  not  charac- 
teristic of  any  form  of  heart  disease,  but  occurs  whenever  the 
interchange  of  gases  in  the  lungs  is  seriously  interfered  with. 
Periodic  interference  with  this  interchange  leads  to  periodic 
dyspnoea,  the  so-called  cardiac  asthma. 

The  dyspnoeaof  heart  disease  is  always  due  to 
an  insufficient  interchange  of  gases  between 
the  blood  and  certain  cells  of  the  medulla  (see 
Chapter  IV).  Two  causes  are  directly  responsible  for  the 
dyspnoea  of  heart  disease.  The  first  is  the  slowing  of  the 
blood-stream,  which  diminishes  the  interchange  of  gases 
in  the  lungs  and  in  the  respiratory  centre  of  the  medulla.  Any 
slowing  of  the  blood-stream  in  the  lungs  beyond  a  certain  limit 
leads  to  an  insufficient  interchange  of  gases  (see  Chapter  IV). 
A  second  cause  for  the  dyspnoea  of  heart  disease  lies  in  the 
changes  which  take  place  in  the  alveolar  epithelial 
cells  of  the  lungs,  and  which  lead  to  a  rigidity  of  the 
pulmonary  tissue. ^^^  These  changes,  which  have  already 
been  described  (see  p.  34)  would,  undoubtedly,  interfere  with  the 
interchange  of  gases  in  the  lungs,  even  though  the  blood-stream 
were  not  retarded. 

The  dyspnoea  which  develops  only  when  the  patient  exerts  him- 
self is  due  to  a  relatively  slow  circulation,  the  rate  of  flow  not 
being  increased  proportionately  to  the  demands  for  fresh  blood. 
Indeed  the  exertion  may  cause  a  fall  of  arterial  pressure  in  patients 
with  heart  disease. 

The  term  cardiac  asthma  is  applied  to  those 
paroxysms  of  extremely  severe  dyspnoea  which  occur  in  individ- 
uals who  have  heart  disease.     The  dyspnoea  is  often  of  the  most 


78  THE  BASIS  OF  SYMPTOMS 

extreme  grade,  and  may  be  accompanied  by  excessive  anxiety  and 
a  terrible  sense  of  impending  death.  The  paroxysms  may  begin 
after  a  m^^al,  after  exercise,  during  the  night  or  without  any 
apparent  cause.  They  occur  most  frequently  in  those  who  have 
arteriosclerosis  or  chronic  nephritis.  During  the  attack, 
the  pulse  is  usually  rapid,  soft  and  irregular  in  force  and 
frequency.  The  blood-pressure  is  usually  lower  than 
normal,  though  in  conditions  of  established  high  tension  it  usually 
remains  above  normal.  The  most  frequent  cause  of  cardiac 
asthma  is  a  transient  weakness  of  the  left  ven- 
tricle. This  raises  the  pressure  in  the  pulmonary  vessels  and 
so  increases  the  work  of  the  right  heart.  If  the  latter  is  unable 
to  accomplish  the  additional  work  so  thrown  upon  it,  there  results 
a  diminution  in  the  velocity  of  the  general  blood-current.  In 
addition  to  this  we  have  a  widespread  and  sudden  overfilling  of 
the  pulmonary  capillaries  which  contributes  toward  the  production 
of  the  symptoms.  In  certain  cases,  the  dyspnoea  becomes  less 
when  the  right  heart  weakens.  Since  the  pulmonary  capillaries 
would  then  be  less  distended,  this  favors  the  view  that  the  dis- 
tention of  the  capillaries  is  to  some  degree  responsible  for  the 
paroxysms  of  dyspnoea. 

Patients  suffering  from  heart  disease  frequently  develop 
dyspnoea  from  pulmonary  complications,  such  as  bronchitis,  pneu- 
monia and  oedema,  to  which  diseases  they  are,  indeed,  peculiarly 
subject.  In  the  French  literature  many  other  causes  for  the 
dyspnoea  of  heart  disease  are  enumerated,  among  which  are  toxic 
and  reflex  influences.  At  present,  however,  there  is  little  real 
proof  of  the  existence  of  such  causes. 

Cardiac  Pain. — As  has  already  been  stated,  a  feeling  of 
intense  anxiety  often  accompanies  cardiac  dyspnoea.  This  feel- 
ing may  occur  alone,  or  it  may  be  associated  with  pain  in  the 
precordium.  The  latter,  however,  rarely  occurs  alone,  except  in 
nervous  individuals,  in  whom  the  pain  is  of  psychic  origin  and 
is  simply  referred  to  the  periphery. 

Cardiac  pain,  originating  in  the  heart  itself, 
is  seen  especially  in  disease  of  the  coronary 
arteries  and  of  the  first  part  of  the  aorta.  It 
accompanies  aortic  more  frequently  than  mitral  lesions,  because 
the  former  are  more  often  associated  with  arteriosclerosis. 
Patients  with  various  forms  of  myocarditis  also  frequently  com- 


THE  CIRCULATION  79 

plain  of  pain  abour  the  heart  and  of  cardiac  distress,  which  may 
either  be  constantly  present  or  may  occur  in  paroxysms.  Often 
there  is  no  relation  between  these  symptoms  and  the  state  of  car- 
diac efficiency ;  generally,  however,  they  represent  a  demand  upon 
the  heart  for  increased  work  which  it  cannot  perform. 

The  severity  of  the  pain  varies  greatly.  On  the  one  hand, 
the  patient  complains  of  sensations  which  trouble  him  mainly  be- 
cause they  are  unusual,  while,  on  the  other  hand,  the  pain  is  of 
such  indescribable  severity  that  death  seems  imminent.  It  is  not 
the  place  here  to  enter  into  a  description  of  the  clinical  features 
of  these  cases  of  angina  pectoris.  ^*^  They  occur,  almost  without 
exception,  in  those  who  have  sclerosis  of  the  coronary  arteries. 
The  attack  may  come  on  without  any  apparent  cause,  though 
usually  it  is  precipitated  by  some  unwonted  excitement,  by  over- 
exertion or  by  digestive  disturbances.  Most  of  the  attacks  are 
due  to  cardiac  weakness  induced  by  these  unfavorable  circum- 
stances. 

We  do  not  know  what  causes  the  pain  of  angina  pectoris. 
Arteriosclerosis  of  the  coronary  arteries  is  certainly  present  in 
most  cases,  frequently  causing  a  narrowing  of  the  lumen  of  the 
vessel.  Perhaps  it  is  the  anaemia  of  certain  parts  of  the  heart 
which  causes  the  pain.  Such  a  theory  finds  an  analogy  in  the 
condition  known  as  intermittent  claudication,^*^  in  which,  owing 
to  a  narrowing  of  the  arteries,  pains  and  disturbances  of  function 
develop  in  the  legs  whenever  the  patient  walks  some  little  dis- 
tance. In  some  cases  the  anginal  paroxyms  cease,  and  this  has 
been  attributed  to  a  reopening  of  the  vessel,  although  we  have  no 
proof  for  such  an  hypothesis.  Breuer  calls  attention  to  the  fact 
that  we  are  not  yet  perfectly  clear  about  intermittent  claudication, 
for  we  do  not  know  how  great  a  role  spasmodic  contraction  of  the 
arteries  may  play  in  this  condition.  (Erb,  who  particularly  stud- 
ied this  condition,  finds  excessive  smoking  a  prominent 
factor  in  the  majority  of  cases.  Elimination  of  tobacco  may  bring 
about  complete  recovery,  not  only  in  intermittent  claudication, 
but  also  in  some  cases  of  angina  pectoris. — Ed.)  Nothnagel 
believes  that  the  pain  may  originate  from  the  vessels  themselves. 
Such  an  hypothesis,  attributing  the  pains  of  angina  directly  to 
the  spasmodically  contracted  vessel,  is  very  attractive.  It  would 
explain  the  fact  that  the  paroxysms  of  pain  may  occur  without 
anatomical  disease  of  the  coronary  vessels,  as  has  been  observed 


80  THE  BASIS  OF  SYMPTOMS 

in  nervous  individuals  and  especially  in  those  who  use  tobacco 
to  excess. 

The  anginal  attack  is  often  associated  with  a  variably  intense 
vasoconstriction  of  other  parts,  especially  of  the  cutaneous  vessels. 
Nothnagel  has  called  this  form  angina  pectoris  vasomotoria.  It  may 
be  present  both  in  cases  due  to  coronary  sclerosis,  and  in  those  of 
purely  psychic  origin. 

Many  other  questions  in  relation  to  angina  are  still  unan- 
swered, as,  for  example,  the  reason  why  the  pains  radiate  to  the 
left  brachial  plexus,  the  cause  of  the  syncope  in  some  cases  and 
finally  the  cause  of  the  sudden  death.  Every  attack  of  true 
angina  is  a  menace  to  the  life  of  the  individual,  and  not  infre- 
quently the  patient  dies  during  the  attack.  In  only  one  other 
condition  do  we  see  an  equally  sudden  death,  and  that  is  in 
coronary  embolism.  The  body  may  be  found  in  the  exact  position 
that  it  was  in  when  the  attack  of  angina  began.  No  other  signs 
of  asphyxia  are  present  The  cause  of  sudden  death  has  never 
been  explained. 

The  Arteries 

The  condition  of  the  arterial  walls  and  the  width  of  the 
arteries  exercise  a  considerable  influence  upon  the  flow  of  blood. 
If  the  arteries  were  all  fully  dilated,  it  would  be  absolutely  im- 
possible for  the  heart  to  maintain  the  circulation,  for  the  relatively 
small  quantity  of  blood  in  the  body  could  not  properly  fill  the 
vessels.  The  width  of  the  arteries  is  regulated  mainly  by  reflexes 
coming  from  various  parts  of  the  body;  and  by  virtue  of  this 
regulatory  mechanism  the  heart  is  enabled  to  graduate  its  own 
work.  The  condition  of  the  vascular  area  under  control  of  the 
splanchnic  nerves  is  of  prime  importance  in  its  effect  upon  the 
general  arterial  tension;  though  in  man  the  cutaneous  vessels 
constitute  a  not  inappreciable  factor. 

If  the  arteries  leading  to  a  certain  part  of  the  body  dilate  or 
contract,  the  blood-supply  to  that  part  will  be  altered.  These 
changes  are  fully  discussed  in  the  ordinary  text-books  on  physiol- 
ogy and  pathological  anatomy,  and  need  not  be  dwelt  upon  here. 
Our  concern  shall  be  with  those  disorders  of  vascular  function 
which  affect  the  circulation  as  a  whole.  An  example  of  this  we 
have  seen  in  arteriosclerosis,  which  frequently  causes  an  increase 
in  arterial  tension,  particularly  if  it  involve  the  root  of  the  aorta 


THE  CIRCULATION  81 

or  the  vessels  of  the  splanchnic  area.  Furthermore,  we  have 
already  emphasized  the  fact  that  hypertension  on  an  arterio- 
sclerotic basis  is  not  purely  of  a  mechanical  nature,  but  is  due,  in 
large  measure,  to  an  altered  vasomotor  tonus.  Indeed,  it  would 
seem  that  certain  cases  of  high  blood-pressure  are  the  result  of  a 
primary  augmentation  of  this  tonus.  These  are  the  cases  of  so- 
called  essential  hypertension.  What  relationship  they 
may  bear  to  arteriosclerosis  is  not  known,  though  it  is  possible  that 
they  are  precursors.  (But  recent  extensive  studies ^^^  appear 
to  indicate  that  a  large  proportion  of  such  cases  of  idiopathic 
hypertension,  especially  those  with  a  systolic  reading  of  i8o  mm. 
and  over,  are  really  due  to  anatomical  changes  in  the  kidneys, 
despite  the  fact  that  they  do  not  betray  themselves  during  life 
by  urinary  findings.  Modern  methods  of  determining  the  func- 
tional efficiency  of  the  kidneys  (see  pp.  427,  430)  promise  much 
in  the  way  of  establishing  the  renal  origin  of  such  cases. — Ed.) 

A  widespread  spasm  of  the  vessel  walls  tends 
to  raise  the  arterial  pressure  by  increasing  the  periph- 
eral resistance  against  which  the  left  ventricle  must  pump.  In 
cases  of  spasm  affecting  the  numerous  vessels  under  the  control 
of  the  splanchnic  nerves,  the  general  pressure  is  also  increased, 
but  here  the  work  of  the  ventricle  is  augmented  by  the  fact  that 
the  volume  of  blood  in  the  periphery  is  greater  because  of  the 
emptying  of  the  splanchnic  vessels.  Vessel-cramps  of  this  sort 
are  seen  in  cases  of  asphyxia  and  in  poisoning  due  to  strychnin 
and  lead;  and  PaP*''  has  emphasized  their  importance  in  other 
conditions.  The  cause  of  these  so-called  vessel-crises  is  but 
little  understood.  In  some  instances  they  are  possibly  of  nervous 
origin ;  while  in  others  they  are  of  reflex  nature,  in  which  case  they 
probably  possess  a  regulatory  function,  and  have  an  intimate 
relation  to  factors  concerned  in  renal  hypertension. 

The  Arterial  Blood-Pressure. — The  blood-pressure  ^^^  in 
the  larger  arteries  is  dependent  mainly  upon  two  factors — ^the 
amount  of  blood  pumped  into  the  arterial  system  by  the  heart,  and 
the  resistance  offered  to  the  escape  of  blood  from  this  system 
through  the  smaller  arteries  and  capillaries.  Of  less  importance 
are  the  elasticity  of  the  vessel- walls  and  the  total  quantity  of 
blood  in  the  body.  These  various  factors  influencing  blood- 
pressure  may  interact  upon  each  other  in  the  most  complicated 
manner.  For  example,  if  the  arterial  pressure  be  increased  from 
6 


82  THE  BASIS  OF  SYMPTOMS 

any  cause,  the  vagus  nerve  is  stimulated,  with  the  result  that  the 
heart  is  slowed  and  less  blood  is  delivered  into  the  aorta.  In  a 
like  manner,  when  the  volume  of  blood  is  rapidly  changed,  the 
blood-vessels  change  their  calibre,  so  that,  within  certain  limits, 
the  blood-pressure  is  not  altered. 

Systolic  and  Diastolic  Pressures.  The  Pulse-Pressure. — 
The  arterial  pulse  is  caused  essentially  by  the  variations  of 
pressure  within  the  artery,  produced  by  the  intermittent  expulsion 
of  blood  from  the  heart.  The  highest  point  on  this  wave  of 
arterial  pressure  is  called  the  systolic  pressure,  and  the 
lowest  point  the  diastolic  pressure.  The  difference  be- 
tween the  two,  i.e.,  the  variation  of  pressure  with  each  pulse,  is 
called  the  pulse-pressure.  By  means  of  the  ordinary  sphygmo- 
manometer it  is  now  possible  to  determine  the  diastolic  pressure 
with  almost  as  great  facility  and  accuracy  as  the  systolic.  This 
has  served  as  a  strong  stimulus  to  the  study  of  the  factors  con- 
cerned in  the  production  and  in  the  variations  of  the  systolic, 
diastolic  and  pulse-pressures  and  has  necessitated  a  certain  revision 
of  ideas  formerly  held  as  to  the  significance  of  hypertension. 

The  diastolic  pressure^*®  measures  the  peripheral  re- 
sistance and  as  such  is  probably  a  better  index  of  the  work  thrown 
upon  the  left  ventricle  than  is  the  systolic.  This  is  all  the  more 
true,  under  given  conditions,  because  the  diastolic  pressure  seems 
to  maintain  a  more  constant  level  than  the  systolic,  which,  as  is 
well  known,  may  undergo  marked  and  rapid  changes,  not  only 
physiologically,  but  especially  in  cases  of  hypertension.  The 
pulse-pressure  represents  the  actual  excess  of  pressure  im- 
pelling the  blood  to  the  periphery,  or  the  "load"  which  the 
heart  must  carry  to  maintain  the  circulation.  Though  observers 
are  not  in  complete  accord  as  to  what  constitutes  a  normal  pulse- 
pressure,  it  may  be  said  in  general  that  a  reading  below  30  mm. 
Hg.  is  low  and  one  above  50  mm.  is  high.  Thus,  in  a  case  of 
hypertension,  the  outlook  would  depend  not  so  much  upon  the 
systolic  pressure,  as  upon  the  pulse-pressure,  which  must  be  high 
to  maintain  compensation.  A  rise  in  the  diastolic  pressure  with- 
out a  corresponding  increase  in  the  systolic  in  such  cases  would 
signify  that  the  growing  peripheral  resistance  is  not  met  by  in- 
creased work  on  the  part  of  the  heart,  or  in  other  words  that 
the  pulse-pressure  was  falling  and  decompensation  was  at  hand. 

The  attempt  has  been  made  to  correlate  thecardiacout- 


THE  CIRCULATION  83 

putperbea  t — the  blood  flow  from  the  heart — with  the  pulse- 
pressure.  In  general,  it  is  true  that  an  increased  systolic  output 
produces  an  augmented  pulse-pressure  and  vice  versa.  That  there 
can  be  no  absolutely  definite  ratio,  however,  between  ventricular 
output  and  pulse-pressure  is  evident  from  the  fact  that  the  elastic 
integrity  of  the  vascular  wall  and  the  fulness  of  the  artery  must 
be  taken  into  consideration.  In  arteriosclerosis,  for  example,  and 
in  aortic  insufficiency,  the  ratio  of  pulse-pressure  to  cardiac  output 
behaves  contrary  to  the  general  rule. 

Physiological  Variations  in  Blood-Pressure. — A  g  e  influences 
the  blood-pressure.  During  infancy  the  systolic  pressure 
usually  ranges  between  75  and  90  mm.  of  mercury;  later,  the 
weight  and  height  of  the  child  appear  to  be  more  influential  in 
determining  the  pressure  than  is  the  age.^^^  In  adults,  age 
and  physical  development,  and  to  a  lesser  degree,  sex 
are  important.  The  systolic  pressure  increases  slightly  with  each 
decade,  ranging  from  100-130  mm.  in  young  adults  to  130-145 
mm.  in  old  people.  A  pressure  consistently  above  150  mm.  is 
pathological.  Women  show  slightly  lower  systolic  values  than 
do  men  of  the  same  age. 

Excitement,  anger  and  worry  generally  cause  a 
considerable  rise  of  pressure.  Though  the  pressure  increase  due 
to  worry  is  usually  transitory,  it  is  not  unlikely  that  long-con- 
tinued worry  may  lead  to  permanent  hypertension.  The  question 
of  the  emotions  and  epinephrin  discharge  is  con- 
sidered in  another  place  (p.  338).  The  effect  of  exercise  is 
variable.  Moderate  exertion — as,  for  example,  walking — may 
diminish  the  diastolic  pressure  and  increase  the  pulse-pressure; 
severe  exertion,  on  the  contrary,  tends  to  increase  both  the  systolic 
and  diastolic  readings,  indicative  apparently  of  the  increased 
cardiac  activity.  The  effect  of  severe  exertion  is  intensified  if 
the  act  requires  mental  effort.  An  increase  of  10  to  20  mm. 
generally  accompanies  the  change  from  the  recumbent  to  the  erect 
position.  This  normal  response  to  exercise  and  to  a  change  in 
position  has  been  made  use  of  as  a  test  of  the  functional  efficiency 
of  the  heart,  an  inefficient  organ  frequently  responding  with  no 
pressure  rise  and  sometimes,  indeed,  with  a  slight  fall.  But  as 
previously  noted,  the  behavior  of  the  diastolic  and  pulse-pressures 
in  these  cases  would  offer  more  valuable  diagnostic  criteria. 

In  the  first  two  hours  of  undisturbed  sleep,  there  may  be 


I 


84  THE  BASIS  OF  SYMPTOMS 

a  fall  amounting  to  20  mm.,  while  the  maximum  for  the  day  is 
observed,  as  a  rule,  in  the  late  afternoon.^  ^^  Considerable  study- 
has  been  devoted  to  the  effect  of  altitude  and  of  low 
atmospheric  pressures  upon  the  blood-pressure.  ^^^ 
Though  some  individuals  exhibit  no  change  under  these  con- 
ditions, the  effect  in  general  would  seem  to  be  a  slight  reduction, 
both  in  normal  individuals  and  in  those  with  hypertension. 

In  this  connection  may  be  mentioned  also  certain  factors  in 
their  bearing  particularly  upon  cases  of  high  arterial  tension. 
We  have  already  noted  that  persons  with  high  blood-pressure  do 
well  rather  than  badly  in  high  altitudes,  in  so  far  as  the  pressure 
itself  is  concerned.  Furthermore,  recent  work  would  indicate 
that  a  protein  diet  and  a  large  fluid  intake  do  not 
influence  an  uncomplicated  hypertension  unfavorably.  Sweat 
baths  generally  cause  a  pronounced  drop  in  pressure,  which 
may  persist  for  weeks ;  while  carbon  dioxide  baths  and 
the  high  frequency  current  have  a  similar,  though  less 
constant,  effect.  ^^* 

Pathologically  Increased  Blood-Pressure. — Emphasis  has 
already  been  placed  upon  the  importance  of  the  nephri- 
tides  in  the  production  of  continuous  high  pressure,  whether 
the  renal  lesion  be  evident  from  the  urine  or  not.  Attention  has 
been  directed  also  to  the  factors  which  seem  active  in  the  causa- 
tion of  this  form  of  hypertension,  and  in  particular  to  mechanical 
and  functional  alterations  in  the  arterial  walls.  The  high  pressure 
observed  in  arteriosclerosis,  either  generalized  or  involv- 
ing particularly  the  first  part  of  the  aorta  or  the  splanchnic  vessels, 
and  in  the  so-called  vessel-crises,  probably  bears  a  close 
etiological  relationship  to  renal  hypertension.  Interesting  in  this 
respect  are  the  most  recent  studies  of  Pal  ^^'^  in  which  cases  of 
high  pressure  seemingly  due  to  an  increased  arterial  tonus,  e.g., 
post-scarlatinal  uraemia,  and  cases  of  more  localized  smooth- 
muscle  spasm — angina  pectoris,  bronchial  asthma  and  pyloro- 
spasm — yield  to  the  action  of  papaverin,  which  is  endowed  with 
the  property  of  relaxing  smooth  muscle. 

Poisoning  with  strychnin  and  lead  probably  pro- 
duces an  augmented  arterial  tension,  as  previously  mentioned,  by 
causing  widespread  vessel-spasm.  The  effect  of  lead  in  this  re- 
spect is  seen  also  in  its  tendency  to  cause  anatomical  vascular 
and  renal  changes,  and  in  its  association  with  gout  and  diabetes. 


THE  CIRCULATION  85 

The  last  diseases,  however,  may  independently  cause  atheroma 
and  hypertension.  Experimentally,  digitalis  raises  the  arte- 
rial pressure  by  increasing  the  work  of  the  heart  and  by  causing 
vasoconstriction.  In  cases  of  hypertension,  however,  particularly 
when  associated  with  cardiac  decompensation,  digitalis  and  allied 
drugs  not  only  improve  the  circulation,  but  often  cause  a  drop  in 
pressure. ^^®  Epinephrin,  in  pharmacological  doses,  produces 
hypertension  by  constricting  the  peripheral  vessels.  The  physi- 
ological action  of  epinephrin  is  discussed  elsewhere  (p.  338). 

Acute  asphyxia  or  acute  anaemia  of  the  medul- 
lary centres  of  the  brain  will  stimulate  the  vasomotor  centre 
most  powerfully,  producing  a  contraction  of  the  splanchnic  vessels 
and  a  great  rise  in  arterial  pressure.  Such  a  cerebral  anaemia 
appears  to  be  the  cause  of  the  extremely  high  blood  pressures  some- 
times seen  in  cases  of  acute  cerebral  compression,  a  subject  which 
will  be  discussed  in  another  place  (p.  446) .  Leadcolicis  usu- 
ally associated  with  high  arterial  pressure,  and  the  early  stages  of 
peritonitis  are  likewise  frequently  accompanied  by  such  a 
rise.  Pain,  even  that  caused  by  pinching  the  skin,  usually 
increases  the  systolic  pressure  in  healthy  individuals. — Ed.) 

The  effect  of  an  increased  peripheral  resistance  upon  the  gen- 
eral circulation  depends,  for  the  most  part,  upon  the  behavior 
of  the  left  ventricle.  If  this  were  to  act  in  an  ideal  manner,  it 
would  contract  more  forcibly,  and  so,  by  raising  the  general 
arterial  pressure,  would  overcome  the  increased  resistance.  Un- 
fortunately, however,  when  the  peripheral  resistance  and  the 
arterial  pressure  are  much  increased,  the  left  ventricle  does  not 
empty  itself  completely,  the  pressure  in  the  left  auricle  rises,  and 
a  retardation  of  the  blood-flow  through  the  lungs  occurs. 

Pathological  Diminution  in  Blood-Pressure. — W  idespread 
dilatation  of  the  blood- vessels  may  lead  to  a  serious 
fall  of  arterial  pressure  and  a  slowing  of  the  circulation,  for,  as 
we  have  said,  the  total  quantity  of  blood  in  the  body  is  insufficient 
to  fill  the  blood-vessels  properly  if  they  are  all  widely  dilated. 

Such  a  widespread  dilatation  may  result  from  a  general  loss 
of  arterial  elasticity  with  a  stretching  and  widening  of  the  blood- 
vessels. This  has  been  observed  in  certain  cases  of  aortic  insuffi- 
ciency (p.  35),  and  apparently  in  the  late  stages  of  arteriosclerosis 
(p.  22). 

Arterial  dilatation  may  also  result  from  a  widespread 


88  THE  BASIS  OF  SYMPTOMS 

loss  of  arterial  tonus.  Thus,  if  the  splanchnic  vessels 
lose  their  tone,  they  become  filled  with  blood,  and  the  arteries 
to  the  other  parts  of  the  body,  especially  to  the  skin  and  muscles, 
are  left  comparatively  empty.  The  patient  becomes  weak  and 
pale,  the  arterial  and  venous  pressures  fall,  and  the  heart  receives 
an  insufficient  supply  of  blood.  The  pulse  becomes  soft  and 
rapid,  and  finally  syncope  supervenes.  Such  a  patient  is  practi- 
cally bled  into  his  own  abdominal  vessels,  and  life  may  last  only 
a  few  hours  or  even  minutes.  If  other  arteries  in  addition  to  the 
splanchnic  vessels  are  dilated,  the  symptoms  are  intensified;  yet 
the  condition  of  the  splanchnic  vessels  is  of  paramount  importance 
on  account  of  their  great  capacity. 

A  clinical  picture,  similar  to  that  just  described,  may  be 
produced  by  toxic  doses  of  such  drugs  as  chloral  and  alcohol, 
both  of  which  will  ultimately  paralyze  the  vasomotor  centre.  A 
similar  picture  is  also  presented  by  the  so-called  collapse  that 
sometimes  occurs  during  the  course  of  infectious  dis- 
eases. These  symptoms  are  not  those  of  ordinary  heart  failure, 
for  the  pulmonary  congestion  and  the  stasis  in  the  veins  of  the 
general  circulation  are  both  lacking.  The  picture  seems  rather 
to  be  caused  by  an  insufficient  supply  of  blood  without  stasis, 
and  is  fully  in  accord  with  the  assumption  of  an  extensive  vaso- 
motor paralysis. 

This  question  has  been  carefully  studied  in  animals.^  ^^  The 
great  falls  in  pressure  which  occur  at  the  height  of  experimental 
infections  with  the  pneumococcus,  the  diphtheria  bacillus  and  the 
bacillus  pyocyaneus,  have  all  been  shown  to  be  due  to  a  paralysis 
of  the  vasomotor  centres.  In  pneumococcus  infections,  the  heart 
may  even  beat  with  more  than  its  usual  force,  and  may  thus, 
to  a  certain  degree,  compensate  for  the  loss  of  vasomotor  tone. 
So  long  as  its  structure  remains  intact  it  can  meet  the  extra 
demands  made  upon  it,  such  as  the  rise  of  blood-pressure  caused 
by  asphyxia.  In  diphtheria  infections,  however,  the  heart  is 
usually  also  injured,  and  some,  indeed,  assert  that  the  injury 
to  the  heart  is  here  the  more  important  cause  of  the  circulatory 
disturbances. ^^^  It  has  also  been  definitely  proved  that  in  a  per- 
forative peritonitis  experimentally  induced,  the  cause  of  death 
is  a  toxic  paralysis  of  the  vasomotor  and  respiratory  centres.^*^^ 

The  result  of  these  animal  experiments  may  be  applied  with 
all  the  more  confidence  to  man  for  the  reason  that  the  clinical 


THE  CIRCULATION  87 

picture  of  collapse  corresponds  so  closely  to  what  we  should 
expect  from  a  vasomotor  paralysis.  I  have  the  impression  that 
the  most  severe  circulatory  disturbances  in  these  diseases  are  due 
to  central  vasomotor  paralyses,  preceded  in  many  cases  by  local 
lesions  of  the  blood-vessels."^  As  a  rule,  the  heart  "^  is  also 
affected  apart  from  the  changes  in  the  arteries  and  thus  the  circu- 
latory apparatus  as  a  whole  is  damaged.  Sometimes,  indeed,  the 
cardiac  weakness  is  more  prominent  than  the  vascular  paralysis 
but  in  either  case  the  therapeutic  indication  is  to  improve  the 
circulation  by  strengthening  the  heart. 

(Another  form  of  extreme  circulatory  depression  is  that  seen 
in  anaphylactic  shock  (see  p.  1 79).  Animal  experiments  have 
shown  that  in  this  condition  there  is  regularly  a  considerable  fall 
in  blood-pressure,  which  may  amount  to  20  to  30  mm.  Hg.  Though 
the  splanchnic  dilatation  and  medullary  anaemia  are  probably  the 
chief  factors  in  the  production  of  this  form  of  shock,  it  would 
appear  from  electrocardiographic  studies  that  the  origin  is  partly 
cardiac.  ^^^ 

The  cause  of  so-called  surgical  shock  is  still  not  definitely  set- 
tled; and  it  is  not  unlikely,  as  Yandell  Henderson  ^"^  has  stated, 
that  the  etiology  is  probably  not  uniform.  In  Crile's  earlier  pub- 
lications,^®^ shock  was  attributed  to  an  exhaustion  of  the  vaso- 
motor centre  caused  by  severe  traumatism  to  the  peripheral 
nerves.  This  in  turn  caused  a  fall  in  blood-pressure  which  was 
regarded  as  the  essential  feature  of  the  picture,  and  to  the  cor- 
rection of  which  remedial  measures  were  directed. 

Objection  has  been  made  to  this  theory  because  it  seemed  inade- 
quate to  explain  all  cases  and  also  because  there  may  be  a  con- 
siderable rise  in  pressure  in  the  early  stages  of  shock  lasting  until 
the  vasoconstriction  caused  by  the  centripetal  stimuli  finally  gives 
way  to  overstimulation  and  depression.  And,  more  recently, 
Crile^®'^  has  come  to  believe  that  the  essential  substratum  of  shock 
resides  in  specific  changes  in  the  brain-cells  which  bring  about  a 
conversion  of  the  potential  energy  of  these  cells  into  kinetic 
energy.  The  direct  cause  of  this  change  is  ascribed  by  Crile  to 
injurious  stimuli  (noci  impulses),  such  as  fear  of  the  operation, 
fatigue,  loss  of  sleep  and  those  due  to  the  anaesthesia  itself,  which 
so  lower  the  cerebral  threshold  of  sensitiveness  as  to  render  it 
susceptible  to  the  trauma  of  the  operation.  The  attempt  is  made, 
therefore,  to  exclude  these  noci  impulses  by  eliminating,  so  far  as 


88  THE  BASIS  OF  SYMPTOMS 

possible,  the  above  mentioned  psychic  predisposing  factors,  and 
also  the  pain  and  trauma  of  operation  by  a  perfect  anaesthesia, 
both  general  and  local.  This  method  Crile  has  called  anoci- 
association. 

Henderson  believes  that  certain  cases  of  shock,  at  least,  are 
due  to  acapnia — a,  deficiency  of  carbon  dioxide  in  the  blood — 
which  occurs  when  various  factors  such  as  pain,  trauma,  exposure 
of  the  tissues,  fever,  faulty  anaesthesia,  etc.,  lead  to  an  increased 
respiratory  activity.  This  in  turn  causes  a  lowering  of  the 
osmotic  tension  of  the  blood,  a  loss  of  fluid  from  the  latter  and 
a  diminution  in  the  total  volume  of  blood.  The  consequent  fall 
in  venous  pressure  deprives  the  heart  of  an  adequate  supply  of 
blood  which  is  evidenced  by  a  diminished  output  in  systole. 
Henderson's  theory,  therefore,  postulates  a  condition  not  unlike 
hemorrhage. — Ed.  ) 

A  comprehensive  and  nice  adaptability  of  the  diameter  of  the 
arterial  tree  to  the  activity  of  the  heart  is  of  great  importance 
in  the  maintenance  of  the  circulation.  An  equal  and  perhaps 
greater  factor  is  the  balance  between  the  volume  of  blood  in  one 
vascular  field  and  that  in  others.  Such  an  adjustment  is  essential 
not  because  the  total  blood  mass  must  be  properly  distributed 
among  the  different  vessels,  but  because  correlated  organs  can 
thus  receive  a  sufficient  supply.  Romberg  and  O.  Miiller^^^ 
have  shown  that  in  art^iosclerosis  the  vascular  reflexes  are  mark- 
edly disturbed.  The  same  is  true  of  those  remarkable  con- 
ditions of  local  anaemia,  such  as  Raynaud's  disease,  which  at 
present  are  regarded  as  of  nervous  origin. 

The  Veins 

Venous  Stasis. — It  has  already  been  shown  that  stasis  of 
the  blood  in  the  veins  may  result  from  cardiac  weakness.  The 
stasis  in  the  pulmonary  circulation,  produced  by  the  weakness  of 
the  left  ventricle,  may  be  overcome  to  a  certain  extent  by  the 
increased  activities  of  the  right  ventricle;  whereas  the  stasis  in 
the  veins  of  the  general  circulation,  resulting  from  a  weakness 
of  the  right  ventricle,  cannot  be  thus  overcome,  and  the  entire 
blood  current  is  slowed. 

General  venous  stasis  may  also  be  caused  by  diseases  of  the 
lungs  or  by  pressure  upon  the  great  veins.  If  the  intrathoracic 
pressure  be  increased,  either  by  a  diminution  in  the  elasticity  of 


THE  CmCULATION  89 

the  lungs  (emphysema)  or  by  a  collection  of  fluid  or  gas  in  the 
pleural  cavities,  or  if  the  thoracic  movements  are  lessened,  as  hap- 
pens during  superficial  breathing,  then  a  diminution  in  the  flow 
of  blood  to  the  heart  results.  Pressure  upon  the  great  veins  by 
tumors  and  especially  by  pericardial  effusions  may  also  interfere 
with  the  return  of  venous  blood  to  the  heart.  A  pericardial 
effusion  may,  indeed,  cause  sudden  death  by  compressing  the 
venae  cavse  just  before  their  entrance  into  the  right  auricle,  and 
so  shutting  off  the  entire  blood-supply  to  the  heart. 

Venous  Murmurs. — In  certain  individuals,  especially  in  chlo- 
rotic  girls,  a  murmur  may  be  heard  over  the  bulbus  jugularis. 
This  is  usually  louder  on  the  right  than  on  the  left  side,  and  is 
known  as  the  venous  hum  (bruit  de  diable).  Its  cause 
is  not  well  imderstood.  Some  believe  that  it  is  a  murmur  of 
stenosis  caused  by  the  passage  of  the  blood  from  the  external 
jugular  vein  into  the  jugular  sinus;  yet  why  this  should  occur 
especially  in  anaemic  individuals  is  not  known.  Sahli  ^^"^  con- 
siders that  the  blood  flows  more  rapidly  in  anaemia,  and  that  this 
is  the  cause  of  the  murmur ;  and  as  the  rate  of  flow  in  the  anaemias 
appears  to  be  more  rapid  than  normal,  this  explanation  seems  the 
best  at  hand. 

The  Circulation  of  the  Lymph 

The  lymph  may  be  looked  upon  as  the  fluid  that  has  escaped 
from  the  capillaries.  It  carries  material  to  the  cells  of  the 
parenchyma,  and,  laden  with  waste  products,  returns  to  the  blood 
by  way  of  the  lymphatic  vessels.  Its  composition,  therefore, 
varies  according  to  the  organ  from  which  it  comes  and  according 
to  the  activity  of  that  organ. 

We  know  of  no  diseases  in  which  too  little  lymph  escapes 
through  the  capillary  walls,  although  it  seems  probable  that  such 
do  exist. 

CEdema. — Certain  conditions  lead  to  an  accumulation  of 
l)miph  in  the  lymphatic  vessels  and  spaces,  among  which  latter 
the  serous  cavities  may  be  included.  Theoretically,  such  an 
accumulation  may  be  brought  about,  first,  by  an  excessive 
formation  of  lymph;  secondly,  by  a  hindrance  to  the 
escape  of  lymph;  and  thirdly,  by  a  combination  of 
the  two.  The  quantity  of  fluid  that  passes  through  the  capil- 
lary walls  depends,  on  the  one  hand,  upon  the  difference  in 


90  THE  BASIS  OF  SYMPTOMS 

pressure  between  the  blood  in  the  capillaries  and  that  of  the  lymph 
in  the  surrounding  tissues,  and,  on  the  other  hand,  upon  the 
permeability  of  the  capillary  walls  themselves. 

CEdema  from  Stasis. — QEdema  may  be  caused  by  a  stasis 
of  blood  in  the  veins.  This  stasis  may  be  merely  local,  as 
when  it  is  caused  by  an  occlusion  of  a  vein  by  thrombosis  or 
external  pressure;  or  it  may  be  general,  as  when  it  results 
from  pathological  changes  in  the  lungs,  weakness  of  the  right 
heart,  intrathoracic  tumors  and  pleural  or  pericardial  exudates. 
The  cedematous  fluid  that  collects  in  the  lymph-vessels  and  spaces 
in  such  cases  is  poorer  in  proteids  and  leucocytes,  but  richer  in 
erythrocytes,  than  is  normal  lymph.  The  organs  that  become 
most  swollen  are  those  in  which  the  tissues  are  under  the  least 
elastic  tension,  and  in  which  the  venous  stasis  is  favored  by 
gravity.  For  this  reason  the  oedema  caused  by  general  stasis  is 
usually  first  observed  about  the  ankles  and  over  the  lower  part 
of  the  back. 

The  mere  obstruction  of  a  vein  does  not  necessarily  lead  to 
oedema,  for  a  collateral  venous  circulation  may  be  established. 
After  the  experimental  ligature  of  a  vein,  the  occurrence  of 
oedema  is  greatly  favored  by  the  frequent  accompanying  arterial 
hyperaemia. 

Even  an  increased  transudation  of  lymph  does  not  necessarily 
cause  an  oedema,  for  the  excessive  amount  may  be  carried  away 
by  the  lymphatics.  There  must  be,  in  addition,  therefore,  some 
interference  with  the  lymph-flow  from  the  part.  When  general 
venous  stasis  causes  the  oedema,  the  blood-pressure  in  the  left 
subclavian  vein  is  naturally  raised,  and  this  would  furnish  the 
interference  with  the  flow  of  lymph  into  this  vein  from  the  thoracic 
duct. 

The  lymph-flow  may  also  be  hindered  in  other  ways.  An  in- 
creased pressure  in  the  capillaries  is  transmitted  to  the  tissues 
about  them,  which  gradually  become  stretched  and  lose  their  elas- 
ticity. The  loss  of  elasticity  diminishes  the  pressure  normally 
exerted  by  the  tissues  upon  the  lymph-spaces,  the  difference  be- 
tween the  blood-  and  the  lymph-pressures  is,  therefore,  increased, 
and  exudation  is  favored.  On  the  other  hand,  the  diminished 
pressure  exerted  by  the  tissues  upon  the  lymph-spaces  tends  to 
lessen  the  rate  of  lymph-flow  from  the  tissues  toward  the  thoracic 
duct.     For  these  reasons,  the  elasticity  of  the  tissues 


THE  CIRCULATION  91 

exercises  a  most  important  influence  upon  the 
occurrence  of  oedema  and  different  organs  become  swollen 
to  different  degrees,  even  though  they  all  are  exposed  to  the  same 
venous  stasis. 

The  mere  obstruction  of  a  lymphatic  vessel  rarely  leads  to 
oedema,  on  account  of  the  numerous  anastomoses  between  the 
lymphatics.  If,  however,  the  thoracic  duct  be  obstructed,  ascites 
and  oedema  of  the  legs  usually  develop. 

Inflammatory  CEdema. — As  is  well  known,  inflammations 
injure  the  walls  of  the  capillaries.  There  is  an  active  local  hyper- 
semia,  and,  at  the  same  time,  a  slowing  of  the  blood-current 
caused  by  the  changes  in  the  vessel  walls.  The  latter  influence 
the  amount  and  character  of  the  transudate,  and  consequently  the 
lymph  of  inflammation  differs  from  that  normally  transuded,  in 
that  it  contains  more  albumin  and  more  numerous  blood- 
corpuscles.  Purulent  inflammations  are  characterized  by  the 
richness  of  their  exudates  in  leucocytes,  which  are  attracted  thither 
by  the  primary  cause  of  the  inflammation. 

Inflammatory  processes  also  interfere  with  the  removal  of 
lymph  from  the  tissues,  for  they  directly  diminish  the  tissue 
elasticity,  with  the  results  just  described.  Even  the  elasticity 
of  tissues  at  some  little  distance  from  the  inflammation  may  be 
diminished,  so  that  these  also  become  oedematous,  thus  producing 
the  so-called  collateral  oed  em  a . 

iNephritic  CEdema. — Of  the  dropsies  that  accompany  neph- 
ritis ^^^  some  are  unquestionably  due  to  simple  stasis.  We 
have  seen  that  the  heart  is  often  weakened  in  nephritis,  in  which 
case  it  is  obvious  that  we  have  to  do  with  the  ordinary  dropsy 
of  heart  disease.  Here,  however,  we  wish  to  consider  those 
nephritic  oedemas  that  occur  independently  of  any  cardiac  weak- 
ness. They  usually  appear  first  in  the  subcutaneous  tissues,  and 
especially  in  those  that  possess  the  least  tension,  as  about  the 
ankles  and  eyelids,  though  not  infrequently  the  great  serous 
cavities  are  early  filled  with  fluid. 

CEdema  of  this  character  is  rarely  seen  in  certain  forms  of 
nephritis,  especially  in  contracted  kidneys,  in  the  nephritides 
caused  by  certain  poisons  (arsenic)  and  in  those  associated  with 
certain  infectious  diseases  (pneumonia  and  typhoid  fever).  On 
the  other  hand,  oedema  is  common  and  often  marked 
in    chronic    parenchymatous    nephritis,     in    in- 


98  THE  BASIS  OF  SYMPTOMS 

flamed  amyloid  kidney,  in  scarlatinal  nephritis 
and  in  primary  acute  nephritis.  We  are  still  in  no 
position  to  state,  however,  whether  the  cedema  in  these  cases 
is  due  to  the  anatomical  lesion  per  se  or  to  the  consequent  func- 
tional disturbance. 

The  urine  inthe  dropsical  cases  is  f rquently  dimin- 
ished in  amount  and  rich  in  albumin;  yet  the  high  percentage  of 
albumin  can  hardly  be  the  cause  of  the  oedema,  for  large  quanti- 
ties may  be  excreted  with  comparatively  slight  oedema,  as,  for 
example,  in  imcomplicated  amyloid  disease  of  the  kidney.  Fur- 
thermore, a  reduction  of  the  albumin  in  the  blood  cannot  be  the 
sole  cause  of  the  oedema,  for  we  know  that  with  plenty  of  food 
there  is  no  diminution  of  albimiin  in  these  cases.  When  cachexia 
develops,  the  albumin  may,  indeed,  be  diminished  and  oedema  may 
api>ear,  but  this  is  of  a  different  character  and  of  relatively  slight 
degree. 

It  is  possible  that  the  oedema  of  nephritis  is  produced  by  a 
primary  retention  of  water  in  the  body.  In  the 
forms  of  the  disease  under  consideration,  less  urine  than  normal 
is  usually  secreted,  and  frequently  the  oedema  increases  as  the 
urine  diminishes,  and  i/ice  versa.  Many  writers,  therefore,  favor 
the  view  that  a  primary  retention  of  water  in  the  bodies  of  these 
patients  dilutes  their  blood  and  so  produces  an  hydraemia  or  an 
hydrsemic  plethora;  and  Hammerschlag^^^  has  shown  that  a 
diluted  blood  is  usually  present  in  these  cases  of  nephritis.  Never- 
theless, the  theory  has  many  opponents.  Most  experimenters  have 
failed  to  produce  an  oedema  by  the  mere  infusion  of  salt  solu- 
tion.^'^*'  Half  of  the  blood  has  been  withdrawn  and  replaced  by 
saline  solution  and  enormous  quantities  of  fluid  have  been  infused 
without  producing  any  oedema.  Some  other  factor,  therefore, 
seems  to  be  necessary,  and  this  is  possibly  an  injury  to  the 
vessel  wall,  just  as  in  the  inflammatory  type.  Magnus  has 
discovered  a  whole  series  of  substances  which  will  produce  exten- 
sive anasarca  if  injected  into  an  hydraemic  animal.  Among  these 
are  substances  that  are  retained  in  the  body  after  removal  of 
the  kidneys. 

One  may  assume,  therefore,  that  some  change  in  the 
capillary  walls  is,  in  part,  responsible  for  the  oedema  of 
nephritis,  though  up  to  the  present  these  changes  have  not  been 
demonstrated  anatomically.     We  have  already  seen  that  such 


THE  CIRCULATION  93 

h3^thetical  changes  in  the  blood-vessels  probably  account  for  the 
cardiac  hypertrophy  in  certain  cases  of  nephritis.  Recent  ex- 
perimental studies  ^^^  devoted  to  this  problem  indicate  that  in 
the  nephritides  produced  by  certain  poisons  the  parenchymatous 
changes  are  inadequate  to  explain  the  cedema,  and  that  the  latter 
is  doubtless  due  to  a  functional  disturbance  of  the  renal  vessels. 
Thus  in  uranium  nephritis,  which  is  essentially  tubular  in  charac- 
ter, cedema  does  not  develop  until  the  permeability  of  the  renal 
vessels  and  their  ability  to  contract,  and  especially  to  dilate,  are 
affected.  This  would  indicate  a  corresponding  injury  of  the 
cutaneous  vessels. 

Some  nephritic  cedemas  apparently  depend  upon  the  reten- 
tion of  sodium  chlorid  in  the  body.^^^  The  normal 
individual  excretes  this  salt  at  about  the  same  rate  as  it  is  ingested, 
so  that  the  amount  in  the  body  remains  nearly  constant.  In 
nephritis,  on  the  contrary,  the  excretion  frequently  does  not  follow 
the  same  curve  as  the  ingestion.  The  French  school,  especially, 
has  explained  certain  cases  of  nephritic  oedema  on  the  basis  of  a 
retention  of  chlorids  in  the  body.  According  to  this  hypothesis 
the  inability  of  the  kidneys  to  eliminate  sodium  chlorid  leads  to 
a  retention  of  this  salt  in  the  body,  and  this  retention,  in  turn, 
necessitates  an  accumulation  of  water  in  the  tissues  in  order  to 
maintain  the  proper  osmotic  relations.  Attractive  as  is  this  con- 
ception, it  leaves  much  to  be  explained,  for  in  many  cases  of 
nephritic  oedema  there  is  no  evidence  of  salt  retention. ^^^ 

(Fischer ^'^^  has  developed  the  theory  of  an  increased 
hydration  capacity  of  the  colloids  to  explain  oedema. 
Different  colloids  vary  considerably  in  their  ability  to  take  up 
water,  a  property  which  depends  upon  the  reaction  of  the  fluid 
in  which  the  colloid  is  immersed  and  upon  the  electrolytic  content 
of  this  fluid.  According  to  Fischer,  oedema  is  produced  when 
acids  accumulate  in  the  tissues  and  thus  increase  the  affinity  of  the 
colloids  for  water,  granting,  of  course,  that  the  supply  of  the 
latter  is  adequate.  The  excess  of  acids  represents  either  an  in- 
creased metabolic  production,  or  a  faulty  removal  of  acids  formed 
in  normal  amount.  In  accordance  with  this  conception  oedema  is 
to  be  combated  by  the  use  of  substances  which  diminish  the  affinity 
of  the  colloids  for  water,  namely,  salts  (electrolytes).  Fischer 
has  recommended  definite  saline  solutions  and  a  definite  technic 
for  the  employment  of  these  in  cases  of  oedema. — Ed.  ) 


94  THE  BASIS  OF  SYMPTOMS 

Other  CEdemas. — We  know  little  concerning  the  dropsies 
caused  by  severe  cachexias  and  by  many  diseases  of  the  cord  and 
of  the  peripheral  nerves.  Changes  in  the  composition  of  the 
blood  probably  contribute  to  the  causation  of  the  fonner,  while, 
in  the  latter,  paralyses  of  the  muscles  would  interfere  with  the 
movements  of  the  lymph  and  so  tend  to  produce  oedema.  Yet  in 
neither  case  do  these  seem  to  be  the  sole  causes. 

Composition  of  Exudates. — The  composition  of  exudates 
varies  with  their  origin.^ "^^  Those  due  to  inflammatory  causes 
usually  contain  four  per  cent,  of  albumin  or  over,  while  those 
due  to  other  causes,  usually  contain  between  o.  i  and  0.8  per  cent. 
The  exudates  that  are  poorest  in  albumin  are  those  caused  by 
cachexias  and  by  chronic  nephritides,  a  percentage  less  than  o.i 
rarely  being  found  except  in  serious  renal  diseases,  especially 
in  amyloid  disease  of  the  kidney.  The  percentages  of  albumin 
in  exudates  of  a  non-inflammatory  character  vary  so  much  in  the 
individual  cases  that  a  classification  according  to  this  standard 
is  not  possible.  (Of  considerably  greater  moment  as  a  diagnostic 
standard  is  the  differential  count  of  the  white  cells  found  in  the 
exudate  (  cytodiagnosis  ).  Three  typical  formulas  are  described, 
according  to  the  variety  of  cells  found  in  greatest  abundance — 
first,  the  lymphocytic,  in  tuberculous  inflammations;  second, 
the  polynuclear  leucocytic  in  non-tuberculous  infec- 
tions ;  and  third,  the  endothelial  in  transudations.  These 
formulas  appear  to  be  fairly  specific  for  the  different  types  of  most 
exudates  except  the  ascitic. — Ed.) 

Chylous  and  Chyliform  Ascites.^^^ — Exudates  into  the  peri- 
toneal cavity,  and  more  rarely  those  into  the  pericardial  and 
pleural  cavities,  may  contain  considerable  amounts  of  fat.  This 
may  arise  from  a  fatty  degeneration  of  the  cells  of  the  exudate, 
with  subsequent  disintegration  of  these  cells.  When  the  blood 
contains  large  quantities  of  fat,  the  latter  sometimes  passes 
through  the  capillary  walls  into  the  exudate.  Such  exudates  into 
the  peritoneal  cavity  are  called  chyliform  ascites. 

In  another  group  of  cases,  usually  caused  by  carcinomata,  the 
abdominal  lymphatics  rupture  and  the  chyle  flows  directly  into 
the  peritoneal  cavity,  producing  the  so-called  true  chylous 
ascites.  The  composition  of  the  ascitic  fluid  then  depends 
largely  upon  the  character  of  the  food,  and  when  certain  fats 
are  ingested,  they  may  be  demonstrated  in  the  ascitic  fluid.     Dur- 


THE  CIRCULATION  95 

ing  life  it  is  often  impossible  to  differentiate  these  two  forms  of 
ascites. 

Pulmonary  (Edema. — CEdema  of  the  lungs  may  result  from 
the  same  causes  as  does  oedema  of  other  parts  of  the  body.  The 
exudation  about  an  inflammatory  area  corresponds  to  the  inflam- 
matory oedema  already  described  (p.  91 ) .  On  account  of  the  rich 
and  peculiar  blood-supply  of  the  lungs,  however,  a  local  oedema 
from  stasis  does  not  occur.  If  there  be  a  hindrance  to  the  blood- 
flow  through  one  part  of  the  lungs,  the  blood  merely  takes  another 
course.  No  sharp  line  can  be  drawn  between  local  inflammatory 
oedema  of  the  lungs  and  a  small  pneumonic  patch. 

Of  great  interest  is  the  cause  of  the  general  pul- 
monary oedema  that  so  frequently  terminates 
cardiac,  pulmonary  and  infectious  diseases. 
Two  hypotheses  have  been  advanced  in  explanation  of  this  oedema. 
The  first  considers  that  it  is  caused  by  stasis.  If,  experi- 
mentally, the  left  ventricle  of  an  animal  be  seriously  injured 
while  the  right  is  left  intact,  pulmonary  oedema  frequently  de- 
velops. The  oedema  in  such  instances  is  evidently  caused  by 
stasis,  and  we  have  reason  to  believe  that  at  least  some  pulmonary 
oedemas  of  man  are  similarly  produced.  This,  in  all  probability, 
is  the  cause  of  the  oedema  that  sometimes  develops  after  sudden, 
severe  injury  to  the  left  heart,  such  as  may  be  produced,  for 
example,  by  an  aortic  insufficiency. 

In  order  to  produce  this  oedema  experimentally,  it  is  necessary 
that  the  left  ventricle  should  be  almost  completely  paralyzed ;  for 
if  it  be  only  relatively  weakened,  no  oedema  of  the  lungs  ensues.^ ^"^ 
Now  the  general  arterial  pressure  of  patients  with  pulmonary 
oedema,  especially  when  the  latter  follows  nephritis  or  arterio- 
sclerosis, rarely  reaches  the  low  level  that  is  experimentally  neces- 
sary, and  in  these  patients,  there  is  certainly  no  complete  paralysis 
of  the  left  ventricle.  Sahli,  therefore,  believes  that  general  pul- 
monary oedema  results  in  most  instances  from  changes  in  the 
capillary  walls. ^''^^  A  number  of  facts  support  this  view. 
First,  the  oedema  is  unevenly  distributed  throughout  the  lungs; 
and  secondly,  it  is  often  associated  with  definite  inflammatory 
processes.  Indeed,  in  heart  disease,  often  no  sharp  line  can  be 
drawn  between  the  oedematous  areas  and  the  pneumonic  patches 
that  are  so  frequently  encountered.  Some  oedemas  of  the  lungs 
are,  therefore,  almost  certainly  of  an  inflammatory  nature.     Pos- 


99  THE  BASIS  OF  SYMPTOMS 

sibly  future  observations  on  the  percentage  of  albumin  in  the 
oedematous  fluid  will  give  some  indication  as  to  the  nature  of 
its  cause. 

Though  it  must  be  acknowledged  that  inflammatory  processes 
do  contribute  to  the  production  of  certain  pulmonary  cedemas, 
nevertheless  it  seems  to  me  that  the  weakness  of  the  left  ventricle 
is,  at  least,  of  equal  importance  in  most  cases.  The  results  of  ani- 
mal experimentation  are  not  directly  applicable  to  man.  The 
chronic  pulmonary  stasis  that  accompanies  heart  and  kidney  dis- 
eases may  induce  changes  in  the  walls  of  the  capillaries  of  the 
lung,  so  that  a  relatively  slight  weakness  of  the  left  ventricle  could 
produce  cedema,  which  would  not  be  the  case  if  the  vessels  were 
entirely  healthy.  Not  infrequently,  the  physician  sees  patients 
in  whom  a  weakening  of  the  left  ventricle  is  followed  by  an  cedema 
of  the  lungs,  which  disappears  with  a  strengthening  of  the 
ventricle. 

LITERATURE 

*  Knoll :  Wiener  Sitzungsber.,  mathem.-naturw.  KL,  1899,  iii,  5. 

*Lewy:  Zeitschft.  f.  klin.  Med.,  xxxi,  321,  520;  Frank,  Zeitschft.  f.  Biol.,  xxxii, 
428,  and  xxxvii,  483. 

*  Stolnikow :  Du  Bois'  Arch.,  1886,  1. 

*  Cohnheim :  AUg.  Path.,  2nd  edit.,  i,  40 ;  v.  Frey  and  Krehl,  Du  Bois' Arch., 

1890,  31 ;  V.  Frey,  Arch.  f.  klin.  Med.,  xlvi,  398;  Frank,  Zeitschft.  f,  Biol., 

xxxii   '^70. 
•Hesse:  Arch.  f.  Anat,  1880,  328. 

•Ludwig  and  Thiry:  Wiener  Sitzungsber.,  xlix,  II,  421. 
^  Cf.  V.  Frey :  Arch,  f .  klin.  Med.,  xlvi,  398 ;  Krehl  and  Romberg,  Arch,  f .  Exp. 

Path.,  XXX,  49. 

*  Zeitschft.  f.  klin.  Med.,  xxi,  61;  cf.  Grossmann,  ibid.,  xxvii,  151. 
'  Bauer  and  Bollinger :  Festschrift  f .  Pettenkof er,  Munich,  1893. 

"  See  Krehl,  in  the  Nothnagel  System  (Diseases  of  the  Heart  Muscle). 

"  Die  Massenverhaltnisse  d.  mensch.  Herzens,  1884. 

"  Arch,  f .  klin.  Med.,  Ixiv,  597. 

"  Bruns :  Miinch.  med.  Wochenschft,  1909,  No.  20. 

"Moritz:  Arch.  f.  klin.  Med.,  Ixxvii,  339  (lit.). 

"  See  Dietlen :  Arch,  f .  klin.  Med.,  Ixxxix,  604 ;  xcii,  383. 

"  Kiilbs :  Kongr.  f .  inn.  Med.,  1906,  430 ;  cf.  Grober,  Arch,  f .  exp.  Path.,  lix, 

424.    But  see  Bruns,  l.c. 
"  See  Albrecht :  Der  Herzmuskel,  Part  I ;  Magnus- Alsleben,  Arch,  f .  exp. 

Path.,  Ivii,  48,  57. 
"  See  Kolle- Wassermann :  Handb.,  1913  (lit.)  ;  D.  Gerhardt,  Die  Endokarditis, 

1914   (lit.);  Lenhartz,  Die  sept.  Erkrankh.,  in  the  Nothnagel  System; 

Norris,  Studies  in  Cardiac  Pathology,  191 1   (refers  to  numerous  Ameri- 
can studies). 
**  See  Poynton  and  Payne :  Researches  on  Rheumatism,  1913 ;  Rosenow,  Jour. 

Inf.  Dis.,  xi,  210  (references  to  previous  work)  ;  Jour.  Am.  Med.  Assn., 

Ix,  1223. 
*"  See  Thorel,  in  Lubarsch-Ostertag,  xiv,  415. 

"  Citron :  Berl.  klin.  Wochenschft.,  1908,  No.  48 ;  Donath,  ibid.,  1909,  No.  45. 
"See  V.  Jurgensen  in  the  Nothnagel  System;  Krehl,  ibid.;  Albrecht,  Der 

Herzmuskel,  1903,  504;  Magnus- Alsleben,  l.c.;  Thorel,  l.c.,  423. 


THE  CIRCULATION  ©7 

"Lewy:  Zeitschft.  f.  klin.  Med.,  xxxi,  539. 

'^Kornfeld,  Zeitschft.  f.  klin.  Med.,  xxix,  91,  344,  450 ;  Lewy,  ibid.,  xxxii,  379. 

*°  Kornfeld :  I.e. ;  Romberg  and  Hasenfeld,  Arch.  f.  exp.  Path.,  xxxix,  333. 

^'Johanssen  and  Tigerstedt:  Skandinav.  Arch.  f.  Phys.,  i,  131. 

"Arch.  f.  exp.  Path.,  ix,  i. 

"See  Stewart,  Arch,  of  Int.  Med.,  i,  102. 

"Miiller:  Die  Massenverhaltnisse,  etc. 

*"  Luderitz :  Zeitschft.  f.  klin.  Med.,  xx,  374. 

"  See  D.  Gerhardt :  Arch,  f .  exp.  Path.,  xlv,  186. 

"^Lenhartz:  Munch,  med.  Wochenschft.,  1890,  No.  22;  Dunbar,  Arch.  f.  klin. 

Med.,  xlix,  271 ;  Baumbach,  ibid.,  xlviii,  267. 
"See  Moritz:  Arch,  f,  klin.  Med.,  Ixvi,  421;  D.  Gerhardt,  Kongr.  f.  inn. 

Med.,  1905,  192. 
•*  For  a  contrary  view,  see  Strubell,  Miinch.  med.  Wochenschft.,  1908,  696. 

*  See  V.  Tabora :  Deutsch.  med.  Wochenschft.,  1908,  No.  48. 

**  Vierordt,  in  the  Nothnagel  System ;  Abelmann,  Ergeb.  d.  inn.  Med.  u.  Kin- 

derheilk.,  1913,  xii,  143  (lit.). 
"  Krehl :  Abhand.  d.  Sachs.  Gesellsch.  d.  Wissensch.,  math.-physik.  Kl.,  xvii, 

No.  5. 

**  Cf.  Brauer :  Kongr.  f .  inn.  Med.,  1904. 

*Lichtheim:  Die  Storungen  d.  Lungenkreislaufes,  1876. 

^'Hirsch:  Arch.  f.  klin.  Med.,  Ixviii,  328  (lit). 

"Hirsch:  I.e. 

*^  Beck :  Arch,  f .  klin.  Med.,  c,  429. 

**Mandl  and  Selig:  Prager.  med.  Wochenschft,  1907,  No.  41;  Foure  Beau- 
lieu,  Revue  d.  1.  tubercul.,  series  2,  vi.  • 

**See  Krehl,  in  the  Nothnagel  System;  v.  Romberg,  Herzkrankheiten,  3rd 
edit.,  430;  V.  Basch,  Die  Herzkrankheiten  bci  Atherosklerose,  1901 ; 
Marchand,  Atherosklerose,  in  Eulenburg's  Realenzyklopadie,  last  edit.; 
Fischer  and  Schlayer,  Arch.  f.  klin.  Med.,  xcviii,  164. 

*  Israel :  Volkmann's  Vortrage,   1907 ;  Krehl,  Deutsch.  med.  Wochenschft, 

1905 ;  Miinzenmayer,  Wiener  med.  Wochenschft.,  1909,  Nos.  22  and  23. 

*"Med.  Klinik,  1913,  No.  44  (refers  to  previous  work).  See  also  Macht, 
Jour.  Am.  Med.  Assn.,  1915,  Ixiv,  1489. 

**PaI:  I.C.;  Macht,  I.e. 

**Lehmacher:  Diss.  Greifswald,  1908;  Pagenstecher,  Deutsch.  med.  Wochen- 
schft., 1905,  327. 

**  Bittorf :  Arch.  f.  klin.  Med.,  Ixxxi ;  Ognos,  Virch,  Arch.,  cxcviii ;  Bruns 
and  Genner,  Deutsch.  med.  Wochenschft,  1910,  No.  37. 

"Burke:  Arch.  f.  klin.  Med.,  Ixxi,  189;  ApeU,  Deutsch.  med.  Wochenschft, 
1905,  Nos.  30  and  31. 

"  Hensen :  Arch,  f .  klin.  Med.,  Ixviii,  479. 

"Hochhaus :  Deutsch.  med.  Wochenschft,  1900,  No.  44;  cf.  Israel,  Volkmann's 
Vortrage,  Nos.  449  and  450. 

•*  See  Senator,  in  the  Nothnagel  System ;  Deutsch.  med.  Wochenschft.,  1903, 
No.  I ;  F.  Miiller,  Path.  Gesellschaft,  1905. 

**  Arch,  f .  klin.  Med.,  Ixviii,  74. 

"  Volkmann's  Vortrage,  No.  408. 

"  See  Jores :  Arch,  f .  klin.  Med.,  xciv,  i. 

"  Buttermann :  Arch,  f .  klin.  Med.,  Ixxiv,  I ;  see  also  v,  Bamberger,  Volk- 
mann's Vortrage,  No.  173. 

**  See  Jores :  I.e. 

"See  Hirsch  and  Beck:  Arch.  f.  klin.  Med.,  Ixix.,  503,  and  Ixxii,  560  (lit)  ; 
Determann,  Die  Viskositat  d.  Blutes,  1910. 

^  Gull  and  Sutton :  Medy-Chir.  Trans.,  Iv ;  Jores,  I.e. 

*^A.  Loeb:  Arch.  f.  klin.  Med.,  Ixxxv,  348;  Israel,  I.e. 

"Kretschmer:  Arch.  f.  exp.  Path.,  Ivii,  423;  Kongr.  f.  inn.  Med.,  1910,  731; 
Schlayer,  Deutsch.  med.  Wochenschft.,  1907,  No.  46;  A.  Fraenkel.  Arch, 
f.  exp.  Path.,  Ix,  405 ;  Broking  and  Trendelenburg,  Arch,  f .  klin.  Med., 
ciii,  168;  Stewart,  jour.  Exp.  Med.,  xiv,  377,  and  xv,  547. 
7 


98  THE  BASIS  OF  SYMPTOMS 

"  Tigerstedt  and  Bergmann :  Skandinav.  Arch.,  viii;  Bingel  and  Claus,  Arch.  f. 

klin.  Med.,  v,  412. 
"See  Volhard:  Vortrag  im  Heidelberger  Naturhistor.  Verein,  191 1. 
"  Moritz :  Miinch.  med.  Wochenschft.,  1908,  No.  14.     See  also  Williamson, 

Amer.  Jour.  Med.  Sc,  1915,  cxlix,  492. 
*  Personal  communication. 
"Hess:  Arch.  f.  klin.  Med.,  xcv,  482  (lit.). 
•*W.  Miiller:  Die  Massenverhaltnisse,  etc.,  217. 
**  Virch.  Arch.,  cxvi,  432 ;  Hasenfeld,  Arch.  f.  klin.  Med.,  Ixxvii,  763. 
**  Martius  :  Lubarsch-Ostertag,  Ergeb.,  1895,  45 ;  Aschoff,  Path.  Gesellschaf t, 

1910,  27,  28. 
"  Romberg  and  Hasenfeld :  Arch,  f .  exp.  Path.,  xxxix,  333. 
"Der  Herzmuskel,  Part  U. 
"  See  Hering :  Kongr.  f.  inn.  Med.,  1901,  603. 
"Krehl:  Erkrankungen  d.  Herzmuskels,  no. 
"Romberg  and  Hasenfeld:  I.e. 
"For   a   comprehensive   consideration    of   this    subject   see   Albrecht,    Der 

Herzmuskel,  Part  H. 
"Aschoff  and  Tawara:   Die  heutige  Lehre  v.  d.  path.-anat.  Grundlage  d. 

Herzschwache,  etc.,  1906;  Lubarsch.  Aerztl.  Fortbildg.,  Jan.,  191 1. 
"Der  Herzmuskel  (lit.)- 
'"Gottlieb:  in  Gottlieb-Meyer,  Exp.  Pharmakologie  (translated  by  Halsey)  ; 

Schmiedeberg,  Grundriss  d.  Pharmakologie;  Janeway,  Arch.  Int.  Med., 

1914,  xiii,  37  (lit.). 
**  Sahli :  Kongr.  f .  inn.  Med.,  1901 ;  Lang  and  Manswetowa,  Arch,  f .  klin. 

Med.,  xciv,  455  (lit.). 
*^  Ehrnrooth :  Ueber  d.  plotzlichen  Tod  durch  Herzlahmung,  Berlin,  IQ04. 
"See  Tigerstedt:  Physiol,  d.  Kreislaufes,  190;  Krehl,  Erkrank.  d.  Herzmus- 
kels, 369  (lit.). 
**  Lawen  and  Sievers :  Zeitschft.  f .  Chirurgie,  xciv,  580. 
*♦  Med.  Klinik,  1908,  No.  14. 
"'Jour,  of  Physiol.,  xv,  122;  Jour,  of  Exp.  Med.,  vol.  i,  p.  i ;  cf.  Hirsch  and 

Spalteholz,  Kongr.  f.  inn.  Med.,  1907. 
*'  See  Romberg :  Herzkrankheiten. 
*" Romberg:  Arch.  f.  klin.  Med.,  xlviii,  369,  and  xlix,  413    (lit);  see  also 

F.  Meyer,  Arch.  f.  exp.  Path.,  Ix,  209,  for  studies  in  experimental  myo- 
carditis. 
®*  Literature  under  Cardiac  Arrh3rthmias. 
**  See  Aschoff  and  Tawara :  Das  Reizleitungssystem,  etc. ;  Monckeberg,  Unter- 

such.  ii.  d.  Atrioventrikularbiindel,  1908;  Berl.  klin.  Wochenschft.,  1909, 

No.  2  (lit). 
•^Mechanism  of  the  Heart  Beat,  1911,  99  (lit). 
"^  See  Kraus,  in  v.  Mehring's  Lehrbuch.,  8th  edit.,  1913 ;  Minnich,  Das  Kropf- 

herz,  1904. 
•^Hezel:  Zeitschft.  f.  Nervenheilk.,  iv,  353. 

*'  Mobius,  in  the  Nothnagel  System ;  Kraus,  Kongr.  f .  inn.  Med.,  1906 
•*  See  O.  Miiller,  Blauel,  Schlayer:  Beitrage  z.  klin.  Chir.,  Ixii,  119. 
"Krehl:  Herzmuskel  (lit);  F.  Meyer,  I.e. 
*•  Welch :  Medical  News,  1888 ;  Pratt,  Johns  Hopkins  Hosp.  Bull.,  Oct,  1904 ; 

Kraus,  Berl.  klin.  Wochenschft.,  1905  (Festnummer). 
•"  Romberg :   Herzkrankheiten,  2nd  edit,  524 ;   Hirsch,  Arch,   f .  klin.  Med., 

Ixiv,  597;  Miinch.  med.  Wochenschft.,  1901,  No.  47. 
**  See  Krehl :  Herzmuskel,  227  (lit.)  ;  de  la  Camp,  Zeitschft  f.  klin.  Med.,  li,  i 

(lit.). 
**  Krehl :  Miinch.  med.  Wochenschft.,  1906 ;  Gibson,  The  Nervous  Affections 

of  the  Heart,  1905 ;  studies  of  Romberg  and  of  Hoffmann  in  Zeitschft.  f. 

Nervenheilkunde,  xxxviii,  171,  186  (Gesell.  deutsch.  Nervenarzte,  1909), 
*°°  Rosenbach :  Krankheiten  d.  Herzens. 
^"^  Bollinger :  Miinch.  med.  Wochenschft.,  1888,  No.  20. 


I 


THE  CIRCULATION  99 

*"*  Bmswanger :  Path.  u.  Therap.  d.  Neurasthenic,  1896. 

'""  Mechanism  of  the  Heart  Beat,  io8. 

^•"See  Ebstein,  in  Asher-Spiro,  Ergeb.,  Ill,  2,  1904;  Brauer,  Kongr.  f.  inn. 

Med.,  1904,  187. 
""D.  Gerhardt:  Arch.  f.  exp.  Path.,  xlvii,  250;  G.  MuUer,  Zeitschft.  f.  klih. 

Med.,  Ivi,  520;  Mackenzie,  The  Study  of  the  Pulse,  etc.,  1902,  Chap.  xx. 
*°*D.  Gerhardt:  Arch.  f.  exp.  Path.,  xxxiv,  402  (Ht.)  ;  Mackenzie,  The  Study 

of   the   Pulse,  etc.,   1902;   Aug.   Hoffmann,   Funktionelle  Diagnostik  u. 

Therap.,  etc.,  1911;  Lewis,  Mechanism  of  the  Heart  Beat,  9  (lit.). 
^•^  Diseases  of  the  Heart,  2nd  edit.,  1914,  212. 
^■^  See  V.  Korosy :  Arch,  f .  klin.  Med.,  ci,  267. 
**  Dehio :  Arch,  f .  klin.  Med.,  xli,  74. 
""Gaskell:  Jour,  of  Phys.,  iv,  44;  Gaskell,  in  Schafer's  Physiology;  Engel- 

mann,  Pfliiger's  Arch.,  Ixv,  535  (Ht.)  ;  Engelmann,  Deutsche  Klinik,  iv,  215; 

Carlson,  Amer.  Jour.  Phys.,  xii,  xv,  xvi,  xviii. 
"^Tawara:  Das  Reizleitungssystem  d.  Saugetierherzens,  1906;  Monckeberg, 

Untersuch,  ii.  d.  Atrioventrikularbundel,  1908;  Keith  and  Flack,  Lancet, 

1906,  359. 
"'Jager:  Arch.   f.  klin.  Med.,  c,  i;  Magnus- Alsleben,  Arch.   f.  exp.  Path., 

Ixiv,  228 ;  cf.  Hering,  Path,  (iesellschaft,  1910,  40. 
""For  the  conflicting  views  on  this  subject  see  Rothberger,  Thorel,  Aschoff, 

Monckeberg,  Fahr:  Path.  Gesellschaft.,  1910. 
"* Hering:  I.e. 
"* Engelmann:  Pfluger's  Arch.,  Ixv,  109,  535;  Ixi,  275;  lix,  309;  Ivi,  149;  lii, 

357;  Arch,  f,  Phys.,  1900,  315;  1902,  103;  1902,  suppL,  i, 
"'  See  Engelmann :  Deutsche  Klinik,  iv,  II,  215 ;  Joh,  Miiller,  Aerztl,  Fortbildg., 

Jan.,  191 1 ;  Nicolai,  Arch,  f .  Physiol.,  1910. 
"*  See  Hoffmann :  Funktionelle  Diagnostik ;  Lewis,  Mechanism  of  the  Heart 

Beat,  186, 
"*  Arch,  f ,  klin.  Med.,  ci,  402. 

"*  Herz :   Die  Herzkrankheiten,  240 ;   Godlewski,   Presse  medicale,   Dec.   10, 
^     1914- 
For  a  discussion  of  the  question,  see  D.  Gerhardt :  Ergeb.  d.  inn.  Med., 

",  431. 

*"  See  Kochmann :  Ztrlbl.  f.  Phys.,  1906,  418. 

^  A.  Hoffmann :  Arch.  f.  klin.  Med.,  c,  174. 

""Brandenburg:  Engelmann's  Arch.,  1903,  suppl.,  149;  Berl.  klin.  Wochen- 
schft.,  1903,  No.  38. 

^See  Hamm:  Miinch.  med.  Wochenschft,  1910,  No.  49  (lit.). 

"•The  reader  can  orient  himself  in  this  large  field  by  consulting  the  literature 
in  such  monographs  as  Lewis,  The  Mechanism  of  the  Heart  Beat ;  Clinical 
Electrocardiography ;  numerous  studies  in  Heart ;  Lectures  on  the  Heart, 
191 5 ;  Mackenzie,  The  Study  of  the  Pulse ;  Diseases  of  the  Heart,  2nd  edit. ; 
A.  Hoffmann,  Funktionelle  Diagnostik,  191 1;  Die  Elektrographie,  1914; 
Vaquez,  Les  arythmies,  191 1. 

^  Hering :  Deutsch,  med.  Wochenschft.,  1906,  No.  6 ;  Rothberger  and  Winter- 
berg,  Wiener  klin.  Wochenschft.,  1909,  No.  24. 

^  Theopold :  Arch,  f .  khn.  Med.,  xc,  77. 

^  Wenckebach  :  Engelmann's  Arch,  1907. 

""Schonberg:  Frankfurter  Zeitschft.  f.  Path.,  ii,  153;  Hedinger,  ibid,,  1910, 
V,  296. 

""Mackenzie:  Brit.  Med.  Jour.,  1905,  i,  585,  702,  759. 

'^  See  Hering:  Deutsch.  med.  Wochenschft,,  1903,  No.  22;  Zeitschft.  f.  exp. 
Path.,  x,  14;  Wenckebach,  Die  Arhythmien  d.  Herzens,  1903,  106;  v. 
Tabora,  Miinch.  med.  Wochenschft.,  1908,  No.  14  (lit.)  ;  Hering,  ibid.. 
No.  27;  Rehberg,  Zeitschft.  f.  klin.  Med.,  Ixviii,  247  (lit.).  For  a  recent 
comprehensive  monograph  on  alternation  see  Gravier,  L'Alternance  du 
coeur,  1914. 


100  THE  BASIS  OF  SYMPTOMS 

**^  Einthoven :  Le  telecardiogramme,  Arch,  internat.  d.  phys.,  1906,  iv,  132; 

Kraus  and  Nicolai,  Das  Elektrokardiogramm,  1910;  cf.  Hewlett,  Arch. 

of  Int.  Med.,  1908,  ii,  139 ;  Aug.  Hoffmann,  1.  c .    See  also  Windle,  Heart, 

1910,  ii,  95. 
""  See  H,  E.  Hering :  Path.  Gesellschaf t,  1910,  60. 
^'^See  Magnus-Alsleben :  Zeitschft.  f.  klin.  Med.,  Ixix,  82;  Lewis,  Mechanism 

of  the  Heart  Beat,  108. 
^^  Arch.  f.  klin.  Med.,  cii,  144. 
"^  In  addition  to  the  literature  already  cited,  see  Erlanger,  Jour,  of  Exp.  Med., 

vii,  676,  and  viii,  8;  Heineke,  v.  Hosslin  and  MiiUer,  Arch.  f.  klin.  Med., 

xciii,  459;  Herxheimer  and  Kohl,  ibid.,  xcviii,  330  (lit.). 
*"  Nicolai  and  Plesch :  Deutsch.  med.  Wochenschft.,  1909,  No.  51. 
"•  Arch.  f.  klin.  Med.,  c,  178. 

"*  F.  M.  Groedel :  Zeitschft.  f.  klin.  Med.,  Ixx,  47 ;  Wenckebach,  ibid.,  Ixxi,  402. 
**"F.  MiiUer:  Miinch.  med.  Wochenschft,  1906,  No.  17;  Pawinski,  Zeitschft. 

f.  klin.  Med.,  Ixiv,  70  (lit.). 
**^Brauer:  Kongr.  f.  inn.  Med.,  1904,  187;  Thayer  and  MacCallum,  Amer. 

Jour.  Med.  Sc,  cxxxiii,  254. 
^■"In  Schmidt- Luthj  e :  Klin.  Diagnostik,  1910,  248;  see  also  Hochsinger,  in 

Pfaundler  and  Schlossman,  Dis.  of  Children,  iii;  Arch.  f.  Kinderheilk., 

1913,  Ix-lxi,  2,77',  Wiener  med.  Wochenschft.,  Ixiii,  1538,  1613. 
***  See  Romanoff :  Arch,  f .  exp.  Path.,  Ixiv,  183 ;  Bittorf  and  Forschbach,  Zeit- 
schft. f.  klin.  Med.,  Ixx,  474;  Siebeck,  Arch.  f.  khn.  Med.,  c,  204. 
***Huchard:  Maladies  du  coeur,  etc.;  Neusser,  Angina  Pectoris,  Ausgewahlte 

Kapitel,  No.  2 ;  Osier,  The  Lumleian  Lectures  on  Angina  Pectoris,  Lancet, 

1910. 
^^'Erb:  Miinch.  med.  Wochenschft.,  1904,  905;  ibid.,  1910,  Nos.  21,  22  and 

47  (lit). 

^**  For  example,  see  Fischer :  Arch,  f .  klin.  Med.,  cix,  469 ;  Orphuls,  Arch. 
Int.  Med.,  ix,  156  (lit.). 

^■^ Gefasskrisen,  1905;  Med.  Klinik,  1913,  No.  44  (previous  work  cited). 

^**  The  editor  has  made  free  use  in  the  following  editorial  note  of  material 
contained  in  Norris,  Blood-Pressure,  1914  (lit.). 

**•  Warfield:  Jour.  Amer.  Med.  Assn.,  Ixi,  1254  (lit.)  ;  Amer.  Jour.  Med.  Sci., 
cxlviii,  880. 

™  Stone :  Jour.  Amer.  Med.  Assn.,  Ixi,  1256. 

^Michael:  Amer.  Jour.  Dis.  Child.,  i,  272. 

*"  See  Carroll:  Assoc.  Amer.  Physicians,  1912,  xxvii,  8;  Weysel  and  Lutz, 
Am.  Jour.  Phys.,  xxxii,  330  (lit.). 

""Schneider  and  Hedblom:  Am.  Jour.  Phys.,  xxiii,  90  (lit);  Gardiner  and 
Hoagland,  Trans.  Amer.  Climat.  Assn.,  1905;  Douglas  et  al.,  Philosoph. 
Trans.,  London  (1913),  B.  203,  185. 

^^  See  Norris:  /.  c,  chap,  xiii  (lit). 

""Med.  Klinik,  1913,  No.  44. 

"•See  Janeway:  Arch.  Int  Med.,  1914,  xiii,  37  (lit). 

"'  Romberg,  Passler,  Bruhns,  Miiller :  Arch,  f .  klin.  Med.,  Ixiv,  652 ;  Passler 
and  Roily,  ibid.,  Ixxvii,  96;  Romberg,  Berl.  klin.  Wochenschft.,  1905, 
No.  SI. 

^■"v.  Steyskal:  Zeitschft.  f.  klin.  Med.,  xliv,  367,  and  Ii,  129. 

"*  Heineke :  Arch,  f .  klin.  Med.,  Ixix,  429. 

^""Wiesel:  Prag.  Zeitschft.  f.  Heilkunde,  1905  and  1906;  Ortner,  ibid.,  1905; 
Wiesel.  Wiener  klin.  Wochenschft.,  1906,  No.  24. 

***  See  Romberg :  Herzkrankheiten ;  Krehl,  Erkrank.  d.  Herzmuskels. 

***  Auer  and  Robinson :  Jour,  of  Exp.  Med.,  xviii,  450. 

"*  Amer.  Jour.  Phys.,  xxvii,  167  (lit.)  ;  Lancet,  August,  1913,  727  (17th  Inter- 
nat. Med.  Congr.) ;  Berl.  klin.  Wochenschft.,  1913,  1938.  See  also  Mori- 
son  and  Hooker,  Am.  Jour.  Phys.,  1915,  xxxvii,  86. 

*"  Blood-Pressure  in  Surgery,  1903. 

*** Anoci- Association,  1914  (lit). 


THE  CIRCULATION  101 

** Romberg:  Kongr.  f.  inn.  Med.,  1904,  60;  Otfried  Miiller,  Deutsch.  med. 

Wochenschft.,  1906,  Nos.  38  and  39. 
*"  Sahli :  Diagnostic  Methods. 
^^  Senator,  in  the  Nothnagel  System ;  Strauss,  Die  chron.  Nierenentziindungen, 

etc.,  1902. 
^"  Zeitschft.  f.  klin.  Med.,  xxi,  475. 
"°  Cohnheim  and  Lichtheim:  Virchow's  Arch.,  Ixix,  106;  Magnus,  Arch.  f.  exp. 

Path.,  xlii,  250. 
"^  Heineke  and  Meyerstein :  Arch,  f .  klin.  Med.,  xc,  loi ;  Schlayer,  Hedinger 

and  Takayasu,  ibid.,  xci,  59. 
^'^Verhandl.  d.  Kongr.  f.  inn.  Med.,  1910  (Magnus-Levy,  Widal,  Strauss); 

Schlayer  and  Hedinger,  1.  c.  (lit.)  ;  Heineke  and  Meyerstein,  1.  c.  (lit.). 
"^  See  Blooker,  Arch.  f.  kUn.  Med.,  xcvi,  80. 
"*  CEdema  and  Nephritis,  2nd  edit.,  191 5. 
""  Hoffmann :  Arch.  f.  klin.  Med.,  xliv,  413  (lit.). 
"'  See  Gandin :  Ergeb.  d.  inn.  Med.  u.  Kinderheilk.,  1913,  xii. 
*"  Cohnheim  and  Welch :  Virch.  Arch.,  Ixxii,  375. 
"*  Sahli :  Zeitschft.  f .  klin.  Med.,  xiii,  482 ;  Arch,  f ,  exp,  Path.,  xix,  433. 


CHAPTER  II 
THE  BLOOD 

General  Considerations. — The  pathology  of  the  blood*  is 
intimately  associated  with  that  of  every  individual  organ  in 
the  body,  for  it  is  the  connecting  link  between  all  of  them,  receiv- 
ing material  from  and  giving  material  to  each.  Its  constitution 
depends,  therefore,  to  a  great  extent  upon  the  functional  condition 
of  the  different  organs.  It  contains  a  great  variety  of  sub- 
stances; yet  the  rapidity  of  the  blood-current,  the  minute  quan- 
tities of  many  of  these  present,  and  the  rapid  excretion  of  those 
which  are  present  in  excess  allow  the  blood  to  maintain  a  fairly 
constant  composition. 

It  is  incorrect,  therefore,  to  designate  any  particular  tissue 
as  the  blood-forming  organ.  Every  tissue  in  the  body  furnishes 
its  contribution  to  the  blood,  and  when  an  organ  is  spoken  of  as 
a  blood-forming  organ  it  is  usually  implied  that  it  gives 
to  the  blood  some  of  its  more  striking  elements,  the  blood- 
corpuscles. 

Obviously  then,  the  composition  of  the  blood  will  change 
whenever  there  are  pathological  changes  in  the  activity  of  any 
organ  that  furnishes  metabolic  products  to  the  circulation.^ 
Viewed  from  this  basis,  there  is  a  great  number  of  blood  diseases, 
among  them  diabetes  and  the  majority  of  hepatic  and  renal  dis- 
orders. Clinically,  however,  it  is  customary  to  speak  of  dis- 
eases of  the  blood  only  when  the  changes  in  the  blood  dom- 
inate the  pathological  picture,  or  when  the  cause  of  the  blood 
changes  is  unknown.  As  our  knowledge  of  these  conditions 
increases,  we  shall  probably  find  that  the  number  of  cases  in  which 
the  blood  changes  are  really  primary,  the  so-called  diseases  of  the 
blood,  is  exceedingly  small,  if,  indeed,  all  such  cases  are  not 
secondary  to  disease  elsewhere.^ 

Changes  in  the  blood-cells  and  in  the  haemoglobin  are  recog- 
nized with  comparative  ease  and  for  this  reason  are  better  known 
than  are  alterations  in  the  composition  of  the  plasma. 

Anemia 

Although  the  term  anaemia  is  used  to  designate  those  con- 
ditions in  which  the  haemoglobin  or  the  red  blood-corpuscles,  or 
102 


THE  BLOOD  103 

both,  are  reduced,  it  should  not  be  assumed  that  these  are  the 
only  changes  of  consequence  in  anaemic  blood.  Alterations  of 
perhaps  equal  importance  take  place  in  other  constituents,  and 
a  proper  understanding  of  anaemia  will  be  possible  only  when  we 
shall  have  become  acquainted  with  all  these  various  changes.  For 
example,  the  integrity  of  the  red  corpuscles  is  intimately  dependent 
upon  the  molecular  concentration  of  the  plasma;*  if  they  be 
placed  in  solutions  which  contain  either  too  large  or  too  small 
a  quantity  of  salts  they  become  either  shrunken  or  swollen,  and 
in  either  case  they  may  lose  their  haemoglobin.  The  proteids  of 
the  plasma  also  seem  to  have  some  influence  upon  the  property 
of  the  red  cells  to  retain  their  haemoglobin;  and  the  presence  of 
certain  poisons  in  the  blood  will,  undoubtedly,  cause  the  escape 
of  the  haemoglobin  from  the  stromata  of  the  corpuscles. 

Anaemia  from  Hemorrhage. — Anaemia  in  its  simplest  form 
is  due  to  an  acute  hemorrhage.  If  the  loss  of  blood  exceed  a 
certain  limit — which  is  about  fifty  per  cent,  of  the  total  quantity — 
the  amount  left  in  the  vessels  is  insufficient  for  the  maintenance  of 
the  circulation,  and  the  patient  dies  with  all  the  symptoms  of  acute 
asphyxia,  owing  to  the  insufficient  supply  of  blood  to  the  tissues 
and  especially  to  certain  parts  of  the  brain.  This  subject  of  acute 
asphyxia  will  be  discussed  in  the  chapter  on  respiration. 

If  the  hemorrhage  does  not  exceed  this  limit,  the  fluid  portion 
of  the  blood  lost  is  rapidly  replaced  by  fluids  from  the  tissues  and 
food.  The  proteids  and  the  corpuscles  are  replaced  more  grad- 
ua,lly  by  an  increased  functional  activity  on  the  part  of  the  tissues 
which  furnish  them;  and  finally,  after  weeks,  or  perhaps  months, 
the  blood  regains  its  normal  composition.  During  the  first  few 
hours  after  a  hemorrhage,  therefore,  the  blood  as  a  whole  is 
reduced  in  quantity.  Then  follows  a  dilution  of  that  present  with 
lymph;  and  after  this  there  comes  the  regeneration  of  the  red 
corpuscles.  The  newly-formed  corpuscles  are  often  smaller  than 
normal,  but  some  may  be  very  large  and  a  few  of  them  may  con- 
tain nuclei.  For  a  considerable  period  after  the  hemorrhage, 
the  individual  corpuscles  contain  less  haemoglobin  than  do  normal 
ones,  for  this  pigment  is  regenerated  slowly  as  compared  with  the 
erythrocytes,^  and  for  some  time,  therefore,  the  proportion  be- 
tween the  percentage  of  haemoglobin  and  the  number  of  red  cor- 
puscles remains  less  than  the  normal.  The  leucocytes  in  the 
peripheral  blood  are  usually  increased  in  number  for  a  short 


104  THE  BASIS  OF  SYMPTOMS 

period  after  the  hemorrhage.  The  rapidity  with  which  the  blood 
is  regenerated  depends  upon  the  amount  of  blood  lost,  upon  the 
general  nutrition  of  the  patient  and  upon  the  treatment  which 
he  receives. 

General  Considerations  Relative  to  the  Chronic  Anaemias. — 
In  the  chronic  anaemias  the  blood  does  not  return  so  quickly 
to  the  normal,  because  the  cause  of  the  anaemia  remains  opera- 
tive. This  cause  may  injure  either  the  blood-forming  organs 
or  the  blood-corpuscles  already  free  in  the  circulation.  It  is  well 
known  that  the  blood  of  one  animal  may  destroy  the  corpuscles  of 
another,  and  we  must  admit  the  possibiHty  that  similar  toxic 
substances  may  develop  in  the  body  under  pathological  con- 
ditions. Indeed,  there  is  evidence  that  this  does  occur  in  certain 
diseases.  Various  poisons  such  as  chloroform  and  potas- 
sium chlorate  exert  a  similar  injurious  action  upon  the  red  blood- 
cells.  It  is  also  possible  that  an  anaemia  may  be 
produced  by  an  acceleration  of  the  normal  de- 
struction of  the  red  blood-cells,  which  becomes  so 
rapid  that  the  regenerative  processes  cannot  keep  pace  with  it. 
Practically  the  same  condition  is  produced  when  repeated, 
small  hemorrhages  take  place,  for  here  again  the  loss 
of  blood  may  be  so  great  that  the  normal  regenerative  processes 
cannot  supply  the  deficiency.  This  is  illustrated  by  the  anaemia 
of  miners,  due  to  the  ankylostoma  duodenale. 

On  the  other  hand,  the  anaemia  may  arise,  not  from  an  ex- 
cessive loss  or  destruction,  but  from  an  insufficient  for- 
mation of  red  blood-corpuscles,  and  it  is  often  ex- 
tremely difficult  in  the  individual  case  to  determine  which  of  the 
two  is  primary.  An  increase  in  the  amount  of  iron  de- 
posited in  the  liver  would  indicate  an  abnormal  destruc- 
tion of  red  corpuscles.^  This  organ  normally  contains  a  small 
amount  of  iron,  but  in  anaemia  the  amount  is  often  greatly  in- 
creased ;  and  not  infrequently  the  spleen,  kidneys  and  bone-marrow 
also  show  abnormal  deposits  of  iron  salts.  In  the  anaemias  that 
are  caused  not  by  destruction  but  by  losses  of  blood  through 
hemorrhage,  such  deposits  do  not  occur;  and,  indeed,  the  iron 
normally  present  in  the  tissues  may  be  reduced,  for  it  is  utilized 
in  the  formation  of  new  corpuscles.  An  increased  excretion  of 
pigments  derived  from  the  haemoglobin,  viz.,  bilirubin  and  uro- 


THE  BLOOD  105 

bilin,  is  also  to  a  certain  extent  indicative  of  an  increased  destruc- 
tion of  the  erythrocytes. 

The  red  blood-corpuscles  themselves  frequently 
undergo  changes  in  anaemia.  In  the  first  place,  they  may  be  of 
irregular  shape,  so  that  hardly  any  two  look  alike  (poikilo- 
cytosis).  Then  they  may  vary  greatly  in  size  (anisocy- 
tosis),  some  being  extremely  small,  the  so-called  micro- 
c  y  t  e  s ,  while  others  are  extremely  large,  the  so-called  macro- 
c  y  t  e  s .  Finally,  they  may  show  clear  spaces  in  their  protoplasm 
(endog'lobular  degenerations).  All  of  these  changes 
are  of  a  degenerative  character. 

Peculiarities  of  the  red  cells  in  the  stained  preparation  are  of 
more  uncertain  significance.  The  normal  mature  erythrocyte  is 
acidophile,  the  stain  being  even,  though  somewhat  more  intense 
toward  the  periphery.  Youthful  types,  on  the  contrary,  take 
both  the  basic  and  the  acid  stains  (polychromatophilia).^ 
Two  facts  speak  distinctly  for  the  view  that  polychromatophilia 
is  an  evidence  of  immaturity.  In  the  first  place,  this  anomalous 
staining  is  shown  by  cells  still  in  the  bone-marrow,  which  are 
definitely  immature  because  they  contain  nuclei;  and  further,  in 
the  circulating  blood,  polychromatic  erythrocytes  are  often  seen 
with  nuclei  in  active  mitosis,  Polychromatophilia  disappears  as 
the  cell  ripens,  though  it  may  return  coincidently  with  the  recur- 
rence of  certain  injurious  influences.  On  the  other  hand,  this 
staining  peculiarity  is  seen  also  in  cells  undergoing  disintegration 
outside  the  blood-vessels,  in  which  case  the  multi-tints  are  diffuse, 
or  collected  where  the  nuclear  remnants  appear  to  be,  or  scattered 
as  granules  through  the  stroma.^  The  latter,  known  as  g  r  a  n  u  - 
lar  basophilia,  is  particularly  well  marked  in  the  anaemia 
of  chronic  lead  poisoning.  The  old  strife  as  to  whether  poly- 
chromatophilia is  a  sign  of  regeneration  or  of  degeneration  seems 
to  have  given  way  to  the  view  that  it  may  indicate  either.  In 
the  circulating  blood,  however,  the  phenomenon  is  generally  an 
index  of  immaturity. 

Another  evidence  of  regenerative  processes  is  the  presence  of 
nucleated  red  cells  in  the  circulation.  Normally,  nuclea- 
tion  is  restricted  to  the  tissues  in  which  erythrocytes  are  produced, 
viz.,  the  red  marrow  of  the  bones,  and  during  fetal  Hfe,  the  liver 
and  spleen,^  The  red  cells  that  pass  into  the  blood,  normally, 
have  already  lost  their  nuclei.     In  conditions  of  active  regenera- 


106  THE  BASIS  OF  SYMPTOMS 

tion,  however,  such  as  are  observed  after  severe  hemorrhage, 
nucleated  red  blood-corpuscles  appear  in  the  blood,  released  in  all 
probability  before  maturity.  In  the  more  severe  grades  of 
anaemia,  we  encounter,  in  addition  to  the  nucleated  cells  of  nor- 
mal size  (normoblasts),  abnormally  large  examples  (  m  e  g  a  - 
loblasts,  gigantoblasts).  The  presence  of  the  latter  is 
considered  by  some  to  indicate  that  regeneration  has  assumed  a 
pathological  trend;  in  other  words,  that  there  has  been  a  return 
to  the  embryonic  state.  For  reasons  which  will  appear  in  the 
discussion  of  pernicious  anaemia,  we  prefer  to  regard  these  cells 
merely  as  the  products  of  an  extremely  stormy  regeneration  of 
red  corpuscles,  and  not  as  pathognomonic  of  pernicious  anaemia 
alone.  If  the  demand  for  new  cells  is  especially  urgent,  the  nor- 
mal resources  prove  inadequate  and  the  blood-forming  tissues 
active  in  fetal  life  are  again  called  upon.  To  this  extent  only 
is  the  megaloblast  a  specific  type  or  an  evolutional  product  of  the 
embryonal  red  cells.  ^° 

The  red  bone-marrow  is  increased  in  quantity  in  many 
forms  of  anaemia.  Normally,  this  tissue  is  limited  to  the  flat 
bones  and  to  the  extremities  of  the  long  bones.  If,  however,  the 
necessity  arises  for  a  greater  production  of  red  cells,  the  red 
marrow  spreads  over  many  bones,  the  change  being  in  the  nature 
of  a  compensatory  process.^  ^  We  are  among  those  who  believe 
that  all  increases  of  red  marrow  are  of  this  nature,  and  that  there 
is  no  necessity  for  making  a  division  between  normal  and  patho- 
logical red  marrow. 

Chlorosis. — Certain  forms  of  chronic  anaemia  are  sufficiently 
well  defined  to  be  distinguished  clinically.  Of  these,  we  shall 
first  consider  chlorosis.^  ^  This  occurs  usually,  perhaps  exclu- 
sively,^^ in  girls  at  about  the  time  of  puberty.  Its  cause  is 
not  well  understood.  Poor  hygienic  conditions  are 
certainly  not  the  sole  determining  factor,  for  the  disease  occurs 
with  about  equal  frequency  among  the  upper  as  well  as  the  lower 
classes.  Some  have  ascribed  chlorosis  to  disturbances  of 
the  nervous  system,  others  to  diseases  of  the  female 
genitalia,  but  to  both,  it  seems  to  me,  without  sufficient  evi- 
dence. As  the  only  predisposing  factors  are  those  of  age  and 
sex,  it  is  not  impossible  that  the  ovaries  play  a  role,  especially 
in  susceptible  individuals  (v.  Noorden). 

The  color  of  the  skin  in  chlorosis  usually  varies  from  a  slight 


THE  BLOOD  107 

pallor  to  the  typical,  pale,  greenish  tint.  The  face,  however, 
may  be  of  an  unusually  brilliant  color  (chlorosis  rubra). 
At  times  the  patient  is  emaciated,  though  more  frequently  the  fat 
is  well  preserved.    Nervous  manifestations  are  usually  prominent. 

The  blood  always  shows  a  diminution  in  the  quantity  of 
haemoglobin  to  the  unit-volume,  and  the  individual  red  cor- 
puscles are  usually  paler  than  normal.  Many  of  them  are 
of  small  size,  and  some  are  deformed.  In  severe  cases,  nucleated 
red  corpuscles  may  be  present,  either  of  normal  size  or  very 
exceptionally  of  the  megaloblastic  type.  In  some  cases,  the  num- 
ber of  red  corpuscles  is  normal,^*  but  usually  it  is  moderately 
diminished.  Limbeck  ^^  states  that  of  two  hundred  and  seventy- 
nine  cases  of  chlorosis,  only  one  hundred  and  five,  or  thirty-seven 
per  cent.,  showed  no  diminution  in  the  number  of  the  red  cor- 
puscles. 

That  the  amount  of  haemoglobin  is  diminished  has  been 
demonstrated  by  colorimetric,  spectrophotometric  and  chemical 
methods.  The  dried  blood  may  show  0.03  i>er  cent,  of  iron  in- 
stead of  the  normal  0.06  per  cent.  Nevertheless,  there  appear 
to  be  mild  cases  of  chlorosis  showing  no  blood  changes  of  signifi- 
cance, despite  the  well-marked  clinical  picture,  and  in  which  iron 
effects  a  complete  cure.^®  This  would  indicate  that  the  blood 
alterations  in  chlorosis  are  merely  symptomatic. 

As  in  other  anaemias,  the  volume  of  the  red  cells  is  also 
changed.  The  leucocytes  do  not  vary  greatly  from  the  nor- 
mal. The  percentage  of  water  in  the  serum  is  approximately 
normal  in  the  milder  cases,  whereas  in  the  more  severe  ones  it 
is  increased.  The  total  quantity  of  blood  in  the  body  seems 
considerable.  Of  other  changes  in  the  serum  we  know  little. 
From  the  fact  that  patients  with  chlorosis  show  a  tendency  to  the 
formation  of  venous  thrombi,  it  has  been  assumed  that  their 
blood  contains  larger  amounts  of  fibrin  ferment — an  assumption, 
however,  which  is  incorrect.  Not  infrequently  there  is  a  retention 
of  water  in  the  body  of  chlorotic  patients,  due  possibly  to  an 
increase  in  the  total  blood  mass.^"^ 

Autopsies  upon  patients  with  chlorosis  are  few  in  number,  and 
these  have  shown  surprisingly  little  that  was  abnormal.^®  No 
degenerative  changes  were  present  in  the  liver,  heart  or  kidneys, 
and  no  changes  in  the  bone-marrow  of  the  tibiae  were  found. 
Virchow  observed  a  general  hypoplasia  of  the  heart  and  blood- 


108  THE  BASIS  OF  SYMPTOMS 

vessels,  and  especially  a  narrowing  of  the  aorta,  and  these  have 
been  assumed  to  be  causative  agents  in  the  production  of  the 
disease.  This  view,  however,  does  not  appear  very  reasonable, 
for  it  is  difficult  to  understand  how  chlorosis  could  heal  as  com- 
pletely as  it  does  if  this  were  its  cause ;  and,  furthermore,  stenosis 
of  the  aorta  is  known  to  produce  quite  a  different  set  of  symptoms. 

Although  chlorosis  heals  spontaneously  in  practically  every 
case,  the  healing  is  greatly  accelerated  by  the 
administration  of  iron.^®  Indeed,  proper  food  seems  to 
be  of  secondary  importance,  for  chlorosis  may  develop  in  indi- 
viduals who  have  lived  in  the  best  of  surrotmdings.  The  bril- 
liant results  achieved  by  the  administration  of  iron  are  in  them- 
selves almost  characteristic  of  this  type  of  anaemia,  for  in  no 
other  form  do  we  see  such  striking  effects,  save  possibly  in  those 
anaemias  which  result  from  hemorrhages. 

The  value  of  the  administration  of  iron  in  chlorosis  lends 
support  to  the  theory  that  the  cause  of  the  disease  is  an  inadequate 
or  improper  formation  of  the  red  blood-corpuscles.  We  possess 
no  evidence  favoring  the  opposite  possibility,  zriz.,  that  there  is 
a  pathological  destruction  of  the  red  cells,  for  degenerative 
changes  in  the  red  corpuscles  are  not  marked,  jaundice  does  not 
occur,  and  the  quantity  of  pigments  in  the  urine  and  faeces  is 
less  than  normal.  These  facts  cannot  be  regarded  as  proof  that 
there  is  no  pathological  destruction  of  red  cells  in  chlorosis,  but 
they  certainly  render  it  very  improbable.  Unfortunately,  we 
possess  no  evidence  on  the  more  decisive  question  as  to  whether 
or  not  there  is  an  excessive  deposit  of  iron  pigment  in  the  liver. 
Nevertheless,  from  the  facts  in  our  possession,  we  may  assume 
that  the  underlying  cause  of  chlorosis  is  an  insuf- 
ficient formation  of  red  blood-corpuscles. 

The  exact  manner  in  which  iron  exerts  a  favorable  effect  upon 
chlorosis  still  remains  unsettled.  The  patients  suffering  from 
this  disease  ordinarily  show  no  marked  digestive  disturbances,^ 
although  some,  at  least,  seem  to  absorb  fats  poorly.  There  is 
likewise  no  conclusive  evidence  that  their  absorption  of  iron  from 
the  intestinal  tract  is  less  than  normal,  though  the  data  upon  this 
point  are  not  very  accurate.  It  is  difficult,  therefore,  to  under- 
stand why  the  iron  salts  in  the  food,  which  are  sufficient  for  all 
ordinary  needs,  are  insufficient  in  chlorosis.  It  seems  to  me  most 
probable  that  iron  cures  chlorosis  by  acting  as  a  stimulant  to  the 


THE  BLOOD  109 

blood-forming  organs,  very  much  as  does  arsenic  in  certain  other 
forms  of  anaemia. ^^  (Indeed,  it  has  been  shown  that  iron  and 
arsenic  in  combination  are  more  efficacious  in  chlorosis  than 
is  iron  alone. — Ed.) 

Secondary  Anaemias. — The  remaining  forms  of  anaemia  ^^ 
are,  for  the  most  part,  merely  symptomatic  of  other  pathological 
conditions.  When  their  etiology  is  known,  they  are  termed  sec- 
ondary anaemias,  in  contradistinction  to  the  so-called  primary 
anaemias,  the  causes  of  which  are  imknown.  This  classification 
into  primary  and  secondary  anaemias  is  serviceable,  but  hardly 
final,  for  it  seems  certain  that  as  we  become  better  acquainted  with 
the  causation  of  anaemias  the  number  of  cases  assigned  to  the 
primary  group  will  progressively  diminish,  and  the  number  classi- 
fied as  secondary  anaemias  will  correspondingly  increase.  So 
closely  may  the  blood  pictures  of  the  two  types  approach  one 
another  that  it  is  often  extremely  difficult,  or  indeed  impossible, 
to  distinguish  them.  (Others,  however,  among  them  Naegeli, 
are  strongly  of  the  opinion  that  the  two  are  readily  distinguish- 
able.— Ed.  ) 

A  great  variety  of  causes  may  give  rise  to  mild 
and  moderately  severe  forms  of  secondary  anae- 
mia. Of  these,  we  may  first  mention  repeated  hemor- 
rhages, such  as  may  occur  from  ulcer  or  carcinoma  of  the 
stomach,  from  intestinal  ulcerations,  from  hemorrhoids,  from 
uterine  myomata,  etc.  Secondary  anaemias  may  result,  further- 
more, from  chronic  poisoning,  as  by  lead  or  mercury, 
from  gastro-intestinal  disease,  from  malignant 
tumors,  from  infections  such  as  tuberculosis,  syphilis 
and  malaria,  and  from  chronic  diseases  of  the  liver, 
kidneys,  heart  or  nervous  system.  It  should  be  re- 
membered, however,  that  none  of  these  diseases  necessarily  gives 
rise  to  an  anaemia,  which  is  the  result  probably  of  some  special 
moment. 

It  is  still  uncertain  in  what  manner  many  of  these  diseases 
produce  the  anaemia.  Infectious  processes  frequently  injure  the 
red  blood-corpuscles  directly,  as  may  be  inferred  from  the  de- 
generation which  they  produce  in  these  cells.  Yet  the  destruction 
of  a  few  corpuscles,  more  or  less,  would  hardly  give  rise  to  an 
anaemia,  for  the  loss  of  a  considerable  number  would  immediately 
be  balanced  by  regenerative  processes.     In  malaria,  the  plasmodia 


110  THE  BASIS  OF  SYMPTOMS 

certainly  destroy  the  corpuscles  in  large  numbers,  and  this  seems 
to  be  the  direct  cause  of  the  malarial  cachexia.  In  nephritis,  the 
reduction  in  the  number  of  red  cells  per  unit  of  volume  may  be 
due  in  part  to  a  dilution  of  the  blood,  and  in  part,  as  in  hemor- 
rhagic nephritis,  to  repeated  losses  of  blood  in  the  urine.  An 
injury  to  the  blood-forming  tissues  is  a  possible  explanation  that 
must  not  be  lost  sight  of. 

Insufficient  nourishment  will  give  rise  to  an  anae- 
mia in  some  cases.  An  absolute  fast,  even  if  continued  up  to 
death,  merely  causes  a  reduction  in  the  total  quantity  of  blood 
with  no  diminution  in  the  haemoglobin  or  red  corpuscles  to  the 
unit  of  volume. ^^  If,  after  such  a  fast,  food  and  liquids  be  taken 
in  sufficient  quantity,  water  is  rapidly  added  to  the  blood,  with 
a  resulting  reduction  in  the  percentage  of  haemoglobin  and  in 
the  number  of  red  cells  per  unit- volume.  The  prolonged  use  of 
food,  deficient  in  some  important  constituent, 
will  also  cause  an  anaemia.  For  example,  a  continuous  milk  diet 
will  have  this  efifect,  on  account  of  the  small  quantity  of  iron  in 
the  milk.  Especially  injurious  is  the  combination  of  improper 
food  and  continued  hard  work.  Other  favoring  factors 
are  care  and  worry,  poor  light,  poor  air,  lack  of  sleep,  etc. 
Patients  with  anaemia  from  such  causes  exhibit  a  striking  im- 
provement if  their  surroundings  are  bettered,  and  although  their 
absorption  of  iron  may  be  less  than  normal,  yet  the  simple 
administration  of  salts  of  this  metal,  without  a  change  in  their 
surroundings,  has  comparatively  little  effect  upon  their  anaemia.^* 

On  the  other  hand,  mild  and  moderately  severe  secondary 
anaemias  of  this  character  may  occur  in  patients  who  live  under 
the  best  of  hygienic  surroundings,  in  which  case  we  are  unable 
to  form  any  conception  as  to  their  cause.  Many  such  individuals 
seem  to  feel  perfectly  well,  so  that  one  might  almost  question 
whether  their  anaemia  was  physiological  or  pathological.  Others, 
however,  suffer  from  the  same  symptoms  as  do  most  anaemic 
patients,  these  symptoms  being  especially  marked  upon  exertion. 

The  blood  picture  in  the  secondary  anaemias 
may  show  considerable  variations.  In  some  patients  the  changes 
are  hardly  demonstrable,  while  in  others  they  may  be  of  the  most 
extreme  grade. 

Certain  possible  fallacies  in  the  methods  of  blood  examination 
should  be  noted.     In  the  first  place,  the  ordinary  examination 


THE  BLOOD  111 

of  the  blood  may  show  nothing  abnormal,  and  yet  there  may  be 
a  reduction  or  an  increase  in  the  total  quantity  of  blood  in  the 
body.  On  the  other  hand,  it  is  possible  that  the  blood  may  be 
of  different  constitution  in  different  parts  of  the  body,  so  that 
the  cutaneous  capillaries  contain  relatively  few  or  relatively  many 
corpuscles.^''  Such  possibilities  of  error  cannot  be  easily  elim- 
inated in  our  clinical  methods  of  blood  examination. 

In  secondary  anaemia  the  red  cells  frequently  vary  in 
staining  properties  (polychromatophilia)  and  in  shape  (poikilo- 
cytosis).  The  dimensions  of  the  cells  may  vary  more  widely 
than  in  health,  so  that  we  find  microcytes  and  occasionally  megalo- 
cytes.  Signs  of  rapid  regeneration  are  also  frequently  met  with, 
especially  nucleated  red  cells  of  normal  size  (normoblasts),  and, 
very  rarely,  nucleated  red  cells  of  large  size  (megaloblasts). 
All  these  changes  are  dependent  rather  upon  the  severity  of  the 
anaemia  than  upon  its  cause.  As  a  rule,  the  white  cells  are 
normal  unless  some  special  cause  for  a  leucocytosis  is  present. 
Changes  in  the  blood-serum  will  be  considered  in  another  place. 

Pernicious  Anaemia. — In  the  third  form  of  anaemia,  the 
so-called  pernicious  form,  the  changes  suffered  by  the  red 
cells  reach  their  maximum.  Their  number  is  greatly  reduced ; 
and  Quincke  has  reported  a  case  in  which  only  one  hundred  and 
forty-three  thousand  per  cubic  millimetre  were  counted.  The 
haemoglobin  is  also  markedly  diminished,  although,  as  a 
rule,  it  is  relatively  less  reduced  than  is  the  number  of  the  red 
corpuscles;  in  other  words,  the  average  red  corpuscle  contains 
as  much  coloring  matter  as  the  normal  cell,  and  often  indeed  more 
(characteristic  high  color-index). ^^  Poikilocy- 
tosis  becomes  extreme.  At  times,  only  a  small  proportion  of 
the  red  cells  present  a  normal  appearance,  the  majority  showing 
some  one  or  other  of  the  many  changes  which  have  already  been 
described.  Nucleated  red  cells  are  especially  numerous — 
the  most  characteristic  and  often  the  predominating  form  being 
the  megaloblast.  The  nuclei  of  these  cells  are  often  found 
in  the  process  of  division.  The  leucocytes  are  only  rarely 
increased ;  usually  their  number  is  normal  or  is  diminished.  ( These 
changes  are  subject  to  great  variations  depending  upon  the  activity 
or  exhaustion  of  the  bone-marrow. — Ed.) 

As  a  rule,  in  pernicious  anaemia,  theblood  serum  is  not 
particularly  deficient  in  solids.     Grawitz^^  found,  however,  that 


112  THE  BASIS  OF  SYMPTOMS 

such  a  deficit  is  apt  to  be  marked  in  those  cases  of  severe  ansemia 
which  are  due  to  malignant  tumors  or  to  chronic  infectious  dis- 
eases. Indeed,  he  has  shown  experimentally  that  pieces  of  car- 
cinoma introduced  into  the  circulation  of  animals  will  attract 
lymph  and  thereby  cause  a  dilution  of  the  blood-plasma.  The 
weight  of  the  total  solids  of  the  blood  is  always  markedly  dimin- 
ished^® owing  to  the  small  number  of  corpuscles.  The  total 
amount  of  blood  in  the  body  also  appears  to  be  less  than  normal, 
if  we  may  judge  from  the  impressions  received  at  the  bedside  and 
at  autopsy. 

The  effects  of  a  very  severe  ansemia  upon  the 
patient  are  often  most  striking.  His  brain  and  muscles  are  easily 
fatigued,  he  suffers  from  shortness  of  breath  and  from  fainting 
spells,  and  gastric  secretion  is  diminished  or  entirely  absent. 
There  is  often  a  great  tendency  to  bleeding,  especially  into  the 
skin  and  retinae.  Fatty  degeneration  of  various  organs  is  the 
rule,  being  especially  marked  in  the  liver,  the  kidneys  and  above 
all  in  the  heart-muscle.  Not  infrequently,  fever  is  present,  due 
possibly  to  substances  liberated  from  the  disintegrated  red  blood- 
c»rpuscles,  though  as  to  this  explanation  there  is  still  some 
uncertainty. 

Very  remarkable  changes  are  found  in  the  central  nervous 
system  in  pernicious  anaemia.^  The  most  frequent  anatomical 
lesion  is  degeneration  of  the  posterior  columns  of  the  spinal  cord, 
though  the  lateral  columns  and  the  gray  matter  may  also  be  dis- 
eased. The  cause  of  these  changes  is  still  uncertain.  Some  be- 
lieve that  they  are  caused  by  hemorrhages,  others  that  they  are 
due  independently  to  toxic  influences. 

The  pernicious  form  of  ansemia  must  be  re- 
garded merely  as  a  symptom-complex  which  may 
be  caused  by  a  variety  of  pathological  processes. 
For  a  certain  group  of  cases  no  cause  has  yet  been 
found, ^^^  and  to  these  is  given  the  name  of  essen- 
tial pernicious  ansemia,  or  the  Biermer- Addi  son 
type  of  ansemia. ^^  Such  cases  appear  to  be  especially  fre- 
quent in  certain  localities,  e.g.,  Switzerland. 

The  blood-picture  which  we  have  described  was  at  one  time 
regarded  as  characteristic  of  this  essential  pernicious  ansemia  of 
tmknown  causation;  yet  time  has  shown  that  the  same 
blood-findings    may    be    present    in    anaemias    of 


THE  BLOOD  113 

known  origin.^^  There  has  been  a  continual  en- 
deavor on  the  part  of  certain  investigators  to 
differentiate  these  two  forms  of  pernicious 
anaemia,  and  special  emphasis  has  been  laid  upon  the  pres- 
ence of  megaloblasts  as  favoring  the  diagnosis  of  the  essential  per- 
nicious form.  Yet  megaloblasts  have  also  been  found  in  the 
secondary  form  of  pernicious  anaemia.  Among  the  diseases 
which  have  given  rise  to  a  pernicious  type  of 
anaemia  are  syphilis,  carcinoma  of  the  stomach,  gastric  ulcer, 
ulcerating  carcinoma  of  the  uterus,  hepatic  affections  and  diseases 
of  the  bone-marrow.  Hunter  has  stated  that  the  condition  may 
be  produced  by  a  chronic  intoxication  from  oral  sepsis,  yet  this 
view  has  not  received  general  acceptance.  It  has  also  been 
asserted  that  pernicious  anaemia  is  caused  by  toxins  of  intestinal 
origin.  Atrophy  of  the  gastro-intestinal  mucous  membrane  is 
frequently  present  in  pernicious  anaemia,  but  we  know  that  it  may 
also  occur  without  causing  the  disease.  Some  believe  that  re- 
peated small  hemorrhages  may  be  a  causative  factor,  although 
this  is  denied  by  others.  It  is  universally  agreed,  however,  that 
at  least  two  forms  of  intestinal  parasites,  bothriocephalus  latus 
and  ankylostoma  duodenale,  may  produce  a  pernicious  type  of 
anaemia.  From  these  numerous  observations  it  has 
been  proved  that  it  is  impossible  to  draw  any 
sharp  distinguishing  line  between  those  anaemias 
of  a  pernicious  type  that  are  due  to  known  causes, 
and  those  that  appear  to  be  primary. 

Our  views  on  pernicious  anaemia  will  hardly 
meet  with  general  approval.  That  the  term  "per- 
nicious" is  applicable  only  to  the  essential  Biermer  type  and  to 
bothriocephalus  anaemia  is  universally  agreed.  But  no  less 
authoritative  a  haematologist  than  Naegeli  denies  that  the  anaemia 
of  gastric  carcinoma  and  of  ankylostomiasis  is  of  this  type.  The 
effort  is  constant  to  find  in  the  blood  changes 
that  will  distinguish  the  pernicious  from  the 
non-pernicious  forms.  The  presence  of  megalo- 
blasts was  at  first  regarded  as  a  distinctive  criterion,  while 
now  the  high  color-index  is  emphasized.  According  to 
Ni£geli,  an  index  over  one  does  not  occur  in  cancer  of  the 
stomach ;  in  this,  however,  Pappenheim  does  not  concur.  In  our 
opinion,  a  high  index  is  merely  a  sign  of  great  regeneration, 
8 


114  THE  BASIS  OF  SYMPTOMS 

such  as  occurs  in  embryonic  blood.^^  Too  great  importance, 
therefore,  must  not  be  attached  to  details  of  this  kind,  and  espe- 
cially must  the  blood  changes  not  be  over-emphasized  at  the 
expense  of  changes  in  other  organs.  Only  a  better  understand- 
ing of  the  etiological  factors  will  enable  us  to  write  the  last  word 
on  these  anaemias. 

In  what  manner  the  various  causes  affect  the 
blood  is  not  always  clear.  With  the  possible  exception 
of  the  ankylostoma  duodenale,  it  seems  improbable  that  losses 
of  blood  play  any  great  role.  In  the  case  of  malignant 
tumors,  hsemolytic  toxins  are  possibly  responsible  for  the 
blood  condition.  It  seems  very  probable  also  that  this  is  the 
case  in  the  anaemia  produced  by  the  bothriocephalus  latus.^^  Re- 
cent studies  have  attached  great  importance  to  the  action  of  a 
lipoid  substance  in  the  causation  of  bothriocephalus  anaemia 
and  of  haemolytic  conditions  generally .^^  Apparently,  many  in- 
dividuals harboring  intestinal  parasites  become  immunized  against 
their  poisons,  a  supposition  which  would  explain  the  fact  that 
a  man  may  have  the  parasites  in  his  intestines  without  manifesting 
any  symptoms,  and  that  periods  of  improvement  and  relapse  may 
alternate. 

Theprognosisof  the  pernicious  form  of  anaemia  depends 
mainly  upon  its  cause.  In  the  primary,  essential  form,  the  out- 
come is  usually  fatal;  in  the  secondary  forms,  recovery  may 
take  place  if  the  cause  be  discovered  and  removed,  and  if  the 
process  be  not  already  too  far  advanced.  This  is  especially  true 
of  those  cases  due  to  intestinal  parasites. 

In  pernicious  anaemia  there  is  unquestion- 
ably an  increased  destruction  of  the  red  blood- 
corpuscles,  as  is  proved  especially  by  the  abnormal  deposits 
of  iron  salts  in  the  liver  and  in  other  organs.  This  destruction, 
further,  is  probably  of  toxic  origin,  for  the  anaemias  caused  by 
losses  of  blood  or  of  serum,  even  though  most  severe,  are  unac- 
companied by  such  deposits  of  iron.  The  pigmentation  so  fre- 
quently found  in  the  spleen,  the  bone-marrow,  the  kidneys  and 
the  liver,  the  not  infrequent  jaundice,^^  the  increase  in  the  coloring 
matter  of  the  urine,  and  the  recently  reported  haemoglobinaemia 
likewise  support  the  idea  that  in  pernicious  anaemia  there  is  an 
unusual  destruction  of  the  red  blood-corpuscles. 

On  the  other  hand,  we  have  evidence  that  there  is  also 


THE  BLOOD  115 

an  increased  regeneration  of  erythrocytes,  for 
the  red  bone-marrow  spreads  to  parts  of  the  bones  from  which  it  is 
normally  absent,  and  in  this  red  marrow  are  found  erythrocytes 
of  various  kinds,  but  more  particularly  the  large  nucleated  variety 
known  as  megaloblasts.  By  the  escape  of  these  cells  into  the 
blood,  one  of  the  most  characteristic  features  of  pernicious 
ansemia  is  produced.  And,  furthermore,  there  is  a  return  to 
embryonic  conditions  in  that  certain  organs,  particularly  the  liver 
and  spleen,  once  more  take  on  a  blood-building  function,  evi- 
denced by  the  myeloid  metaplasia. 

In  pernicious  anaemia,  therefore,  there  is  both  an  increased 
destruction  and  an  increased  regeneration  of  red  corpuscles,  but 
we  do  not  know  at  present  which  process  is  primarily  at  fault. 
Perhaps  the  destruction  of  the  erythrocytes  is  so  intense  that  even 
the  most  marked  regeneration  does  not  replace  the  cells  destroyed ; 
or  perhaps  the  new  cells  are  so  imperfect  that  they  cannot  resist 
the  normal  wear  and  tear  in  the  body,  and  consequently  disinte- 
grate with  abnormal  ease.  Some  hold  that  the  disease 
consists  essentially  in  a  return  to  the  embryonal 
type  of  blood  formation.  Yet  there  is  no  reason  to 
consider  that  the  blood  and  marrow  changes  are  other  than  would 
result  from  an  excessively  active  regeneration  of  erythrocytes, 
with  the  escape  of  immature  corpuscles  into  the  circulating  blood. 
We  do,  however,  possess  direct  evidence  that  the  red  corpuscles  of 
pernicious  ansemia  are  more  vulnerable  to  injury  than  the  normal 
corpuscles,  and  that  they  may  be  destroyed  with  comparative  ease. 
This  seems  to  be  especially  true  of  the  malignant  ansemia  of 
syphilis.  (A  considerable  literature  ^^  has  appeared  in  the  past 
few  years  relative  to  the  removal  of  the  spleen  in  cases 
of  pernicious  ansemia.  The  indication  for  the  opera- 
tion cannot  be  drawn  along  the  same  lines  as  that  for  haemolytic 
jaundice,  because  pernicious  ansemia,  as  a  rule,  exhibits  no 
fragility  of  the  red  blood-cells,  but  rather  an  increased  resistance 
to  hypotonic  salt  solutions  (Tiirk).  Observers  are  by  no  means 
in  accord  as  to  the  cases  appropriate  for  operation,  nor  as  to  the 
evidence  of  improvement  following  splenectomy. — Ed.) 

In  addition  to  the  Biermer  type  of  pernicious  ansemia,  there 
is  one  in  which  the  regeneration  of  erythrocytes  seems  to  be 
particularly  at  fault.  This  is  the  so-called  aplastic  anaemia." 
The  blood-picture  is  not  especially  characteristic,  aside  from  the 


116  THE  BASIS  OF  SYMPTOMS 

complete  absence  of  all  forms  of  nucleated  red  corpuscles.  The 
prognosis  of  the  aplastic  anaemias  is  no  less  grave  than  that  in  the 
usual  form.  At  autopsy,  the  bone-marrow  appears  excessively 
poor  in  erythroblasts  and  sometimes  also  in  leucocytes.  Infec- 
tions of  different  sorts,  malaria  for  example,  are  possible  causa- 
tive factors  in  some  of  these  ansemias.^^  Animals  subjected  to 
repeated  venesection,  and  at  the  same  time  receiving  insufficient 
food,  may  show  a  similar  bone-marrow.*** 

It  must  be  emphasized,  incidentally,  that  in  severe  anae- 
mias especially,  the  blood-picture  is  by  no  means 
an  infallible  index  of  conditions  in  the  blood- 
building  organs.  Megaloblast  formation  in  the  bone- 
marrow  may  be  marked  without  the  appearance  of  a  single  one 
of  these  cells  in  the  circulation.  A  certain  reserve,  therefore,  is 
indicated  in  the  diagnosis  of  aplastic  anaemia. 

Haemoglobinaemia. — Thus  far  we  have  considered  the  haemo- 
globin only  as  it  constitutes  a  part  of  the  red  blood-corpuscles. 
If  it  escapes  from  the  latter  into  the  plasma,  the  condition  is 
known  as  haemoglobinaemia.'*^  Haemoglobin  which  has  become 
free  in  the  plasma  is  quickly  removed,  principally  by  the  liver, 
and,  to  a  lesser  extent,  by  the  spleen  and  the  bone-marrow.  If 
these  organs  fail  to  remove  it  completely,  it  is  excreted  in  the 
urine,  giving  rise  to  haemoglobinuria.  According  to 
Ponfick,  the  latter  is  produced  when  about  one-sixtieth  of  the 
total  haemoglobin  of  the  blood  is  set  free  from  the  cells.  The 
stromata  of  the  cells  which  have  lost  their  haemoglobin  are  de- 
posited in  the  spleen,  and  cause  a  swelling  of  that  organ.  Since 
the  liver  manufactures  bile-pigments  from  haemoglobin,  the  bile 
becomes  unusually  rich  in  coloring  matter  and  the  faeces  become 
darker.  The  haemoglobin  which  is  removed  by  the  liver  and 
kidneys  is  naturally  lost  to  the  body,  but  even  that  which  remains 
dissolved  in  the  plasma  is  in  part  rendered  useless  as  an  oxygen- 
carrier  by  being  transformed  into  methaemoglobin,  a  compound 
isomeric  with  oxyhaemoglobin,  but  differing  from  it,  in  that  it  is 
unable  to  give  up  its  oxygen  in  the  tissues. 

Such  a  passage  of  the  haemoglobin  from  the  corpuscles  into 
the  plasma,  or,  as  it  is  called,  haemo lysis,  may  be  brought 
about  by  several  causes.  The  osmotic  tension  of 
the  red  cells  may  be  so  increased  that  they  become 
unable  to  retain  their  haemoglobin;  or,  on  the  other  hand,  a 


THE  BLOOD  117 

lowering  of  the  osmotic  pressure  of  the  plasma 
may  bring  about  the  same  result.  The  latter  seems  to  be  of 
comparatively  little  importance,  for  normal  red  cells  are  resistant 
to  considerable  changes  in  the  osmotic  pressure  of  the  plasma, 
and  large  amounts  of  water  may  be  infi^sed  into  the  circulation 
without  causing  a  laking  of  the  blood.  Of  far  greater  importance 
as  a  cause  of  laking  are  chemical  changes  in  the  cor- 
puscular stromata  and  envelopes,  v^hich  are  com- 
posed largely  of  fat-like  substances.*^ 

We  have  said  that  the  haemoglobin  free  in  the 
plasma  may  become  converted  in  part  into  met- 
hsemoglobirt.  Certain  poisons  possess  the  property  of  effect- 
ing this  conversion  of  the  haemoglobin  directly  within  the  red 
cells.  If  the  injury  to  these  cells  be  not  too  severe,  it  is  possible 
that  the  methaemoglobin  so  produced  may  be  transformed  again 
into  oxyhaemoglobin.  If  the  corpuscles  are  more  seriously  dam- 
aged, however,  they  disintegrate  and  their  coloring-matter  passes 
into  solution. 

Three  different  processes  may,  therefore,  give  rise  to  hsemo- 
globinaemia:  first,  osmotic  changes  in  the  plasma;  secondly,  a 
primary  injury  to  the  red  blood-corpuscles ;  and  thirdly,  a  primary 
transformation  of  the  oxyhaemoglobin  into  methaemoglobin. 
These  processes  may  run  courses  quite  independent  of  each  other, 
but  for  the  most  part  they  are  combined,  to  some  extent,  and 
it  is  often  difficult,  in  the  individual  case,  to  say  which  was  really 
the  primary  change. 

Of  the  poisons*^  which  will  give  rise  to  a  lak- 
ing of  the  blood,  we  may  name  those  of  the  poisonous 
fungi,  the  bile  salts,  arseniuretted  hydrogen  and  the  plasma  of 
alien  animals.  The  toxins  produced  by  micro- 
organisms may  also  injure  the  corpuscles;  and  haemoglo- 
binaemia  has  been  observed  in  severe  cases  of  typhoid  fever, 
scarlet  fever  and  other  infectious  processes,  being  especially 
severe  in  certain  forms  of  tropical  malaria  (black-wafer 
fever).  In  such  cases  the  plasma  dissolves  its  own  corpuscles. 
Italian  observers  have  described  such  a  globulicidal  action  of 
the  plasma  in  association  with  a  great  variety  of  diseases.  When- 
ever the  destruction  of  the  corpuscles  exceeds  a  certain  limit, 
haemoglobinaemia  and,  ultimately,  haemoglobinuria  occur. 

According  to  the  recent  observations**   from  Hofmeister's 


118  THE  BASIS  OF  SYMPTOMS 

laboratory,  it  seems  probable  that  those  substances  which  dissolve 
erythrocytes  do  so  by  dissolving  or  precipitating  the  constituents 
of  the  stromata,  especially  the  lecithin  and  cholesterin. 

Paroxysmal  Haemoglobinuria. — The  condition  known  as 
paroxysmal  haemoglobinuria^^  is  characterized  by  the  pas- 
sage of  red  to  dark-brown  urine.  The  latter  contains 
some  of  the  more  usual  forms  of  albumin,  but  its  characteristic 
color  is  due  to  the  presence  of  free  oxyhsemoglobin  and  met- 
hsemoglobin,  with  few  if  any  red  blood-corpuscles  in 
the  typical  cases.  The  paroxysm  is  usually  accompanied 
by  chills,  fever  and  pains  in  various  parts  of  the  body.  As  a 
rule,  the  liver  and  spleen  become  enlarged,  and,  in  addition,  jaun- 
dice may  develop.  Occasionally,  a  sense  of  anxiousness,  or  of 
suffocation,  is  complained  of.  After  a  few  hours  or  days,  the 
symptoms  disappear,  and  only  the  dark-colored  faeces  remain  as 
evidence  of  the  paroxysm  which  has  just  ceased.  In  other  cases, 
subjective  manifestations  may  be  practically  absent,  or  on  the 
contrary,  extremely  severe. 

Malaria  and  particularly  syphilis  appear  to  be 
predisposing  causes  of  this  disease.  In  some  individuals  the 
attack  is  precipitated  by  muscular  exertion,  in  others  by 
exposure  to  cold.  Indeed,  some  patients  void  the  charac- 
teristic urine  whenever  they  are  exposed  to  a  low  temperature, 
or  even  when  a  hand  is  dipped  into  iced  water.  During  the  inter- 
vals between  the  paroxysms,  the  patient  may  appear  to  be  per- 
fectly well,  or  he  may  continue  to  show  albumin  in  the  urine. 
Ralfe  has  reported  the  case  of  a  man  who  had  cyclic  albuminuria 
in  conjunction  with  paroxysmal  haemoglobinuria,  and  a  similar 
case  has  been  observed  by  the  author. 

The  escape  of  the  haemoglobin  is  due  to  the 
action  of  an  haemolysin^^  of  inconstant  properties.  In 
the  majority  of  cases,  it  would  seem  that  an  amboceptor-like 
body  is  fixed  to  the  red  blood-cells  only  at  low  temperatures. 
The  haemolytic  system  would  then  be  completed  by  complement 
normally  present  in  the  individual's  serum.  The  amount  of  com- 
plement available,  however,  apparently  varies  greatly,*''^  being 
especially  low  at  the  height  of  an  attack.  Such  a  diminution 
would  be  compensatory  in  nature,  as  it  would  halt  further 
Jiaemolysis  and  thus  end  the  paroxysm;  while  in  the  intervals 


THE  BLOOD  119 

between  attacks,  it  is  likely  that  the  haemolytic  amboceptor  is 
greatly  reduced  or  even  absent. 

There  is  no  evidence  to  show  that  the  red  cells  themselves  have 
suffered  an  injury  in  paroxysmal  hsemoglobinuria ;  nevertheless 
they  are  generally  credited  with  harboring  the  noxious  factor, 
because  the  serum  does  not  contain  it.  As  a  matter  of  fact,  the 
red  corpuscles  sometimes  appear  to  have  an  abnormally  low  resis- 
tance, though  the  significance  of  this  is  not  clear.^®  Possibly 
variations  in  the  partial  pressure  of  carbon  dioxide  in  the  blood 
play  a  part  in  the  haemolytic  process. 

The  haemoglobinuria  is  generally  accompanied  by  a  haemo- 
globinaemia,  though  cases  are  on  record  in  which  the  plasma  con- 
tained no  coloring  matter.  It  is  by  no  means  impossible,  there- 
fore, that  complement  first  becomes  active  in  the  kidneys.  The 
position  of  syphilis  in  this  condition  presents  an  interesting  prob- 
lem, namely,  that  of  a  possible  relationship  between  the  hsemolysin 
concerned  in  the  Wassermann  reaction  and  the  haemolytic  ambo- 
ceptor active  in  haemoglobinuria. 

The  periodic  attacks  in  the  condition  under  discussion  bear 
a  close  resemblance  clinically  to  those  following  transfusion  with 
an  alien  blood.  It  is  reasonable  to  assume,  therefore,  that  both 
are  of  similar  origin,  this  being  an  intoxication  with  substances 
derived  from  the  erythrocytes — in  one  case  the  individual's  own 
corpuscles,  and,  in  the  other,  cells  of  a  foreign  blood.  It  is  of 
practical  importance,  however,  to  remember  that  the  blood  par- 
ticularly of  anaemic  individuals  may  contain  isolysins,*^  so  that 
the  transfusion  even  of  human  blood  may  not  be  entirely  free 
from  danger.  On  the  other  hand,  it  is  possible  that  severe 
haemolytic  paroxysms  lead  to  improvement  or  complete  recovery 
in  anaemic  conditions  by  stimulating  the  bone-marrow. 

Other  Causes  Which  Injure  the  Red  Blood-Corpuscles. — 
Extensive  superficial  burns  may  cause  the  red  cor- 
puscles to  break  up  into  smaller  particles,^*'  and  lead  to  a  libera- 
tion of  haemoglobin  in  the  plasma,  not  only  from  these  disinte- 
grated corpuscles  but  from  others,  which,  microscopically  at  least, 
appear  to  be  normal.  The  oxyhaemoglobin,  dissolved  in  the 
plasma,  is  taken  up  by  the  liver  and  kidneys,  partly  as  methaemo- 
globin,  the  urine  consequently  containing  both  these  pigments. 
The  cellular  residues  are  taken  up  especially  by  the  spleen  and 


120  THE  BASIS  OF  SYMPTOMS 

bone-marrow,  and,  to  a  lesser  extent,  by  other  organs.  The 
symptoms  they  produce  will  be  described  later. 

Many  poisons  are  able  to  convert  the  haemoglobin  of  the 
red  blood-corpuscles  into  methsemoglobin,^^  among  the  more  im- 
portant of  which  are  potassium  chlorate,  acetanilid 
and  other  coal-tar  products.  The  first  does  not  exert  the  same 
action  upon  the  blood  of  all  species  of  animals,  the  corpuscles 
of  some  appearing  to  be  especially  resistant  to  its  action.  Even 
in  the  same  individual,  accessory  factors  may  render  the  cor- 
puscles more  or  less  vulnerable  to  the  action  of  potassium  chlorate. 
Thus,  Mering  has  shown  that  the  red  cells  are  rendered  susceptible 
by  fever  or  by  a  reduction  in  the  normal  alkalinity  of  the  blood, 
produced  by  the  administration  of  mineral  acids.  The  toxic 
effects  of  the  administration  of  potassium  chlorate  appear,  there- 
fore, to  depend  upon  two  factors — ^first,  upon  the  amount  of  the 
salt  in  the  blood  at  a  given  time,  and  secondly,  upon  the  resistance 
possessed  by  the  red  corpuscles. 

Systemic  Effects  Resulting  from  the  Rapid  Destruction  of 
Red  Blood-Corpuscles. — The  effects  of  such  a  rapid  disintegra- 
tion of  red  cells  upon  the  body  as  a  whole  depend  partly  upon 
the  loss  of  functioning  haemoglobin  and  partly  upon 
the  toxicsubstances  derived  from  the  destroyed  corpuscles. 
In  very  severe  intoxications  with  potassium  chlorate,  death  results 
from  the  diminution  in  the  respiratory  capacity  of  the  blood, 
caused  by  the  loss  of  haemoglobin.^^ 

The  destruction  of  a  large  number  of  red  corpuscles  sets  free 
in  the  plasma  certain  substances,  apparently  enzymes,  which  tend 
to  produce  intravascular  clotting.  A  limited  quantity 
of  such  substances  may  be  neutralized  or  destroyed  by  the  living 
organism ;  but  when  they  appear  in  very  large  amounts,  they  give 
rise  to  thrombi  in  the  smaller  blood-vessels.^^  As  results  of  such 
thrombi,  necroses  occur  in  various  tissues;  and  the  gravity  of  the 
intoxication  often  depends  upon  the  localities  in  which  the  coagula 
form. 

The  fact  that  there  is  a  slow  coagulation  of  the  blood  in 
certain  cases  of  extensive  burns  in  no  way  excludes  the  possi- 
bility that  thrombi  have  formed,  for  we  know  that  the  presence 
of  substances  in  the  blood  which  favor  coagulation  may  in  turn 
give  rise  to  substances  having  the  very  opposite  effect,  so  that  ulti- 
mately coagulation  will  be  retarded.    Opinions  differ  as  to  the  role 


THE  BLOOD  121 

played  by  these  thrombi  in  states  of  rapid  blood  destruction. 
Some  observers  have  found  them  in  the  majority  of  cases,  while 
others  have  missed  them  with  equal  frequency.^^ 

The  large  quantities  of  haemoglobin  or  methsemoglobin  which 
may  pass  into  the  urine  in  these  conditions  seem  to  injure  the 
kidneys  directly,  and  not  infrequently  the  urine  contains  large 
amounts  of  albumin,  numerous  blood  and  epithelial  cells,  and  a 
great  variety  of  casts,  the  most  characteristic  of  which  are  com- 
posed of  clumps  of  blood-pigment.  The  quantity  of  urine  may 
diminish  up  to  complete  anuria,  and  the  patient  may  die  of  uraemia. 
Anatomically,  the  uriniferous  tubules  are  found  to  be  blocked 
with  masses  of  pigment,  and  in  addition  the  epithelium  itself 
seems  to  be  injured.  It  is  quite  possible  that  some  of  these 
changes  are  due  to  the  products  of  destruction  of  the  stromata, 
but  this  is  not  certain.''^ 

The  White  Blood-Corpuscles 

The  white  blood-corpuscles  ^°  may  be  divided  into  groups 
according  to  their  size,  the  character  of  their  nuclei  and  the 
staining  reactions  of  their  protoplasm.  About  seventy  per  cent, 
are  made  up  of  cells  that  are  slightly  larger  than  red  corpuscles, 
and  that  contain  irregular  nuclei  and  protoplasmic  granules  stain- 
ing with  neutral  anilin  stains  (polymorphonuclear  neu- 
trophil es).  From  twenty-five  to  twenty-eight  per  cent,  are 
made  up  of  mononuclear  cells,  from  two  to  four  per  cent,  of  which 
are  quite  large  (large  mononuclears  and  transi- 
tional cells),  while  the  remainder  are  about  the  size  of  red 
blood-corpuscles  (lymphocytes).  In  addition  to  these  cells, 
there  are  from  one  to  four  per  cent,  of  eosinophiles, 
characterized  by  the  presence  of  large  acid-staining  granules  in 
their  protoplasm,  and  from  one-half  to  two  per  cent,  of  cells  con- 
taining large  irregular  basic  granules  (the  mast-cells).  In 
infants  and  young  children,  the  lymphocytes  are  relatively  more 
numerous  and  they  may  even  exceed  the  neutrophilic  polymorpho- 
nuclears. 

Arneth,^^  more  recently,  has  further  subdivided  the  poly- 
nuclear  leucocytes  on  the  basis  of  the  shape,  number  and  size  of 
their  nuclear  subdivisions,  and  has  studied  the  variations  in  these 
particulars  in  different  infections.  His  views  rest  upon  the 
assumption  that  the  immature  polynuclears  possess  a  nucleus 


122  THE  BASIS  OF  SYMPTOMS 

which  is  almost  round,  whereas  more  mature  cells  exhibit  a  num- 
ber of  more  or  less  distinct  nuclear  parts.  From  this  general 
aspect,  Arneth's  view  may  be  subscribed  to.  Further  study, 
however,  is  needed  to  substantiate  the  rather  far-reaching  de- 
ductions as  to  degeneration  and  regeneration,  diagnosis,  prog- 
nosis and  treatment,  etc.,  which  some  observers  see  fit  to  draw 
on  the  strength  of  Arneth's  work.  More  recent  writings,^^  in- 
deed, have  vigorously  questioned  the  full  scope  of  Arneth's  inter- 
pretation. Nevertheless,  a  definitive  judgment  as  to  the  value 
of  the  method  is  not  justifiable  at  this  time.  (Naegeli,  in  the 
second  edition  of  his  book,  summarizes  the  present  status  of  the 
question  and  points  out  that  there  remains  little  of  the  original 
structure  of  the  Arneth  theory. — Ed.) 

Little  is  known  of  the  chemistry  of  the  different 
types  of  white  cells.  Minkowski  has  found  the  same 
nucleinic  acids  in  all  white  cells,  though  combined  with  different 
substances  in  the  various  types.  Pus-cells,  as  well  as  bone-mar- 
row elements,  and  the  ordinary  polynuclear  leucocytes  of  the 
blood,  are  able  to  oxidize  certain  substances  ^^  such  as  the  acid 
in  guaiac  resin,  by  means  of  an  enzyme-like  body,  or  oxydase, 
which  they  contain — a  property  not  possessed  by  the  mono- 
nuclear cells  originating  in  the  thymus,  spleen  and  lymph-nodes. 
Still  other  oxydase  reactions  are  shown  by  cells  of  the  myeloid 
system,  and  not  by  those  of  the  lymphoid.  The  recently  described 
indophenol  reaction ^^  of  Winkler  and  Schultz  is  of  this 
character.  (The  oxydase  reactions  have  found  a  considerable 
application  in  the  differentiation  of  acute  myeloid  from  acute 
lymphoid  leukaemia,  by  determining,  among  other  methods,  the 
source — whether  myeloid  or  lymphoid — of  certain  large  mono- 
nuclear cells,  with  a  non-granular  cytoplasm,  which  occur  in 
both  forms  of  acute  leukaemia.*'^ — Ed.) 

The  source  of  the  different  leucocytes  is  still, 
in  my  opinion,  an  open  question,  and  this  must  be  settled  before 
a  classification  is  possible.  The  observer  who  believes  that  a 
given  white  blood-cell  has  invariable  characteristics  is  inclined 
to  ascribe  it  to  a  definite  origin.  Ehrlich  has  attempted  such  a 
classification,  as  is  well  known.  The  lymphocytes,  according  to 
him,  arise  only  in  lymphoid  tissue,  and  the  ordinary  polynuclears 
are  descendants  of  mononuclear  bone-marrow  cells.  By  many, 
however,  this  division  is  criticised  because  based  upon  too  uncer- 


THE  BLOOD  128 

tain  and  variable  a  standard.^^  Thus,  the  lymphocytes  are  also 
said  to  be  capable  of  spontaneous  movement.  Nevertheless,  in 
a  general  way,  and  especially  in  recent  years,  hsematologists  are 
inclined  to  accept  Ehrlich's  strictly  genetic  subdivision  into 
lymphoid  and  myeloid.  Nsegeli  and  Schridde  are  the  strongest 
proponents  of  this  dualistic  theory.  Unlike  Pappenheim  and 
others,  they  do  not  believe  in  a  common  lymphoid  mother  cell  in 
extra-uterine  life,  inclining  rather  to  the  view  that  the  fore- 
runners of  the  myelocytes — the  myeloblasts — can  be  distinguished 
morphologically  from  the  original  lymphoid  cell. 

It  is  best,  perhaps,  to  concede  that  some  of  these  problems 
are  still  unsettled ;  in  my  opinion,  they  require  a  constant  revision 
to  prevent  further  research  from  taking  a  restricted  bent  because 
of  pre-existing  premature  conclusions. 

Physiological  Leucocytoses. — The  number  of  leucocytes  in 
a  cubic  centimetre  of  blood  is  normally  between  six  and  eight 
thousand.  Children  have,  on  the  average,  somewhat  more — 
about  nine  thousand;  weak  and  poorly  nourished  persons  appre- 
ciably fewer.  Arneth  gives  as  the  average  for  the  fasting  healthy 
adult,  five  to  six  thousand.  The  number  of  leucocytes  in  the 
peripheral  blood  varies  even  in  the  same  individual  at  different 
times.  Thus  it  is  usually  increased  after  a  meal,  especially 
one  rich  in  proteids.^^  Such  a  digestion  leucocy- 
te s  i  s  is  absent  in  some  individuals  normally,  but  it  is  especially 
apt  to  be  absent  in  certain  diseases,  above  all  in  carcinoma  of  the 
stomach.  During  pregnancy,  more  particularly  in  the 
later  months,  the  number  of  leucocytes  is  increased.  A  leucocy- 
tosis  is  also  physiological  in  the  new-born.  Cold  baths 
and  exercise®^  likewise  increase  the  number  of  leucocytes  in 
the  peripheral  blood.  Some  regard  this  latter  as  an  effect  of  the 
more  rapid  blood-current,  which  tears  the  leucocytes  away  from 
the  vessel  walls  of  the  internal  organs  and  throws  them  into  the 
general  circulation,  and  especially  into  the  peripheral  capillaries 
from  which  the  samples  of  blood  are  taken.  Grawitz  looks  upon 
it  as  a  genuine  new  formation  of  corpuscles. 

The  conditions  which  we  have  just  been  describing  have  been 
termed  physiological  leucocytoses.  The  increase  in  the  number 
of  white  cells  does  not  usually  exceed  thirty  per  cent,  of  the  nor- 
mal, although  in  children  the  number  may  be  doubled.  The  pro- 
portion between  the  mononuclear  and  the  polynuclear  cells  remains 


124  THE  BASIS  OF  SYMPTOMS 

unchanged  in  this  form  of  leucocytosis.  Since  the  counts  are 
made  from  the  blood  of  the  peripheral  capillaries,  the  question 
arises,  Is  there  an  actual  increase  in  the  total  number  of  leucocytes 
in  the  blood,  or  is  there  merely  a  redistribution  of  the  cells,  more 
going  to  the  periphery  and  fewer  remaining  in  the  interior  of  the 
body?  Studies  on  animals  have  shown  that  there  is  normally  a 
greater  number  of  leucocytes  at  the  periphery  than  in  the  internal 
organs,  but  that  during  the  digestion  leucocytosis,  at  least,  the 
number  in  both  places  is  increased.  The  new  cells  are  probably 
derived  from  the  lymph  and  from  the  various  organs  of  the  body, 
for  no  signs  of  an  active  regeneration  of  these  cells  are  to  be 
found.  The  digestion  leucocytosis  seems  to  be  due  to  the  presence 
of  substances  in  the  blood  which  attract  the  leucocytes  (chemo- 
taxis).  Such  substances  appear  to  be  present  in  largest  amounts 
after  the  ingestion  of  proteid  food,  though  not  all  varieties  of 
proteid  food  exert  the  same  influence.  Indeed,  it  is  uncertain  just 
which  products  of  digestion  are  responsible  for  the  normal  diges- 
tion leucocytosis.  Possibly  this  leucocytosis  indicates  a  trans- 
portation of  proteid  material  from  the  intestines  to  other  parts  of 
the  body. 

A  hyperleucocytosis  is  frequently,  but  not  always,  preceded 
by  a  hypoleucocytosis.*'^  Lowit  interpreted  this  as  a  primary- 
destruction  of  the  white  corpuscles  which  precedes  a  regeneration. 
Goldscheider  and  Jacob  and  others,  on  the  contrary,  failed  to  find 
any  sign  of  destruction,  and  believe  that  this  hypoleucocytosis  is 
caused  by  a  massing  of  the  leucocytes  in  the  capillaries  of  the 
lungs.     More  work  is  necessary  to  decide  this  question. 

Pathological  Leucocytoses. — Many  infections  cause  an 
increase  in  the  number  of  white  blood-corpuscles  in  the  peripheral 
blood — the  so-called  pathological  leucocytosis.^®  Although  the 
same  varieties  of  leucocytes  are  present  as  in  health,  the  relative 
proportions  are  usually  changed.  In  the  more  common  forms  of 
pathological  leucocytosis,  the  percentage  of  lymphocytes  is  dimin- 
ished, whereas  that  of  the  polymorphonuclear  neutro- 
philes  is  increase d — from  eighty-eight  to  ninety-five  per 
cent,  of  the  latter  being  frequently  found,  as  compared  with  the 
normal  of  seventy  to  eighty  per  cent. 

In  other  forms  of  pathological  leucocytosis,  the  relative 
number  of  the  lymphocytes  is  increased,  such  a 
blood-picture  being  presented  by  many  cases  ofpertussis.     Of 


THE  BLOOD  125 

special  interest  would  be  the  investigation  of  the  blood-changes 
in  those  diseases  which  give  rise  to  exudates  rich  in  lymphocytes, 
such  as  tuberculous  meningitis  and  pleurisy,  and  certain  chronic 
cord  lesions. 

The  influence  of  the  nervous  system  upon  the  number  of  white 
cells  would  seem  to  be  shown  by  recent  studies. *^'^  Substances  like 
epinephrin,  which  stimulate  the  sympathetic  system,  produce 
neutrophilic  leucocytoses,  while  those  acting  upon  the  vagus,  such 
as  pilocarpin,  cause  an  eosinophilic  leucocytosis,  or  a  lymphocy- 
tosis. These  observations,  however,  must  be  viewed  conserva- 
tively. 

Still  another  form  of  leucocytosis  is  characterized  by  the 
relative  increase  in  the  eosinophilic  white 
blood-corpuscles.  This  has  been  observed  in  bronchial 
asthma,  trichinosis  and  a  variety  of  other  diseases.  (In  most 
infections — scarlet  fever  being  an  exception — the  eosinophiles  are 
absent  during  the  height  of  the  disease.  Their  reappearance  is 
regarded  as  a  favorable  sign. — Ed.) 

Pathological  leucocytosis  of  the  neutrophilic 
type  occurs  especially  as  the  result  of  inflammatory  processes 
and,  above  all,  in  association  with  those  which  are  accompanied  by 
a  purulent  exudation,  although  the  latter  is  not  a  necessary  con- 
comitant. In  certain  infectious  diseases,  e.g.,  typhoid  fever, 
malaria  and  uncomplicated  tuberculosis,  there  is  usually  no  increase 
in  the  number  of  white  blood-corpuscles  in  the  circulating  blood. 

The  infectious  leucocytoses  are  probably  caused 
either  by  the  secretions  of  the  living  bacteria,  or  by  the  disinte- 
grated bodies  of  dead  ones.  Experimentally,  it  has  been  shown 
that  various  constituents  of  the  bacterial  cell  may  exert  an  attrac- 
tive influence  upon  the  leucocytes  (positivechemotaxis).^^ 
Many  other  substances  also  appear  to  exert  such  a  chemotactic 
influence;  and  the  same  substance  may,  under  one  set  of  circum- 
stances, attract  the  leucocytes,  and,  under  another,  repel  them. 
The  origin  of  the  extra  leucocytes  has  not  yet  been  definitely  set- 
ted — we  do  not  know  whether  they  are  derived  from  the  bone- 
marrow,  the  lymph-glands  or  possibly  from  other  tissues.  The 
purpose  of  these  pathological  leucocytoses  is  probably  one  of 
resistance  to  the  invading  micro-organisms. 

Leucocytoses  of  the  neutrophilic  type  may  also  result  from 
hemorrhage  and  from  malignant  cachexias. ^^     The 


126  THE  BASIS  OF  SYMPTOMS 

latter,  however,  do  not  always  cause  an  increase  in  the  number  of 
leucocytes  in  the  peripheral  blood;  nor  do  we  know  what  is  the 
determining  factor  in  the  individual  case.  Grawitz  found  that 
after  injecting  carcinomatous  material  into  an  animal's  blood, 
the  latter  became  more  dilute,  and  the  number  of  leucocytes  was 
frequently  increased.  These  changes  were  believed  to  result 
from  an  increased  flow  of  lymph  into  the  blood — a  possible  ex- 
planation not  only  of  the  leucocytoses  due  to  malignant  disease, 
but  of  those  which  follow  acute  hemorrhage. 

Leucocytoses  in  which  the  eosinophilic  cells 
are  increased  occur  in  a  variety  of  diseases,  of  which  we 
may  mention  bronchial  asthma,  various  cutaneous  lesions,  tri- 
chinosis'^^ and  infections  with  intestinal  parasites.  It  is  interest- 
ing that  in  most  of  these  diseases  there  exists  a  local  collection 
of  eosinophilic  cells  at  the  main  seat  of  the  disease :  for  example, 
in  the  bronchi  and  in  the  exudate  of  bronchial  asthma,'^ ^  in  the 
lesions  of  certain  skin  affections  and  about  the  embryos  in 
trichinosis. 

The  number  of  white  cells  in  the  blood  in  pathological  leucocy- 
toses usually  ranges  between  ten  thousand  and  thirty  thousand 
per  cubic  millimetre.  Higher  counts  do  occur,  however,  though 
rarely,  if  ever,  exceeding  eighty  thousand. 

Leucopaenia. — A  diminution  in  the  number  of  leucocytes  in 
the  peripheral  blood,  a  leucopaenia,  occurs  in  a  variety  of  diseasae. 
It  has  been  observed  in  cachexias,  intoxications,  many  anaemias 
and  in  some  infectious  diseases,  notably  in  typhoid  fever 
and  malaria. 

In  such  leucopaenias,  the  proportion  between  the  numbers  of 
the  various  kinds  of  white  cells  is  usually  changed.  For  example, 
in  typhoid  fever  there  is  a  relative  increase  in  the  number  of 
lymphocytes.  The  cause  of  the  leucopsenias  is  un- 
known. Possibly  they  are  due  to  a  negative  chemotaxis,  or  to 
some  lesion  of  the  sites  of  origin  of  the  leucocytes.  In  typhoid, 
indeed,  the  bone-marrow  is  poor  in  myelocytes,  which  would 
explain  the  relative,  but  not  the  absolute,  lymphocytosis  generally 
observed. 

Little  is  known  of  pathological  alterations  in  the  blood- 
platelets."^*  It  is  generally  agreed  that  these  bodies  are  intimately 
associated  with  the  phenomena  of  blood  coagulation,  in  that  they 
take  a  part  in  the  formation  of  fibrin- ferment.     In  certain  con- 


THE  BLOOD  127 

ditions,  indeed,  for  example,  in  severe  anaemias,  delayed  clotting 
and  a  diminished  number  of  platelets  go  hand  in  hand.  The 
platelets  contain  also  a  ferment  capable  of  splitting  polypeptids.'^^ 
These  facts  would  indicate  that  the  platelets  are  biological  entities, 
and  not  merely  disintegrated  erythrocytes.  Their  origin  is  not 
known,  nor  are  the  variations  they  undergo  in  pathological  con- 
ditions, aside  from  the  fact  that  they  are  reduced  in  certain  severe 
anaemias.  (Their  extreme  reduction  in  pernicious  anaemia  seems 
to  have  a  diagnostic  value ;  while  in  chronic  myeloid  leukaemia  they 
are  generally  enormously  increased. — Ed.) 

Leukaemia  and  Pseudoleukaemia. — (The  author  uses  the  term 
pseudoleuksemia,  for  the  most  part,  in  the  strict  sense,  as  denoting 
the  condition  in  which  the  pathological  picture,  both  gross  and 
microscopic,  is  typically  leukaemic,  but  in  which  the  characteristic 
leukaemic  changes  are  absent  in  the  blood.  This  so-called  aleukaemic 
leukaemia  may  be  either  lymphoid  or  myeloid.  This  strict  inter- 
pretation excludes  the  many  conditions,  such  as  malignant  granu- 
lomatosis (Hodgkin's  disease),  tuberculosis,  syphilis,  lymphosar- 
coma tosis,  etc.,  which  clinically  may  bear  a  close  resemblance  to 
pseudoleukaemia. — Ed,  ) 

In  leukaemia  and  pseudoleukaemia,'^*  there  is 
obviously  a  conjoined  disturbance  of  the  bone- 
marrow,  the  lymphadenoid  tissues  and  of  the 
spleen;  and,  in  addition,  there  are  generally 
changes  in  the  blood.  It  is  convenient,  first,  to  consider 
the  two  diseases  together  and  then  in  their  relationship  to  on^ 
another.  The  change  in  both  consists  of  a  hyperplasia  of  the 
spleen,  lymph-nodes  and  bone-marrow,  or  only  of  two  of  these 
organs;  in  leukaemia,  the  bone-marrow  is  apparently  involved  in 
all  cases. 

Two  types  of  leukaemia  are  recognized,  depend- 
ing upon  the  character  of  the  cells  present  in  the  circulation  and 
in  the  haemapoietic  organs.  Corresponding  also  to  the  types  of 
cells  found  increased  in  the  blood,  the  hyperplasias  in  the  different 
organs  concerned  in  blood  building — bone-marrow,  spleen,  lymph- 
nodes,  liver,  intestines — exhibit  diverse  cells  (myeloid  and 
lymphoid  hyperplasia).  In  pseudoleukaemia,  the  histo- 
logical changes  in  the  above-mentioned  organs  generally  resemble 
those  of  lymphoid  leukaemia,  though  In  some  cases  the  myeloid 
type  is  observed. 


128  THE  BASIS  OF  SYMPTOMS 

The  bone-marrovv'^^  of  the  long  bones  does  not  consist 
chiefly  of  fat  cells,  as  in  the  healthy  adult,  but  returns  to  its 
lymphoid  character,  such  as  one  sees  in  childhood,  and  in  the 
anaemias.  In  color  it  varies  from  a  deep  red  to  a  grayish-yellow, 
though  the  findings  are  not  uniform  in  all  cases  either  of  leukaemia 
or  of  pseudoleuksemia.  At  times,  the  marrow  is  indistinguish- 
able, grossly  and  microscopically,  from  that  seen  in  many  anaemias. 
Histologically,  there  are  observed  nucleated  red  cells  of  all  types, 
and  in  addition  an  enormous  number  of  leucocytes.  The  latter, 
indeed,  may  be  so  numerous  as  to  lend  to  the  marrow  a  pus-like 
appearance.  These  white  cells  are  of  myeloid  type  in  some  cases, 
and  of  lymphoid  in  others. 

In  the  spleen  and  lymph-nodes  the  hyperplasia, 
according  to  the  general  opinion,  has  no  specific  anatomical  char- 
acter. The  growth  in  lymphoid  leukaemia  concerns  the  autoch- 
tonous lymphoid  tissue;  while  in  the  myeloid  form,  there  is  a 
growth  of  cells  of  the  bone-marrow  type,  i.e.,  there  occurs  a 
myeloid  conversion  of  the  lymph-node. 

These  hyperplasias  are  not  confined  to  the  bone-marrow, 
lymph-nodes  and  spleen,  but  appear  wherever  there  is  lymphoid 
or  myeloid  tissue  capable  of  growth.  Even  the  cells  of  the  vessel 
walls — comprising  the  original  mother-substance — may  be  the 
source  of  new  cells.  The  lymphoid  and  myeloid  cell-accumula- 
tions occurring  in  the  liver,  spleen,  intestines,  thymus,  skin,  ton- 
sils, choroid,  etc.,  are  partly  metastatic  in  nature  and  partly  meta- 
plastic. Pappenheim,  Naegeli,  indeed  haematologists  generally, 
view  this  as  a  metaplasia  in  loco  and  not  as  a  blood-cell  coloniza- 
tion, i.e.,  transported  from  elsewhere.  In  the  lymphoid  processes, 
the  hyperplasia  seems  to  be  more  widely  distributed  than  in  the 
myeloid."^® 

In  the  leukaemias  there  is  generally  a  marked, 
often  an  enormous,  increase  in  the  white  cells  in 
the  blood,  while  in  pseudoleukaemia  there  is 
either  no  increase  or  at  most  a  moderate  one.  Ac- 
cording to  Pinkus,'^^  there  is  regularly  a  relative  increase  in  the 
lymphocytes  in  pseudoleukaemia,  and  herein  lies  the  intimate  rela- 
tionship between  the  latter  and  lymphoid  leukaemia.  Indeed,  the 
two  conditions  differ  only  in  the  fact  that  the  number  of  white 
cells  in  the  blood  is  increased  in  the  one  and  normal  in  the  other. 
This  criterion  has  certain  limitations,  however,  for,  as  already 


THE  BLOOD  120 

mentioned,  pseudoleukaemias  occur  with  a  myeloid  type  of  origin 
and  with  myeloid  blood-changes  (amyelsemic  and  sub- 
myelaemic  leukaemias).  We  distinguish,  therefore,  be- 
tween myeloid  and  lymphoid  tissue  hyperplasias,  with  or  without 
an  increase  of  the  corresponding  cells  in  the  circulating  blood. 

The  leukaemias  may  be  differentiated  from  the  leucocytoses,  in 
a  general  way,  by  the  greater  increase  in  the  white  cells.  In  the 
former,  values  of  three  to  five  hundred  thousand  cells  are  not 
infrequent ;  at  times,  indeed,  the  white  cells  may  be  as  numerous 
as  the  red.  In  a  leucocytosis,  on  the  contrary,  a  white  count  above 
eighty  thousand  scarcely  occurs.  A  more  important  index,  how- 
ever, of  the  leuksemic  nature  of  a  process  resides  in  the  types 
of  white  cells  present,  for  the  number  of  cells  may  undergo  con- 
siderable variations  during  the  course  of  the  disease.  (A  diminu- 
tion, for  example,  may  occur  during  an  intercurrent  acute  infec- 
tion, and  also  as  a  result  of  X-ray  therapy."^®  The  use  of  ben- 
zene,"^^  as  recommended  by  Koranyi,  has  produced  similar  results. 
In  these  cases,  however,  though  the  total  number  of  white  cells 
may  be  reduced  even  to  a  normal  level,  the  differential  count 
ordinarily  shows  little  change  in  the  relative  proportion  of  patho- 
logical cells  present,  the  blood  remaining  typically  leukaemic. — 
Ed.)  The  former  tendency,  therefore,  of  looking  upon  the  num- 
ber of  white  cells  as  the  sole  criterion  of  a  leukaemia  resulted  in 
a  narrow  and  indistinct  picture  of  the  disease,  so  that  to-day  it  is 
difficult  to  interpret  the  earlier  literature  on  the  subject.  An 
unequivocal  diagnosis  of  leukaemia  demands  not 
only  a  careful  histological  scrutiny  of  the  organs 
involved,  but  also  the  demonstration  of  certain 
types  of  wh ite  cells  in  the  blood. 

Characteristic  of  the  leukaemias  is  the  presence  in  the  circu- 
lation of  cells  normally  absent,  and  particularly  is  the  relative 
proportion  of  the  different  forms  unlike  that  in  the  leucocytoses. 
In  the  latter,  the  polynuclear  neutrophiles  preponderate;  in  leu- 
kaemia, on  the  contrary,  mononuclear  types  are  always  strongly  in 
evidence,  their  number  varying  within  wide  Hmits.  In  the  acute 
leukaemias  the  mononuclear  forms  are  much  more  numerous  than 
in  the  chronic;  indeed,  they  may  comprise  ninety-nine  per  cent, 
of  all  the  white  cells  present. 

Two  types  of  leukaemia  are  distinguished  ac- 
cording to  their  blood-pictures.  The  first  exhibits 
0 


ISO  THE  BASIS  OF  SYMPTOMS 

a  great  many  large  mononuclear  cells  with  abundant,  predom- 
inantly neutrophilic,  granules  in  the  cytoplasm  (myelocytes). 
The  polytiuclear  neutrophils  are  absolutely  increased  though  rela- 
tively diminished.  Various  atypical  leucocytes  are  common,  as 
are  nucleated  red  corpuscles,  usually  of  moderate  size.  (Indeed 
the  very  multiplicity  of  atypical  forms  is  indicative  of  myeloid 
leukaemia. — Ed.  ) 

Myelocytes,  though  absent  from  normal  blood,  are  not  pathog- 
nomonic of  leukaemia,  for  they  occur,  less  abundantly  it  is  true,  in 
other  conditions,^^  notably  in  the  infectious  diseases,  and  in 
severe  anaemias.  An  interesting  resemblance  to  the  blood  of 
myeloid  leukaemia  is  that  due  to  tumors  which  have  given  rise 
to  metastases  in  the  bone-marrow. 

In  the  second  type  of  leukaemia  (lymphoid  or  lymph- 
aticleukaemia),  the  prevailing  cell  is  the  small,  or  moderately 
large,  mononuclear,  the  so-called  lymphocyte,  with  a  large  nucleus 
and  a  narrow  rim  of  non-granular  cytoplasm.  The  other  types 
of  white  cells,  in  particular  the  polynuclear  neutrophiles,  are  rela- 
tively and  often  absolutely  decreased.  Eosinophiles  and  myelo- 
cytes are  usually  absent,  though  in  certain  cases  of  lymphatic 
leukaemia  the  latter  cell  may  be  fairly  numerous.  The  red  cell 
count  may  remain  unchanged  for  a  long  time,  later  being  dimin- 
ished.   Nucleation  is  rare. 

The  two  forms  just  described  are  readily  differentiated,  for 
the  predominant  cell  in  each  points  to  a  hyperplasia  of  the  myeloid 
or  lymphoid  tissues,  as  the  case  may  be.  The  type  of  cell  found 
in  the  blood  is  not  indicative  of  the  organ  whence  it  originated ; 
whether  the  spleen  or  lymph-nodes  are  predominantly  affected  is 
more  readily  judged  from  the  ordinary  methods  of  physical 
examination. 

A  genuine  anaemia  is  generally  observed  in 
leukaemia  and  pseudoleukaemia;  both  oligoc3rthaemia 
and  oligochromaemia  are  present.  Poikilocytes  and  nucleated  red 
cells  of  various  sizes  may  be  seen.  In  certain  cases,  therefore,  the 
blood  may  closely  resemble  that  of  myeloid  pseudoleukaemia  and 
of  the  Bicrmer  type  of  pernicious  anaemia.*^  These  are  the  cases 
of  so-called  leukanaemia  (Leube),  the  nature  of  which  is  little 
understood,  though  the  blood-changes  point  to  a  coincident  injury 
to  the  erythropoietic  and  leukopoietic  functions  of  the  bone- 
marrow.     (Certain  observers,  such  as  Naegeli,  seriously  doubt  the 


THE  BLOOD  131 

existence  of  such  a  leukanaemia,  believing  that  more  rigid  analyses 
would  show  that  conditions  going  under  this  name  are  in  reality 
pernicious  anaemia,  myeloid  leukaemia — acute  or  chronic — or  other 
processes. — Ed.  ) 

The  blood-serum  in  leukaemia  sometimes  contains 
proteids  not  normally  present.  Nucleo-albumins  and  deutero- 
albumoses  have  been  found,  but  at  present  the  meaning  of  these 
findings  is  not  clear.  Charcot-Leyden  crystals  have  been  found 
in  myeloid  leukaemia  in  the  blood,  as  well  as  in  the  fluids  of  the 
spleen.  These  crystals  appear  to  bear  some  relation  to  the  pres- 
ence of  eosinophilic  cells. 

Leukaemia  is  generally  a  disease  of  middle  life,  though  it  may 
occur  both  in  children  and  in  the  aged.  It  terminates  fatally  in 
practically  all  cases :  instances  of  recovery  were  not  unlikely  leuco- 
cytoses.  The  beneficial  action  of  the  X-ray ^^  has  recently 
come  to  the  fore,  thorough  rcentgenization  of  the  spleen  and  of 
the  long  bones  often  producing  not  only  a  marked  decrease  in  the 
number  of  leucocytes,  but  also  a  decided  reduction  in  the  size  of 
the  spleen  and  lymph-nodes.  The  action  of  the  rays  seems  to  be 
exerted  both  upon  the  marrow  and  upon  the  white  cells  in  the 
blood.  Improvement,  approaching  recovery,  has  been  observed; 
but  this  is  temporary  and  the  blood  qualitatively  usually  remains 
leukaemic.  The  author  has  seen  conditions  aggravated  by  the  use 
of  the  rays.  (The  use  ofbenzene  has  already  been  commented 
upon.  Its  effects  are  generally  similar  to  those  of  the  X-ray ;  the 
results,  indeed,  seem  best  when  the  two  methods  are  combined. 
The  toxic  action  of  benzene,  particularly  upon  the  kidneys,  and 
perhaps  also  upon  the  erythrocytes,  demands  caution  in  its  em- 
ployment.— Ed.  ) 

The  course  of  the  leukaemias  is  essentially  chronic. 
In  recent  years,  however,  acute  cases  have  been  described  which 
lead  to  exitus  within  a  period  of  weeks,  or  even  days. 

The  acute  leukaemias  are  truly  remarkable  conditions  charac- 
terized by  a  pronounced  hemorrhagic  diathesis  and  by  an  extremely 
rapid  course.  As  fever  is  generally  present,  there  may  be  a  great 
resemblance  to  an  acute  infection.  The  leukaemic  nature  of  the 
process  consists  in  an  increase  in  the  white  blood-cells  and  in  an 
alteration  in  the  types  present.  The  number  of  leucocytes  is 
highly  variable  and  the  increase  is  often  insignificant.  As  a  rule 
the  predominating — sometimes  practically  the  only — cell  present 


182  THE  BASIS  OF  SYMPTOMS 

isalargemononucleartype^^withan  undifferen- 
tiated protoplasm,  resembling  the  lymphoid  mother-cell. 
In  other  cases,  however,  somewhat  similar  mononuclear  cells  sug- 
gest rather  a  myeloid  origin.  (These  two  cells  are  the  1  y  m  p  h  o  - 
blast  and  myeloblast,  respectively,  and  the  leukaemias 
themselves  are  known  as  acute  lymphatic  (lymphoid)  and  acute 
myeloid  (myeloblastic). — Ed.)  A  classification  of  these  acute 
conditions  is,  for  the  present,  best  not  attempted,  first  because  of 
the  difficulty  of  distinguishing  between  these  two  types  of  large 
mononuclear  cells ;  further,  because  in  certain  cases  in  which  the 
cells  in  the  blood  were  apparently  lymphoid,  no  hyperplasia  of  the 
corresponding  tissue  was  found;  and  finally  because  "mixed- 
cell"  leukaemias  occur,  or  one  type  may  apparently  go  over 
into  the  other.  The  general  tendency  to-day  is  to  catalogue  the 
major  part  of  these  acute  leukaemias  as  myeloid ;  for  though  the 
large  cells  of  the  latter  are  very  similar  to  cells  of  lymphoid  origin, 
yet  the  staining  properties  of  the  protoplasm  are  more  suggestive 
of  the  forerunners  of  the  myelocytes. 

Two  manifestations  of  leukaemia — ^the  fever  and  the  hemor- 
rhages— are  of  particular  interest.  The  temperature,  which  is 
often  of  a  hectic  type,  cannot  be  explained  on  the  basis  of  a  compli- 
cation. A  tendency  to  hemorrhage  into  the  skin,  the  choroid  and 
the  organs  generally  is  particularly  common  in  the  acute  leu- 
kaemias. 

Both  of  these  manifestations  are  important  because  of  the 
possible  relation  they  bear  to  the  destruction  of  the  blood-cor- 
puscles. Hemorrhages  and  fever  may  also  occur  in  pseudoleu- 
kaemia,  the  temperature  at  times  assuming  a  characteristic  relap- 
sing character  with  periods  of  apyrexia  (Ebstein).^^  (This  type 
of  fever  is  not  present  in  aleukaemic  leukaemias,  but  rather  in  those 
pseudoleukaemic  types  of  a  granulomatous  nature,  which  will  be 
discussed  below. — Ed.  )  Pseudoleukaemia  may  also  run  a  rapidly 
fatal  course. 

The  chief  feature,  therefore,  differentiating 
pseudoleukaemia  from  the  ordinary  types  of  leu- 
kaemia is  the  number  of  leucocytes  in  the  unit- 
volumeofblood.  A  conversion  of  a  pseudoleukaemia  into  a 
true  lymphatic  leukaemia  is  very  rare,  although  a  few  such  cases 
have  been  reported.  In  one  of  these,  a  rupture  of  the  hyper- 
plastic tissue  of  a  pseudoleukaemic  gland  into  a  vein  could  be 


THE  BLOOD  133 

directly  demonstrated,  and  coincidently  a  lymphatic  leukaemia 
developed.®^  Nevertheless,  border-line  types  of  both  leukaemia 
and  pseudoleuksemia,  as  well  as  transitional  forms,  are  surely  very 
infrequent.  Much  more  commonly,  each  disease  runs  a  typical 
clinical  course  from  beginning  to  end.  Yet  the  two  are  doubt- 
lessly closely  related,  being  perhaps  different  forms  of  the  same 
morbid  process. 

Of  prime  importance  is  the  question  of  the  relation  which 
the  changes  in  the  spleen,  the  lymphatic  apparatus  and  the  bone- 
marrow  bear  to  each  other — and  of  the  relation  which  these 
changes  bear  to  the  causation  of  the  diseases  under  consideration. 
As  a  rule,  all  three  of  these  organs  are  involved,  usually  in  such 
a  manner  that  the  changes  in  two  predominate.  A  normal  bone- 
marrow  is  never  present,  though  specific  alterations  may  be  absent. 
In  some  cases,  the  marrow  changes  can  be  recognized  only  with 
the  microscope;*^  and  not  infrequently  the  bone-marrow  is  the 
only  tissue  involved. 

Also  of  great  importance  is  the  question  whether  the  anatomi- 
cal changes  in  these  organs  are  primary  or  secondary.  This  much 
is  certain,  that  in  lymphatic  leukaemia  and  lymphatic  pseudoleu- 
kaemia,  the  lymphadenoid  tissue  is  hyperplastic,  while  in  the  mye- 
loid forms,  the  bone-marrow  elements  are  in  a  state  of  growth.  If 
one  regards  these  processes  as  affections  of  the  myeloid  and 
lymphoid  systems  respectively,  the  question  as  to  the  primary 
focus,  from  the  general  pathological  point  of  view,  is  of  no  great 
moment,*^  for  the  disease  may  originate  wherever  there  is  lymph- 
oid or  myeloid  tissue.  In  myeloid  leukaemia,  nevertheless,  the 
tendency  is  to  emphasize  the  crucial  importance  of  the  bone- 
marrow,  because  in  adults  this  is  the  principal  myeloid  organ. 

The  conditions  still  grouped  under  the  common  caption 
pseudoleukaemia  undoubtedly  differ  clinically  in  many  particu- 
lars. The  recent  tendency**  is  to  separate  those  on  an  infectious 
(granulomatous)  basis  from  others  hyperplastic  in  character. 
The  last  only  are  leukaemic  in  nature,  differing  from  the  usual 
leukaemias,  as  has  already  been  stated,  merely  in  the  absence  of 
leukaemic  elements  in  the  circulating  blood. 

(A  great  deal  of  attention  has  been  devoted  in  recent  years 
to  that  type  of  pseudoleukaemia  belonging  properly,  it  would  seem, 
to  the  granulomas,  and  known  otherwise  as  Hodgkin's  disease  or 
malignant  granuloma."       This  does  not  include   the  varieties  due 


184  THE  BASIS  OF  SYMPTOMS 

to  syphilis  or  to  tuberculosis  in  its  usual  form.  Clinically,  it 
may  be  indistinguishable  from  the  true  pseudoleukaemias 
(a leuksemic  leukaemias)  on  the  one  hand,  and  from  neo- 
plastic growths  on  the  other.  The  microscopic  examination,  how- 
ever, usually  makes  a  diagnosis  possible,  revealing  changes  more 
or  less  constantly  observed,  but  variously  interpreted,  Sternberg 
regards  the  condition  as  a  peculiar  form  of  tuberculosis  and  finds  an 
unusual  type  of  giant-cell,  to  which  Reed^*'  has  also 
called  attention.  Frsenkel  and  Much®^  consider  the  disease  to  be 
due  to  a  granular  form  of  the  tubercle  bacillus  which  appears  only 
with  a  special  staining  technic.  More  recently,  Bunting  and 
Yates  and  others ^^  have  isolated  a  pleomorphic  diph- 
theroid bacillus  from  the  affected  lymph-nodes,  by  means 
of  which  they  state  that  they  have  transferred  the  disease  to 
rhesus  monkeys.  The  former  also  describes  a  characteristic 
blood-picture  for  the  disease.^^  The  monograph  of  Kurt  Ziegler 
will  give  the  reader  a  comprehensive  insight  into  the  present  con- 
ceptions of  the  condition. — Ed.) 

Kundrat's  lymphoBarcoma  occupies  a  peculiar  position  among 
the  pseudoleukaemias.  The  localized  swellings  of  the  lymph- 
nodes  which  characterize  it  are  genuine  neoplasms.  This  con- 
dition, therefore,  both  etiologically  and  pathologically,  is  an  entity, 
and  a  third  type  of  pseudoleukaemia.  The  microscopic  examina- 
tion of  a  specimen  of  excised  node  may  be  essential  to  distin- 
guish this  from  the  other  two  forms  of  pseudoleuksemia. 

In  lymphoid  leukaemia,  the  lymphatic  tissues  of  the  lymph- 
glands,  the  spleen,  the  intestines  or  of  the  bone-marrow,  are 
increased.  Whether  the  lymphocytes  present  in  the  blood  orig- 
inate solely  from  the  bone-marrow,  or  from  the  various  collec- 
tions of  lymphoid  cells  throughout  the  body,  is  not  yet  definitely 
known.  It  is  of  considerable  interest,  however,  that  instances  of 
lymphatic  leukaemia  without  enlargement  of  the  lymph-glands  have 
been  reported.  Such  cases  demonstrate  how  careful  we  must  be 
not  to  assume  that  lymphatic  leukaemia  is  essentially  a  disease  of 
the  lymphatic  glands.  It  seems  more  probable,  indeed,  that  it  is 
primarily  a  disease  of  the  lymphoid  tissue  of  the  bone-marrow, 
though  recent  work  has  shown  that  numerous  mitoses  may  be 
present  in  other  organs;  and  it  is  quite  possible  that  white  cor- 
puscles may  arise  in  tissues  which  normally  produced  these  cells 
only  during  embryonic  life,  as,  for  example,  the  liver. 


THE  BLOOD  186 

In  regard  to  the  nature  of  the  pathological  process  in 
leukaemia,  we  wish  again  to  recall  the  observation  from 
Marchand's  laboratory  on  a  case  of  lymphatic  leukaemia  which 
apparently  originated  from  the  rupture  of  a  hyperplastic  lymph- 
atic gland  into  a  vein.  Many  facts  favor  the  view  that  a  growth 
of  cells  into  the  blood-stream  is  the  cause  of  the  blood-changes 
in  leukaemia.  Thus,  as  illustrated,  pseudoleukaemia  may  change 
into  a  true  leukaemia  by  the  rupture  of  a  hyperplastic  gland  into 
the  circulation. 

This  is  readily  understood  because  hyperplasias  of  myeloid  and 
lymphoid  tissues  give  rise  to  tumor-like  growths  (possibly  of  in- 
fectious origin).®^  In  the  present  opinion  of  most  observers, 
however,  the  leukaemias  are  to  be  separated  from  the  genuine 
tumors.®^  Since  the  conditions  in  the  bone-marrow  especially 
favor  such  a  rupture  into  the  blood-stream,  pathological  changes 
in  this  tissue  are  most  apt  to  give  rise  to  leukaemia. 

The  theory  that  leukaemia  is  due,  not  to  an  excessive  produc- 
tion, but  to  a  diminished  destruction  of  the  leucocytes,  deserves  to 
be  considered  merely  to  be  condemned,  for  it  has  been  proved  that 
the  destruction  of  these  cells,  far  from  being  decreased,  is  actually 
increased.  Many  leucocytes  may  be  seen  in  blood-preparations  in 
various  stages  of  degeneration,  and  the  increased  elimination  of 
uric  acid  and  of  the  xanthin  bases  in  the  urine  indicates  an  in- 
creased destruction  of  the  nucleoproteids  of  the  body,  which  are 
derived,  in  all  probability,  from  the  nuclei  of  the  leucocytes  (see 

P-365). 

Toxic  influences  also  play  an  undoubted  part  in  the  pathology 
of  leukaemia.  Speaking  for  this  are  the  peculiar  forms  of  retinitis 
occasionally  seen;  further,  a  characteristic  nephritis;  and  also 
degenerative  changes  in  the  central  nervous  system. 

The  ultimate  cause  of  leukaemia  and  pseudoleukaemia  is  still 
imknown.  It  is  possible  that  the  recent  experimental  production 
of  the  disease  in  birds  by  the  injection  of  leukaemic  blood ®^  may 
pave  the  way  for  a  fuller  understanding  of  the  conditions. 

Plasma  and  Serum.    The  Total  Quantity  of  Blood 

Little  is  known  about  pure  plasma,  principally  because  it  is  so 

difficult  to  preserve  it  without  coagulation.     The  serum  resulting 

from  coagulation  differs  from  the  plasma  within  the  blood-vessels 

in  that  it  contains  no  fibrinogen,  but  does  contain  fibringlobulin 


136  THE  BASIS  OF  SYMPTOMS 

and  the  fibrin  ferment.  Probably  other  changes,  at  present  but  lit- 
tle understood,  also  take  place  in  the  proteids  of  the  blood  during 
coagulation. 

Coagulation. — When  normal  blood  coagulates,  about  o.i  to 
0.4  per  cent,  of  its  weight  separates  as  fibrin.  This  may  be  patho- 
logically increased  up  to  i.o  or  1.3  per  cent.,  an  increase  which 
is  seen  especially  in  diseases  accompanied  by  inflammatory  exuda- 
tions, such  as  pneumonia,  pleurisy  and  acute  articular  rheumatism. 
In  other  infections,  notably  in  typhoid  fever,  this  increase  of 
fibrin  is  not  found.  There  exists  a  certain  parallelism  between 
the  number  of  leucocytes  and  the  amount  of  fibrin  in  the  blood, 
but  the  parallelism  is  by  no  means  a  strict  one,^''  and  in  leukaemia 
the  fibrin  may  not  be  increased  at  all.*® 

In  other  diseases  the  quantity  of  fibrin  in  the  blood  is  dimin- 
ished; and  in  a  case  of  hemorrhagic  smallpox,  for  example,  no 
fibrin  could  be  obtained.  The  same  has  been  noted  in  phosphorus 
poisoning.  Diminution  of  fibrin  is  usually  found  in  severe  infec- 
tions and  in  severe  injuries  to  the  general  nutrition,  as  in  septi- 
caemias, long-continued  suppurations,  anaemias,  etc. 

Our  knowledge**  of  the  physiology  of  blood-coagulation  is 
still  so  limited  that  it  would  be  hazardous  to  speculate  on  the 
significance  of  pathological  variations  in  the  amount  of  fibrin 
in  the  blood  and  the  effect  that  these  variations  have  upon  coagula- 
tion. It  has  been  assumed  that  if  the  amount  of  fibrin  be  dimin- 
ished, the  blood  will  coagulate  slowly  and  there  will  be  a  tendency 
to  hemorrhages;  whereas,  if  the  amount  be  increased,  coagulation 
will  be  rapid  and  there  will  be  a  tendency  to  thrombosis.  These 
assumptions,  however,  are  not  sufficiently  supported  by  facts. 

Disturbances  of  coagulability  ^^^  have  been  generally  assumed 
to  explain  the  family  disease  of  haemophilia.  As  a  matter 
of  fact,  Sahli^^^  was  able  to  demonstrate  that  the  coagulation 
time  between  the  periods  of  hemorrhage  was  slower  in  these 
patients  than  normal ;  but  that  during  the  hemorrhages  it  was  not 
particularly  slow.  He  is  inclined  to  attribute  the  bleeding  of 
haemophilics  to  lesions  of  the  vessel  walls,  which  on  the  one  hand 
tear  with  abnormal  ease  and  on  the  other  yield  too  little  of  a 
substance  that  is  necessary  for  coagulation  (thrombokinase). 

The  Blood-Serum. — ^All  substances  formed  in  the  metabolic 
processes  within  the  body  and  all  food-stuffs  introduced  from  with- 
out pass  through  the  blood ;  they  may,  however,  be  present  there 


THE  BLOOD  137 

only  in  minute  traces,  because  they  are  so  quickly  removed  by 
the  various  organs.  It  would  be  impossible  to  discuss  in  this 
place  all  those  conditions  in  which  some  constituent  or  other  of 
the  serum  is  changed,  as  happens,  for  example,  in  diabetes,  and 
it  seems  better  to  reserve  such  a  discussion  for  the  chapters  on 
metabolic  disorders. 

One  substance,  however,  may  be  mentioned  in  this  connec- 
tion, viz.,  fat.  Fatty  substances  are  constantly  present  in  the 
blood, ^^2  the  amount  being  increased  during  the  digestion  of  meals 
containing  much  fat.  Under  pathological  conditions,  the  quantity 
of  fat  in  the  blood  may  become  so  great — even  up  to  20  per  cent. — 
that  particles  can  be  recognized  microscopically  between  the  red 
corpuscles,  especially  if  they  have  been  stained  by  osmic  acid.^**^ 
This  condition,  known  as  1  i  p  ae  m  i  a ,  is  relatively  uncommon. 
It  occurs  in  various  pathological  conditions,  especially  in  diabetes, 
and  is  frequently  merely  transitory. 

In  discussing  the  chemistry  of  the  blood-serum, 
we  shall  consider  especially  the  proportions  of  proteids,  salts  and 
water.  According  to  Hammarsten's  analyses,  9.2  per  cent,  of  the 
serum  consists  of  solids,  of  which  7.6  per  cent,  are  proteids.  Since 
the  proteids  form  the  greater  part  of  the  solid  material  in  the 
serum,  they  and  the  water  ordinarily  vary  in  inverse  ratio  to 
each  other,  a  high  percentage  of  proteids  being  accompanied  by  a 
relatively  low  percentage  of  water,  and  vice  versa. 

The  proteids  of  the  serum  consist  chemically  of  albu- 
min and  various  forms  of  globulin.  Recent  biological  work, 
however,  has  shown  such  a  variety  in  the  proteids  of  the  blood 
that  we  can  no  longer  regard  the  above  simple  chemical  division 
as  in  any  way  a  final  one;  and  when  we  remember  that  in  all 
probability  each  organ  contributes  its  quota  to  the  blood,  it  seems 
impossible  that  the  division  into  the  albumin  and  globulins  could 
be  any  other  than  a  mere  classification  of  the  proteids  present 
under  these  group  names.  The  serum  of  healthy  men  contains 
somewhat  more  albumin  than  globulin,  the  ratio  being  about  4.5 
to  3.1.  This  ratio  differs  in  different  species  of  animals,^*'*  and 
varies  in  the  same  individual  under  different  circumstances.  Dur- 
ing fasting,  the  globulins  become  relatively  increased  to  a  slight 
extent. 

Our  knowledge  of  the  proteids  of  the  blood  has  undergone  a 
complete  revolution  within  recent  years.**^"     The  researches  on 


138  THE  BASIS  OF  SYMPTOMS 

immunity  have  brought  to  light  important  functions  of  the  blood 
which  were  hardly  suspected  previously.  The  substances  which 
bring  about  these  so-called  biological  reactions  cannot  be  separated 
from  the  proteids  by  purely  chemical  means,  though  we  have  no 
direct  proof  that  they  are  themselves  of  a  proteid  nature. 

Among  the  substances  under  consideration  are  those  which 
possess  the  property  of  accelerating  the  decomposition  of  other 
compounds,  i.e.,  they  are  of  the  nature  of  ferments.  If  we 
may  assume  that  the  decomposition  of  different  compounds  re- 
quires the  action  of  different  ferments,  then  the  number  of  fer- 
ments present  in  the  blood  must  be  considerable.  Some  of  these 
are  proteolytic,  some  amylolytic,  others  oxydases  and  coagulating 
enzymes,  ^^^ 

Recent  studies  indicate  the  presence  also  of  numerous  a  n  t  i  - 
ferments.  Whether  these  are  actually  antibodies,  or  merely 
the  products  of  the  action  of  colloids  upon  the  ferments,  is  not 
definitely  known.  Anti  ferments  occur  normally  in  the  blood  of 
healthy  individuals  and  may  also  be  produced  by  the  injection  of 
ferments,  in  the  nature  of  an  immunization.  Particular  interest 
has  lately  been  directed  to  the  subject  of  antitrypsin,  which  is 
often  abundantly  present  in  the  cachexias.***'^ 

Besides  the  proteids  there  are  many  other  nitrogenous  sub- 
stances regularly  present  in  small  amounts  in  the  serum,  with  many 
of  which  we  are  still  unfamiliar.  Taken  together  they  are  known 
as  the  residual  or  non-coagulable  nitrogen. ^^^ 
This  residue  is  comprised  chiefly  of  the  end-products  of  metabol- 
ism, substances  which  go  over  into  urea,  and  are  ordinarily  re- 
moved by  the  urine.  They  are  increased,  therefore,  when  elimina- 
tion is  imperfect — for  example,  in  nephritis,  uraemia  and  in 
different  febrile  conditions.  In  great  part  such  an  increase  is  to 
be  attributed  to  urea  retention.  (The  importance  of  this  in 
modern  renal  functional  tests  will  be  considered  in  Chapter  XI. — 
Ed.)  The  entire  fabric  of  proteid  metabolism  would  reveal  itself 
if  the  building-stones  of  the  proteids — ^t  heamino-acids  and 
similar  bodie s — could  be  isolated  from  the  blood,  and  espe- 
cially from  the  intestinal  veins. 

In  processes  such  as  phosphorus  poisoning,  accompanied  by 
considerable  tissue  necrosis,  amino-acids  have  been  found  in  the 
blood,  but  here  the  proteid  split-products  have  naturally  no  rela- 
tion to  digestive  processes.     Recently  Bingel  ^^^  has  demonstrated 


THE  BLOOD  189 

glycocoll  in  normal  serum,  a  discovery  possibly  significant  in  view 
of  what  has  been  said. 

(Considerable  progress,  indeed,  has  been  made  along  these 
very  lines.  Abderhalden,^^^  using  enormous  amounts  of  blood 
at  a  time,  has  succeeded  in  demonstrating  the  presence  of  amino- 
acids  in  the  serum  by  the  direct  isolation  and  identification  of 
a  number  of  these  proteid  split-products.  As  the  blood  contains 
these  acids  even  in  starvation,  Abderhalden  conceives  of  the  possi- 
bility of  a  fixed  amino-acid  content,  comparable  in  a  way  to  the 
constant  sugar  concentration. 

More  recently  Abel,  Rowntree  and  Turner  ^^^  have  isolated 
from  the  blood,  by  a  process  of  dialysis,  two  amino-acid  deriva- 
tives of  proteid — alanin  and  valin — in  crystalline  form.  By  the 
same  method  they  have  identified  histidin  and  creatinin  and  lactic 
and  beta-oxybutyric  acids. — Ed.) 

The  Salts  of  the  Serum. — ^The  salts  of  the  serum  are  for  the 
most  part  made  up  of  sodium  chlorid,  sodium  carbonate  and  the 
phosphates  of  the  alkalies.  Other  salts  are  present  only  in  minimal 
quantities,  and  some,  such  as  calcium  phosphate,  are  present  in 
the  plasma,  but  are  removed  from  the  serum  by  the  fibrin  during 
coagulation.  The  variations  of  the  salts  of  the  blood  in  health 
and  in  disease  have  never  been  satisfactorily  worked  out.*^^  This 
is  unfortunate,  for,  without  doubt,  they  exercise  an  important 
influence  upon  the  blood-corpuscles  and  upon  the  proteids  of  the 
plasma.  The  maintenance  of  the  molecular  concentration  of  the 
serum  at  a  constant  level,  as  determined  by  cryoscopy,  is  extremely 
important.  ^^^ 

The  Percentage  of  Water  in  the  Blood.  Hydraemia. — The 
relative  amounts  of  proteids  and  water  in  the  serum  vary  even 
in  health,  although  the  limits  of  these  variations  are  not  accurately 
known.  The  variations  in  disease  have  been  only  incompletely 
studied ;  ^^^  but  we  know  that  they  frequently  remain  within 
the  normal  limits,  even  in  the  severest  diseases.  The  most  evi- 
dent thickening  of  the  blood,  i.e.,  the  greatest  relative  increase 
in  the  proteids,  is  seen  in  Asiatic  cholera,  and  depends  upon  the 
loss  of  fluids  from  the  body. 

When  the  unit  of  blood  is  deficient  in  proteid  material,  we 
speak  of  an  h  y  d  r  se  m  I  a ,  or  a  watering  of  the  plasma.^  ^^  This 
condition  frequently  develops  as  a  result  of  emaciating 
diseases.    If  the  heart  and  kidneys  are  in  order,  the  hydraemia 


140  THE  BASIS  OF  SYMPTOMS 

is  probably  due  to  a  primary  diminution  in  the  pro- 
teids  of  the  blood,  although  we  must  remember  that  a 
destruction  of  the  proteids  of  the  body  does  not  necessarily  pro- 
duce a  watery  condition  of  the  plasma.  Among  the  emaciating 
diseases  which  may  cause  an  hydrsemia  of  this  character  are  inani- 
tion, repeated  hemorrhages,  anaemias,  malignant  tumors  and 
severe  chronic  infections.  Although  an  hydrsemia  frequently 
develops  in  the  above  conditions,  it  does  not  necessarily  do  so. 
We  are  not  justified,  therefore,  in  concluding  that  a  rapid  con- 
sumption or  a  diminished  supply  of  proteid  material  is  alone  re- 
sponsible for  the  hydrsemias  of  this  class.  Other  factors,  at  pres- 
ent little  understood,  undoubtedly  play  a  part.  Until  we  know 
more  of  the  functions  and  source  of  the  proteids  of  the  plasma, 
it  will  be  impossible  to  harmonize  the  many  contradictory  facts 
relating  to  this  class  of  hydraemias. 

It  is  possible  that  an  hydrsemia  may  be  caused  not  only  by  a 
primary  reduction  of  the  proteid  constituents  of  the  blood,  but 
also  by  a  primary  increase  in  the  amount  of  water. 
The  hydrsemias  associated  with  the  diseases  of  the  kidneys  and 
with  cardiac  insufficiencies  are  probably  in  part  of  this  nature. 
According  to  Hammerschlag,  chronic  interstitial  nephritis  rarely 
causes  a  watery  condition  of  the  blood,  and  chronic  parenchy- 
matous nephritis  sometimes  fails  to  do  so.  Hydrsemia  is  fre- 
quently present  in  the  latter,  however,  and  it  is  most  marked 
when  there  is  polyuria.  Under  such  circumstances,  the  specific 
gravity  of  the  blood  may  fall  from  the  normal  of  1.030  to  1.020. 
Other  observers  have  obtained  results  which  differ  somewhat  from 
those  of  Hammerschlag;  yet  some  of  these,  based  upon  total  nitro- 
gen determinations,  must  be  rejected  as  inaccurate  on  account  of 
the  frequent  retention  in  nephritic  blood  of  other  nitrogenous 
bodies  than  proteids. 

The  hydrsemia  which  is  undoubtedly  present  m  many  cases 
of  nephritis  can  be  caused  only  in  part  by  the  loss  of  albumin, 
for  the  hydrsemia  and  the  amount  of  albumin  in  the  urine  bear 
no  definite  relation  to  each  other.  In  many  cases  of  nephritis, 
water  is  retained  in  the  body,  for  less  is  excreted  through  the 
kidneys,  and  often  less  also  through  the  skin.  These  two  factors 
— ^the  loss  of  albumin  in  the  urine  and  the  retention  of  water  in 
the  body — are  sufficient  to  explain  the  hydrsemia  present  in  many 
cases  of  nephritis,  though  hardly  in  all,  for  some  patients  with 


r 


THE  BLOOD  141 

hydrsemia  are  excreting  large  amounts  of  urine.  Recent  stud- 
ies ^^^  attribute  the  retention  of  water  to  a  deficient 
sodium  chlorid  elimination,  the  retained  water  serving 
merely  to  restore  the  balance  of  osmotic  tension.  To  what  extent 
variationsinthecolloid  s — in  this  case  the  proteids  of  the 
serum — are  influential  in  water  retention,  is  a  question  that,  for 
the  present,  cannot  be  answered.  (See  p.  93  in  chapter  on 
oedema. ) 

Certain  patients,  suffering  from  heart  disease  in  the  stage 
of  broken  compensation,  show  a  watery  condition  of  the  blood — 
both  the  specific  gravity  and  the  proportion  of  proteids  in  the 
blood  being  diminished.  A  weakness  of  the  right  ven- 
tricle is  apparently  the  prime  factor  in  the  production  of  such 
an  hydraemia.^  ^'  When  the  circulation  improves  and  the  venous 
pressure  falls,  the  blood  tends  to  return  to  its  normal  composition. 
This  hydrsemia  occurs  in  a  comparatively  small  profKDrtion  of  all 
cases  of  broken  compensation ;  but,  where  it  does  occur,  it  usually 
disappears  with  an  improvement  in  the  circulation.  In  these 
cases,  the  loss  of  proteids  from  the  blood  is  ordinarily  not  very 
great,  but  there  is  frequently  a  retention  of  water  which  would 
tend  to  dilute  the  blood. 

It  seems  very  probable  to  us  that  the  hydrsemias  which  accom- 
pany cardiac  and  renal  diseases  are  for  the  most  part  caused  by 
such  a  retention  of  water  in  the  body ;  that  there  is,  in  fact,  an 
increased  quantity  of  watery  blood  in  the  body,  a  so-called 
hydraemic  plethora.  Such  an  hypothesis  would  well  ex- 
plain the  fact  that  with  the  development  of  cardiac  insufficiency 
not  only  the  proteids,  but  the  number  of  corpuscles  to  the  unit- 
volume  of  blood,  are  diminished,  and  that,  with  an  improvement 
in  the  circulation,  the  blood  again  becomes  normal.  There  is  no 
reason  why  the  blood  should  not  become  oedematous  just  as  do  the 
tissues.  Possibly  the  waj:er  is  held  back  in  the  body  by  substances 
which  attract  it  (see  above).  Grawitz  believes  that  the  increased 
amount  of  water  in  the  blood  is  derived  from  the  lymph  which 
diffuses  into  the  capillaries,  owing  to  the  low  pressure  existing 
there.  Yet  we  know  that  in  the  conditions  under  consideration, 
fluids  pass  from  the  capillaries  into  the  lymph-spaces,  so  that  these 
become  distended.  The  relations  must,  therefore,  be  quite  com- 
plicated, and  the  final  results  are  dependent  upon  which  process 
takes  place  the  more  rapidly. 


142  THE  BASIS  OF  SYMPTOMS 

Polycythaemia. — In  not  a  few  cases  of  chronic  stasis,  the  capil- 
lary blood  is  more  concentrated  than  normal.  At  least  it  contains 
many  more  red  blood-corpuscles  and  correspondingly  more  haemo- 
globin to  the  unit-volume.  The  composition  of  the  serum  in  these 
cases  has  not  yet  been  finally  settled,  but  good  observers  ^  ^^  have 
found  it  to  be  diluted.  This  increase  in  the  number  of  the  ery- 
throcytes is  found  especially  in  cases  of  long-continued 
venous  stasis,  such  as  occurs  in  congenital  heart  lesions,  in 
chronic  pulmonary  disease  and  in  insufficiency  of  the  right  ven- 
tricle. Investigations  thus  far  have  all  been  made  upon  the  blood 
of  the  cutaneous  capillaries  or  veins,  so  that  we  are  unable  to  dis- 
cuss the  relative  concentration  of  the  blood  in  the  different  vessels 
of  the  body.  The  observations  of  Askanazy,  however,  would 
indicate  that  conditions  are  the  same  in  the  visceral  as  in  the 
peripheral  vessels — that  is,  that  the  polycythaemia  is  general. 

The  number  of  erythrocytes  in  these  cases  is  often 
very  great — from  six  to  even  twelve  million  per  cubic  millimetre ; 
and  at  the  same  time  the  serum  is  usually  more  dilute  than  normal. 
This  latter  fact  would  seem  to  indicate  that  the  increased  number 
of  corpuscles  is  not  due  to  a  loss  of  water  from  the  blood.  Marie 
and  Hayem  explain  the  increase  in  the  number  of  red  blood- 
corpuscles  as  a  compensatory  process  which  tends  to  neutralize 
the  insufficient  oxidation  of  the  blood  caused  by  the  stasis. ^^® 

There  is  another  form  ^^^  of  polycythaemia,  apparently  primary 
in  nature,  in  which  the  corpuscular  increase  is  persistent.  This 
type  (polycjrthaemia  rubra  vera),  first  described  by  Vaquez,  regu- 
larly shows  an  increase  in  the  red  corpuscles,  as  high  often  as 
ten  million  per  cubic  millimetre.  This  condition  is  due,  in  all 
probability,  to  an  increased  formation  of  red  cells, 
rather  than  to  a  retarded  degeneration,  in  view  of  the  presence  of 
nucleated  erythrocytes  and  of  myelocytes  in  the 
blood  (Tiirk),  and  because  of  the  finding  of  a  hyperplastic  red 
bone-marrow.  In  many  cases,  in  addition  to  the  polycythaemia, 
there  is  present  also  an  enlargement  of  the  spleen  and 
liver  and  an  increased  arterial  tension  (Geis- 
bock).  It  is  possible  that  nephritis  and  arteriosclerosis  play 
a  part  in  the  hypertension  cases.  The  causes  of  this  primary 
polycythaemia  are  unknown.  The  theory  that  the  haemoglobin  is 
primarily  at  fault  and  that  its  lessened  oxygen-carrying  power 
necessitates  a  compensatory  increase  in  the  red  cells  is  hardly 


THE  BLOOD  148 

tenable.  In  the  author's  case,  indeed,  there  was  an  increased 
gaseous  interchange  in  the  tissues.  A  more  probable  explanation 
is  that  the  condition  depends  upon  a  hyperplasia  of  the  red 
marrow,  of  unknown  origin. 

Extremely  interesting  are  the  changes  which  take 
place  in  the  blood  when  an  animal  passes  from  a 
region  of  high  to  one  of  low  atmospheric  pres- 
sure.^^^  Within  a  short  period  of  time,  the  number  of  red 
corpuscles  to  the  cubic  millimetre  of  blood  is  increased,  and  the 
haemoglobin  likewise,  but  more  slowly.  These  changes  affect  the 
blood  in  all  parts  of  the  circulatory  apparatus,  though  they  are  less 
marked,  possibly,  in  the  arteries  than  in  the  veins  and  capillaries 
of  the  skin.  The  higher  the  elevation,  the  greater  is  the  number 
of  red  corpuscles.  The  highest  figures  which  have  been  reported 
are  from  the  Cordilleras,  at  an  elevation  of  over  twelve  thousand 
feet.  All  the  animals  at  these  heights  have  an  extraordinary- 
number  of  red  corpuscles — the  llama,  for  example,  having  sixteen 
million  to  the  cubic  millimetre.  The  amount  of  oxygen  in  the 
blood,  however,  is  about  the  same  as  in  that  of  animals  at  lower 
levels.  When  a  man  or  animal  descends  from  these  heights  to  the 
sea  level,  the  number  of  red  cells  diminishes  correspondingly. 
There  is  almost  universal  agreement  among  authors  in  regard  to 
the  increase  in  the  number  of  erythrocytes  per  unit-volume  at  high 
elevations,  and  the  few  negative  observations  are  due  probably 
to  too  short  a  stay  at  the  high  altitude,  or  to  complicating  con- 
ditions, such  as  mountain  sickness. 

This  increase  is  unquestionably  caused  by  the 
low  atmospheric  pressure,  for  it  can  be  produced  ex- 
perimentally by  subjecting  animals  to  low  pressures  under  the 
air-pump.  Some  consider  that  the  total  number  of 
red  cells  in  the  body  is  actually  increased  in  such 
cases,  and  that  this  serves  to  compensate  for  the  lessened  pressure 
of  the  oxygen  in  the  lungs.  If,  indeed,  new  cells  are  formed,  we 
have  little  microscopical  evidence  of  it,  for  nucleated  red  cor- 
puscles have  been  seen  by  very  few,  and  most  authors  expressly 
state  that  they  were  absent.  Furthermore,  it  is  difficult  on  such 
an  hypothesis  to  account  for  the  rapid  disappearance  of  red  cells 
when  the  animal  returns  to  a  lower  altitude,  for  positive  signs  of 
a  destruction  of  red  corpuscles,  such  as  jaundice  and  a  deposition 
of  iron  in  the  liver,  have  not  been  observed  under  these  conditions. 


144  THE  BASIS  OF  SYMPTOMS 

Yet  we  know  that  the  absence  of  these  signs  is  by  no  means  abso- 
lute proof  that  no  destruction  of  the  red  cells  has  taken  place, 
for  they  have  been  missed  in  cases  in  which  an  extensive  destruc- 
tion certainly  had  occurred. 

Another  explanation  that  has  been  offered  for  the  increase 
in  the  number  of  the  erythrocytes  at  high  altitudes  is  that  it  is 
due  to  a  loss  of  water  from  the  blood;  yet  this  meets 
with  almost  equal  difificulties.  Beyond  question,  the  dryness  of 
the  air,  the  exposure  to  the  sun's  rays,  and  the  deeper  respirations 
increase  the  loss  of  water  from  the  body,  yet  a  healthy  man  would 
ordinarily  replace  this  water  by  taking  more  fluids  by  the  mouth. 
The  supposed  loss  of  water  should  also  lead  to  a  more  concen- 
trated serum,  as  well  as  to  an  increased  number  of  red  blood- 
corpuscles;  but  it  is  very  doubtful  if  this  concentration  of  the 
serum  actually  occurs.  The  sera  of  two  rabbits  in  Basel  contained 
7.62  and  7.96  per  cent,  of  solids  respectively,  whereas  in  Arosa,  at 
a  high  elevation,  the  percentages  were  7.79  and  8.02,  an  incon- 
siderable change  compared  with  the  changes  in  the  erythrocytes, 
Grawitz  found  some  increased  concentration  in  the  sera  of  ani- 
mals which  had  been  kept  under  low  pressures  in  Berlin,  but  here 
again  the  increased  concentration  was  in  no  way  proportional 
to  the  increase  in  the  number  of  the  red  blood-corpuscles.  Fur- 
thermore, a  concentration  of  the  blood  by  evaporation  is  only 
possible  when  the  tissues  likewise  lose  large  quantities  of  water, 
and  such  a  loss  of  weight  certainly  does  not  occur  either  in  men 
or  in  animals  subjected  to  low  atmospheric  pressures.  Finally,  an 
increase  in  the  number  of  erythrocytes  also  takes  place  when  the 
animals  are  prevented  from  losing  excessive  amounts  of  water  by 
being  kept  in  rarefied  air  saturated  with  water  vapor. 

According  to  a  third  theory,  the  increase  in  the  number  of  red 
blood-corpuscles  at  high  elevations  is  due  to  the  passage  of 
plasma  out  of  the  blood-vessels  into  the  lymph- 
atic system.  At  present,  this  seems  to  be  the  most  plausible 
explanation  for  the  known  facts ;  yet  it  is  also  open  to  objections, 
especially  in  view  of  the  fact  that  the  red  blood-corpuscles  and 
the  haemoglobin  do  not  increase  at  precisely  the  same  rate. 

The  crucial  test  for  deciding  whether  or  not  the  haemoglobin 
actually  increases  at  high  altitudes  would  be  the  determination  of 
the  total  quantity  of  haemoglobm  in  the  body.  If  this  be  in- 
creased in  animals  exposed  to  low  atmospheric  pressures,  we  may 


THE  BLOOD  145 

then  assume  that  there  is  indeed  a  total  increase  in  the  red  blood- 
cells  and  in  their  pigment  under  these  influences.  Unfortunately, 
the  experiments  which  have  been  undertaken  to  decide  this  point 
have  given  contradictory  results.  Some  observers  found  no  in- 
crease in  the  total  amount  of  haemoglobin  in  the  body,  others  have 
found  a  slight  increase,  while  still  others  have  found  a  marked 
increase.  The  inaccuracies  in  the  methods  for  determining  the 
total  haemoglobin  in  the  body  probably  account  for  these  discrepan- 
cies in  results. 

An  increase  in  the  number  of  the  red  blood-corpuscles  to  the 
unit-volume  is  also  seen  in  phosphorous  and  carbon  monoxide 
poisoning,  but  we  are  ignorant  as  to  its  exact  cause. 

Plethora. — There  is  no  reason  a  priori  why  an  increase  in  the 
total  quantity  of  blood  in  the  body  should  not  take  place,^^^  for 
it  is  known  that  the  parenchyma  of  other  organs  may  increase  in 
bulk.  It  is  impossible,  however,  to  obtain  direct  proof  of  such  an 
increase  so  far  as  human  blood  is  concerned,  for  as  yet  we  have 
no  accurate  method  of  determining  the  total  quantity  of  the  blood 
in  man. 

The  doctrine  of  an  increased  quantity  of  blood — a  true  ple- 
thora— played  a  great  role  in  the  older  hsematology,  and  various 
symptoms  were  believed  to  be  caused  by  the  "  full-blooded  "  con- 
dition of  the  patient.  While  we  must  acknowledge  that  many  of 
these  cases  will  not  stand  the  rigid  criticism  of  modern  times,  and 
that  the  anaemia  of  many  of  these  individuals  was  the  probable 
cause  of  their  symptoms,  yet  there  are  certain  facts  which  favor 
a  belief  in  the  occurrence  of  a  true  plethora.  Thus,  many  patients 
feel  better  after  having  been  bled,  and  although  this  fact  is  in  no 
sense  a  proof  that  a  condition  of  plethora  existed  previous  to  the 
bleeding,  nevertheless  it  cannot  be  entirely  disregarded.  More 
important  is  the  testimony  of  such  pathologists  as  v.  Reckling- 
hausen and  Bollinger,  who  give  it  as  their  impression  that  at 
autopsy  many  bodies  seem  abnormally  rich  in  blood.  That  the 
amount  of  blood  in  animals  may  vary  greatly  not  only  in  different 
species,  but  in  different  individuals  of  the  same  species,  has  been 
definitely  proved  by  the  work  of  Bergmann  and  Bollinger.  They 
have  demonstrated  that  the  character  of  the  food  may  exert  a 
marked  influence  upon  the  total  quantity  of  blood  in  the  bodies  of 
animals. 

We  are  justified  in  suspecting  a  condition  of  plethora  whenever 
10 


146  THE  BASIS  OF  SYMPTOMS 

an  individual  who  habitually  consumes  excessive  amounts  of  food 
and  drink,  and  who  has  large  muscles  and  much  fat,  shows  a 
continued  hypersemia  of  the  surface  of  his  body,  and  has  an 
enlarged  heart,  a  full  pulse  and  wide  arteries.  Although  we  may 
be  unable  to  prove  that  a  plethora  exists  in  such  individuals,  never- 
theless the  experience  of  pathologists,  and  the  experimental  evi- 
dence above  referred  to,  both  justify  such  a  probable  diagnosis. 
The  interesting  observations  of  Geisbock^^^  would  indicate  that 
a  plethora  of  this  kind  may  accompany  a  condition  of  hyper- 
globulism  and  increased  blood-pressure  (polycythaemia 
hypertonica). 

Certain  observations  seem  opposed  to  the  doctrine  of  plethora, 
more  especially  the  fact  that  if  animals  are  infused  with  sera 
or  salt  solution,  the  excess  of  fluid  is  rapidly  removed  from  the 
circulation,  and  no  increase  in  the  total  quantity  of  blood  is  pro- 
duced. Yet  the  conditions  of  such  an  experiment  are  quite  dif- 
ferent from  the  chronic  changes  which  are  believed  to  lead  to 
plethora  in  man ;  and,  furthermore,  it  is  quite  possible  that  under 
pathological  conditions  the  ability  thus  to  remove  large  quantities 
of  fluid  from  the  circulation  may  be  lost. 

We  hold,  therefore,  that  although  the  doctrine  of  a  true 
plethora  has  not  been  absolutely  proved,  its  existence  is  very 
probable.  The  long-continued  ingestion  of  excessive  amounts 
of  food  seems  to  be  the  most  potent  causative  factor.  Yet  it  is 
apparently  only  one  factor,  and  others  of  which  we  are  now 
ignorant  may  play  a  part  in  its  causation. 

Until  recently,  the  doctrine  of  a  diminution  in  the  total  quan- 
tity of  blood  was  as  little  capable  of  direct  proof  as  was  the  doc- 
trine of  plethora.  The  improvements  in  the  methods  ^^^  for  the 
determination  of  the  total  blood  mass  have  brought  with  them  a 
greater  accuracy  in  this  respect,  with  the  result  that  clinicians, 
as  well  as  pathologists,  have  been  strengthened  in  their  belief  that  a 
plethora  does  exist.  Especially  interesting  is  the  plethora  of 
chlorosis,  nephritis  and  of  polycythaemia.  In  severe  anaemias,  on 
the  contrary,  there  would  appear  to  be  a  diminution  not  only  in  the 
number  of  cells  to  the  unit  of  volume,  but  in  the  quantity  of  blood 

as  a  whole. 

LITERATURE 

*  Newer  works  on  haematology:  Tiirk,  Klin.  Hamatologte ;  Pappenheim, 
Folia  hamatologica ;  Naegeli,  Blutkrankh.  u.  Blutdiagnostik,  2nd  edit., 
1912;   Straus,  Blutkrankh.,  in  v.  Noorden's  Handb.  d.   Path.   d.   Stoflf- 


THE  BLOOD  147 

wechs.,  and  edit.,  1906  (Metabolism  and  Practical  Medicine)  ;  Hunter, 
Severest  Anaemias,  1909;  Ehrlich,  Lazarus  and  Naegeli,  Die  Anamie, 
2nd  edit.,  1909.  For  the  pathology  of  the  blood  in  childhood,  see  Flesch, 
Ergeb.  d.  inn.  Med.,  1909,  iii,  and  Japha,  in  Pflaundler  and  Schlossmann, 
1910,  ii. 

'  Erben :  Ueber  d.  chem.  Zuzammensetzg.  d.  Blutes,  etc.,  1905. 

•Pappenheim:  Fol.  hamatol,  ix,  II,  177. 

*  Hamburger :  Osmot.    Druck.  u.  lonenlehre,  Wiesbaden,  1902  and  1904;  Over- 

ton, in  Nagel's  Handb.  d.  Physiologic,  ii,  828;  v.  Koranyi  and  Richter,  in 
Physikal.  Chemie  u.  Medizin,  1907,  i,  265. 

'Inagaki:  Zeitschft.  f.  Biol.,  1907,  xlix,  JT,  Stornjakoff,  Arch.  f.  klin.  Med., 
ci,  251. 

'  Quincke :  See  Stiihlen,  Arch,  f ,  klin.  Med.,  liv,  248 ;  Meyer,  Ueber  Resorp- 
tion u.  Ausscheidung  d.  Eisens,  in  Asher-Spiro,  Ergeb.,  1906,  v. 

^Ehrlich:  Kongr.  f.  inn.  Med.,  1892,  39;  Dunin,  Volkmann's  Vortrage,  N.S., 
cxxxv,  413. 

*  Cohn:  Miinch.  med.  Wochenschft.,  1900,  No.  6  (lit.). 

*  Neumann :  Virchow's  Arch.,  cxix,  385 ;  Noll,  in  Asher-Spiro,  Ergebnisse, 

1903,  ii ;  Seemann,  ibid.,  1904,  iii. 
'^  See  Naegeli,  Blutkrankheiten,  2nd  edition. 
"  Neumann :  1.  c. 

"  Graeber :   Zur   Diagnostik   d.   Blutkrankheiten,   Studies   from  the  Medico- 
Clinical  Institute,  Munich,  1890,  ii ;  v.  Noorden,  in  Nothnagel's  System. 
"  For  a  contrary  opinion,  see  Byron  Bramwell,  Clinical  Studies,  1907,  v. 
**  Graeber :    1.    c. ;    Naegeli,    Die    Blutkrankheiten ;    Morawitz,    Munch,    med. 

Wochenschft.,  1910,  No.  27. 
"Limbeck:  Klin.  Path.  d.  Blutes. 

"  Morawitz :  1.  c. ;  Seiler,  Korresp.-Blatt  f .  Schweiz.  Aerzte,  1909,  No.  17. 
"See  especially  v.  Noorden,  1.  c. ;  Grawitz,  Klin.  Path.  d.  Blutes,  191 1. 
"  Birch-Hirschfeld :  Kongr.  f .  inn.  Med.,  1892,  17 ;  Grawitz,  1.  c. 
^  Kongr.  f.  inn.  Med.,  Munich,  1895;  Wandel,  Arch.  f.  klin.  Med.,  xc,  52. 
'"v.  Noorden:  1.  c,  68  (lit.). 

°  Meyer :  Ergebn.  d.  Physiol.,  1906,  v ;  Morawitz,  1.  c. 
^  Gerhardt :  Kongr.  f.  inn.  Med.,  1910. 
"  Miiller,  Munck  et  al. :  Virchow's  Arch.,  cxxxi,  Suppl. 
**  V.  Hosslin :  Miinch.  med.  Wochenschft.,  1890,  Nos.  38  and  39. 
"•Sahli:   Schweiz.   Korrespondenzblatt,   1886,   Nos.  21   and  22;   Vermehren, 

reviewed  in  Deutsch.  med.  Wochenschft.,  1903,  No.  16. 
** Naegeli:  2nd  edition  (lit.). 
"Klin.  Path.  d.  Blutes,  297. 

"  Rumpf :  Mittheil.  aus  d.  Hamburger  Staatskrankenanstalten,  iii,  1. 
"Nonne:  Arch.  f.  Psychiatric,  xxv,  421;  Zeitschft.  f.  Nervenheilk.,  vi,  311, 

and  xiv,  192;  Mosse  and  Rothmann,  Deutsch.  med.  Wochenschft.,  1906, 

Nos.  4  and  5. 
^  Pappenheim :  Fol.  hamatol.,  x,  II,  217 ;  Roth,  Zeitschft.  f.  klin.  Med.,  1914, 

Ixxix,  266. 
"Hunter:  Severest  Anaemias,  1909.     Sec  Med.  Klinik,  1908,  Nos.  41-43  for 

a  comprehensive  survey  of  the  etiology,  diagnosis  and  treatment  of  per- 
nicious anaemia. 
**  For  a  very  complete  discussion  and  literature  on  the  etiology  of  pernicious 

anaemia,  see  Naegeli,  2nd  edition,  1914 ;  also  Grawitz,  4th  edition.    See  also 

Schnitter,  Arch.  f.  klin.  Med.,  1915,  cxvii,  151. 
"Meyer  and  Heineke:  Miinch.  med.  Wochenschft.,  1906,  No.  17;  Gesell.  f. 

Morph.  u.  Physiol,  in  Munich,  1908,  V. 
"^Schaumann   and   Tallquist:   Deutsch.   med.   Wochenschft.,    1898,   No.   20; 

Tallquist,  Zeitschft.  f.  klin.  Med.,  Ixi,  427- 
"Bang:  Ergeb.  d.  Physiol.,  viii,  463;  Korschun  and  Morgenroth,  Berl.  klin. 

Wochenschft,   1902,   No.   37;    Kongr.   f.   inn.   Med.,   1910;    Schaumann, 

Deutsch.  med.  Wochenschft.,  1910,  No.  26. 


148  THE  BASIS  OF  SYMPTOMS 

"  Syllaba :  Reviewed  in  Fol.  hamatol.,  1904,  i,  283. 

"Eppinger:  Wiener  Gesell.  f.  inn.  Med.,  April  15,  1913;  Decastello,  Wiener 

Gesell.  d.  Aertze,  May  30,  1913;  Klemperer  and  Hirschfeld,  Therap.  d. 

Gegenwart,  1913,  No.  9 ;  Tiirk,  Deutsch.  med.  Wochenschft.,  1914,  No.  8. 
•*  Pappenheim :  Fol.  hamatol.,  1908,  v,  758. 
**  Aubertin :  Les  reactions  sanguines,  These  de  Paris,  1905. 
**  Blumenthal  and  Morawitz :  Arch.  f.  klin.  Med.,  xcii,  25. 
*^  Lazarus :  Die  Hamoglobinamie,  in  Nothnagel's  System. 
**Albrecht:  Verhandlg.  d.  path.  Gesellschaft,  1903,  104;  Koeppe,   Pfliiger's 

Arch.,  xcix,  33. 
**Hoflfmann:  Konstitutionskrankheiten,  185  (lit.);  Ponfick,  Virchow's  Arch., 

Ixxxviii,  445. 
**  Pascucci :  Hof  meister's  Beitrage,  vi,  543,  552. 
"  Chvostek:  Uber  d.  Wesen  d.  paroxys.  Hamoglob.,  1894  (lit.)  ;  Stempel,  Zen- 

tralbl.  f.  d.  Grenzgeb.,  1902,  Nos.  5  and  7  (lit.  to  1900)  ;  Widal  and  Ros- 

taine,  C.  r.  soc  biol.,  1905 ;  Donath  and  Landsteiner,  Zeitschft.  f .  klin. 

Med.,  Iviii,  173 ;  Eason,  Jour,  of  Path,  and  Bact.,  xi,  167 ;  More,  Noda  and 

Benjamin,  Munch,  med.  Wochenschft.,  1909,  No.  11. 
*•  Donath  and  Landsteiner :  1.  c. ;  Zentralbl.  f .  Bakt.,  xlv,  205. 
**  Graf e  and  Miiller :  Arch,  f .  exp.  Path.,  lix,  97. 
**  Choroschiloff :  Zeitschft.  f .  klin.  Med.,  Ixiv,  430 ;  Meyer  and  Emmerich, 

Arch.  f.  klin.  Med.,  xcvi,  Nos.  3  and  4. 
*•  Landsteiner  and  Leiner :  Zentralbl.  f .  Bakt,  xxxviii,  458. 
** Wilms:  Mitth.  a.  d.  Grenzgeb.,  viii,  393;  Hedinger,  Schweiz.  Korrespon- 

denzblatt,  1907,  No.  20. 
"Hoffmann:   (footnote  43);  v.  Mering,  Das  chlorsaure  Kali,  1885;  Falken- 

berg,  Diss.  Marburg,  1890  (Marchand). 
"*  Marchand :  1.  c. ;  Limbeck,  Arch,  f .  exp.  Path.,  xxvi,  39. 
"Morawitz:  Arch.  f.  klin.  Med.,  Ixxix,  I. 
"*  Silbermann :   Virchow's   Arch.,   ccxix,  488;   Welti,   Ziegler's   Beitrage,   iv, 

519;  Wilms,  Grenzgebiete,  viii,  393. 
"  Schmidt :  Arch,  f .  klin.  Med.,  xci,  225. 
**  Cf.  footnote  i  and  also  Sternberg,  Path.  d.  Primarerkrankungen  d.  lymphat. 

u.  hamatopoietischen  Apparate,  1905;  Helly,  Die  hamatopoietischen  Or- 

gane,    1906;    Turk   u.    Schridde,    Verhandl.    d.    80.    Naturforschervers., 

Cologne,  1908;  Pappenheim,  Fol.  hamatologica  (many  studies). 
•'  D.  neutroph.  Leukozyten,  etc.,  1904 ;  Hiller,  Fol.  hamatolog,  ii,  85. 
"Bourmoff  and  Brugsch:  Zeitschft.  f.  klin.  Med.,  Ixiii,  489;  Pollitzer,  Arch. 

f.  kUn.  Med.,  xcii,  i ;  Naegeli,  Blutkrankheiten,  2nd  edit.,  2^3  (lit.). 
^  Brandenburg :  Miinch.  med.  Wochenschft.,   1900,  No.  6 ;  E.  Meyer,  ibid., 

1903,  No.  35- 
•*  Schultze :  ibid.,  1909,  No.  4,  and  1910,  No.  42 ;  Winkler,  Fol.  hamatol.,  iv,  32. 
"Herz:  Die  akute  Leukamie,  191 1;  Naegeli,  1.  c. 
"  See  especially  Pappenheim :  Virchow's  Arch.,  clvii,  54 ;  clix,  40 ;  clxiv,  374 ; 

Fol.  hamatolog.,  1904-1908;  Atlas  d.  mensch.  Blutzellen;  Blumenthal,  La 

genese  des  cellules  sanguines,  1904;  K.  Ziegler,  Exp.  u.  klin.  Untersuch. 

ii.  d.  Histogenese  d.  myeloid.  Leukamie,  1906. 
•*Goodall,  Gulland  and  Paton:  Journ.  of  Phys.,  xxx,  i. 
•*  Grawitz :  Deutsch.  med.  Wochenschft.,  1910,  No.  29;  EUermann  and  Erland- 

sen.  Arch.  f.  exp.  Path.  u.  Pharm.,  Ixiv,  28. 
*°  Schwenkenbecher  and  Siegel :  Arch,  f .  klin.  Med.,  xcii,  303. 
'°  Ziegler  and  Schlecht :  Arch,  f .  klin.  Med.,  xcii,  564. 
"  Bestelli,  Falta  and  Schweiger :  Zeitschft.  f .  klin.  Med.,  Ixxi. 
**  Lowit :  Studien  z.  Phys.  u.  Path.  d.  Blutes  u.  d.  Lymphe,  1892 ;  Goldscheider 

and  Jakob,  Zeitschft.  f.  klin  Med.,  xxv,  403;  Fohl,  Arch.  f.  exp.  Path., 

XXV,  51. 
•»v.  Limbeck:  L  c,  267  (lit). 

"Brown:  Jour,  of  Exp.  Med.,  1898,  No.  3;  Staubli,  Die  Trichinosis,  1911. 
*^  Heineke  and  Deutschmann :   Munich,  med.   Wochenschft.,   1906,   No.   17 ; 

Staubli,  Ergeb.  d.  inn.  Med.,  1910,  vi. 


THE  BLOOD  149 

"Schwalbe,    in    Lubarsch-Ostertag,    Ergeb.,    1904,    viii,    150;    Aynauds,    Le 

globulin  des  mammi feres,  These  de  Paris,  1909. 
'*  Abderhalden  and  Deetjen:  Zeitschft.  f.  physiol.  Chem.,  liii,  280;  Deetjen, 

Virchow's  Arch.,  clxiv,  239. 
"  Newer  literature :  Sternberg,  Pathol,  d.  Primarerkrankung  d.  lymphat.  u. 

hamapoiet.  Apparates,  1905 ;  Schridde,  Miinch.  med.  Wochenschf t.,  1908, 

No.  20;  V.  Domarus,  Fol.  hamatolog.,   1908,  vi,  337;   Ebstein,  Path.  u. 

Thierap.  d.  Leukamie,  1909;  Herz,  Die  akute  Leukamie,  191 1;  numerous 

studies  in  the  Folia  hamatologica,  1904-15. 
"  Helly :  Die  hamatopoietischen  Organe,  1906. 
"Ziegler:  Fol.  hamatolog.,  vi,  113;  Butterfield,  Arch.  f.  klin.  Med.,  xcii,  336; 

Fischer,  Myeloische  Metaplasie  u.  fotale  Blutbildung,  1909. 
"  In  the  Nothnagel  System. 
"Kongr.  f.  inn,  Med.,  1905, 
"Koranyi:   Berl.  klin.  Wochenschft.,  1912,  xlix,  1357.     Literature  to   1913 

in  Sappington  and  Pearson,  Jour.  Am.  Med.  Assn.,  1914,  Ixiii,  143. 
**MiilIer:  Zentralbl.  f.  Path.,  1894,  623  (lit.);  Tiirk,  Wiener  klin.  Wochen- 
schft., 1907,  No.  6. 
"v.  Leube:  Ueber  Leukamie,  Deutsche  Klinik,  III;  Nsegeli,  Die  Blutkrank- 

heiten  (contrary  view). 
^'De  la  Camp:  Therap.  d.  Gegenwart,  1905  (lit.)  ;  Helber  and  Linser,  Arch.  f. 

klin.  Med.,  Ixxxiii,  479. 
**For  a  discussion  of  this  subject  and  the  complete  literature,  see  Herz,  Die 

acute  Leukamie. 
**Berl.  klin.  Wochenschft.,  1887,  Nos.  31  and  45;  Hoffmann,  1.  c,  106;  West- 

phal.  Arch.  f.  klin.  Med.,  li,  103. 
"  Marchand,  published  by  Claus :  Ueber  das  maligne  Lymphom,  Dissert.  No. 

SI,  Marburg,  1888;  Benda,  Kongr.  f.  inn.  Med.,  1897,  380. 
**Dennig:  Miinch.  med.  Wochenschft.,  1901,  No.  4. 
*'  Cf.  Naegeli :  1.  c. ;  Schridde,  Miinch.  med.  Wochenschft.,  1908,  No.  20. 
**  Pappenheim :  Fol.  hamatol.,  ii,  291 ;  Verhandl,  d.  Berl.  hamatolog.  Gesellsch., 

ibid.,  1909,  vii;  K.  Ziegler,  Die  Hodgkinsche  Krankheit,  191 1. 
**0.  Meyer,  and  K.  Meyer:  Berl.  klin.  Wochenschft.,  1912,  No.  36;  Blumberg, 

Mitth.  a.  d.  Grenzgeb.,  xxiv,  1912;  Jacobsthal,  Munch,  med.  Wochenschft., 

1910,  No.  19;  Beumelburg,  Beitr.  z.  Klinik.  d.  Tuberk.,  1912,  xxiii;  Negri 

and  Mieremet,  Centralbl.  f.  Bakt.,  1913,  Ixviii;  Hirschfeld,  Ergeb.  d.  inn. 

Med.,  191 1,  vii,  161;  Steiger,  Zeitschft,  f.  klin.  Med.,  1914,  Ixxix,  452. 
"Johns  Hopkins  Hosp.  Reports,  x,   133   (lit.  to  1902);  Longcope,  Bull,  of 

the  Ayer  Clin.  Lab.,  No.  i;  Simmons,  Jour,  of  Med.  Research,  ix;  Gib- 
bons, Am.  Jour,  of  Med.  Sci.,  cxxxii.  No.  11. 
*^  Munch,  med.  Wochenschft.,  1910,  No.  13 ;  Zeitschft.  f.  Hyg.,  1910,  Ixvii ; 

Fraenkel,  Miinch.  med.  Wochenschft.,  1911,  No.  23,  and  Deutsch.  med. 

Wochenschft.,  1912,  No.  14. 
"Arch,  of  Int.  Med.,  1913,  236;  Bunting,  Jour.  Am.  Med.  Assn.,  1913,  Ixi, 

1803 ;  Billings  and  Rosenow,  ibid.,  2122. 
"Johns  Hopkins  Hosp.  Bull.,  xxii,  369,  and  xxv,  173. 
•*Banti:  Zentralbl.  f.  Path.,  xv,  i;  Sternberg,  Verhand.  d.  path.  Gesellsch., 

1903,  vi,  30,  34- 
•°  Fabian,  Naegeli  and  Schatiloff :  Virch.  Arch.,  clxxxx,  436. 
"Ellermann  and  Bang:  Zentralbl.  f.  Bakt.,  1908,  xlvi,  No.  7;  Zeitschft.  f. 

Hyg.  u.  Inf ektionskrank.,  Ixiii ;  Jutaka  Kon,  Virch.  Arch.,  clxxxx. 
"  Moll :  Wiener  klin.  Wochenschft.,  1903,  No.  44. 
•"Pfeiffer:  Zentralbl.  f.  inn.  Med.,  1904,  No.  32. 
•*  Morawitz  and  Rehn :  Arch,   f .  exp.  Path.,  1907,  Iviii,  41 ;  Langstein  and 

Meyer,  Hofmeister's  Beitrage,  v,  69. 
*""  Schittenhelm  and  Lutter :  Zeitschft.  f .  exp.  Path.,  ii,  562. 
*""Arch.  f.  klin.  Med.,  xcix,  Nos.  5  and  6;  Morawitz  and  Lessen,  ibid.,  xciv, 

no. 
^"Rumpf :  Virch.  Arch.,  clxxiv,  163. 


160  THE  BASIS  OF  SYMPTOMS 

White:  Lancet,  1903,  1007;  Magnus-Levy  and  Meyer,  in  Oppenheimer, 
Handb.  d.  Biochem.,  1908,  iv,  459. 

***  Halliburton :  TTie  Essentials  of  Chem.  Physiology,  1909;  Hammarsten, 
Lehrb.,  7th  edition,  1910  (translation  1911). 

**"  Morawitz  and  Oppenheimer :  Handb.  d.  Biochem.,  1908,  91. 

*•*  Oppenheimer :  Die  Fermente  u.  ihre  Wirkungen,  2nd  edit.,  1909. 

*"  Brieger  and  Trebing:  Berl.  klin.  Wochenschft,  1908,  1041,  1349;  v.  Berg- 
mann  and  Meyer,  ibid.,  1908,  No.  37. 

*°* Strauss:  Die  chron.  Nierenkrankh.,  etc.,  1902  (lit.);  v.  Noorden,  Handb. 
d.  Path.  d.  Stoffwechs.,  2nd  edition,  i,  1026;  Letsche,  Zeitschft.  f.  physiol. 
Chem.,  1907,  liii,  31.  For  other  literature,  see  pp.  427,  430  (renal  func- 
tion). 

*°*Bingel:  Zeitschft.  f.  physiol.  Chem.,  Ivii,  382;  Howell,  Am.  Jour.  Physiol- 
ogy, 1906,  xvii,  273. 

"'Zeitschft.  f.  physiol.  Chem.,  1913,  Ixxxviii,  478. 

"^Jour.  Pharm.  and  Exp.  Therapy,  1914,  v,  275,  6n. 

*"  Albu  and  Neuberg :  Physiol,  u.  Path.  d.  Mineralstoffwechsels,  1906. 

"'  Hamburger :  Osmot.  Druck  u.  lonenlehre,  1902. 

"* Morawitz:  Oppenheimer,  Handb.  d.  Biochemie,  1910,  iv  (Path.  d.  Wasser- 
u.  Mineralstoflfwechsels). 

*"  V.  Limbeck :  Klin.  Path.  d.  Blutes,  2nd  edit.,  86. 

"*  Widal :  Les  regimes  dechlorures,  etc.,  Congres  f  rangais  de  med.,  Liege, 
1905 ;  Ambard,  Les  retentions  chlorures,  Paris,  1905. 

"^  Stintzing  and  Gumprecht :  Arch,  f .  klin.  Med.,  liii,  265 ;  Grawitz,  ibid.,  liv, 
588. 

"*  Hammerschlag :  Zeitschft.  f .  klin.  Med.,  xxi,  475  ;  Grawitz,  1.  c. 

^  Literature  on  this  type :  Hess,  Arch.  f.  klin.  Med.,  Ixxix,  128  (lit.)  ;  Marie, 
Mercredi  med.,  1895,  No.  3;  Hayem,  ibid..  No.  4;  Fromherz,  Miinch.  med. 
Wochenschft.,  1903,  No.  40. 

""Vaquez:  C.  r.  soc.  biol..  May  7,  1892;  Osier,  Am.  Jour.  Med.  Sc,  August, 
1903;  Tiirk,  Wiener  klin.  Wochenschft.,  1904,  Nos.  6  and  7;  Geisbock, 
Arch.  f.  klin.  Med.,  Ixxxiii,  396;  Senator,  Die  Polyzythamie,  1910. 

"^  Jaquet :  Ueber  d.  physiol.  Wirkung  d.  Hohenklimas,  Programm.  Basel,  1904 ; 
Douglas,  Haldane  et  al.,  Phil.  Trans.,  London,  1913,  B.  203,  185 ;  Masing 
and  Morawitz,  Arch.  f.  klin.  Med.,  xcviii,  i ;  Cohnheim  and  Weber,  ibid., 
1913,  ex,  225;  Laquer,  ibid.,  189;  Fitz  Gerald,  Proc.  Roy.  Soc.  (B),  1914, 
Ixxxviii,  248. 

"** Meyer:  Jahreskurse  f.  arztl.  Fortbild.,  March,  1910. 

"*  Geisbock :  Arch,  f .  klin.  Med.,  Ixxxiii,  396. 

^Haldane  and  Smith:  Jour,  of  Physiol.,  xxv,  334;  ibid.,  xliv,  305;  Plesch, 
Hamodynamische  Studien,  1906;  Morawitz  and  Siebeck,  Arch.  f.  exper. 
Path.  u.  Pharm.,  lix,  364. 


CHAPTER  III 
INFECTION  AND  IMMUNITY 

(  With  the  Collaboration  of  Dr.  E.  Levy,  Strassburg) 

In  this  chapter  we  purpose  considering  the  various  means  by 
which  the  animal  body  resists  the  invasion  of  pathogenic  micro- 
organisms.^ 

The  Portals  of  Entry. — How  bacteria,  under  ordinary  con- 
ditions, gain  entrance  to  the  body  is  still  not  definitely  known. 
The  body-surfaces  are  constantly  beset  by  innumerable  micro- 
organisms, among  them  the  ordinary  agents  of  inflammation  and 
suppuration :  they  are  present  on  the  skin,  in  the  nose  and  mouth, 
in  the  trachea  and  gastro-intestinal  tract,  and  in  the  vagina  and 
urethra.  Despite  their  intimate  relation  to  the  major  part  of 
those  surfaces  which  lie  between  the  organs  and  the  outer  world, 
they  seldom  gain  access  to  the  former ;  at  least,  according  to  our 
present  conception,  morbid  processes  are  initiated  with  relative 
infrequency  by  bacteria  which  are  normally  present  on  these 
surfaces. 

It  is  evident,  therefore,  that  some  protective  mechanism  holds 
the  organisms  in  check — this  protective  function,  without  doubt, 
residing  in  the  cells  which  constitute  these  surfaces  (see  below)  ; 
for  the  normal  epithelium  of  the  skin  and  of  the 
respiratory  and  digestive  tracts  is  able,  as  a  rule, 
to  prevent  the  invasion  of  micro-organisms. 

Solid  particles  other  than  bacteria  encounter  an  equal  diffi- 
culty. In  the  case  of  mercurial  ointment,  which  seems  to  be  an 
exception  to  this  rule,  soluble  fatty-acid  salts  ^  are  no  doubt 
formed  on  the  skin  in  a  manner  analogous  to  the  emulsification 
of  fat  before  its  absorption  by  the  intestines.  In  view  of  the 
fact  that  leucocytes  can  pass  between  the  epithelial  cells,  it  is 
possible  that  they  may  carry  back  with  them  bacteria  which  they 
have  taken  up  on  the  body-surfaces.  Were  this  true,  it  would 
indeed  be  a  marvellous  process,  for  the  body  would  thereby  infect 
itself.  The  ingested  bacteria  would,  undoubtedly,  be  destroyed  in 
many  instances  by  the  white  cells ;  yet  this  would  not  be  the  case 
in  aerogenic  tuberculosis  of  the  bronchial  lymph-nodes.    Here  the 

151 


152  THE  BASIS  OF  SYMPTOMS 

survival  of  the  bacteria,  per  se,  might  be  regarded  as  evidence 
of  the  disease  and  indeed  its  very  incipiency.  And  in  the  present 
status  of  our  knowledge  this  would  actually  seem  to  be  true. 

This  migration  of  the  leucocytes  might  have  a  double  purpose : 
first,  to  carry  to  the  organs  the  solid  portions  of  the  food,  and 
secondly,  to  take  up  the  bacteria  similarly  as  solid  particles,  rely- 
ing upon  their  ability  to  destroy  them.  Such  a  mechanism  would 
be  advantageous  to  the  body,  in  that,  without  danger,  it  could  pro- 
tect itself  against  certain  micro-organisms. 

The  acute  infections  due  to  the  entrance  of 
bacteria  through  the  skin  presuppose  an  injury  to  the 
epithelium,  which  may,  however,  be  insignificant.^  Thus  Garre 
was  able  to  produce  a  genuine  furuncle  on  his  left  arm  by  rubbing 
staphylococcus  pyogenes  into  the  skin;  and  guinea-pigs  may  be 
infected  with  plague  by  rubbing  the  cultures  into  the  freshly- 
shaved  skin.  The  minimal  injury  to  the  epithelium  in.  both  of 
these  examples  enabled  the  micro-organisms  to  enter. 

Our  knowledge  of  the  method  by  which  infections 
enter  through  the  mucous  membranes  is  very  lim- 
ited. Tonsillar  diseases  appear  to  play  an  important  role 
in  predisposing  to  infections  with  the  pyogenic  cocci.  The  wan- 
dering of  the  leucocytes  through  the  epithelium  of  the  tonsils,  and 
the  frequent  local  lesions,  render  them  especially  permeable  to 
bacteria,  and  in  turn  to  a  general  bactersemia. 

The  nose,  with  the  accessory  sinuses  and  the 
nasopharynx,  catches  and  holds  in  its  numerous  corners 
and  folds  the  micro-organisms  that  enter.  Its  lymphatic  tissues, 
and  especially  the  nasal  tonsil,  are  exposed  to  the  same  dangers  as 
are  the  faucial  tonsils.  The  secretions  of  the  nose  are  bacteri- 
cidal; but  in  the  rat,  at  least,  this  does  not  afford  efficient  pro- 
tection against  plague  bacilli,  for  the  introduction  of  a  few  of 
the  latter  into  the  nose  of  this  animal  will  lead  to  a  fatal  infection. 

(The  importance  of  so-called  focal  infections  *has  only  re- 
cently, it  would  seem,  received  the  emphasis  it  deserves.  That 
a  systemic  or  localized  disease  may  arise  on  the  basis  of  a  pre- 
existing sluggish,  or  even  latent,  infectious  focus,  has  l6ng  been 
known.  It  is  to  clinical  and  experimental  observations  of  the  last 
few  years,  however,  that  we  owe  a  better  understanding  of  the 
part  these  infections  play  in  pathological  processes. 

The  focus  is  most  commonly  located  in  the  head,  the  ton- 


INFECTION  AND  IMMUNITY  163 

sils  and  the  lymphatic  tissues  of  the  nasopharynx  being  the 
favorite  sites.  An  infected  tonsillar  crypt,  often  in  a  deeply  buried 
organ,  which  may  have  caused  few  if  any  symptoms,  is  a  frequent 
finding.  Chronic  alveolar  abscess,  infections  of  the  nasal  sinuses, 
of  the  middle  ear  and  mastoid,  and  less  often  of  the  gall-bladder, 
appendix  or  prostate,  may  be  foci  in  other  cases. 

The  morbid  processes  induced  by  bacteria,  or  bacterial  toxins, 
emanating  from  these  sources  are  manifold ;  and  they  may  be  acute 
or  chronic  in  nature.  To  the  former  belong  rheumatic  fever, 
endocarditis,  both  ulcerative  and  benign,  and  the  different  bacter- 
aemias;  to  the  latter,  chronic  arthritis  (often  the  so-called  arthritis 
deformans),  myocarditis,  nephritis  and  degenerative  changes  in 
the  vessel-walls. 

The  brilliant  results  in  many  cases  following  the  surgical  re- 
moval of  the  offending  focus  speak  forcefully  for  the  correctness 
of  this  conception  of  the  significance  of  focal  infections. 

It  was  in  connection  with  his  studies  on  focal  infections  that 
Rosenow^  elaborated  his  view  of  mutation  in  the  strep- 
tococcus-pneumococcus  group.  This  would  say,  in 
brief,  that  the  streptococcus,  the  organism  most  frequently  con- 
cerned in  these  infections,  may  undergo  changes  in  pathogenicity 
and  in  cultural  characteristics  by  a  variation  in  the  conditions  of 
growth  and  by  animal  passage.  Thus  in  one  phase  of  mutation 
the  streptococcus  may  cause  an  arthritis,  in  another  an  endocar- 
ditis, and  in  still  another  a  pneumonia.  The  production  of  acute 
gastric  ulcer,^  as  a  mutation  phase,  will  be  discussed  in  another 
place. — Ed.  ) 

Theair-passagesof  healthy  individuals,  below  the  upper 
part  of  the  trachea,  are  generally  considered  sterile;  only  on  forced 
inspiration  may  bacteria  penetrate  to  the  finer  bronchi.  Should 
the  bacteria  penetrate  to  the  alveoli  themselves,  the  delicate  epi- 
thelium of  the  air-cells  would  hardly  prevent  them  from  passing 
through,  for  we  know  that  solid  particles,  if  inhaled  in  great 
numbers,  such  as  occurs  in  the  dust-diseases,  are  often  deposited 
in  the  pulmonary  tissues.  Many  observers  believe  that  bacteria 
may  similarly  enter  the  lungs  if  they  are  sufficiently  numerous  in 
the  inspired  air.  Such  invaders  may  cause  diseases  of  the  lungs 
themselves,  or  they  may  be  carried  to  the  neighboring  lymph- 
nodes,  there  to  multiply,  or  to  be  destroyed  or  to  remain  latent. 
The  lungs  seem  to  be  well  equipped  to  destroy  bacteria  that  may 


154  THE  BASIS  OF  SYMPTOMS 

reach  them,  and  even  though  they  become  inflamed,  this  inflamma- 
tion may  protect  the  rest  of  the  body  from  a  general  invasion. 
Indeed,  it  seems  to  be  rare  for  a  general  infection  to  gain  admit- 
tance to  the  body  via  the  lungs,  without  causing  a  primary  disease 
of  these  organs  or  of  their  lymphatic  apparatus. 

The  factors  which  favor  an  infection  of  the 
air-passages  have  been  accurately  determined  in  animals,'^ 
much  more  so,  indeed,  than  in  man.  A  large  number  of 
micro-organisms  in  the  inspired  air  undoubtedly 
favors  infection,  especially  if  the  individual  breathes  deeply.  These 
bacteria  may  be  present  not  only  in  dry  dust,  but  may  be  car- 
ried by  minute  moist  droplets  which  have  been  thrown  out  into  the 
air  by  other  persons  in  coughing,  sneezing  or  talking.*  Infection  of 
the  lungs  may  also  be  induced  by  the  aspiration  of  substances,  such 
as  food  and  water,  carrying  bacteria  in  with  them. 

The  virulence  of  the  bacteria  inhaled  is  also  of 
importance,  as  is  likewise  an  inflammation  of  the  upi>er  air- 
passages,  which  favors  the  migration  of  micro-organisms  into  the 
lungs.  Exposure  to  cold  and  to  dampness  is  generally 
believed  to  predispose  to  the  development  of  infectious  processes 
in  the  bronchi  and  lungs,  possibly  by  lowering  the  resistance  of  the 
epithelial  linings.  If  the  inspired  air  is  not  filtered  by  passage 
through  the  winding  upper  respiratory  tract,  infection  of  the  lungs 
is  directly  favored;  for  this  reason  a  tracheal  cannula  is  always 
a  menace.  Animals  with  weak  respiratory  muscles  are  prac- 
tically certain  to  die  if  they  breathe  through  such  a  cannula ;  and, 
for  the  same  reason,  inflammations  of  the  air-passages  are  rela- 
tively frequent  in  mouth-breathers. 

The  gastro-intestinal  tract  is  continually  receiving 
micro-organisms  which  have  been  swallowed  in  the  food  and 
saliva.  Some  of  these  are  quickly  destroyed  by  the  action  of 
the  hydrochloric  acid;  yet  since  the  stomach  begins  to  empty  itself 
shortly  after  the  food  enters,  and  since  the  acid  first  secreted  is 
bound  by  the  proteids  of  the  food,  and  since,  finally,  the  gastric 
juice  does  not  penetrate  the  interior  of  many  large  food  particles, 
the  possibility  always  exists  that  virulent  organisms  will  pass 
through  the  stomach  into  the  intestines. 

As  to  the  bowel  itself,  it  may  be  said,  in  general,  that  solid 
particles,  without  amoeboid  movements,  are  unable  to  penetrate 
the  intact  mucous  membrane,  even  fat  first  requiring  emulsifi- 


INFECTION  AND  IMMUNITY  155 

cation.  Though  phagocytic  white  cells  are  able  to  pass  between 
the  epithelial  cells,  it  is  still  undetermined  whether  they  can  carry 
back  with  them  solid  substances.  It  is  possible  that  micro-organ- 
isms penetrate  the  bowel  wall  in  some  way  peculiar  to  themselves. 
That  penetration  does  occur  is  illustrated  in  the  case  of  cholera,  of 
tuberculosis  and  of  trypanosomiasis.  The  crucial  question  is 
whether  the  organisms  can  pass  through  an  intact  epithelium  or 
must  first  injure  the  latter  in  such  a  way  as  to  facilitate  their 
entrance.  Ficker^  found  in  rabbits,  dogs  and  cats  of  the  suckling 
age  that  the  normal  epithelium  was  no  barrier  to  the  passage  of 
bacteria,  while  in  adults  of  the  same  species,  a  certain  period  of 
fasting  was  necessary  to  render  the  epithelium  permeable.  Hard 
work,  thirst,  and  inflammatory  changes  in  the  intestinal  lining  are 
all  factors  favoring  the  penetration  not  only  of  micro-organisms, 
but  also  of  proteid  substances,  ferments  and  toxins,  according  to 
Holle.i<^ 

Baumgarten^^  has  shown  experimentally  that  tubercle  bacilli 
rapidly  disappear  from  the  intestinal  contents,  and  that  a  few 
may  afterwards  be  found  in  the  lymphatic  follicles  and  nodes 
of  the  intestines,  having  been  carried  in,  in  all  likelihood,  during 
the  absorption  of  fluid.  As  the  tubercle  bacilli  are  not  motile, 
and  as  there  is  no  evidence  that  the  leucocytes  have  carried  the 
bacilli  through  the  mucosa,  the  conception  of  a  transportation  by 
the  fluids  absorbed  seems  not  unlikely,  particularly  in  view  of 
the  very  low  specific  gravity  of  the  Koch  bacillus. 

It  is  not  impossible  that  the  mode  of  penetration  is  peculiar 
to  the  organism.  Thus  the  typhoid  bacillus  and  the  cholera  vibrio 
multiply  prodigiously  in  the  lumen  before  invading  the  mucosa, 
thereby  possibly  producing  toxins  which  first  injure  the  epithelium 
and  pave  the  way.  In  dogs,  for  example,  the  congestion  caused 
by  podophyllin  renders  the  intestinal  lining  permeable  to  bacteria.^ ^ 
And,  finally,  the  possibility  of  organisms  entering  the  blood  during 
digestion  has  never  been  disproved. 

Granting  that  bacteria  can  penetrate  the  intact  intestinal  wall, 
they  certainly  cannot  do  this  easily,  and  many  circumstances  in- 
fluence the  process.  In  the  first  place,  the  number  of  bac- 
teria present  is  of  great  importance.  Then,  too,  a  rapid 
transit  through  the  intestines  may  serve  as  a  protec- 
tion against  invasion.  Possibly  this  is  the  reason  that  many 
diseases  of  the  intestines,  such  as  typhoid  fever,  affect  principally 


156  THE  BASIS  OF  SYMPTOMS 

the  ileum,  where  peristalsis  is  slower  than  in  the  jejunum,  and 
where  the  organisms  have  a  better  chance  to  cling  to  the  walls  and 
multiply.  Furthermore,  as  is  well  known,  thenormal  floraof 
the  intestines  may  cause  strange  bacteria  to  dis- 
appear by  outgrowing  them;  and  thus  many  pathogenic 
micro-organisms,  if  introduced  into  the  intestines,  rapidly  disap- 
pear without  producing  symptoms.  Finally,  the  normal 
mucous  membrane  seems  to  have  the  property  of 
exerting  a  destructive  influence  upon  the  micro- 
organisms in  the  intestinal  canal. ^^  Toxins,  except- 
ing that  of  botulism,  are  not  absorbed  by  the  normal  mucosa  of 
the  bowel ;  they  are  either  destroyed  or  rendered  non-toxic  by  the 
digestive  fexments. 

Conditions  in  the  vagina  are  somewhat  similar  to  those 
in  the  bowel.  There,  also,  we  have  a  normal  flora,  which  may 
injure  strange  invaders ;  while  the  acid  reaction  of  the  secretions 
of  the  vagina  is  unfavorable  to  the  development  of  most  patho- 
genic bacteria. 

It  is  evident  from  all  that  has  been  said,  that  numerous  de- 
fenses against  the  invasion  of  micro-organisms  are  present  on 
the  surfaces  of  the  body.  The  difficulty  of  passing  the  intact  epi- 
thelium, the  acidity  and  bactericidal  properties  of  many  of  the 
secretions,  the  conflict  with  the  normal  flora — all  of  these  serve 
to  protect  the  body  against  bacterial  invasion.  The  very  efficacy 
of  these  barriers  resides,  it  would  seem,  in  their  complexity. 
V,  Behring  ^^  has  called  attention  to  the  fact  that  an  animal  may 
be  highly  susceptible  to  inoculation  with  a  micro-organism  and  yet 
be  quite  insusceptible  to  the  corresponding  natural  disease,  appar- 
ently because  it  is  able  to  prevent  the  entrance  of  the  organism  into 
its  body  (mouse  anthrax,  guinea-pig  tuberculosis).  Infection 
under  natural  conditions  is,  therefore,  a  complicated  process  and 
points  to  the  breaking  down  of  the  defensive  forces  at  the  body 
surfaces. 

The  Factors  Determining  the  Character  of  an  Infection. — 
The  manifestations  of  infection  vary  considerably,  depending 
upon  the  virulence  of  the  invading  organisms,  the  number  of  the 
latter,  their  toxicity,  the  portal  of  entry  and  the  resistance  of  the 
individual. 

Upon    what    factors  the  virulence  of  micro-organisms   depends 


INFECTION  AND  IMMUNITY  157 

is  only  partly  understood.  With  a  few  exceptions,  such  as  an- 
thrax and  plague,  the  virulence  varies  considerably  from  time  to 
time,  and  even  during  the  course  of  a  single  infection.  As  a 
rule,  it  increases  up  to  the  height  of  a  disease  and  diminishes  with 
convalescence.  Organisms  possessing  capsules  are  in  general  less 
readily  destroyed  than  those  without.  Bail  and  his  co-workers  ^^ 
believe  that  the  virulence  of  bacteria  depends  upon  substances  they 
secrete,  called  by  them  aggressins,  which  keep  the  phagocytes  at  a 
distance.  This  conception,  however,  is  by  no  means  generally  held. 
Though  the  contagiousness  of  a  disease  ordinarily  runs  hand  in 
hand  with  the  virulence  of  the  causative  organism,  this  need  not 
be  true,  as  is  proved  by  an  epidemic  of  typhoid  fever  which  we 
observed.  The  mode  of  transmission  was  by  direct  contact,  and 
in  the  seventy  cases  there  were  no  deaths,  despite  the  fact  that  the 
majority  were  in  children  and  many  in  enfeebled  individuals. 

The  number  of  micro-organisms  introduced  into  the  body  is 
also  of  great  importance.  A  certain  number  of  even  highly 
virulent  bacteria  is  necessary  in  order  to  cause  a  fatal  infection. 
This  minimum  lethal  dose  varies  indirectly  as  the  resis- 
tance of  the  animal  and  directly  with  the  virulence  of  the  bacteria. 
Only  a  very  few  of  the  most  virulent  may  be  necessary  to  infect 
highly  susceptible  animals.  If  more  are  introduced,  the  period 
of  incubation  becomes  shorter  and  death  follows  more  quickly. 

The  portal  of  entry  of  infecting  organisms  influences  both  the 
character  and  the  course  of  the  infection.  If  bacteria  are  intro- 
duced directly  into  the  blood-stream,  as  happens  in  general  in- 
fections with  the  pus  cocci,  or  with  the  bacilli  of  anthrax  or  tuber- 
culosis, the  resulting  disease  runs  a  stormy  course.  Furthermore, 
the  same  staphylococci  which  will  cause  a  pyaemia  if  introduced 
into  a  vein,  usually  produce  only  a  local  lesion  if  injected  subcu- 
taneously.  There  are  indeed  exceptions  to  this  general  rule. 
Cattle,  for  example,  are  readily  infected  with  rauschbrand  subcu- 
taneously,  but  withstand  intravenous  injections  of  the  same 
material ;  and  man  is  most  susceptible  to  the  cholera  vibrio  when 
the  latter  is  in  the  gastro-intestinal  tract. 

The  virulence  of  infecting  micro-organisms,  and  their  tendency 
to  cause  a  general  intoxication,  depend  to  a  great  extent  upon  the 
toxins  they  produce.  In  the  case  of  the  diphtheria  and  tetanus 
bacilli  these  toxins  pass  into  solution;  and  filtered  cultures  con- 
taining these  soluble  poisons  give  rise  to  the  same  symptoms  as 


158  THE  BASIS  OF  SYMPTOMS 

do  the  bacilli  themselves.  The  bacterial  toxins  resemble  ferments 
in  many  ways,  for  example,  in  their  susceptibility  to  moist  heat,  to 
light,  to  oxygen,  etc.  Their  extreme  potency,  exceeding  that  of 
any  other  known  substance,  also  suggests  a  relationship  to  the 
enzymes. 

The  method  of  dissemination  of  tetanus  toxin  is  quite 
unlike  that  of  any  known  alkaloidal  poison,  such  as  strychnin,  for 
example.  The  latter  is  carried  to  the  susceptible  cells  by  the  blood- 
current,  whereas  tetanus  toxin  travels  through  the  nerves  from 
the  point  of  infection  to  the  central  ganglion  cells,  upon  which  it 
exerts  its  poisonous  action.^*  These  ganglion  cells  cannot  be 
reached  directly  by  way  of  the  blood  or  lymph,  though  they  are 
affected  by  injections  of  the  toxins  directly  into  the  nerves  or  into 
the  spinal  cord.  It  is  this  mode  of  diffusion  of  the  tetanus  toxin 
that  renders  so  unsatisfactory  the  specific  therapy  of  the  disease. 
(Recent  clinical  and  experimental  studies ^'^  point  the  way  to  a 
more  rational  and  successful  treatment  of  tetanus.  The  use  of 
antitoxin  as  early  as  possible,  and  the  employment  of  a  suffi- 
ciently large  dosage — injected  at  the  outset  intravenously  and 
intraspinously,  and  later  subcutaneously,  in  order  to  maintain  the 
antitoxin  content  of  the  blood  at  an  efficient  level — ^have  materially 
lowered  the  mortality  statistics  of  those  who  have  employed  this 
method. — Ed.  ) 

When  the  injections  of  tetanus  toxin  are  made  into  the  cord, 
the  incubation  period  intervening  before  the  development  of 
symptoms,  which  is  otherwise  so  prolonged  in  tetanus,  is  much 
shortened  or  entirely  absent.  The  incubation  period  for  tetanus, 
therefore,  appears  to  be  the  time  consumed  by  the  toxin  in  travel- 
ling from  the  point  at  which  it  enters  the  body  to  the  cells  upon 
which  it  exerts  its  poisonous  action.  This  mode  of  dissemination 
explains  the  fact  that  in  experimental  tetanus  the  spasm  first 
develops  in  the  extremity  infected ;  for  the  toxin  travelling  up  the 
nerve,  first  acts  upon  the  corresponding  part  of  the  cord.  In  man, 
however,  the  muscles  of  the  jaw  are  usually  first  affected. 
Diphtheria  toxin,  in  so  far  as  it  affects  the  nervous  sys- 
tem, may  likewise  travel  along  the  nerves,  for  it  is  a  well-known 
clinical  fact  that  the  nerves  most  frequently  paralyzed  are  those 
situated  in  the  neighborhood  of  the  local  lesion.  The  virus 
of  hydrophobia,  and  of  acute  anterior  poliomyelitis,  also 
progress  along  the  nerve  trunks. 


INFECTION  AND  IMMUNITY  159 

Potent  toxins  can  be  extracted  from  the  bodies  of  many  bac- 
teria which  previously  have  been  carefully  killed.  This  was  first 
demonstrated  by  Pfeiffer  in  the  case  of  the  cholera  vibrio,  and  later 
was  shown  to  be  true  also  of  the  typhoid  and  colon  bacilli  and  of 
other  organisms.  These  poisons  are  called  endotoxins  be- 
cause they  adhere  very  closely  to  the  bodies  of  the  bacteria,  and 
unlike  the  toxins  of  diphtheria  and  tetanus,  are  practically  insolu- 
ble. They  may  be  compared  with  the  endoenzymes  of  the  yeast 
plant.  With  every  infection,  therefore,  there  is  an  intoxication 
from  substances  produced  by  the  bacteria,  whether  they  form 
soluble  toxins  or  not ;  this  has  recently  been  established  in  the  case 
of  dysentery.^^  It  is  probable,  further,  that  insoluble  toxins  may 
provoke  the  formation  of  antitoxins  ^^  (anti-endotoxins)  just 
as  do  those  of  diphtheria  and  tetanus,  though  this  view  is  not 
generally  accepted.^® 

The  infecting  organisms  may  do  harm  in  still  other  ways,  as 
when  in  a  general  bactersemia  they  plug  the  smaller 
blood-vessels  of  important  organs.  We  have  learned  in  recent 
years  that  blood  infections  are  by  no  means  uncommon.  Bacteria 
may  be  cultivated  from  the  blood  of  most  typhoid  fever  patients, 
and  from  no  small  proportion  of  patients  with  pneumonia,  ery- 
sipelas and  other  diseases.  We  have  come,  therefore,  to  regard 
bactersemias  with  less  apprehension  than  formerly. 

Many  pathogenic  organisms  produce  toxins  that  will  dissolve 
red  blood-corpuscles,  as  was  first  shown  by  Ehrlich  for  the  tetanus 
bacillus. 

The  resistance  of  the  individual,  finally,  is  of  great  significance 
in  determining  whether  infection  shall  occur  and  what  character 
it  shall  exhibit.  The  pre-bacteriological  era  laid  great  emphasis 
upon  exposure  to  cold,  over-exertion,  poor  nutri- 
tion and  trauma  as  the  direct  causes  of  disease ;  to-day,  even 
though  we  recognize  them  merely  as  predisposing  causes,  we  prob- 
ably pay  too  little  attention  to  them.  Certain  organisms,  such 
as  those  of  anthrax,  plague  and  glanders,  are  so  intensely  virulent 
that  they  need  no  such  predisposing  factors  to  pave  the  way  for 
them;  but  with  the  majority  of  bacteria  some  such  favoring  in- 
fluence seems  necessary  unless  the  infective  agent  is  present  in 
overwhelming  numbers.  It  is  possible  that  the  bacteria  them- 
selves produce  substances  that  enable  them  to  gain  a  foothold. 
In  typhoid  epidemics  due  to  contaminated  milk,  the  latter  acts  not 


160  THE  BASIS  OF  SYMPTOMS 

only  as  a  vehicle,  but  also  as  an  excellent  culture  medium  in  which 
the  bacilli  may  grow  and  throw  out  their  metabolic  products. 

It  cannot  be  doubted  that  chilling  of  the  body  predisposes 
to  tonsillitis,  bronchitis  and  pneumonia,  though  how  it  does  this 
is  not  known,  despite  the  many  attempts  made  to  solve  the  prob- 
lem.^^  Of  the  various  explanations  offered,  such  as  lowering  of 
the  body  temperature,  circulatory  disorders  and  injuries  to  the 
cells,  none  has  been  definitely  established.  Possibly  the  action  of 
cold  is  to  inhibit  the  formation  of  bacteriolytic  amboceptors. 
Fatigue  and  inanition  also  lower  the  individual's  resistance  in 
some  undetermined  way.  And,  finally,  trauma  and  alcoholic  in- 
toxication ^2  have  been  shown,  both  clinically  and  experimentally, 
to  render  the  individual  more  susceptible  to  infection. 

Mixed  and  Secondary  Infections. — In  a  number  of  infectious 
diseases,  more  than  one  variety  of  micro-organism  is  found; 
streptococci  are  often  present  in  diphtheria,  and  the  pus-cocci  in 
tetanus.  This  is  spoken  of  as  a  mixed  infection.  This 
symbiotic  growth  may  either  increase  or  diminish  the  virulence 
of  one  of  the  organisms.  For  example,  isolated  tetanus  spores 
injected  into  the  tissues  of  susceptible  animals  produce  the  dis- 
ease only  when  in  association  with  other  bacteria.  The  latter 
seem  to  prepare  the  way  by  causing  a  necrosis  of  the  tissues; 
for  an  aseptic  mechanical  injury  will  do  the  same.  The  converse 
— a  diminution  of  the  virulence  of  one  organism  caused  by  the 
presence  of  another — ^has  not  been  positively  demonstrated.  Were 
this  not  a  possibility,  however,  it  would  be  difficult  to  explain 
the  comparative  in  frequency  of  tetanus  in  view  of  the  wide  dis- 
tribution of  the  bacillus  and  the  marked  susceptibility  of  man. 
The  cultural  antagonism  of  bacteria  is  more  an  inhibition  of 
growth  by  soluble  bacterial  metabolic  products  than  an  actual 
destruction.23 

We  speak  of  a  secondary  infection  when  a  second, 
or  even  a  third,  infection  is  superimposed  upon  the  primary  one. 
Secondary  infections  occur  most  frequently  in  those  diseases 
which  damage  the  skin  or  mucous  membranes,  thereby  inviting  the 
entrance  of  whatever  bacteria  that  may  happen  to  be  present 
there.  The  secondary  infections  with  streptococci,  such  as  may 
develop  in  the  course  of  scarlet  fever,  smallpox  or  dysentery,  are 
especially  feared.  They  often  change  the  clinical  picture  com- 
pletely ;  the  fever  'takes  on  a  different  type,  and  various  compli- 


INFECTION  AND  IMMUNITY  161 

cations  develop  such  as  otitis,  arthritis  or  endocarditis.  Not  in- 
frequently the  secondary  infection  dominates  the  scene  and  be- 
comes the  immediate  cause  of  death.  This  is  well  illustrated 
in  cases  of  septic  diphtheria  or  scarlatina,  in  which  the  strepto- 
coccus infection  provokes  the  fatal  issue.  An  appropriate  therapy 
will  take  into  account  both  the  primary  disease  and  the  secondary 
infection. 

Varieties  of  Immunity. — Even  after  bacteria  have  succeeded 
in  passing  the  protective  barriers  at  the  surfaces,  there  is  con- 
siderable evidence  to  show  that  there  exists  a  marked  individual 
variation  in  the  ability  to  resist  infection.  Of  the  many  exposed 
to  a  disease,  only  certain  individuals  contract  it,  although  we  may 
be  certain  that  many  others  have  received  the  pathogenic  bacteria 
into  their  bodies.  Certain  bacteria  may  be  very  pathogenic  for 
one  species  of  animals  and  almost  without  effect  on  another  closely 
related  species.  Indeed  the  resistance  of  the  same  individual 
varies  under  different  conditions. 

These  facts  lead  us  to  believe  that  the  animal  body  has  the 
power  to  render  pathogenic  organisms  innocuous,  even  after  they 
have  entered  the  body,  and  before  they  have  done  any  harm.  This 
phenomenon  is  called  immunity,  which,  in  turn,  may  be  natural  or 
acquired.  The  former  is  natural  to  the  individual ;  the  latter  has 
been  acquired  either  naturally  by  having  passed  through  the 
disease  in  question,  or  artificially  by  some  method  of  inoculation. 

There  are  two  general  methods  of  producing  an  artificial 
immunity.  In  the  first,  the  causative  organism,  or  some  material 
derived  from  it,  is  injected  into  the  individual  to  be  immunized. 
The  latter  then  passes  through  a  sickness  with  a  febrile  reaction, 
etc.,  following  which  he  becomes  more  or  less  immune  to  future 
infections  with  the  same  organism.  This  is  the  active  type 
of  artificially  acquired  immunity,  because  it  is 
gained  by  the  individual's  having  had  the  disease  in  a  more  or  less 
modified  form.  In  establishing  this  form  of  immunity,  the 
material  used  is  either  injected  in  very  small  amounts,  or  its 
virulence  is  attenuated,  so  that  a  mild  type  of  the  disease  will 
be  produced.  The  immunity  following  such  procedures  develops 
gradually,  but  it  is  very  durable,  and,  even  though  antibodies  are 
withdrawn  from  the  blood  by  venesection,  new  ones  are  formed. 
As  examples  of  active  artificial  immunization,  we  may  mention 
Wright's  antityphoid  inoculations,  the  Pasteur 
11 


162  THE  BASIS  OF  SYMPTOMS 

treatment  of  rabies  and  the  antitoxic  immunity  against 
anthrax  acquired  by  animals  after  injections  of  attenuated  anthrax 
bacilli. 

The  second  form  of  artificial  immunity — passive  immunity- 
is  produced  by  the  injection  of  antibodies  formed  in  the  blood  of 
another  animal.  For  this  purpose,  it  is  customary  to  use  the 
blood-serum  of  animals  that  have  already  acquired  an  active  im- 
munity to  the  disease  in  question.  Passive  acquired  immunity 
develops  immediately  after  the  injection,  but  it  soon  disappears, 
usually  in  the  course  of  a  few  weeks,  probably  because  antibodies 
produced  in  another  animal  are  in  the  nature  of  foreign  substances, 
and  as  such  are  rapidly  eliminated.  Precipitins  may  also  play  a 
part  in  this  elimination,^*  It  is  perhaps  due  to  the  close  relation- 
ship of  these  antibodies  to  the  normal  proteids  of  the  plasma  that 
the  former  are  able  to  exist  at  all  in  an  alien  blood. 

The  disadvantages,  therefore,  of  an  active  immu- 
nity are  first  that  the  animal  organism  must  pass  through  a 
given  disease,  and  secondly,  that  protection  is  delayed  for  at  least 
ten  days.  The  weakness  of  the  passive  form  is  its 
short  duration.  To  offset  these  drawbacks,  recourse  has  been 
taken  to  active-passive  immunization,  in  which 
attenuated  bacteria,  or  their  products,  plus  an  immune  serum,  are 
injected  together  or  separately.^^  But  one  must  bear  in  mind, 
in  connection  with  this  modification,  that  the  greater  the  bulk  of 
serum  injected,  the  fewer  are  the  antibodies  formed.^^  Bea- 
red k  a  has  obviated  this  difficulty  by  employing  only  the  amount 
of  serum  that  the  bacteria  can  bind,  removing  the  excess  by  cen- 
trifugation  and  washing.  This  method  produces  an  immunity 
in  twenty-four  to  ninety-six  hours,  which  persists  for  months.^'^ 

The  Factors  Concerned  in  Immunity,  (a)  General  Con- 
siderations.— Bacterial  poisons  stimulate  the  production  in  the 
body  of  substances  capable  of  entering  into  a  kind  of  combination 
with  these  poisons,  and  thus  rendering  them  harmless.  We  call 
these  substances  antitoxins.  When  the  defenses  of  the  body 
against  microbic  infection  are  strengthened  by  an  increased  for- 
mation of  these  immune  bodies,  the  animals  thereby  become  insus- 
ceptible to  the  disease  in  question,  irrespective  of  the  employment 
of  any  other  means  calculated  to  increase  their  resistance. 

The  natural  ability  to  resist  bacteria  is  assumed  to  be  aug- 
mented in  part  by  an  increase  of  bactericidal  substances  in  the 


INFECTION  AND  IMMUNITY  1& 

blood — a  leucocytosis  perhaps  representing  the  intermediate  step, 
in  that  these  substances  are  supposed  to  be  the  products  of  the 
white  cells.  It  is  true  that  many  of  the  phenomena  of  immunity 
are  associated  with  a  leucocytosis;  and,  indeed,  a  blood  rich  in 
white  cells  is  supposed  to  be  more  strongly  bactericidal  than  one 
with  few  leucocytes. ^^ 

The  invading  organisms  are  destroyed,  therefore,  in  the  im- 
mune bodies  before  they  can  produce  morbid  changes.  This 
destruction  must  occur  rapidly  if  the  host  is  to  suffer  no  injury, 
because  bacterial  activity  is  itself  rapid.  The  actual  cause 
of  the  death  of  micro-organisms  would  seem,  in 
many  cases,  to  reside  in  unfavorable  conditions 
for  their  growth,  such  as  the  composition  of  the  tissues 
which  they  have  invaded,  and  perhaps  also  the  body  tempjerature 
of  the  host.  (The  matter  of  the  oxygen  tension  of  the 
tissues  would  seem  to  be  an  important  factor  in  this  connec- 
tion. The  streptococcus,  for  example,  when  grown  under  differ- 
ent oxygen  conditions,  exhibits  variable  characteristics,  not  only 
in  its  cultural  behavior  and  its  morphology,  but  also  in  the 
experimental  lesions  which  it  produces.^^ — Ed.) 

Mycotic  growth  in  vitro  is  influenced  by  the  character 
of  the  salts  present  in  the  media  and  by  their  osmotic 
tension.  These  considerations  scarcely  apply  to  the  living  host, 
however,  as  the  animal  body  is  unceasing  in  its  effort  to  keep 
osmotic  conditions  constant. 

More  important,  in  our  opinion,  in  their  influence  on  bacterial 
life  are  variations  in  the  proteids  of  the  lymph  and 
blood.  The  blood-serum  is  often  endowed  with  bactericidal 
and  antitoxic  properties,  whereby  bacteria  are  disintegrated,  either 
at  once,  or  after  preliminary  agglutination.  That  this  is  not 
merely  the  action  of  an  alien  medium  upon  the  micro-organisms  is 
shown  by  the  fact  that  this  bactericidal  power  is  lost  if  the  serum 
be  heated  for  thirty  minutes  at  55°  C,  a  temperature  which  does 
not  produce  changes  in  the  proteids.  As  enzymic  activity  is  also 
frequently  subject  to  similar  conditions,  it  is  not  unnatural  to 
assume  that  the  bactericidal  properties  of  sera  are  comparable  in  a 
way  to  ferment  action,  and  are,  therefore,  attributes  of  the  serum 
proteids.  The  nature  of  the  bactericidal  substances  will  be  more 
fully  considered  in  another  place. 

Also  important  in  the  part  played  by  the  bactericidal  power  of 


164  THE  BASIS  OF  SYMPTOMS 

the  blood  is  the  question  whether  the  lymph  and  other  tissue-juices 
are  similarly  endowed.  As  a  matter  of  fact,  the  latter  do  contain 
bactericidal  substances,  though  it  is  questionable  whether  they  are 
comparable  to  those  of  the  serum. 

The  bactericidal  property  of  the  body  fluids  does  not  neces- 
sarily go  pari  passu  with  the  degree  of  immunity  present.  White 
rats,  for  example,  are  insusceptible  to  anthrax,  yet  their  serum 
readily  destroys  the  anthrax  bacillus ;  while  the  blood  of  rabbits, 
which  are  highly  susceptible  to  the  same  disease,  readily  destroys 
the  organism.^''  In  these  instances,  however,  the  bacteria-destroy- 
ing substances  differ  from  those  just  discussed,  for  they  are  inac- 
tive in  vivo;  furthermore  they  are  not  of  leucocytic  origin,  but 
arise  from  the  blood  platelets  in  the  process  of  coagulation ;  and, 
finally,  they  are  not  inactivated  by  a  temperature  of  56°  C. 
Herein  lies  a  justification  of  the  warning  of  Metchnikoff  not  to 
apply  unreservedly  the  results  of  experiments  in  vitro  to  con- 
ditions in  the  living  organism. 

The  problems  of  acquired  immunity  demand  special  considera- 
tion. This  type  is  characteristically  seen  after  recovery  from 
certain  diseases,  the  acute  exanthems  being  most  constant  in  this 
respect.  Other  diseases,  such  as  typhoid  fever,  generally  render 
the  individual  immune  for  many  years,  or  even  permanently. 
Diphtheria  and  cholera,  on  the  contrary,  confer  a  briefer  protec- 
tion; while  in  still  others,  such  as  erysipelas,  after  a  short  im- 
munity the  predisposition  to  another  attack  is  actually  increased. 
The  degree  of  immunity  does  not  run  parallel  with  the  severity 
of  the  disease  which  produced  it;  in  certain  individuals,  indeed, 
a  very  mild  infection  may  cause  a  high  degree  of  protection. 

We  are  in  no  position  to  interpret  immunity  phenomena  in  the 
acute  exanthems,  because  the  causative  organisms  are  not  known. 
It  is  not  unlikely,  however,  that  in  conditions  such  as  typhoid 
fever  and  cholera,  to  which  certain  individuals  are  naturally  im- 
mune, the  inherited  bactericidal  power  is  appreciably  reinforced 
by  active  immunization.  This  reinforcement  is  specific,  extend- 
ing only  to  the  micro-organisms  which  have  brought  about  the 
immune  state.  The  serum  of  typhoid  convalescents,  for  example, 
is  highly  bactericidal  to  typhoid  bacilli,  and  only  in  a  lesser  degree 
to  organisms  closely  related  to  the  latter. 

The  study  of  these  problems  has  illuminated  in  a  most  extra- 


INFECTION  AND  IMMUNITY  166 

ordinary  way  many  fundamental  processes,  of  which  only  the  most 
important  can  be  touched  upon  here. 

First  in  importance,  is  the  ability  of  the  blood-serum  to  in- 
hibit the  chemical  action  of  certain  alien  substances  and  to  destroy 
unicellular  organisms  of  all  types  and  also  individual  cells  of 
more  complex  life.  Herein  lies  the  power  of  the  higher  animals 
to  protect  themselves  against  the  toxins  and  bacteria  which  have 
passed  the  barriers  at  the  body  surfaces.  Nor  does  this  process 
of  bacteriolysis  set  free  the  toxic  materials  contained  in  the  bac- 
terial bodies,  for  the  resulting  split-products  of  the  latter  are  non- 
toxics^ 

(b)  Complement  and  Amboceptor. — Two  bodies  take  part  in 
the  destruction  and  lysis  of  alien  cells.  Of  these,  one  is  of  the 
nature  of  an  enzyme;  and  the  reaction  and  osmotic  tension  of 
normal  serum  and  a  suitable  temperature  are  essential  to  its 
action.  Kept  at  56°  C.  for  thirty  minutes  or  cooled  at  0°,  it  is 
inactivated;  while  at  body  temperature,  it  is  most  potent.  This 
substance  is  constantly  present  in  normal  blood,  though  in  variable 
amount;  but  what  causes  it  to  appear  and  to  disappear  is  not 
known.  This  body  has  been  variously  called  alexin  (  Buchner) , 
complement  (Ehrlich)  and  cytase  (Metchnikoff).  Ob- 
viously there  are  many  different  alexins,  in  view  of  their  differing 
behavior,  and  also  of  the  similarity  of  their  action  upon  diverse 
micro-organisms.  The  controversy  over  the  question  of  the  unity 
or  multiplicity  of  these  substances  is  still  active  {cf.  Haemolysis). 
Metchnikoff  distinguishes  between  macrocytases,  the  fer- 
ment of  the  macrophages  (large  lymphocytes)  and  micro cy- 
tases,  formed  by  the  microphages  (polynuclears).  We  are  of 
the  opinion  of  Ehrlich  that  there  are  many  complements,  in  view 
of  studies  showing  that  these  bodies  may  lose  one  type  of  activity 
and  still  exhibit  one  or  more  other  types. 

Complement,  per  se,  is  probably  inactive  both  in  immunized 
and  non-immunized  animals.  The  source  of  complement  is  gener- 
ally attributed  to  the  leucocytes,  though  whether  it  arises  through 
destruction  or  injury  of  the  white  cells  (phagolysis),  or  represents 
the  secretion  of  the  living  cells,  is  unsettled.  Fluids  rich  in 
leucocytes  generally  exhibit  a  strong  alexin  action,  hence  Metchni- 
koff's  view  that  the  type  of  white  cells  is  a  factor.^^  The  com- 
position of  complement  will  be  considered  under  "  Haemolysis  " 
(p.  168). 


166  THE  BASIS  OF  SYIVIPTOMS 

The  other  substance  essential  to  complement  activity  is  gener- 
ally resistant  to  temperatures  over  60°.  If  present  in  normal 
serum,  its  amount  is  insignificant.  It  increases  enormously,  how- 
ever, if  the  blood  has  been  subjected  to  certain  preliminary  prep- 
arations, or  the  individual  has  passed  through  a  disease.  Im- 
munization is  synonymous  with  an  increase  in  the  second  body, 
complement  remaining  unaltered.  Various  names  have  also  been 
given  to  this  substance — immune  body  (Pfeiffer),  sub- 
stance sensibilitatrice  (Bordet),  preparator 
(Gruber) ,  f  i x a t e u r  (Metchnikoff ) ,  and  intermediary 
body  or  amboceptor  (EhrHch). 

That  complement  and  amboceptor  are  distinct  bodies  is  evi- 
denced by  their  differing  behavior  to  heat,  as  already  noted. 
Thus,  serum  containing  both,  if  heated  to  56°  C,  becomes  inac- 
tive, but  if  added,  after  heating,  to  normal  serum  (containing  only 
complement),  its  activity  is  restored  (reactivation).  Activation 
and  reactivation  do  not  represent  newly-discovered  phenomena, 
though  they  were  differently  interpreted  in  the  past. 

Amboceptor  is  taken  up  and  held  by  cells  (bacteria)  to  the 
destruction  of  which  it  is  indispensable.  Upon  this  phenomenon 
rested  Ehrlich's  method  of  separating  the  immune  bodies  from 
the  serum.  The  union  of  amboceptor  and  micro-organism  occurs 
even  at  temperatures  only  slightly  above  0°  C,  hence  quite 
excluding  the  possibility  of  complement  activity. 

The  intermediary  body  has  a  specific  affinity  for  the  cells 
which  it  attacks.  The  property  of  a  serum  to  act  upon  different 
bacteria,  and  upon  cells  of  higher  organisms,  resides  in  the 
possession  of  different  immune  bodies,  each  the  product  of  a 
specific  process.  This  specificity  is  the  fundament  of  immunity, 
and  will  be  discussed  in  that  connection. 

(c)  The  Side-Chain  Theory. — We  come  now  to  the  considera- 
tion of  the  mode  of  action  of  the  amboceptor  upon  the  cells  of 
the  animal  organism,  and  of  its  relationship  to  complement.  The 
very  multiplicity  of  names  speaks  for  the  divergence  of  opinion 
as  to  the  behavior  of  the  immune  bodies.  Gruber  and  Metchnikoff 
attribute  to  the  latter  merely  the  function  of  enabling  complement 
to  act  upon  the  cells.  Bordet  compares  its  action  with  that  of 
a  mordant;  while  Ehrlich  looks  upon  it  as  an  intermediate  sub- 
stance which  links  complement  to  the  cells. 

Ehrlich's  views  are  based  upon  stereochemical  con- 


INFECTION  AND  IMMUNITY  167 

siderations.  Complement  possesses  no  atom-groups  by 
means  of  which  it  can  unite  with  those  of  the  cells;  amboceptor, 
however,  is  endowed  with  such  haptophore  groups.  In 
addition,  and  by  virtue  of  similar  groups,  amboceptor  is 
complementophile.  The  avidity  of  the  intermediary 
body  is  greater  for  the  cell  than  for  complement,  hence  the  union 
with  the  former  occurs  first.  This  phenomenon  makes  possible 
the  extraction  from  the  serum  of  specific  amboceptors. 

How  is  this  specific  affinity  of  amboceptor  for  certain  cells  to 
be  explained?  If  proteid-like  substances  gain  entrance  to  the 
body,  some  are  quickly  eliminated,  obviously  because  they  are 
taken  up  by  cells.  As  this  robs  them  of  their  identity,  or,  in  the 
case  of  toxins,  renders  them  non-toxic,  it  must  be  assumed  that 
they  combine  with  some  peripheral  atom  of  the  cellular  proto- 
plasm. Ehrlich  conceives  of  these  protoplasmic  atoms  as  "  side- 
chains"  of  the  large  proteid  molecule,  each  cellular  proteid 
having  numerous  and  diverse  side-chains.  The  alien  substance 
is  held  if  an  appropriate  side-chain  is  present.  This  is 
evident  in  tissues  which  have  been  functionally  injured  by  the 
alien  body ;  and  upon  this  local  phenomenon  the  theory  of  Ehrlich 
was  originally  founded.  To-day,  however,  the  process  is  no 
longer  considered  purely  a  local  one;  for  amboceptor  formation 
and  alien  cell  fixation  are  thought  to  occur  also  in  tissues  not  so 
injured. 

It  is  a  characteristic  of  the  living  cell  to  react 
to  the  stimulus  produced  by  the  union  of  side- 
chains  in  amount  far  out  of  proportion  to  the  de- 
mand. The  excess  are  cast  off  and  circulate  in 
the  blood  as  antibodies.  The  degree  of  new  formation 
of  chains  depends  essentially  upon  the  character  and  intensity  of 
the  stimulus;  thus  the  cells  may  be  so  injured  by  an  espyecially 
severe  infection  as  to  be  rendered  incapable  of  producing  immune 
bodies. 

The  vulnerable  point  in  the  side-chain  theory,  in  our  opinion, 
is  that  relating  to  the  production  of  new  chains  by  the  injured 
molecule.  This  has  been  likened  to  the  reaction  of  tissues  to  an 
irritant,  a  reaction  which  may  be  so  pronounced  that  the  new 
tissue  is  produced  in  excess.  The  two  processes,  however,  are 
fundamentally  different,  for,  on  the  one  hand,  we  are  dealing  with 
the  reaction  of  living  tissues  as  a  whole  to  an  injury,  while,  on  the 


168  THE  BASIS  OF  SYMPTOMS 

other,  it  is  a  reaction  involving  individual  molecules.  No  reaction 
analogous  to  this  is  known  to  chemistry. 

The  Haemolytic  Action  of  Alien  Plasmas. — The  destruction 
of  red  blood-corpuscles  by  alien  blood  has  become  a  matter  of 
great  interest  in  recent  years,  for  the  study  of  the  factors  con- 
cerned in  the  phenomenon  has  enormously  increased  our  knowl- 
edge not  only  of  physiological  processes  in  general,  but  also  of  the 
principles  of  the  bactericidal  action  of  the  blood-serum.^^ 

That  the  blood  of  a  given  animal  can  dissolve  out  the  haemo- 
globin of  the  erythrocytes  of  another  species  has  long  been  known. 
Certain  animals  are  particularly  sensitive  in  this  respect  and  some 
sera  are  especially  toxic.  To  a  certain  degree,  indeed,  the  mutual 
interaction  of  the  sera  of  different  animals  is  constant;  yet  enor- 
mous individual  variations  occur,  and  sera  are  known  which 
produce  haemolysis  even  in  animals  of  the  same  species.^*  As 
hypotonic  salt  solutions  likewise  cause  laking, 
it  is  natural  to  ask  whether  haemolysis  is  merely 
the  effect  produced  by  a  serum  of  different 
osmotic  tension. ^^  Morphologically,  indeed,  red  cells  sub- 
jected to  the  action  of  an  alien  blood,  on  the  one  hand,  and  to  a 
hypotonic  salt  solution  on  the  other,  are  much  alike. 

Other  investigators  see  in  haemolysis  a  proc- 
ess similar  to  that  just  discussed  in  connection 
with  bacterial  destruction,  i.e .,  based  upon  the 
action  of  a  complement  plus  an  amboceptor.  The 
complement  in  this  case  is  also  unable  to  withstand  a  temperature 
of  56°  C,  and  is  inactive  without  the  intermediate  action  of  an- 
other body  even  in  the  normal  destruction  of  red  cells.  Dog 
serum,  for  example,  heated  to  56°  is  no  longer  haemolytic,  but  if  to 
it  be  added  fresh  guinea-pig  serum,  per  se  inactive,  the  haemolyzing 
power  is  restored.  This  experiment  indicates  incidentally  that 
amboceptor  is  present  in  normal  dog  serum.  By  a  process  of 
dialysis,  complement  (guinea-pig  serum)  can  be  shown  to  con- 
sist of  two  simpler  bodies,  the  so-called  mid-piece  and  end-piece, 
which  differ  physically  and  chemically.^^ 

The  haemolytic  action  of  a  serum  may  be  intensified  if  the 
animal  (A)  from  which  it  is  derived  be  first  injected  over  a  long 
period  with  the  red  cells  of  the  animal  of  the  other  species  (B)." 
The  essential  element  provoking  the  haemolytic  power  is  the  stro- 
mata  of  the  red  cells  of  B,  irrespective  of  whether  the  serum  of 


INFECTION  AND  IMMUNITY  169 

A  was  haemolytic  for  B  before  the  preliminary  treatment.  In 
other  words,  the  stromata  of  B's  cells  injected  into  A,  endow  the 
serum  of  the  latter  with  the  power  of  dissolving  out  the  haemo- 
globin of  the  cells  of  the  former.  The  haemolytic  action  is  specifi- 
cally confined  to  the  red  cells  of  the  species  used  in  the  experiment. 

Immune  (haemolytic)  serum,  like  normal  serum,  is  inactivated 
by  a  temperature  of  56°,  and  reactivated  by  the  addition  of  fresh 
serum  from  an  untreated  animal. 

There  are  additional  points  of  analogy  to  the  process  of  bac- 
terial immunization.  Thus,  essential  to  the  haemolytic  power  of 
the  body  destroyed  at  56°  is  the  action  of  another  which  may  be 
heated  to  60°  with  impunity ;  and  further,  this  second  body  tends 
to  multiply.  Unlike  complement,  it  is  specific,  being  fixed  only  by 
those  red  cells  marked  for  haemolysis.  The  amboceptor  con- 
cerned in  haemolysis  may  be  isolated  in  a  manner  similar  to  that 
described  for  the  bacterial  immune  body  (see  p.  167). 

As  a  given  serum  is  able  on  the  one  hand  to  dissolve  red  cells 
of  diverse  animals,  and,  on  the  other,  after  being  heated  to  56°,  is 
susceptible  of  reactivation  by  the  addition  of  various  complements, 
it  is  natural  to  assume  that  normal  blood  contains  diverse  ambo- 
ceptors and  complements.  In  fact,  both  normal  and  immune  sera 
may  be  deprived  seriatim  of  specific  haemolysins.  Ehrlich  has 
shown  this  experimentally  in  the  varying  behavior  of  haemolysins 
toward  the  red  cells  of  the  same  species.  We  shall  return  to  this 
question  of  multiple  amboceptors,  both  for  red  cells  and  for  bac- 
teria, particularly  because  in  a  physiological  way  it  is  difficult  of 
conception. 

Recent  studies ^^  indicate  that  in  the  haemo- 
lytic process,  a  lipoid  envelope,  or  a  union  of 
lipoids  and  proteids  in  the  red  cells,  undergoes 
disintegration,  and  that  the  antigen  of  artificially  pro- 
duced haemolysis  is  a  lipoid  body.  This  conception  is  even  more 
probable  in  the  case  of  substances  from  the  red  cells  which  inhibit 
haemolysis  in  vitro.  Complement  also  is  supposed  to  contain 
lipoids.^*^  A  definite  conclusion,  however,  as  to  the  significance  in 
haemolysis  of  these  fat-like  bodies  is  not  yet  warranted.  Meyer  ^® 
disputes  the  part  played  by  lipoids,  because  they  are  insoluble  in 
the  ordinary  fat  solvents,  and  even  in  specific  lipoid  solvents. 

Antitoxins. — In  the  matter  of  the  immunity  gained  by  the 
animal  body  to  toxins  in  general,  we  shall  confine  ourselves  to 


170  THE  BASIS  OF  SYMPTOMS 

the  fact  that  bacterial  poisons  are  robbed  of  their  toxicity  by 
certain  constituents  of  the  serum.  For  this  discovery  we  are  in- 
debted to  V.  Behring,  who  found  that  the  blood  of  animals  inocu- 
lated with  the  diphtheria  bacillus,  rendered  innocuous  the  toxin 
of  this  organism. 

A  considerable  number  of  chemical  substances  of  diverse 
origin  and  closely  related  to  the  enzymes  are  altered  by  bodies 
which  they  encounter  in  certain  sera.  That  actual  destruction 
of  the  poisons  does  not  occur  is  shown  by  the  fact  that  they  may 
still  be  demonstrated  after  the  antitoxic  action.  What  actually 
occurs  is  a  fixation  of  the  toxin  by  the  antitoxin. 
This  would  indicate  that  the  reaction  is  one  of  col- 
loids,*^ at  least  in  the  case  of  antitoxin,  which  is  always  com- 
bined with  a  proteid. 

The  source  of  antitoxin  is  variously  ascribed.  Buch- 
ner  originally  contended  that  it  arose  within  the  body  through 
alterations  in  the  toxin,  thus  explaining  its  essential  specificity. 
It  is  our  opinion  that  antitoxin  is  the  reaction  product  of  the 
organism  to  the  poison.  Behring's  famous  formula  reads:  In 
the  living  organism  a  given  substance,  which,  if  present  in  the 
cells  means  poisoning,  occurring  in  the  blood  itself  promotes 
recovery. 

To  discuss  certain  factors  pertinent  to  the  question  of  anti- 
toxins would  be  repetition.  Thus,  Ehrlich's  conception  of  anti- 
body formation  is  based  on  that  of  antitoxin  production.  The 
principles  of  the  side-chain  theory  apply  equally  well  to  the 
process  of  toxin  fixation,  and  to  the  conception  of  immoderate 
over-production  of  side-chains,  which,  cast  into  the  circulation, 
represent  the  individual's  immunity  to  the  poison  in  question. 

Antitoxin  formation  is  not  confined  to  those  cells  which  clini- 
cally have  been  subjected  to  the  action  of  the  poison,  but  is  the 
product  of  all  cells  with  suitable  side-chains.  This  is  a  further 
evidence  of  the  comprehensiveness  of  the  Ehrlich  theory.  The 
hen  and  the  alligator  are  highly  insensitive  to  tetanus,  yet  they 
readily  produce  tetanus  antitoxin;  in  other  words,  tissues  other 
than  nervous  possess  the  appropriate  receptors.  Again,  tetanus 
toxin  remains  inert  for  a  long  time  in  the  blood  of  the  turtle,  and 
yet  no  antitoxin  is  formed,  because  suitable  side-chains  are  not 
present.  Hence,  tetanus  occurs  only  when  the  central  nervous 
system  can  fix  the  toxin. 


INFECTION  AND  IMMUNITY  171 

Once  the  stimulation  to  antitoxin  formation  is  initiated,  anti- 
bodies continue  to  be  produced  for  a  long  period.  For  this  reason, 
the  immimity  acquired  by  passing  through  a  disease  is  more  or  less 
durable,  and  for  the  same  reason,  the  blood  of  animals  strongly 
immunized  may  be  repeatedly  withdrawn,  and  yet  that  which 
is  left  will  always  develop  new  antitoxin.  Similarly  the  injection 
of  pilocarpin  will  increase  the  amount  of  antitoxin  in  the  blood, 
probably  because  it  stimulates  the  cells  to  secrete. 

Remarkable  it  is,  however,  that  antibodies — this  applies  less 
to  antitoxins  than  to  other  immune  bodies — can  persist  in  the 
blood.  No  other  explanation  seems  possible  than  that  their  molec- 
ular construction  is  altered  and  that  they  become,  in  fact,  normal 
constituents  of  the  blood,  endowed  with  the  properties  of  its 
proteids.  This  would  explain  both  their  permanence  and  their 
chemical  action.* ^ 

Antitoxin  is  constant  and  abundant  only  in 
the  blood  of  animals  which  have  passed  through 
a  disease  or  have  been  artificially  immunized  to 
that  disease.  Yet  it  may  be  present  in  the  serum  of 
healthy  individuals,  and  even  in  the  blood  of  the  new-born.  This 
remarkable  fact  is  explainable  in  accordance  with  the  Ehrlich 
hypothesis  on  the  assumption  that  for  some  reason  the  side-chains 
for  which  the  toxin  has  an  affinity  have  been  cast  loose  into  the 
circulation. 

Antitoxins  multiply  exclusively,  or  at  least 
most  energetically,  in  response  to  the  toxins 
which  have  stimulated  their  production.  They 
are  less  resistant  than  toxins  to  light  and  oxygen,  and  are  injured 
by  a  moist  heat  of  6o°-70°  C.  In  experimental  immunization, 
the  antitoxin  content  of  the  blood  begins  to  increase  with  the 
fifth  day — the  maximum  for  diphtheria  occurring  on  the  tenth 
day  and  for  tetanus  on  the  seventeenth.  Thereupon  occurs  a  de- 
cline which  reaches  a  stationary  level  in  about  two  weeks  and  is 
maintained  for  some  time.  Antitoxin  is  present  not  only  in  the 
blood,  but  to  some  extent  in  all  the  body  fluids,  even  in  the  milk."*^ 

Precipitation  and  Precipitins. — ^Just  as  microbic  poisons  are 
rendered  harmless  by  normal,  and  particularly  by  immune,  sera, 
so  any  type  of  proteid  (in  clear  solution)  may  be  precipitated  by 
blood  artificially  inoculated  with  the  same  material.  The  bodies 
calling  forth  this  reaction  are  known  as  precipitins.**     The 


172  THE  BASIS  OF  SYMPTOMS 

proteid  substances  (antigens)  employed  in  this  type  of  immu- 
nization are  called  precipitinogens  and  the  resulting 
product  a  precipitate.  Most  precipitinogens  are  proteids 
alien  to  the  animal  injected,  isoprecipitins  rarely  being  formed. 
These  precipitins  cannot  be  separated  from  the  globulins  of  the 
blood. 

An  acid  reaction,  especially  if  due  to  organic  acids,  is  most 
favorable  to  precipitation,  and  salts,  irrespective  of  their  nature, 
are  essential.  An  excess  of  precipitinogen  prevents  the  reaction 
(so-called  specific  inhibition). ^^  Inhibition  is  spoken  of 
as  non-specific  if  an  alien  proteid  solution  of  high  con- 
centration retards  the  appearance  of  the  precipitate,  or  holds  it 
in  suspension.  For  these  reasons,  the  phenomenon  is  regarded 
as  a  colloidal  reaction;  and  as  precipitinogen  and  pre- 
cipitin are  used  up  in  the  process,  there  can  be  no  question  of  an 
enzymic  action. 

Precipitins  are  relatively  resistant  to  certain  influences,  as, 
for  instance,  to  a  long-continued  temperature  over  60°  C,  to 
desiccation  and  even  to  putrefaction.  They  cause  precipitates 
not  only  with  their  specific  precipitinogens,  but  also,  though  less 
actively,  with  related  prot&ids.  The  more  closely  related  a  given 
proteid  is  to  the  body  employed  in  immunization,  the  more  pro- 
nounced is  the  precipitate.  Upon  this  basis  rests  the  employ- 
ment of  the  reaction  in  the  problems  of  evolution.  Only  in 
a  quantitative  way,  therefore,  may  the  reaction 
be  regarded  as  specific. 

Furthermore,  the  precipitins  of  an  immune  serum  cause  pre- 
cipitation with  other  proteids  of  the  organism  which  furnished  the 
original  precipitinogen;  thus,  the  serum  of  an  animal  immunized 
with  human  blood,  precipitates  human  sperm,  human  milk,  etc. 
Ehrlich  looks  upon  precipitins  as  side  chains  comparable  in  general 
with  antitoxins  and  bacterial  antibodies. 

The  precipitin  reaction  has  already  found  a  considerable  prac- 
tical application  and  with  further  development  will  undoubtedly 
prove  of  great  value  in  differential  diagnosis.  In  the  infectious 
diseases,  the  proteids  of  bacterial  metabolism — the  precipitinogens 
— ^may  be  found  in  the  blood  and  tissues;  and  at  a  later  period, 
the  corresponding  precipitins.  It  is  not  necessary  to  know  the 
organism  itself  to  identify  these  two  bodies.  Attempts  have  also 
been  made  to  adapt  the  reaction  to  the  diagnosis  of  carcinoma; 


INFECTION  AND  IMMUNITY  173 

further,  to  demonstrate  that  the  substances  responsible  for  puer- 
peral eclampsia  are  of  fetal  origin ;  and  finally,  to  isolate  the  toxic 
proteid  of  bothriocephalus  infection,  and  to  establish  that  the 
albumin  in  nephritic  urine  comes  from  the  body  proteid  itself. 

In  medical  jurisprudence  the  precipitation  reaction 
has  proved  of  great  assistance,  particularly  in  determining  whether 
a  given  specimen  of  blood  is  from  man  or  not.  Uhlenhuth's  ^^ 
method  of  immunization  with  proteids  of  allied  species,  e.g.,  man 
and  ape,  faciHtates  the  diagnosis  between  the  blood  of  these  two. 
The  precipitin  reaction  persists  in  material  which  has  been  exposed 
to  desiccation  for  as  long  as  seventy  years,  or  which  has  been 
frozen,  or  exposed  to  sunlight  or  moderately  decomposed. 

Complement  Fixation.  The  Wassermann  Reaction. — Still 
another  advance,  eventuating  in  the  combination  of  the  precipi- 
tation and  the  hsemolysis  reactions,  followed  the  discovery  by 
Bordet  and  Gengou**^  that  the  bringing  together  of  red  corpuscles 
or  bacteria  with  their  specific  immune  sera  (so-called  sensi- 
tization) led  to  the  fixation  of  complement.  In  other  words, 
each  time  antigen  is  brought  into  contact  with  its  antibody,  com- 
plement vanishes.  The  disappearance  of  comple- 
ment, evidenced  by  the  non-appearance  of  haemo- 
lysis, is  striking  even  in  minimal  precipitin  reactions.  To 
an  otherwise  suitable  hsemolytic  system,  composed  of  red  cells, 
amboceptor  and  complement,  the  addition  of  precipitinogen  and 
its  antiserum  inhibits  haemolysis  if  complement  is  fixed.  The 
proteids  of  human  blood  are  sensitive  in  this  way  up  to  a  dilution 
of  one  hundred  thousand  and  more.*^ 

Antigens  and  their  antibodies  may  also,  as  already  noted,  be 
demonstrated  in  the  case  of  micro-organisms  not  susceptible  of 
cultivation,  or  where  we  have  to  do  with  unknown  viruses,  for 
they  are  present  in  extracts  of  definitely  diseased  organs,  and 
late  in  the  process  in  the  serum  of  the  affected  individual,  and 
also  in  the  serum  of  animals  immunized  with  the  organ  extracts. 
The  evidence  of  the  presence  of  antigen  and 
antibody  in  a  hsemolytic  system  is  the  inhibition 
of  haemolysis.  This  phenomenon  enables  one,  by  varying 
the  experimental  conditions,  to  demonstrate  in  a  given  serum, 
or  inflammatory  fluid,  the  presence  of  antigen  in  the  early  stages 
of  a  disease,  and  of  antibody  in  the  later  stages,  or  whether  the 
disease  is  actually  infectious  or  not.*^ 


174  THE  BASIS  OF  SYMPTOMS 

Wassermann  and  his  co-workers,  on  the  basis  of  these  reac- 
tions, have  evolved  a  serum  reaction  for  syphilis.  It  was  at  first 
beheved  that  the  bringing  together  of  syphiHtic  antigen  (ex- 
tract of  the  fetal  luetic  liver)  and  antibody  (luetic  serum)  was 
essential  to  the  fixation  of  complement  and  the  consequent  inhibi- 
tion of  haemolysis  when  red  cells  with  their  specific  amboceptors 
were  added.  Further  study,  however,  revealed  the  astonishing 
fact  that  extracts  of  luetic  organs  were  by  no  means  necessary 
and  that  alcoholic  extracts  of  normal  organs  sufficed.  Com- 
plement fixation,  therefore,  occurs  as  a  consequence  not 
of  the  meeting  of  luetic  antigen  and  luetic  antibody,  but  as  the 
result  of  the  contact  of  a  normal  body  substance  with  luetic 
serum.  These  substitutes  for  antigen,  being  soluble  in  alcohol, 
are  probably  lipoids. 

An  entirely  satisfactory  explanation  of  the  Wassermann  reac- 
tion is,  for  the  present,  wanting.  This  does  not  detract,  however, 
from  its  great  practical  value.®*^  Many  observers  insist  on  the 
use  of  syphilitic  antigen  in  order  to  obtain  the  most  dependable 
results.  If  extracts  of  normal  organs  (heart-muscle)  are  em- 
ployed, great  care  must  be  exercised  in  keeping  them  of  uniform 
composition. 

(The  principle  of  complement  fixation  has 
been  adapted  to  the  diagnosis  of  other  condi- 
tions, though  with  results  far  less  satisfactory  and  constant 
than  in  the  case  of  syphilis.  In  certain  types  of  gonorrhoeae^ 
and  in  echinococcus  disease,^^  the  reaction  has  proved  of  consider- 
able practical  value;  in  tuberculosis,^^  typhoid  fever  and  other 
diseases,  it  has  generally  been  discarded.  Gonorrhoeal  comple- 
ment fixation,  unlike  that  occurring  in  syphilis,  is  a  biologically 
specific  antigen-antibody  interaction. — Ed.) 

Agglutination  and  Agglutinins. — The  phenomenon  of  agglu- 
tination is  a  further  type  of  reaction  exerted  by  the  blood-serum, 
upon  alien  cells  and  bacteria.  It  is  manifested  by  a  clumping  and 
precipitation  of  the  latter.^*  The  relation  of  agglutination  to  the 
process  of  immunity  is  still  not  clear.  The  fact  that  the  agglu- 
tinins are  less  sensitive  to  heat  than  are  immune  bodies  is  scarcely 
a  distinguishiiig  mark,  for  the  latter  are  themselves  not  constant 
in  this  respect.  Though  the  agglutinating  property  of  a  serum 
is  largely  independent  of  its  bactericidal  power,  yet  it  appears  that 
agglutination  has  some  influence  upon  the  destruction  of  the 


INFECTION  AND  IMMUNITY  175 

clumped  cells.    Nevertheless  agglutinated  bacteria  may  live  a  long 
time,  and,  furthermore,  dead  bacteria  will  also  clump. 

The  current  interpretation  of  the  nature  of  agglutination  is 
that  a  portion  of  the  bacterial  substance  (the  agglutinogen) 
is  bound  by  the  antibody  (agglutinin)  which  it  gives  rise 
to.  This  is  also  in  all  probability  a  reaction  of  colloids. 
The  agglutinins  are  combined  in  a  few  minutes,^^  but  hours  may 
elapse,  especially  at  low  temperatures,  before  agglutination  is 
distinctly  manifested.  Centrifugation  noticeably  hastens  the  pre- 
cipitate.^® In  the  Ehrlich  theory,  agglutinins  are 
analogous  to  precipitins,  antitoxins,  hsemoly- 
sins,  etc.  Temperatures  over  70°  C.  are  necessary  to  destroy 
them;  and  they  resist  desiccation,  to  a  certain  degree  light,  and 
even  decomposition,  but  they  are  inactive  in  solutions  not  con- 
taining salts. 

Normal  serum  is  only  feebly  agglutinating,  dilutions  of  i :  50 
generally  inhibiting  the  phenomenon.  Immune  sera,  on  the  con- 
trary, are  powerfully  agglutinative,  dilutions  of  even  i :  100,000 
clumping  typhoid  baciUi.  Quantitatively,  therefore, 
agglutination,  like  precipitation,  is  specific; 
for  although  closely  related  micro-organisms  may  also  be  agglu- 
tinated (group  agglutinins)  by  a  specific  serum,  this  occurs  only 
in  comparatively  low  dilutions.  The  higher  dilutions  act  only 
on  the  specific  micro-organisms  that  caused  the  infection.  Agglu- 
tinins may  also  be  found  in  insignificant  amounts  in  extracts  of 
organs  freed  from  their  blood,  and  in  milk,  pus,  etc. 

The  agglutinins  appear  in  the  blood  of  warm-blooded  animals 
in  from  three  to  ten  days  after  the  inoculation  of  bacteria  or  their 
products.  They  increase  rapidly  in  amount  for  about  a  week,  and 
then  diminish  more  or  less  gradually.  As  a  rule,  the  typhoid 
agglutinins  disappear  from  the  blood  of  man  after  about  one 
year,  though  there  are  many  exceptions  to  this  rule. 

(In  this  connection  may  be  mentioned  the  method  of  vac- 
cination against  typhoid  introduced  by  Wright."  The 
vaccine  is  obtained  from  a  bouillon  or  agar  culture  of  the  bacilli, 
killed  at  a  temperature  of  54°  to  55°  C.  Three  injections  are 
made  at  intervals  of  ten  days,  the  first  of  five  hundred  million  of 
the  bacteria,  the  last  two  of  one  billion  each.  The  injections 
usually  produce  a  mild  local  reaction,  and  variably  severe  con- 
stitutional symptoms  of  fever,  headache,  malaise,  etc.     Immunity 


k 


176  THE  BASIS  OF  SYMPTOMS 

is  granted  by  an  increase  in  the  agglutinating  and  bactericidal 
powers  of  the  blood.  The  duration  of  the  Widal  reaction  after 
vaccination  is  as  yet  undetermined;  at  any  rate,  in  cases  sugr 
gestive  of  typhoid,  a  previous  vaccination  must  be  taken  into 
account  when  the  agglutinating  power  of  the  suspected  serum  is 
being  determined. 

Statistics  based  upon  vaccination  in  the  British  and  American 
armies  ^^  indicate  that  protection  against  typhoid  is  granted  in 
the  vast  majority  of  cases.  How  long  this  immunity  endures 
has  not  been  definitely  established ;  it  would  seem,  however,  that 
revaccination  every  four  years  is  quite  sufficient. — Ed.) 

The  Relation  of  Antitoxins  and  Bacteriolysins  to  Immunity. — 
Observers,  generally,  have  attributed  the  state  of  immunity  pro- 
duced by  spontaneous  and  experimental  infection  with  organisms 
not  known  to  f  onn  soluble  toxins,  to  the  appearance  of  bactericidal 
substances  in  the  blood.  Investigation  has  shown,  however,  that 
the  blood-serum  becomes  bactericidal  before  the  disease  has  run 
its  course — in  typhoid,  for  example,  at  a  time  when  immunization 
could  not  possibly  have  been  established;  and  furthermore,  that 
the  same  serum  is  less  bactericidal  in  cultural  studies  than  when 
employed  in  the  living  animals.^®  These  facts  indicate  that  the 
power  of  destroying  micro-organisms  is  not  the 
only  element  in  the  acquisition  of  immunity. 

In  diseases  due  to  bacteria  producing  a  solu- 
ble toxin,  the  formation  of  antitoxin  is,  with- 
out doubt,  one  of  the  chief  factors  in  recover y — 
hence,  the  adaptation  of  antitoxin  immediately  after  its  discovery 
both  to  the  prevention  and  the  cure  of  diphtheria.  Recovery  is 
possible  only  if  toxin  already  anchored  is  rendered  harmless  by  the 
antitoxin  introduced.  It  soon  became  apparent,  however,  that 
to  cure,  considerably  more  antitoxin  was  needed  than  to  im- 
munize, and  that  the  longer  the  disease  had  been  in  progress, 
the  more  antitoxin  was  called  for,  so  that  at  a  certain  point  even 
enormous  doses  were  unavailing.^^'  In  the  practical  application 
of  serum  therapy,  a  knowledge  of  these  factors  is  indispensable. 
Large  doses  of  serum,  therefore,  are  indicated,  and  of  a  concen- 
tration as  high  as  possible  to  obviate  the  effects  of  large  amounts 
of  an  alien  proteid. 

Ehriich  introduced  a  method  of  standardization  of 
the  different  immune  sera.     In  the  case  of  diphtheria 


INFECTION  AND  IMMUNITY  177 

antitoxin,  for  instance,  the  immunizing  unit  was  contained  in  a 
serum  one  cubic  centimetre  of  which  neutraHzed  toxin  equivalent 
to  one  hundred  times  the  lethal  dose  for  the  guinea-pig.  But 
as  the  standard  toxin  solutions  were  not  stable,  this  method  has 
not  continued  in  use,  and,  at  present,  sera  are  controlled  with  a 
standard  immune  serum  in  powdered  condition  and  protected  from 
the  light  and  air,  in  the  Ehrlich  Institute. 

The  curative  value  of  diphtheria  antitoxin  as 
against  living  Klebs-Loeffler  bacilli,  according  to  some  observers, 
does  not  run  parallel  with  its  antitoxic  titer.  It  is  possible  that 
the  avidity  with  which  toxin  and  antitoxin  combine  is  also  a 
factor,  and  that  a  serum  of  high  potency  may  display  only  a  slight 
avidity  of  this  sort.^^  This  conception,  however,  is  vigorously 
attacked  by  those  who  say  that  the  therapeutic  value  of  a  serum 
depends  upon  the  number  of  immunizing  units  it  contains.^ ^ 

Antitoxic  sera  disappear  rapidly  from  the  circulation  (see 
p.  162).  In  diphtheria  epidemics,  therefore,  the  indication  is  to 
repeat  the  prophylactic  dose ;  yet  the  danger  of  anaphylaxis  must 
be  considered  (see  below) . 

(B.  Schick®^  has  suggested  a  method  for  de- 
termining whether  an  individual  exposed  to 
diphtheria  is  in  need  of  prophylactic  injections 
of  the  serum,  in  this  way  obviating  the  promiscuous  use  of 
the  latter  and  the  dangers  of  anaphylaxis  when  the  disease  has 
actually  developed.  This  method,  which  is  based  upon  the  exist- 
ence of  some  degree  of  natural  immunity  in  the  individual,  con- 
sists of  the  intracutaneous  injection  of  an  exceedingly  small  fixed 
dose  of  diphtheria  toxin.  If  the  serum  of  the  person  who  has 
been  exposed  contains  no  antibodies,  a  local  inflammatory  reaction 
occurs,  and  antitoxin  is  indicated. — Ed.  ) 

Injected  subcutaneously,  antitoxin  is  slowly  absorbed,  the 
blood  not  attaining  its  maximum  concentration  until  after  the 
third  day.  The  advantage  of  the  intramuscular  method  resides 
in  the  fact  that  absorption  is  well  advanced  within  the  first  twenty- 
four  hours.  The  most  rapid  results  follow  intravenous  injec- 
tion.^^ In  meningococcus  meningitis  the  serum  must  be 
brought  into  direct  contact  with  the  micro-organisms.  It  would 
seem  that  the  tendency  has  been  to  employ  antitoxin  in  too  small 
doses,  especially  when  sufficient  time  has  elapsed  to  have  allowed 
12 


178  THE  BASIS  OF  SYMPTOMS 

toxin  to  become  anchored  to  the  cells.     In  recent  years,  indeed, 
heavier  doses  have  been  the  rule.^^ 

In  the  therapeutic  application  of  the  principles  of  immunity, 
attempts  were  made,  even  at  an  early  period,  to  create  an  active 
immunity  both  during  the  incubation  period  of  a  disease  and 
during  its  early  course.  The  Pasteur  treatment  in  rabies  is  an 
example.  Later,  efforts  were  made  to  cure  typhoid  fever  by 
injections  of  killed  bacilli.  (The  results  both  with  the  method 
of  active  immunization  and  with  injections  of  typhoid  immune  sera 
have  been  generally  unsatisfactory;  at  any  rate,  far  less  encourag- 
ing than  those  obtained  by  prophylactic  vaccination  against  typhoid 
fever.  The  sensitized  virus-vaccine  of  Besredka  seems  to  offer  a 
more  encouraging  outlook. — Ed.  )  In  chronic  infections  the  indi- 
cation for  vaccine  and  serum  therapy  is  clearer.  (Vaccines  and 
immune  sera  have  proved  highly  efficacious  in  certain  well-chosen 
chronic  conditions ;  but  their  promiscuous  use  and  their  commer- 
cialization have  brought  this  method  of  active  immunization  into 
more  or  less  disrepute,  so  that  to-day  it  is  much  less  employed 
than  formerly. — Ed.)  The  introduction  of  tuberculin  by  Koch 
also  led  to  the  extensive  application  to  tuberculosis  of  this  mode 
of  treatment.  The  so-called  opsonic  therapy  of  Wright  (see 
p.  189)  is  based  upon  similar  principles.  The  rapid  and  enduring 
immunity  given  by  the  combined  active-passive  method  with  ex- 
tremely small  doses  of  sera  has  led  to  its  therapeutic  adaptation,^* 
in  puerperal  septicaemia  among  other  conditions. 

Anaphylaxis.  Serum  Disease. — In  all  types  of  immunization 
the  tissues  build  reactive  substances  more  rapidly  and  abundantly 
when  antigen  is  repeatedly  injected.  The  cells  thereby  become 
endowed  with  an  altered  power  of  reaction,  by  v.  Pirquet,  who 
first  recognized  the  practical  significance  of  the  phenomenon, 
termed  allergic;  instead  of  immune,  they  become  hyper- 
sensitive. This  was  observed  by  v.  Behring  in  horses,  which 
succumbed  to  a  relatively  small  dose  of  toxin,  though  their  blood 
contained  abundant  antitoxin.  The  Ehrlich  theory  would  ex- 
plain this  paradox  on  the  assumption  that  side-chains  held  closely 
by  the  tissue-cells  possess  a  greater  affinity  for  toxin  than  does 
antitoxin — the  chains  free  in  the  blood. 

Allergie  is  exhibited  more  regularly  after  the  parenteral  intro- 
duction of  alien  proteids  than  after  toxin  injection.  This  type 
of  hypersensitiveness,  known  as  anaphylaxis,  after  Richet,®'^ 


INFECTION  AND  IMMUNITY  179 

must  be  reckoned  with  as  an  unwelcome  by-eflfect  both  in  active 
and  passive  immunization.  Untiring  research  speedily  estab- 
lished this  apparently  enigmatic  process  on  a  firm  basis.®®  Fried- 
berger,  indeed,  has  recently  demonstrated  anaphylatoxin  in  vitro. 

The  fundamental  experiment  best  suited  to 
demonstrate  the  phenomenon  is  the  following:  A 
guinea-pig  is  injected  subcutaneously  with  a  foreign  proteid,  e.g., 
one  milligram  of  normal  sheep  serum.  This  injection  represents 
the  preparation  or  sensitization.  In  ten  days,  five 
milligrams  of  the  same  serum  are  given  intravenously — the 
reinjection.  The  animal  at  once  becomes  restless,  has 
severe  convulsions  and  within  five  minutes  dies  in  asphyxia.  The 
characteristic  manifestations  are  dyspnoea,  paralysis 
of  the  peripheral  vasomotor  apparatus — ^hence  a  marked  fall  in 
blood-pressure — leucopaenia,  even  to  the  absence  of  the  poly- 
nuclears,  a  fall  in  temperature  as  great  at  times  as  io°  C,  spasm 
of  the  bronchial  muscles  and  a  consequent  pronounced  pulmonary 
emphysema,  a  diminished  coagulability  of  the  blood,  and  a  reduc- 
tion of  complement  in  the  serum. 

An  intraperitoneal  reinjection  produces  the  same  symptom- 
complex,  except  that  the  duration  is  prolonged  and  death  is  not 
inevitable.  If  the  second  injection  be  subcutaneous  and  not  too 
large,  there  appears  locally  an  oedema  which  quickly  becomes 
hemorrhagic  and  ends  in  sluggish  ulcers  (Arthus).  By  the  intra- 
venous route,  sensitization  may  be  produced  and  reinjection  made 
with  infinitesimally  small  amounts  of  sheep  serum — for  the  for- 
mer, the  one  five-thousandth  part  of  the  fatal  intravenous  dose, 
and  for  the  latter,  the  one  one-thousandth. 

An  incubationperiodof  about  ten  days  must  be  allowed 
to  elapse  between  the  first  and  second  injections — a  fact  allying 
anaphylaxis  with  the  phenomena  of  infection  and  immunity.  The 
allergic  state  may  continue  for  a  long  period,  in  guinea-pigs  up 
to  two  years  (Rosenau  and  Anderson)  and  in  man  up  to  five 
(Curie),  Man,  however,  is  far  less  sensitive  to  reinjection  than 
is  the  guinea-pig.  All  warm-blooded  animals  are  more  or  less 
predisposed  to  anaphylaxis,  while  of  cold-blooded,  only  the  frog 
has  thus  far  been  sensitized. 

The  reaction  occurs  irrespective  of  the  kind  of  alien  proteid 
used,  whether  animal,  vegetable  or  bacterial.  The  determining 
component  of  the  serum  is  the  euglobulin.     Pointing  to  the 


180  THE  BASIS  OF  SYMPTOMS 

specificity  of  anaphylaxis  is  the  fact  that  the 
same  proteid  must  be  used  for  sensitization  and 
reinjection.  Rosenau  and  Anderson  showed  that  guinea- 
pigs  could  be  sensitized  by  the  oral  administration  of  abundant 
proteid  in  the  food,  followed  by  parenteral  inoculation  of  the 
same  proteid.  Indeed,  using  the  proteid  of  the  crystalline  lens, 
rabbits  were  made  allergic  by  oral  introduction  both  in  sensitiza- 
tion and  in  reinjection. 

Certain  non-alien  proteids  may  also  provoke  anaphylaxis  in  a 
manner  analogous  to  precipitation  phenomena  already  noted. 
Guinea-pigs,  for  example,  may  be  so  sensitized  by  the  proteid  of 
the  guinea-pig's  lens — even  by  its  own  lens  proteid — as  to  react 
typically  upon  reinjection  of  the  same  body.  Similar  results  have 
been  obtained  with  the  spermatozoa  and  ova  of  the  same  species, 
especially  when  the  former  are  injected  into  pregnant  animals. 

The  transmission  of  allergic  to  the  offspring  is  the  first  evi- 
dence of  the  hereditary  nature  of  an  apparent  predisposition  to 
a  disease.  Such  an  inherited  sensitiveness  lasts  only  about  six 
weeks  and  is  transmitted  exclusively  by  the  mother's  serum  (to 
the  offspring). 

The  fact  that  the  blood-serum  of  a  sensitized  animal,  if  intro- 
duced into  another  animal,  renders  the  latter  also  allergic 
(passive  anaphylaxis)  points  convincingly  to  the  immu- 
nologic character  of  anaphylaxis. 

Serum  disease,  a  special  type  of  anaphylaxis  which  we 
shall  consider  in  another  place,  is  ascribed  by  v.  Pirquet  to  the 
meeting  of  an  alien  proteid  with  its  specific  antibody.  It  would 
carry  us  too  far  afield  to  review  the  various  theories  adduced  in 
explanation  of  the  anaphylactic  reaction.  That  of  Nicolle,^® 
which  seems  to  explain  the  phenomena  of  immunity  in  general, 
merits  special  consideration.  According  to  this  theory,  there  are 
two  classes  of  antibodies  formed,  coagulins  and  lysins,  the  for- 
mer embracing  antitoxins,  precipitins  and  agglutinins,  the  latter 
perhaps  all  lytic  antibodies  which  together  with  complement  ren- 
der accessible  the  actual  poison  in  antigen.  If  the  latter  is  rein- 
jected into  the  immune  organism,  it  is  held  by  the  coagulin  and 
destroyed  by  the  lysins.  If  these  last,  however,  prematurely  grasp 
antigen,  then,  with  the  aid  of  complement,  toxin  is  quickly  set 
free.  On  this  assumption  Nicolle  was  able  to  demonstrate  that 
the  serum  of  anaphylactized  animals,  together  with  the  antigen 


INFECTION  AND  IMMUNITY  181 

employed,  led  to  fixation  of  complement  (diphtheria  toxin  with 
the  serum  of  animals  sensitized  with  the  same  toxin). 

Friedberger  has  succeeded  in  isolating  anaphylatoxin 
starting  with  these  premises,  viz.,  first,  that  unprepared  animals 
may  be  made  anaphylactic  by  receiving  a  mixture  of  sensitized 
serum  plus  the  specific  antigen;  and,  secondly,  that  complement 
is  essential  to  the  formation  of  the  anaphylactic  poison.  His 
method  was  as  follows:  Horse  serum  (antigen)  was  mixed  with 
its  antibody  (rabbit  serum  sensitized  with  horse  serum)  and  to 
the  resulting  precipitate — ^first  carefully  washed  with  physiologi- 
cal salt  solution — was  added  complement  (fresh  guinea-pig 
serum).  The  precipitate  occurring  here  was  removed  by  cen- 
trifugation.  The  supernatant  guinea-pig  serum  produced  in  ani- 
mals (not  previously  sensitized)  classical  anaphylactic  shock,  and 
must,  therefore,  have  contained  the  anaphylactic  poison.  One 
milligram  of  an  alien  serum  was  sufficient  to  call  forth  an  active 
anaphylatoxin;  in  the  production  of  the  latter,  therefore,  not 
the  amount  but  rather  the  number  of  antibodies  is  important.  If 
the  latter  are  over-abundant,  the  proteid  molecules  disintegrate 
too  rapidly,  while  the  toxic  intermediary  products  are  transformed 
into  simpler,  innocuous  substances.  The  same  is  true  when  the 
antibody  action  is  too  prolonged. 

Anaphylaxis,  therefore,  is  an  antibody  reac- 
tion and  as  such  must  be  identified  with  other 
immunity  phenomena.  Antiproteins,  then,  would  prop- 
erly be  classed  with  the  amboceptors,  though  they  are  not  to  be 
identified  with  the  bacteriolytic  amboceptor.  Bacteriolysis  indeed 
interferes  with  anaphylatoxin  formation.  Normal  serum,  among 
the  other  antibodies  it  contains,  also  contains  one  in  small  amount 
which  can  split  proteid  in  the  presence  of  complement  and  which 
is  increased  enormously  if  the  specific  antigen  be  injected. 

A  foreign  proteid  after  the  first  injection  is  slowly  disin- 
tegrated; after  the  second,  when  antibodies  are  abundantly  pres- 
ent, the  latter  and  the  alien  proteid  are  brought  into  sudden 
contact,  the  proteid  is  rapidly  split  with  the  aid  of  complement, 
and  the  intermediate  products — probably  identical  with  those  of 
intestinal  digestion — exert  a  toxic  action,  in  all  likelihood,  because 
they  cannot  be  eliminated  as  is  the  case  in  the  digestive  tract. 
This  conception  of  the  mechanism  of  anaphylaxis  is  strengthened 
by  the  fact  that  certain  anaphylactic  manifestations  are  identical 


182  THE  BASIS  OF  SYMPTOMS 

with  those  of  peptone  poisoning;  anatomically,  too,  the  picture 
is  the  same. 

If  a  sensitized  animal  be  reinjected  with  a  dose  of  foreign 
proteid,  insufficient  to  cause  death,  antibody  formation  is  arrested 
in  such  a  manner  that  a  third  injection  of  the  same  antigen,  even 
in  large  amount,  and  following  quickly  upon  the  second,  is  borne 
with  impunity.  This  condition  is  called  antianaphylaxis 
(seep.  185). 

What  is  known  as  primary  anaphylaxis  may  be  illus- 
trated as  follows :  If  a  normal  animal  receives  a  large  dose  of 
an  alien  proteid — not  great  enough,  however,  to  cause  death — 
this  proteid  is  partially  split  by  those  antibodies  normally  present 
in  the  serum.  Simultaneously,  the  injection  leads  to  the  formation 
of  new  antibodies,  with  the  result  that  a  certain  residue  of  the 
foreign  proteid,  together  with  these  antibodies,  exist  side  by 
side  without  interaction,  due  apparently  to  some  peculiar  regula- 
tory mechanism.  If  this  serum  be  injected  into  a  normal  animal, 
however,  this  mechanism  is  ineffective,  the  antigen  residue  com- 
bines with  antibody  and  anaphylaxis  results.  The  practical  im- 
portance of  this  is  obvious :  a  serum  must  not  be  withdrawn  too 
soon  after  the  reinjection,  as  free  antigen  may  still  be  present.  It 
is  advisable,  furthermore,  to  test  curative  sera  before  distribution 
with  this  possibility  in  mind. 

One  millionth  of  a  milligram  of  a  protein  substance  injected 
into  a  sensitized  guinea-pig  causes  fever,  whereas,  in  a  normal 
animal  five  centigrams  are  necessary.  In  this  connection,  we 
would  note  that  several  decades  ago,  the  author  ^*^  produced  a 
febrile  reaction  with  proteids  of  all  kinds  and  also  with  their 
split-products,  the  reaction  becoming  more  marked  with  the  repe- 
tition of  the  injections.  Even  at  that  early  period,  the  author 
asked  himself  whether  substances  of  different  thermic  attributes 
arose  only  after  the  disintegration  of  the  bacteria  in  the  living 
organism.  A  more  or  less  constant  fever  was  produced  by  Fried- 
berger  and  Mita,  in  sensitized  animals,  by  continued  parenteral 
injections  of  minimal  proteid  doses.  Injection  of  larger  amounts, 
however,  at  the  height  of  the  artificial  fever,  led  to  a  pronounced 
fall  in  temperature  and  to  the  condition  of  anaphylaxis.  Further, 
if  the  sensitized  animal  was  injected  with  the  given  proteid  during 
the  incubation  period,  a  febrile  reaction  took  place,  but  with  a 
considerably  smaller  dose  than  in  normal  animals.     Friedberger 


INFECTION  AND  IMMUNITY  188 

concludes  from  this  that  antibody  formation  does  not  take  place 
suddenly  from  the  seventh  to  the  tenth  day,  but  that  it  begins 
in  the  second  twenty- four  hours  and  gradually  increases.  This 
observation  is  of  importance  in  the  matter  of  the  negative  phase. 

Local  anaphylaxis  does  not  predicate  the  existence  of 
sessile  receptors,  but  rather  the  local  accumulation  of  antigen 
which  combines  with  antibody  free  in  the  circulation  at  that  par- 
ticular point.  On  this  basis,  Friedberger  explains  pulmonary  in- 
filtration in  pneumonia,  pneumococci  collecting  in  the  lungs  and 
there  coming  into  contact  with  their  specific  antibodies.  The 
resultant  systemic  manifestations  are  due  to  anaphylatoxin  for- 
mation. Friedberger  and  Mita  produced  fever  and  aseptic  in- 
flammation in  the  lungs  of  sensitized  guinea-pigs  by  having  them 
inhale  the  specific  serum.  Thus  the  fever  curve,  and  all  of  the 
other  characteristic  symptoms  of  different  infections,  may  be 
imitated  by  the  continued  parenteral  injection  of  a  foreign,  per  se 
non-toxic,  proteid  by  varying  the  dosage,  the  interval  between 
injections  and  the  point  of  injection,  and  by  producing  a  variation 
in  the  number  of  antibodies  formed  and  used  up — or  otherwise 
expressed,  in  the  resultant  amount  of  anaphylatoxin.  Herein 
would  reside  the  link  between  infection,  immunity  and  anaphylaxis 
as  set  forth  at  an  earlier  period  by  Wolff-Eisner,  whose  concep- 
tion, however,  was  purely  hypothetical  and  differently  formulated. 

Infection  from  this  point  of  view  represents 
an  attenuated  and  protracted  anaphylaxis,  the 
incubation  period  corresponding  to  the  preparation  of  the  animal. 
As  long  as  the  infection  continues,  a  minimal  parenteral  proteid 
introduction  is  taking  place,  for  the  infectious  agents  are  constantly 
multiplying  and  undergoing  destruction.  The  analogues  in  the 
anaphylactic  process  would  be  minimal  doses  of  artificially  intro- 
duced amorphous  proteid,  a  variably  great  consumption  of  anti- 
bodies, antianaphylaxis,  local  processes,  fever,  etc. 

In  the  opinion  of  Friedberger,  there  is  only  one  anaphylatoxin. 
The  analogue  of  this  he  finds  in  the  uniform  protein  split-products 
arising  from  the  most  diverse  proteids  in  the  course  of  intestinal 
digestion.  The  union  of  antibody  with  its  appropriate  antigen, 
therefore,  would  represent  the  only  element  of  specificity  in  the 
process.  He  bases  this  conception  upon  the  observation  that  by 
intravenous  injection  of  proteid  split-products,  a  symptom- 
complex  is  produced  identical  with  that  of  anaphylaxis.     This  has 


184  THE  BASIS  OF  SYMPTOMS 

been  confirmed  from  many  sides.  Biedl  and  Kraus  had  similar 
results  with  peptone.  In  Friedberger's  mind  it  is  unnecessary  to 
assimie  that  in  the  different  infectious  diseases — excluding  those 
which  give  rise  to  soluble  toxins  (tetanus,  diphtheria,  botulism) — 
in  addition  to  anaphylatoxin,  there  is  formed  another  peculiarly 
specific  poison. 

In  our  opinion,  Friedberger  has  gone  too  far  in  his  attempt  to 
identify  the  phenomena  of  infection  with  those  of  anaphylaxis, 
granting  that  much  in  the  clinical  picture  of  the  former  can  best 
be  interpreted  on  an  allergic  basis.  Nevertheless,  peculiar  to  each 
infection  are  many  features  not  thereby  accounted  for  and  which 
postulate  the  assumption  of  a  specific  poison.  The  striking* 
somnolence  in  hen  cholera  is  a  case  in  point,  as  Pasteur  has  shown 
that  this  same  symptom  may  be  produced  without  the  injection 
of  living  bacilli  if  a  bouillon  filtrate  of  the  organism — enormous 
in  amount  it  is  true — be  introduced.  Here  it  is  not  an  indifferent 
poison  that  is  acting,  for  still  larger  doses  of  the  filtrate  cause 
death.  Klemperer  is  also  of  the  opinion  that  the  characteristic 
pictures  of  the  different  infections  are  to  be  interpreted  with  diffi- 
culty except  on  the  basis  of  specific  toxins,  citing  as  an  example 
the  necessity  of  assuming  the  presence  of  the  toxin  of  the  tubercle 
bacillus  to  explain  caseation.  Friedberger,  in  reply,  calls  atten- 
tion to  the  fact  that  reinjection  of  proteid  in  sensitized  rabbits 
causes  necrosis  and  caseation.  Citron,  on  the  other  hand,  points 
out  that  if  there  were  but  one  anaphylatoxin,  active  immunization 
to  one  infection  would  necessarily  mean  that  it  existed  to  all. 

As  we  have  already  noted,  the  anaphylactic  state  may  also  be 
produced  by  feeding  foreign  proteids.  On  this  ground,  possibly, 
are  to  be  explained  those  urticarial  conditions  which 
follow  the  ingestion  of  a  particular  food.  Here 
we  must  assume  that  as  a  result  of  abnormal  intestinal  permea- 
bility, due  in  turn  perhaps  to  digestive  disorders,  proteid  enters 
the  circulation  after  a  preliminary  splitting  by  the  intestinal  fer- 
ments. This  would  be  equivalent  then  to  parenteral  introduction, 
and  minute  amounts  would  suffice.  Possibly,  an  albuminous  food 
is  not  unequivocally  necessary  to  produce  this  urticarial  phe- 
nomenon ;  the  specific  antibody  may  have  been  previously  formed, 
or  have  arisen  with  the  first  occurrence  of  intestinal  permeability. 
The  idiosyncrasy  of  certain  children  to  cow's  milk,  evidenced  by 


INFECTION  AND  IMMUNITY  185 

fever,  vomiting  and  diarrhoea,  asthma,  convulsions  and  collapse, 
is  very  likely  anaphylactic  in  nature. 

The  so-called  serum  disease,  because  of  its  clinical  bearing,  is 
the  best  known  and  most  important  type  of  anaphylaxis.  To 
V.  Pirquet  and  Schick  is  due  the  credit  of  first  calling  attention 
to  the  symptom-complex.  It  occurs  in  about  ten  per  cent,  of  indi- 
viduals receiving  for  the  first  time  an  injection  of  an  immune 
serum  (as  a  rule  that  of  immunized  horses).  The  incuba- 
tion period  is  roughly  ten  days,  which  represents  the  time 
required  for  the  formation  of  sufficient  antibodies.  Accompa- 
nied by  fever,  there  occurs  an  urticarial,  sometimes  a  polymorphous 
exanthem,  generally  starting  from  the  site  of  injection.  The  rash 
persists  for  two  to  three  days,  or  longer,  the  lesions  appearing 
in  crops.  Pain  in  the  joints  and  muscles  and  an  albuminuria  may 
be  present.  Indeed,  the  picture  of  serum-sickness  may  differ  in 
no  respect  from  that  of  an  acute  infection. 

It  is  evident  from  the  foregoing  that  serum  anaphylaxis  occurs 
most  frequently  after  the  reinjection  of  an  immune  serum,  when 
the  interval  between  the  injections  is  not  less  than  ten  to  twelve 
days.  With  this  incubation  period,  the  symptoms  begin  at  once 
(v.  Pirquet's  immediate  reaction).  Serum  disease,  like  experi- 
mental anaphylaxis,  occurs  most  readily  after  intravenous  injec- 
tions. 

To  prevent  serum  disease,  it  has  been  suggested  that  the 
prophylactic  injection  be  made  with  an  immune  serum  obtained 
from  sheep  or  cattle,  to  the  end  that  horse  serum  may  then  be 
employed  without  risk  if  the  disease  develops  despite  the  pre- 
ventive dose.  In  the  Pasteur  Institute  the  sera  are  heated  at  56° 
C.  for  a  number  of  days  and  are  thus  made  less  toxic.  The  same  is 
true  of  sera  which  have  been  allowed  to  stand  for  a  long  period. 
Apparently  the  best  method  of  guarding  against  serum  disease 
is  by  first  rendering  the  individual  antianaphylactic,  by  introducing 
subcutaneously  or  intravenously,  in  high  dilution,  a  small  amount 
of  the  serum  indicated,  and  gradually  increasing  the  dose,  until 
after  several  hours  the  full  injection  may  be  made  (Besredka).'^* 
Friedberger  accomplishes  the  same  purpose  by  running  the  full 
dose  into  a  vein,  very  slowly,  consuming  at  least  ten  minutes  in 
the  process.  The  good  results  of  both  methods  reside  in  the 
using  up  of  anaphylactic  antibodies. 

To  anaphylaxis,  further,  are  ascribed  the  toxic  manifestations 


186  THE  BASIS  OF  SYMPTOMS 

sometimes  observed,  when  in  the  course  of  an  operation,  the  fluid 
contents  of  an  echinococcus  cyst  escape  into  the  free 
peritoneal  cavity.  In  this  case,  the  individual  has  been  prepared 
by  the  absorption  of  the  proteid  of  the  parasite  during  the  course 
of  the  disease;  while  the  shock  itself  is  due  to  the  peritoneal 
absorption,  consequent  to  the  operation.  Eclampsia  is  also 
classified  by  some  among  the  anaphylactic  processes.  The  mother 
is  assumed  to  be  sensitized  by  the  amniotic  fluid,  the  onset  of 
symptoms  following  a  later  more  energetic  absorption.  This 
hypothesis  seems  to  be  borne  out  by  the  observation  that  guinea- 
pigs,  sensitized  with  the  serum  of  an  eclamptic,  exhibit  anaphy- 
lactic shock  after  a  subsequent  injection  of  liquor  amnii.  Hay 
f-ever  is  undoubtedly  an  allergic  manifestation.  Symptoms 
do  not  appear  until  the  second  decade;  during  the  first  years  of 
life  there  is  taking  place,  by  inhalation,  an  absorption  of  the 
foreign  proteid  (pollen)  leading  to  antibody  formation.  Repe- 
tition of  the  inhalation,  analogous  to  the  reinjection  of  some  alien 
proteid,  calls  forth  the  hay  fever  attack  in  the  late  summer.  That 
this  conception  is  well  founded  is  evidenced  by  the  fact  that  injec- 
tions of  the  same  pollen  proteid,  at  any  time  of  the  year,  cause  hay 
fever.  Whether  the  sensitization  due  to  tuberculin  belongs  in  this 
category  remains  to  be  seen ;  thus  far,  at  any  rate,  it  has  not  been 
passively  conferred. 

(Many  local  allergic  manifestations  are  of  con- 
siderable diagnostic  worth.'^^  Prominent  among  these  are  the 
different  local  tuberculin  reactions — the  v.  Pirquet  and  the  Moro 
percutaneous  tests,  the  intracutaneous  test  of  Mantoux,  the 
ophthalmo-tuberculin  reaction  of  Calmette  and  Wolff-Eisner,  and 
the  "  Stichreaktion  "  of  Escherich ;  further,  the  luetin  percutaneous 
phenomenon  of  Noguchi;  the  gonococcus  local  reaction  (Irons)  ; 
and  the  ophthalmo-reaction  in  typhoid  ( Chantemesse) .  Essential 
to  a  proper  interpretation  of  these  reactions  is  an  understanding 
not  only  of  their  value,  but  also  of  their  limitations  in  the  different 
types  and  stages  of  the  above-mentioned  conditions. 

The  Abderhalden  immune-ferment  reaction  may  properly  be 
spoken  of  in  this  place,  as  it  represents  an  outgrowth  of  studies 
directed  toward  the  explanation  of  the  phenomena  of  anaphylaxis. 
Observers  generally  agree  with  Vaughan  that  the  toxic  manifes- 
tations of  anaphylaxis  are  due  to  the  poisonous  substances  formed 
by  the  rapid  splitting  of  foreign  proteids.     That  is  to  say,  the 


INFECTION  AND  IMMUNITY  187 

process  of  sensitization  leads  to  the  production  of  ferments  capable 
of  splitting  proteid  when  reinjected.  Some  of  these  ferments  are 
non-specific,  i.e.,  they  can  disintegrate  other  proteids  than  those 
which  stimulated  their  formation.  Certain  ferments,  on  the  con- 
trary, are  specific  for  a  particular  proteid.  Of  the  latter  the 
first  to  be  thoroughly  studied  was  that  produced  in  the  maternal 
organism  by  the  action  of  the  chorionic  epithelium  (placenta). 
Placental  extract  brought  into  contact  with  the  blood-serum  of 
pregnant  women  is  split  into  the  simpler  proteid  molecules,  such 
as  the  amino-acids,  etc. 

The  technical  phase  of  the  test  rests  upon  the  principle  that 
proteid,  being  a  colloid,  does  not  dialyze  through  appropriate 
membranes,  but  that  the  crystalloid  split-products  do  pass  through 
such  membranes,  after  which  their  presence  can  be  recognized 
by  appropriate  tests  (ninhydrin). 

From  the  adaptation  of  the  immune- ferment  reaction  to  the 
early  diagnosis  of  pregnancy,  the  test  has  found  a  wide  application 
in  other  morbid  processes,  particularly  carcinoma,  psycopathic 
conditions,  tuberculosis,  thyroid  anomalies,  etc. 

Despite  the  vast  amount  of  work  reported  in  the  past  few 
years,  tending  to  confirm  the  conception  of  Abderhalden,  the 
specificity  of  the  reaction  has  lately  been  seriously  questioned.''^^  A 
final  judgment  as  to  its  value,  therefore,  must  be  reserved. — Ed.) 

Phagocytosis  and  Immunity.-^Wandering  cells,  derived  partly 
from  the  white  cells  of  the  blood,  and  in  part  from  the  fixed  tissue 
cells,  pervade  all  parts  of  the  body,  carrying  with  them  materials 
of  diverse  kinds.  They  appear  wherever  there  is  a  foreign  body 
— one  not  soluble  in  the  tissue  juices,  or  assimilable  by  the  cells — 
and  remove  it.  This  activity  is  not  purely  mechanical,  for  they 
can  also  dissolve  and  destroy  substances  by  means  of  an  enzyme- 
like body  which  they  secrete.  The  wandering  cells  posssess,  there- 
fore, a  double  function :  the  one  of  dissolving  foreign  bodies,  that 
they  may  be  washed  away  by  the  blood  and  lymph ;  the  other  of 
first  disintegrating  these  bodies  and  then  carrying  them  away. 

These  cells  appear  in  certain  morbid  processes,  being  attracted 
to  the  proper  place,  in  all  likelihood,  by  chemotrophic  influences. 
Their  role  in  disease  is  merely  a  broadening  and 
a  continuation  of  their  physiological  activity. 
Nevertheless,  in  our  opinion,  these  cells  cannot  be  regarded  merely 
as  scavengers.     Even  though  the  end-products  of  metabolism  are 


188  THE  BASIS  OF  SYMPTOMS 

absorbed  only  in  solution,  there  is  nothing  to  indicate  that  these 
cells  do  not  play  a  part  in  the  transportation  of  intermediate  solid 
metabolic  products.  Or,  in  the  vernacular,  it  might  be  said  that 
they  not  only  clean  the  streets,  but  also  take  part  in  the  business 
activities  of  those  who  dwell  in  the  street. 

These  functions  of  the  wandering  cells  were  early  adduced  in 
the  explanation  of  immunity  phenomena.  The  theory  of  phago- 
cytosis, linked  with  the  name  of  Metchnikoff,  has  been  defended 
by  him  with  great  acumen  and  against  many  dissenters."^*  It  is 
beyond  question  that  these  cells  seize  upon  micro-organisms,  even 
living  ones,  for  Metchnikoff  was  able  to  grow  anthrax  bacilli 
engulfed  by  phagocytes;  and  it  is  no  whit  less  certain  that  the 
greater  number  of  invading  bacteria  in  certain  experimental  infec- 
tions are  removed  from  the  inflammatory  focus  by  the  phagocytes. 

The  polynuclear  leucocytes  constitute  an  important  factor  in 
the  fight  against  bacteria.  To  them  Metchnikoff  has  given  the 
name  microphages,  in  distinction  to  the  macrophages, 
the  large  mononuclear  phagocytes  which  are  able  to  devour  and 
digest  foreign  cells.  The  microphages  digest  the  bacteria  by  means 
of  an  enzyme  (microcytase)  which  is  analogous  to  Buchner's 
alexin;  the  macrophages,  for  their  part,  digest  blood-corpuscles 
and  other  cells  by  means  of  their  macrocytase.  Metch- 
nikoff leaves  open  the  question  as  to  whether  there  are  only  these 
two  cytases,  in  contradistinction  to  Ehrlich  who  conceives  of  the 
multiplicity  of  complement  in  every  species  of  animal. 

The  bacteria-destroying  cytase  escapes  from  the  phagocytes 
only  when  they  are  injured  by  noxious  substances  in  the  blood  or 
in  the  products  of  inflammation  (phagolysis).  In  this  re* 
spect,  the  views  of  Metchnikoff  and  Buchner  are  diametrically 
opposed,  for  the  alexins  of  the  latter  are  assumed  to  be  circulating 
free  in  the  body  fluids.  The  work  of  Gruber  and  Futaki"^^ 
indicates  that  the  outspoken  phagocytic  power  of  the  leucocytes 
of  the  hen  toward  anthrax  is  the  source  of  the  inherited  immunity 
of  the  hen  to  this  disease.  The  same  observers  found  that  anthrax 
bacilli  protected  themselves  against  the  phagocytes  by  the  forma- 
tion of  capsules,  which  have  no  chemotactic  influence;  but  after 
subcutaneous  injection  of  the  same  micro-organism  into  the  hen 
and  dog,  the  bacilli  produced  no  capsules  and  were  immediately 
destroyed.  In  the  sensitive  guinea-pig  and  rabbit,  however,  the 
phagocytes  are  not  of  great  defensive  worth;  this  is  due  probably 


INFECTION  AND  IMMUNITY  189 

to  complicated  biochemical  differences  between  the  lymph  of 
susceptible  and  non-susceptible  animals. 

As  to  amboceptor,  Metchnikoff's  point  of  view  is  as  follows: 
In  the  course  of  the  intracellular  digestion  of  bacteria  by  the 
microphages,  two  enzymes  are  successively  active,  the  so-called 
fixateurs,  which  prepare  the  ground,  and  thereupon  the  micro- 
cytase.  The  fixateurs,  in  most  infections,  differ  from  the  cytases 
in  their  looser  combination  with  the  phagocytes,  and  in  their 
tendency  to  an  enormous  increase  in  the  immuninizing  process. 
Immune  sera,  therefore,  are  rich  in  fixateurs.  In  the  living 
organism  the  digestion  takes  place  for  the  most  part  within  the 
phagocytes.  In  the  Pfeiffer  phenomenon,  according  to  Metchni- 
koff,  there  occurs  first  of  all  phagolysis  in  consequence  of  the 
injection  of  injury-producing  bacteria,  and  following  this  the 
escape  of  cytase.  Phagocytosis  plays  a  determining  role  in  other 
phases  of  the  Pfeiffer  reaction.  For  example,  if  an  animal  im- 
munized to  cholera  be  killed  at  a  time  when  the  inflammatory 
exudate  shows  only  spores,  a  careful  examination  of  the  j>eri- 
toneal  folds  and  of  the  omentum  yields  many  leucocytes  filled 
with  vibrios. 

That  an  augmented  phagocytosis  is  the  only 
constant  phenomenon  observed  in  the  process  of 
immunity  is  undeniable.  We  have  already  called  attention 
to  the  fact  that  the  factors  concerned  in  bacteriolysis  are  insuffi- 
cient to  explain  all  of  the  elements  of  an  acquired  immunity. 
Indeed,  the  effect  of  certain  immune  sera — Aronson's  strepto- 
coccus serum,  pneumococcus  serum,  etc. — which  are  not  bacteri- 
cidal, Metchnikoff  ascribes  entirely  to  phagocytic  activity.  And 
this  view  has  been  confirmed  by  experiments  in  vitro. 

The  action  of  an  immune  serum,  according  to  this  conception, 
is  exerted  solely  upon  the  bacteria,  even  in  high  dilution  specifically 
preparing  them  for  inclusion  in  the  phagocytes  (bacteriotropic 
serum) ;  and  bacteriotropins  have  been  demonstrated  even  in  the 
bacteriolytic  sera  of  typhoid  and  cholera  (Neufeld)."^^  Wright 
and  his  collaborators,'^'''  prior  to  Neufeld's  publication,  described 
the  opsonins,  bodies  found  in  normal  serum,  and  similar  in 
behavior  to  bacteriotropins. 

Wright  has  elaborated  a  most  detailed  procedure  to  estimate 
this  action  of  the  serum  quantitatively.  The  patient's  serum,  and, 
as  a  control,  that  of  a  healthy  individual,  are  brought  into  contact 


190  THE  BASIS  OF  SYMPTOMS 

with  leucocytes  and  bacteria  and  kept  at  a  temperature  of  37°  C. 
for  fifteen  minutes,  after  which  by  counting  the  organisms  con- 
tained within  one  hundred  leucocytes,  the  average  per  white  cell 
can  be  determined  (phagocytic  count).  The  opsonic 
index  is  obtained  by  dividing  the  phagocytic  count  of  the 
patient's  serum  by  that  of  the  normal  serum.  The  ratio  between 
two  healthy  sera  is  fairly  constant,  varying  only  between  0.8  and 
1.2;  in  disease,  on  the  contrary,  the  index  is  diminished  or  very 
inconstant.  Wright  has  recommended  a  therapeutic  appHcation 
of  the  opKSonic  theory  by  means  of  the  subcutaneous  injection  of 
killed  micro-organisms  or  of  their  metabolic  products  (vaccines, 
see  p.  178),  this  procedure  tending  to  raise  the  opsonic  index. 
Wright's  method  is  merely  active  immunization  during  the  course 
of  the  morbid  process. 

Following  an  injection  the  index  first  falls  (negative 
phase  ;  period  of  antitoxin  formation).  The  dosage  must  be 
so  gauged  as  not  to  produce  too  great  a  reduction  of  the  index; 
and  the  injection  must  be  so  timed  as  to  allow  the  preceding  nega- 
tive phase  to  have  run  its  course.  The  possible  dangers  attending 
this  last,  however,  have  surely  been  exaggerated,'^^  and  Wright 
himself  now  insists  only  that  the  dosage  be  such  that  the  general 
reaction  be  slight.  (Indeed  the  routine  determination  of  the 
opsonic  index  in  vaccine  therapy  has  generally  been  discarded 
as  being  too  laborious  and  not  necessary.  The  focal  and  consti- 
tutional manifestations  seem  to  be  safe  guides  for  the  determina- 
tion of  the  dose  and  the  time-interval. — Ed.) 

Opsonins  and  tropins  are  not  identical.  The  former  are  inacti- 
vated at  56°  C,  the  latter  not.  Opsonins,  further,  are  supposed 
to  have  a  complex  structure,  i.e.j  composed  of  amboceptor  and 
complement.  Nor  can  opsonins  be  grouped  with  the  lysins  in  the 
present  status  of  our  knowledge.  In  the  process  of  immunization, 
tropins,  as  such,  and  the  amboceptor  portion  of  the  opsonins,  are 
increased.  The  phagocytes  are  able  to  destroy  certain  types  of 
bacterial  life,  but  as  this  is  not  true  with  respect  to  all  micro- 
organisms, the  action  of  the  tropins  and  opsonins  cannot  be  com- 
pared throughout.  If  we  assume  that  the  fixateurs  of  Metchnikoff 
are  the  equivalents  of  the  bacteriotropins,  i.e.,  that  their  role  is 
that  of  fixateurs  phagocytaires,  then  the  phagocytic  theory  and  the 
humoral  theory  can  readily  be  harmonized.  The  aggressins,  as 
inhibitors  of  phagocytosis,  fit  well  into  this  conception,  and  are 


INFECTION  AND  IMMUNITY  191 

perhaps  to  be  regarded  as  the  antagonists  of  opsonins  and  tropins. 
The  theory  of  Metchnikoff  would  accordingly  assume  a  kind  of 
antitoxic  immunity,  both  because  the  aggressins  are  credited  with 
a  toxic  action,  and  because  soluble  metabolic  products — and  there 
is  no  essential  difference  between  soluble  toxins  and  the  substances 
of  the  bacterial  bodies — have  an  aggressin-like  power.  Indeed,  a 
specific  antiaggressin  serum  has  been  produced  for  filtrates  of 
typhoid  bacilli.  Nevertheless  the  school  of  Metchnikoff  is  firmly 
of  the  opinion  that  the  phagocytes  per  se  can  seize  upon  even 
highly  virulent  bacteria  (spontaneous  phagocytosis). 

Bacillus  Carriers. — Even  after  complete  recovery  from  an  in- 
fectious disease,  an  individual  may  harbor  the  specific  micro- 
organism (bacillus  carriers).  After  cholera  and  typhoid  fever, 
the  causative  organism  may  be  isolated  from  the  faeces,  and  after 
diphtheria  from  the  mucous  membrane  of  the  throat.  This  per- 
sistence of  the  bacteria  may  be  brief,  or  a  matter  of  months,  years 
and  even  decades.  Bacillus-carriers  can  undoubtedly  be  the  source 
of  infection  in  others,  even  though  the  organism  may  be  of  an 
attenuated  type,  for  the  latter  can  readily  infect  individuals  with 
a  lowered  resistance.  Many  endemics  are  unquestionably  due  to 
bacillus-carriers.  In  protozoon  affairs,  carriers  play  an  even 
more  important  role,  for  here  the  parasite  may  persist  not  only 
after  the  conclusion  of  the  disease  proper,  but  even  after  prophy- 
lactic inoculation. 

Chemotherapy.  Salvarsan. — In  the  conflict  between  the  living 
organism  and  bacteria,  the  former  may  be  victorious,  the  latter 
may  gain  the  upper  hand,  or  there  occurs  a  mutual  adaptation  in 
the  matter  of  metabolic  products,  protective  forces,  etc.  Toler- 
ance represents  the  stage  of  perfect  adaptation.  The  host  is  then 
a  bacillus-carrier.  It  may  happen,  however,  during  an  infection 
that  the  major  portion  of  the  bacteria  is  rendered  harmless,  while 
the  more  resistant  minority  survives.  These  multiply,  becoming 
more  resistant  to  the  individual's  protective  forces,  and  finally, 
after  a  short  interval  of  apparent  good  health,  lead  to  a  recurrence 
of  symptoms.  This  is  probably  the  case  in  relapsing  fever.  The 
splendid  studies  of  Ehrlich,'^^  indeed,  have  shown  that  micro- 
organisms can  be  made  resistant  to  certain  well-characterized 
poisons,  as,  for  example,  trypanosomes  to  atoxyl,  to  fuchsin  and 
to  trypan  red,  preparations  injurious  to  these  parasites,  and  thus 
producing  atoxyl-fast  strains,  etc.    This  resistance  to  poisons  is 


192  THE  BASIS  OF  SYMPTOMS 

inheritable  and  specific  with  respect  to  all  the  members  of  a  chemi- 
cal group.  This  is  practically  important  in  showing  the  necessity 
of  changing  remedial  agents  from  time  to  time,  and  of  combining 
them;  which  is  in  keeping  with  the  most  recent  work  of  the 
Ehrlich  Institute  showing  that  trypanosomes  may  be  made  to  lose 
acquired  characteristics  in  the  process  of  fecundation  and  trans- 
mission through  insects. 

These  observations  have  enabled  Ehrlich  ®°  to  identify  atoxyl, 
which  is  so  important  in  the  destruction  of  trypanosomes,  as  the 
sodium  salt  of  p-aminophenylarsanilic  acid — a  discovery  which 
paved  the  way  for  the  synthetic  elaboration  of  the  arsenic  domain. 
By  acetylization,  for  example,  sodium  acetyl  arsinalate  (arsacetin) 
was  produced,  a  body  less  toxic,  but  not  less  potent  than  atoxyl, 
and  therapeutically,  therefore,  because  of  the  larger  dose  per- 
missible, much  more  efficacious.  The  foregoing  applies,  however, 
only  to  animals,  for  in  man  arsacetin  was  found  to  be  just  as 
toxic  as  atoxyl.  Some  of  the  trypanosome-destroying  substances, 
the  arsenious  acids,  for  instance,  act  promptly  upon  the  parasite, 
in  vitro,  while  atoxyl  and  arsacetin,  even  in  a  one  or  two  per  cent, 
solution,  have  no  such  effect,  despite  their  brilliant  action  in  vivo. 

Ehrlich  has  shown  this  paradoxical  behavior  to  be  associated 
with  reduction  processes ;  that  is,  with  the  reduction  products  of 
atoxyl  and  arsacetin — these  products  in  turn  having  a  marked 
reducing  power — ^he  succeeded  in  producing,  in  vitro  also,  an 
enormous  trypanosomicidal  action;  while  in  the  animal  body, 
they  exhibited  an  even  greater  toxicity  to  the  parasites.  In  the 
reduction  products,  arsenic  has  only  a  triple  valence,  similar  to 
arsenious  acid,  itself  intensely  potent,  but  far  too  toxic  for  animals. 

The  problem,  then,  was  to  elaborate  reduction  products,  not 
to  leave  their  formation  to  the  animal  organism,  and  to  combine 
these  products  with  other  reducing  substances.  Ehrlich  conceived 
of  the  cells  as  possessing  different  molecular  groups,  or  chemo- 
receptors,  which  are  able  to  unite  with  different  combinations,  as, 
for  example,  trypanosomes  with  an  arseno-receptor  and  also  with 
an  acetico-receptor.  If  the  latter  unites  more  readily  with  the 
acetic  acid  group  of  the  arsacetin  than  do  the  cells  of  the  infected 
animal  with  the  arsenic  group,  arsenic  will  be  drawn  to  the  parasite 
and  thus  the  acetic  acid  group,  per  se  harmless,  makes  possible 
the  arsenic"  action.  In  the  Ehrlich  nomenclature  the  acetic  acid 
group  is  parasitotropic,  the  arsenic  itself  being  organotropic;  the 


INFECTION  AND  IMMUNITY  19S 

latter,  however,  plays  no  part  in  the  process  because  the  parasito- 
tropic groups  cause  too  rapid  a  union  with  the  parasite.  The  crux 
of  the  matter  then  was  to  find  molecules  or  groups  which  should 
bind  the  arsenic  element  of  the  poison  to  the  parasite. 

On.  the  basis  of  work  carried  out  along  these  lines,  Ehrlich 
gave  to  the  world  his  spirochgeticidal  preparation  606  (sal- 
varsan),  dioxydiaminoarsenobenzol,  after  convincing  himself 
that  the  spirilla  possessed  an  amino-oxy-receptor ;  and  he  thus 
paved  the  way  for  successful  chemotherapy. 

Autoinfection. — In  individuals  who  are  not  demonstrably  sick, 
particularly  in  those  from  the  milieu  of  a  patient,  specific  organ- 
isms, Klebs-Loefiler  bacilli,  pneumococci,  typhoid  bacilli,  may 
often  be  found.  It  remains  to  be  determined  whether  the  pus- 
cocci  present  on  the  body  surfaces  are  to  be  looked  upon  as  relics 
of  an  earlier  infection,  or  as  pathogenic  organisms  residing  in  the 
ostensibly  healthy.  These  various  bacteria  are  generally  harmless, 
perhaps  because  the  host  has  been  rendered  immune  by  a  mild 
infection.  To  another,  however,  they  may  be  virulent;  indeed, 
even  in  the  host  himself,  they  may  cause  disease  if  his  resisting 
powers  have  been  lowered  (autoinfection). 

Conclusions. — We  may  sum  up  the  question  of  specific  im- 
munity thus:  The  blood,  both  under  certain  normal  conditions 
and  after  recovery  from  disease,  natural  or  artificial,  is  able  at 
times  to  destroy  micro-organisms,  to  prepare  them  for  phagocy- 
tosis and  to  neutralize  their  toxic  products.  In  the  second  place, 
the  phagocytes  are  capable  of  engulfing  bacteria  and  rendering 
them  harmless.  Both  mechanisms,  depending  upon  circum- 
stances, provide  the  animal  body  with  a  defense  against  harmful 
bacteria.  But  neither  each  by  itself  nor  even  the  two  combined 
are  sufficient  in  all  cases  to  explain  immunity  in  its  entirety.  A 
fuller  understanding  of  these  problems  will  come  only  with 
further  study. 

In  what  way  do  certain  individuals  successfully  resist  an  infec- 
tion, and  why  do  others  succumb?  And  why  do  fewer  bacteria 
cause  an  infection  in  animals  living  under  ordinary  conditions 
than  experimental  results  would  teach  ?  Once  again  we  must  fall 
back  upon  the  protective  forces  residing  in  the  body-surfaces  to 
explain  these  individual  variations.  Even  different  groups  of  the 
same  species  react  differently  to  microbic  invasion.     Race,  age, 

18 


194  THE  BASIS  OF  SYMPTOMS 

mental  depression  and  a  subnormal  state  of  nutrition — all  of  these 
are  additional  factors.®^ 

The  mechanism  of  recovery  from  an  infection  has  an  intimate 
bearing  upon  the  question  of  the  protective  forces.  In  those 
diseases  which  exert  a  toxic  action — and  in  the  final  analysis,  all 
diseases  will  probably  belong  in  this  category — the  result  is  death 
if  the  toxin,  because  of  its  amount  or  strength,  can  no  longer  be 
neutralized.  Recovery  may  occur  by  the  formation  or  artificial 
introduction  of  antitoxin,  though  cure  is  sometimes  spontaneous. 
This  may  occur  in  tetanus  with  no  antitoxin  in  the  blood,®^  in 
which  case  the  cells  evidently  become  insensitive  to  the  toxin 
(histogenic  immunity). 

LITERATURE 

*Aschoff:  Ehrlich's  Seitenkettentheorie,  etc.,  Zeitschft.  f.  allg.  Phys.,  1902. 
i;  Buchner,  Schutzimpfung,  in  Penzoldt-Stintzing,  Gesamte  Therapie,  3rd 
edit.,  1902,  i — revision  in  4th  edit.,  1909  (Levy)  ;  Ehrlich,  Gesam.  Abhandl. 
ii.  Immunitat,  1904;  Metchnikoff,  Immunity  in  Infect.  Diseases,  1905; 
Jacoby,  Immunitat  u.  Disposition,  1906;  v.  Baumgarten,  Lehrb.  d.  Pathog. 
Bakterien,  191 1;  Krause,  Allg.  Mikrobiol.,  1910;  Jordan,  Bacteriology, 
1912;  Kolle  and  Wassermann,  Handb.  d.  Path.  Mikro-organismen,  1911-13. 

*  Schmiedeberg :  Grundriss  d.  Arzneimittellehre,  5th  edit. 
*Cf.  Lenhartz,  in  the  Nothnagel  System. 

*  Billings:  Arch.  Int.  Med.,  1909,  iv,  409;  ibid.,  1912,  ix,  484;  Jour.  Am.  Med. 

Assn.,  1913,  Ixi,  819. 
'  Jour.  Infect.  Dis.,  1910,  vii,  410 ;  Jour.  Am.  Med.  Assn.,  1913,  Ix,  1223 ;  Jour. 

Infect.  Dis.,  1914,  xiv,  i.    See  also  Thiele  and  Embleton,  Zeitschft.  f.  Im- 

munitatsforsch.,  1913,  xix,  643. 
'  Jour.  Am.  Med.  Assn.,  1913,  Ixi,  1942, 
*Klipstein:  Zeitschft.  f.  klin.  Med.,  xxxiv,  191. 
*Fliigge:  Zeitschft.  f.  Hygiene,  xxv,  179;  xxx,  107;  xxxviii,  i. 
'  Arch.  f.  Hygiene,  lii,  179 ;  liv,  354 ;  Ivii,  56. 
"Zentralbl.  f.  Bakt.,  xliv  (orig.),  325. 
"Zeitschft.  f.  klin.  Med.,  x,  49. 
"  Basset  and  Carre :  Sem.  med.,  1907,  264. 
"Bienstock:  Die  med.  Wochenschft.,  1901,  Nos.  2>i,  34- 
"Diphtherie,  in  the  Bibliothek  Coler.,  1901,  95. 
"Arch.  f.  Hygiene,  lii,  272;  liii,  302;  Zentralbl.  f.  Bakt.,  xl,  371;  E.  Levy  and 

Fornet,  Deutsch.  med.  Wochenschft.,  1906,  No.  26'  E.  Levy  and  Gran- 

strom,  Zentralbl.  f.  Bakt.,  xlv,  360. 
"  Meyer  and  Ransom :  Arch,  f .  exp.  Path.,  xlix,  369. 
"  Irons :  Jour.  Infect.  Dis.,  xv,  367 ;  Ashhurst  and  John,  Amer.  Jour.  Med.  Sc, 

cxlv,  860;  ibid.,  clvi,  yj;   Park  and  Nicoll,  Am.  Med.  Assn.,  Ixiii,  235. 
"Dorr:  Das  Dysenterietoxin,  1907. 
"MacFayden  and  Rowland:  Zentralbl.  f.  Bakt.,  xxxiv,  618,  and  xxxv,  415; 

Besredka,  Annal.  Pasteur,  xix,  xx;  Kraus  and  v.  Stenitzer,  Wiener  klin. 

Wochenschft,  1907,  No.  12. 
■"Pfeiffer  and  Bessau:  Zentralbl.  f.  Bakt.,  Ivi,  344   (Part  I);  Bessau,  ibid., 

Ivii,  27. 
"^Siegel:  Zeitschft.  f.  exp.  Path.,  v. 
*■  C.  Frankel :  Berl.  klin.  Wochenschft.,   1905 ;   Kruschilin,  Zeitschft.  f.  Im- 

munitatsforsch.,  i,  407. 
"  E.  Levy  and  Gaehtgens :  Arbeiten  a.  d.  Kais.  Gesundheitsamt,  xxv,  1907. 


INFECTION  AND  IMMUNITY  195 

'*  Dehne  and  Hamburger :  Wiener  klin.  Wochenschft,  1907,  817. 

*°  Koch :  Reisberichte,  1908 ;  Kolle  and  Turner,  Zeitschft.  f .  Hygiene,  xxix, 

309;  Calmette  and  Salimbeni,  Annales  Pasteur,  xiii,  905. 
*•  Beinarowitsch :  Arch.  d.  sciences  biol.,  vi. 
"  Annales  Pasteur,  xvi,  918. 
""Hahn:  Arch.  f.  Hygiene,  1907,  xxviii,  312. 
**Rosenow:  Jour.  Infect.  Dis.,  1914,  xiv,  31. 
**  Gruber  and  Futaki :  Miinch.  med.  Wochenschft.,  1907,  No.  6. 
"  Pfeiffer  and  Bessau :  Zentralbl.  f.  Bakt,  1910,  Ivi,  344. 
"  For  a  different  view  as  to  the  source  of  complement,  see  Neufeld,  Arbeiten 

a.  d.  Kais.  Gesundheitsamt,  xxviii,  125 ;  Schneider,  Arch,  f .  Hyg.,  Ixx,  40. 
''Aschoff:^  Zeitschft.  f.  Allg.  Phys.,  i,  389;  Sachs,  Ergeb.  d.  allg.  Path.,  vii 

and  xi. 
**  Ehrlich  and  Morgenroth :  Berl.  klin.  Wochenschft.,  1900.  No.  21. 
"v.  Baumgarten:  Festschrift  f.  Jaffe,  Braunschweig,  igoi,  279. 
■•Ferrata:  Berl.  klin.  Wochenschft.,  1907,  366;  Brand,  ibid.,  1907,  1075. 
"  Belfanti  and  Carbone,  cited  by  Aschoff,  1.  c ;  Bordet,  many  studies  in  the 

Annales  Pasteur;  Ehrlich,  Gesam.  Arbeit,  z.  Immunitatsforsch.,  1904. 
"  Eisler :  Zeitschft.  f.  Immunitatsforsch.,  ii,  159. 
"  Landsteiner  and  H.  Ehrlich :  Zentralbl.  f .  Bakt.,  xlv,  247. 
*•  Zeitschft.  f.  Immunitatsforsch.,  iii,  114. 
*^  Porges,  in  Handb.  d.  Technik.  u.  Methodik  d.  Immunitatsforsch.,  of  Kraus 

and  Levaditi,  ii,  1136. 
**v.  Behring.  Kasseler  Naturforscherversammlung,  1903;  Romer,  Beitrage  z. 

exp.  Therap.,  Part  9;  Dehne  and  Hamburger,  Wiener  klin.  Wochenschft., 

1904,  No.  29;  Hamburger,  Miinch.  med.  Wochenschft.,  1907,  No.  6. 
*•  Ehrlich  and  Wassermann:  Zeitschft.  f.  Hyg.,  xviii,  239;  Romer,  Zeitschft.  f. 

Immunitatsforsch.,  i,  171. 
**  Wassermann  and  Schiitze :  Berl.  klin.  Wochenschft.,  1901,  187 ;  Uhlenhuth, 

Das  biol.  Verfahr.  z.  Erkennung  u.  Unterscheid.  von  Menschen  u.  Tierblut., 

1905 ;  Blum,  Zentralbl.  f.  allg.  Path.,  xvii,  1905. 
"  Michaelis :  Hof meister's  Beitrage,  iv,  59. 
•* Uhlenhuth :    Zentralbl.    f.    Bakt.,   xxxviii,    suppl.,    36    (review).    See   also 

Deutsch.  med.  Wochenschft.,  1906,  No.  31. 
■"  Annales  Pasteur,  xv,  289. 

**  Neisser  and  Sachs :  Berl.  klin.  Wochenschft.,  1905,  No.  44 ;  ibid.,  1906,  No.  3. 
*  Wassermann,    Neisser    and    Bruck,    Wassermann    and    Plant,    Bruck    and 

Schlucht,  in  the  Deutsch.  med.  Wochenschft.,  1906,  and  the  Berl.  klin. 

Wochenschft.,  1907. 
"  See  collective  article  of  Meyer  in  Fol.  neurobiol.,  1908,  652.    See  also  Noguchi, 

Jour.  Exp.  Med.,  xv,  557;  Serum  Diag.  of  SyphiHs,  2nd  edit.,  1915. 
"Mueller  and  Oppenheim:  Wiener  klin.  Wochenschft.,  xx,  849;  Schwartz  and 

McNeil,  Amer.  Jour.  Med.  Sc,  cxli,  964,  and  cxliv,  815. 
"Hahn:  Miinch.  med.  Wochenschft.,  1912,  1483;  Thomsen  and  Magnussen, 

Berl.  klin.  Wochenschft.,  1912,  1183. 
"Lowenstein  and  Liidke,  in  Kraus-Levaditi  (supplement,  vol.),  191 2. 
•* Gruber  and  Durham:  Miinch.  med.  Wochenschft.,  1896,  285;  Gruber,  ibid., 

1899,  No.  41. 
"■  Eisenberg  and  Volk :  Zeitschft.  f .  Hyg.,  xl,  155. 
"Gaethgens:  Munch,  med.  Wochenschft.,  1906,  1351. 
"  Brit.  Med.  Jour.,  Jan.,  1897,  16 ;  Lancet,  Sept.,  1896,  807 ;  ibid.,  Sept.,  1902,  654. 

See  also  Metchnikoff  and  Besredka,  Ann.  Pasteur,  xxv,  193   (sensitized 

vaccine). 
"  Russell :  Am.  Jour.  Med.  Sc,  clxvi,  803 ;  Ann.  Report  Surg.-Gen.,  U.  S.  Navy, 

1913- 
■•  Topper  and  Jaffe :  Zeitschft.  f.  Hyg.,  hi,  393. 
•"v.  Behring:  Zeitschft.  f.  Hyg.,  xii,  i,  10,  45;  v,  Behring  and  Knorr,  ibid., 

xiii,  407. 
"Kraus  and  Schwoner;  Zentralbl.  f.  Bakt.,  xlvii,  124. 


196  THE  BASIS  OF  SYMPTOMS 

"Berghaus:  Zentralbl.  f.  Bakt.,  xlviii,  450. 

"Mtinch.  med.  Wochenschft.,  1913,  2608;  Zeitschft.  f.  d.  ges.  exp.  Med., 
1914,  83 ;  Park,  Zingher  and  Serota,  Archives  of  Pediatrics,  xxxi,  481 ; 
Weaver  and  Maher,  Jour.  Inf.  Diseases,  1915,  xvi,  342. 

"Smith  and  Henderson:  Jour,  of  Hyg.,  vii,  205;  Levin,  Zeitschft.  f.  Im- 
munitatsforsch.,  i,  3. 

*  Meyer :  Berl.  med.  Gesell.,  June  9,  1909 ;  Arch,  f .  exp.  Path.,  Ix,  208. 

"  Levy  and  Hamm :  Miinch.  med.  Wochenschft.,  1909. 

"Ann.  Pasteur,  xxi,  497. 

"  v.  Pirquet  and  Schick :  Serum  Disease ;  H.  Pf eiffer.  Das  Problem  d.  Eiweiss- 
anaphylaxie,  1910  (lit.  to  June,  1910)  ;  Friedberger,  Deutsch.  med.  Woch- 
enschft., 191 1 ;  Miinch.  med.  Wochenschft.,  1910;  Berl.  klin.  Wochenschft, 
1910,  191 1 ;  Zeitschft.  f.  Immunitatsforsch.,  vii,  viii;  Vaughan,  Prot.  Split 
Products  in  Relation  to  Immunity  and  Disease,  1913  (Ht.),  and  Jour.  Am. 
Med.  Assn.,  1914,  Ixii,  583 ;  Rosenau  and  Anderson,  Hyg.  Bull.,  Nos.  29, 
36,45,50  (P.  H.  and  M.  H.  S.). 

•*  Ann.  Pasteur,  xxii,  Nos.  i,  2,  3. 

^"Krehl,  and  Krehl  and  Matthes:  Arch.  f.  exp.  Path.,  xxxv,  222;  xxxvi,  417 

,       (1895). 

"  See  Besredka's  report  on  antianaphylaxis,  read  at  the  17th  Inter.  Med.  Cong., 

London,  1913,  abstracted  and  translated  in  the  Lancet,  Aug.,  1913,  462. 
"  For  the  literature  bearing  on  these  phenomena  and  on  the  Abderhalden 

reaction,  see  Dick,  in  Billings-Irons,  Therapeusis,  v. 
"  For  example,  see  Jobling,  Eggstein  and  Petersen,  Jour.  Exp.  Med.,  191 5,  xxi, 

227  (lit). 
"  Metchnikoff :  Immunity  in  Infect  Diseases,  1905 ;  also  Ergeb.  d.  allg.  Path.,  xi. 
"  Miinch.  med.  Wochenschft.,  1907,  No.  6. 
'^^See  Neufeld,  in  Kolle-Wassermann,  Handb.  ii  (suppl.),  1908. 
"  Proc.  Royal  Soc,  London,  Ixxii,  357 ;  Ixxiii,  128 ;  Ixxiv,  147 ;  Rosenthal,  Med. 

Klinik,  1907;  Wright  and  Bullock,  Michaelis,  Handb.  d.  Path.  Microorg., 

1913,  iii- 

"  Pf  eiffer  and  Friedberger :  Zentralbl.  f .  Bakt.,  xlvii.  Part  I,  503. 

"  Berl.  klin.  Wochenschft.,  1907,  233,  280,  310,  341. 

*"  Ehrlich  and  Hata :  Die  exp.  Chemotherapie  d.  Spirillosen,  1910 ;  Ehrlich, 
address  in  Path,  and  Chemotherap.,  17th  Inter.  Med.  Congr.,  London, 
1913  (Lancet,  Aug.,  1913,  445).  See  also  Abhand.  ii.  Salvar.san,  with  pref- 
ace and  remarks  by  Ehrlich,  i,  ii,  iii. 

"  Dieudonne :  Schutzimpf ung  u.  Serumtherapie,  2nd  edit,  4. 

**Vincenzi:  Deutsch.  med.  Wochenschft,  1908. 


CHAPTER  IV 
RESPIRATION 

The  cells  of  the  body  continually  receive  oxygen  from  the 
blood  and  continually  give  up  the  carbon  dioxide  formed  in  their 
metabolism  to  the  blood-  and  lymph-streams.  In  the  lungs  the 
blood  takes  up  a  new  supply  of  oxygen  and  unburdens  itself  of  the 
carbondioxide  it  has  transported  from  the  tissues.  These  proc- 
esses, as  a  whole,  constitute  respiration.^  The  interchange  of 
gases  between  the  tissues  and  the  blood  is  called  internal 
respiration,  and  that  between  the  blood  and  the  air,  ex- 
ternal respiration.  It  is  obvious  that  each  is  intimately 
dependent  upon  the  other — the  ventilation  of  the  lungs,  for  exam- 
ple, serving  merely  to  guarantee  a  fresh  supply  of  oxygen  to  the 
blood  and  the  elimination  of  accumulated  carbon  dioxide. 

External  Respiration. — Essential,  first  of  all,  to  external  res- 
piration is  an  uninterrupted  supply  of  air.  A  pregnant  source  of 
danger  is  the  juxta-position  of  the  air-  and  food-passages  in  the 
pharynx,  for  foreign  bodies  that  may  enter  the  former  often  cau^^ 
grave  inflammatory  conditions.  The  mechanism  designed  to  pre- 
vent this  will  be  discussed  elsewhere  (see  p.  198) . 

Means  for  Removing  Harmful  Material  from  the  Air- 
Passages. — The  respiratory  apparatus  is  able,  as  a  rule,  to  rid 
itself  of  foreign  particles  that  have  passed  the  defenses  at  the 
glottis,  or  have  reached  the  bronchi  in  other  ways.  Of  first  im- 
portance in  this  respect  is  the  movement  of  the  epithelial  cilia,' 
which  by  their  slight  but  constant  activity  impel  such  particles 
from  the  bronchioles  into  the  larynx.  Were  we  more  familiar 
with  disturbances  of  this  protoplasmic  movement,  we  might  better 
understand  the  underlying  causes  of  certain  bronchial  and  pul- 
monary diseases. 

As  the  activity  of  the  cilia  is  probably  the  most  important 
factor  in  transporting  foreign  bodies  from  the  lower  to  the  upper 
respiratory  passages,  any  disturbance  of  this  movement  is  ob- 
viously a  more  potent  source  of  harm,  in  contributing  to  the  stag- 
nation of  inflammatory  products,  than  is  even  the  suppression  of 
coughing,    Furthermore,  since  the  cilia  seem  to  be  whipped  on  by 

197 


198  THE  BASIS  OF  SYMPTOMS 

inflammatory  irritation,  it  is  reasonable  to  assume  that  they 
attempt  also  to  expel  invading  bacteria,  as  a  defensive  measure. 

The  second  mechanism  that  aids  in  protecting  the  lungs  is 
the  secretion  of  mucus  upon  the  surfaces  of  the  air-passages.'  Small 
bodies,  such  as  particles  of  coal-dust  and  bacteria,  are  caught  in 
this  mucus  and  thereby  prevented  from  penetrating  the  air-cells ; 
they  are  then  carried  away  by  the  action  of  the  ciliated  epithelium. 
When  the  foreign  bodies  are  inspired  in  great  numbers,  however, 
or  the  secretion  of  mucus  or  the  movements  of  the  cilia  are  ham- 
pered by  inflammation,  these  defensive  barriers  fall  away. 

The  lungs  are  guarded,  further,  by  our  sense  of  smell,  which 
warns  against  noxious  admixtures  in  the  air  to  be  breathed. 
Sneezing^  also  plays  a  part  by  keeping  the  nasal  passages  clear  for 
the  entrance  of  air.  Sneezing  begins  with  a  deep  inspiration. 
The  powerful  expiration  succeeding  this,  forcibly  carries  with 
it  through  the  mouth  and  nose  the  movable  foreign  bodies  which, 
by  their  irritation  of  the  nasal  mucous  membrane,  have  initiated 
the  reflex. 

Coughing  serves  as  an  additional  guard  and  eliminating  force. 
The  reflex  which  induces  the  act,  and  which  is  gen- 
erally carried  by  the  vagus,  may  be  initiated  from  the  larynx  below 
the  vocal  cords,  from  the  posterior  part  of  the  trachea  and  the 
region  of  the  bifurcation,  from  a  diseased  pleura,  from  a  patho- 
logically enlarged  spleen  or  liver,"*  and  according  to  some  observ- 
ers, from  the  stomach  and  uterus.^ 

Th  e  act  of  coughing  begins  with  a  deep  inspiration. 
This  is  followed  by  a  powerful  contraction  of  the  expiratory 
muscles.  At  first,  the  air  that  should  be  forced  out  meets  the 
obstruction  of  a  closed  larynx;  later,  the  vocal  cords  yield  to  the 
pressure  of  the  air  and  the  latter  is  propelled  through  the  opening 
with  great  violence.  As  the  soft  palate  closes  the  passage  into 
the  nose,  the  current  of  air  carries  whatever  is  in  the  larynx  or 
trachea  up  into  the  mouth.  Possibly  the  contents  of  the  larger, 
and  even  those  of  the  smaller,  bronchi  may  be  removed  by  cough- 
ing, despite  an  antagonistic  force  arising  at  the  bifurcation.  In 
our  opinion,  however,  the  movements  of  the  cilia  play  the  main 
part  in  transporting  material  from  the  alveoli  up  to  the  bifur- 
catioft  of  the  trachea,  whence  coughing  readily  carries  it  into  the 
mouth. 

The  impulse  setting  in  motion  the  mechanism  of  coughing  orig- 


RESPIRATION  199 

inates  in  the  medulla,  near  the  respiratory  centre,  and  responds 
to  stimuli  carried  by  the  pneumogastric  nerve  from  the  regions 
already  enumerated.  That  coughing  may  also  be  of  central  origin 
is  indicated  from  observations  in  nervous  individuals :  our  ability 
to  cough  voluntarily  is  further  evidence. 

A  reflex  cough  from  the  regions  mentioned  occurs  when  they 
have  been  stimulated  beyond  a  certain  point,  the  degree  of  stimu- 
lation necessary  varying,  however,  with  conditions.  We  may  say, 
in  general,  that  the  irritability  of  the  nerves  is  increased  by  acute 
inflammations  of  the  mucous  membranes,  in  which  case  coughing 
is  produced  by  abnormally  slight  stimulation.  Certain  drugs,  on 
the  contrary,  as  well  as  certain  diseases  of  the  brain,  diminish  the 
irritability  of  the  nervous  mechanism  and  thus  raise  the  threshold 
of  stimulation.  Chronic  inflammation  of  the  mucosa  may  have  a 
similar  effect. 

In  the  first  class  of  cases,  coughing  may  be  induced  by  very 
slight  chemical  or  mechanical  impurities  in  the  inspired  air ;  in  the 
second,  no  coughing  results  from  stimuli  that  would  ordinarily  be 
effective.  An  absence  or  weakness  of  coughing  may  likewise 
result  from  disease  of  the  motor  half  of  the  reflex  arc,  as  has  been 
observed  in  serious  lesions  of  the  nervous  system,  as  well  as 
in  any  condition  of  enfeebled  musculature.  Whatever  the  cause 
of  the  diminished  ability  to  cough,  the  lungs  are  endangered 
because  undesirable  substances,  whether  exogenous  or  endogenous, 
are  not  expelled.  This  danger  is  much  enhanced  when  the  move- 
ments of  the  ciliated  epithelium  are  also  hampered.  Every  phys- 
ician knows  and  fears  the  dangers  of  such  conditions,  so  often  met 
with  in  the  aged  and  in  those  greatly  weakened  by  disease. 

The  stagnating  material  readily  decomposes,  but  whether  this 
is  due  to  micro-organisms  which  are  held  back  simultaneously,  or 
to  others  which  have  entered  from  the  larger  tubes  because  of  the 
inefficacy  of  the  defensive  forces  previously  described,  is  not 
known.  The  latter  seems  to  me  the  more  probable  inasmuch  as 
many  observers  have  found  the  normal  lungs  sterile,®  though 
it  is  true  that  pathogenic  organisms  may  be  present  in  the  lungs 
of  healthy  animals.'''  The  variations  in  the  depth  of  respiration 
and  in  the  number  of  organisms  inspired  probably  explain  the 
divergent  observations.  That  the  bacteria  of  the  inspired  air, 
though  relatively  few  in  number,  do  not  always  reach  the  finer 


200  THE  BASIS  OF  SYMPTOMS 

bronchi  and  the  alveoli  is  due,  no  doubt,  to  the  various  protective 
forces  mentioned  above. 

The  act  of  coughing  is  beneficial  when  it  protects 
the  lungs  against  disease  by  removing  foreign  material  and  ex- 
cessive secretions,  but  it  is  useless  when  caused  by  an  abnor- 
mal irritability  of  the  air-passages,  or  by  reflexes  from  other 
organs,  because  in  these  cases  it  has  nothing  to  expel.  Here, 
indeed,  it  becomes  highly  undesirable,  for  it  is  by  no 
means  an  indifferent  process  to  the  organism.  The  forcible  ex- 
pirations cause  a  distinct  increase  in  intrathoracic  pressure,  thereby 
interfering  with  the  entrance  of  blood  into  the  chest,  and  also 
a  general  rise  in  arterial  tension.  These  may  have  as  their  sequelae 
the  rupture  of  an  artery,  an  incomplete  filling  of  the  heart  and 
a  marked  pulmonary  distention  (volumen  pulmonum  auctum). 

Stenosis  of  the  Air-Passages. — External  respiration  is  endan- 
gered by  any  narrowing  of  the  air-passages  which  hinders  the 
access  of  fresh  air  and  the  egress  of  vitiated.  The  signifi- 
cance of  such  a  stenosis  depends  upon  its  loca- 
tion. The  nasal  passages,  for  example,  may  be  com- 
pletely blocked,  and  yet  cause  only  a  temporary  discomfort  and 
feeling  of  suffocation,  for  breathing  goes  on  through  the  mouth 
and  is  not  interfered  with  by  eating.  To  the  infant  at  the  breast, 
however,  a  severe  "  snuffles  "  may  render  nursing  so  difficult  as  to 
cause  grave  inanition. 

A  stenosis  situated  between  the  pharnyx  and 
the  bifurcation  of  the  trachea  has  a  quite  different 
significance.  The  obstruction  may  be  the  result  of  pressure  from 
without — struma,  mediastinal  tumor,  aneurism — ^pressing  upon  the 
air-passages,  or  of  disease  of  the  respiratory  tract  itself,  such  as 
an  oedema  of  the  larynx.  The  most  frequent  site  of 
mischief  is  at  the  glottis,  for  here,  especially  in  the 
case  of  children,  the  passage  is  narrowest.  Illustrative  of  this 
are  three  conditions,  characterized  by  their  sudden  onset  and 
brief  duration.  These  are  pseudocroup,  spasm  of  the  glottis 
and  the  paroxysm  of  pertussis.  Each,  in  our  opinion,  is  essen- 
tially the  result  of  a  spasm  of  the  adductor  muscles  of  the  cords. 

In  pseudocroup,  an  added  factor  is  an  ultra-acute  laryngitis, 
which  may  be  seen  under  favorable  conditions  and  may  persist 
for  hours  after  the  attack  has  ceased,  as  is  evidenced  by  the 
hoarseness  and  cough.    The  adductor  spasm  in  this  condition  is 


RESPIRATION  201 

possibly  the  result  of  the  inflammatory  process ;  it  need  not  be  of 
high  degree  to  occlude  the  narrow  laryngeal  opening  of  the  child. 

Whooping-cough,'  on  the  contrary,  is  generally  not  associ- 
ated with  inflammatory  changes.  The  voice  is  clear,  and  the 
laryngoscopic  examination  negative.  The  factors  involved  in 
the  muscle-spasm — at  the  basis,  apparently,  of  the  paroxysm — are 
not  clear. 

Spasm  of  the  glottis  (laryngismus  stridulus)  affects  chiefly  rhach- 
itic  children  and  is  often  associated  with  thymus  enlargement 
and  manifestations  of  tetany.  In  this  connection  paediatricians 
speak  of  a  spasmophilic  constitution. 

A  stenosis  of  the  respiratory  passages  would 
materially  curtail  the  ventilation  of  the  lungs 
were  it  not  for  a  compensatory  increase  in  the 
rate  and  depth  of  respiration.  This  equalizing 
mechanism  is  unquestionably  the  result  of  a 
varying  activity  of  the  respiratory  centre  de- 
pending upon  alterations  in  the  carbon  dioxide 
tensionoftheblood.  A  diminished  oxygen  content,  with 
a  correspondingly  augmented  carbonic  acid  concentration,  is 
known  to  render  the  centre  more  active.  It  would  be  decidedly 
advantageous,  however,  if  sufficient  oxygen  were  furnished 
through  increased  respiratory  movements  before  a  change  were 
manifested  in  the  partial  pressure  of  the  blood  gases. 

In  the  light  of  more  recent  studies®  it  would  appear  that  in 
the  stenoses  under  consideration  the  respiratory  type  actually 
does  undergo  a  change,  becoming  slower  and  deeper,  and  this 
before  the  oxygen  and  carbon  dioxide  partial  pressures  in 
the  alveoli  are  affected.  In  this  way  is  obviated  tissue-injury 
consequent  to  oxygen  deficiency.  In  tracheal  stenosis,  therefore, 
the  alteration  in  respiration  would  be  of  reflex  nature  and  inde- 
pendent of  the  changes  in  gas  tension. 

The  effect  of  a  tracheal  stenosis  is  seen  in  the 
more  forcible  contraction  of  the  usual  inspiratory  muscles  and  in 
the  innervation  from  the  respiratory  centre  of  new  groups  of 
muscles.  As  the  air  cannot  enter  the  chest  cavity  readily,  a  con- 
siderable negative  pressure  prevails  there  during  inspiration,  and 
the  softer  parts  of  the  thorax  are  forced  inward  by  the  atmos- 
pheric pressure  without.  The  result  is  the  well-known  in- 
spiratory retraction  of  the  epigastrium,  of  the  soft  tis- 


202  THE  BASIS  OF  SYMPTOMS 

sues  above  the  sternum  and  clavicles,  and  of  the  lateral  portions  of 
the  chest  wall. 

The  last-mentioned  phenomenon,  as  shown  by  Gerhardt,  can 
scarcely  be  due  to  the  direct  pull  of  the  diaphragm,  for  this  would 
demand  a  downward  dislocation  of  the  liver  or  a  marked  fixation 
of  the  lower  ribs.  Yet  even  without  these  prerequisites,  the  soft 
ribs  of  rickets  exhibit  a  distinct  retraction  in  cases  of  laryngeal 
stenosis. 

It  is  to  be  noted  further  that  the  difference  between  the  intra- 
alveolar  and  atmospheric  pressures  in  itself  creates  a  not  incon- 
siderable resistance  to  the  inspiratory  muscles,  and  thereby  an 
added  respiratory  obstruction. 

The  inspirations  accompanying  laryngeal  or 
tracheal  stenosis  are  not  only  more  powerful 
than  normal,  but  more  prolonged.  This  is  to  be 
explained  on  the  basis  of  an  automatic  regulation  (Selbst- 
steuerung^®)  of  the  duration  of  the  respiratory  phases,  i.e., 
when  the  distention  of  the  lungs  has  reached  a  certain  point,  ex- 
piration is  initiated  by  a  reflex  through  the  vagus.  (The  recent 
experimental  studies  of  Boothby  and  Berry,  however,  do  not  tend 
to  confirm  this  conception.!^ — Ed.)  As  the  air  enters  the  lungs 
slowly  in  tracheal  stenosis,  a  distention  sufficient  to  induce  this 
reflex  is  delayed  and  inspiration  is  accordingly  prolonged.  Ex- 
piration is  also  lengthened  because  the  air  cannot  escape  readily 
from  the  lungs  on  account  of  the  stenosis,  added  to  which  is  the 
inherent  inferiority  of  the  expiratory  muscles. 

Expiration,  normally,  is  a  purely  passive  act  due  to  the  elastic 
recoil  of  the  chest  wall  and  the  lungs;  but  in  the  conditions  under 
consideration,  expiration  becomes  active  through  the  intervention 
of  certain  accessory  muscles  called  into  action  by  the  respiratory 
centre  and  tending  to  force  up  the  diaphragm  and  to  compress 
the  thorax  laterally.  In  stenosis  of  the  trachea  and  larynx,  there- 
fore, expiration  is  lengthened,  is  more  powerful  and  is  converted 
from  a  passive  into  an  active  process. 

During  both  respiratory  phases  there  may  be  heard  a  charac- 
teristic stridor  as  the  air  passes  through  the  narrowing.  The 
respiratory  rate  is  naturally  slower  in  view  of  the  prolongation  of 
both  inspiration  and  expiration.  Another  consequence  of  these 
conditions  is  the  relatively  high  position  of  the  lung  bases  during 


RESPIRATION  203 

the  respiratory  pause,  as  is  evidenced  by  observations  on  the  posi- 
tion of  the  diaphragm  in  diphtheritic  laryngeal  stenosis. ^^ 

This  slowing  and  deepening  of  respiration  is  advantageous  to 
the  patient;  for  experimental  work  has  shown  that  if  the  trachea 
be  artificially  narrowed,  such  a  compensatory  mechanism  allows 
more  air  to  enter  and  to  escape  from  the  lungs  than  is  represented 
by  the  normal  tidal  air.^^  Conditions  have  been  shown  to  be 
similar  in  man.  Coincident  with  the  increase  in  respired  air  per 
minute  is  a  considerable  diminution  of  the  partial  pressure  of 
carbon  dioxide  in  the  alveoli.  It  is  true  that  the  extra  exertion 
involved  consumes  more  oxygen,  but,  with  the  individual  at  rest, 
the  deeper  inspirations  enable  the  supply  to  meet  the  demand. 

A  paralysis  of  the  posterior  crico-arytenoid  muscles,  which 
separate  the  cords  during  inspiration,  interferes  purely  with  this 
phase,  for  the  cords  then  hang  limply  and  are  sucked  in  by  the 
air  as  it  enters,  leaving  only  a  chink  between  them.  This  pro- 
duces an  inspiratory  stenosis,  while  expiration  is  free  and  unhin- 
dered. Membranes  and  polyps  which  float  loosely  above  the 
glottis  may  similarly  give  rise  to  an  inspiratory  dyspnoea ;  whereas 
those  below  are  likely  to  affect  only  expiration. 

The  entrance  of  air  into  the  alveoli  may  also 
be  hindered  by  a  narrowing  of  the  coarser  or 
finer  bronchi.  The  results  will  depend  entirely  upon  the 
site  and  extent  of  the  lesion.  If  the  main  bronchus  on  one  side 
be  obstructed,  the  corresponding  half  of  the  chest  expands  less 
than  the  other,  the  normal  respiratory  murmurs  are  diminished 
or  absent  on  this  side  and  a  stridor,  caused  by  the  stenosis,  is  heard. 
The  breathing  becomes  labored,  but  ordinarily  it  does  not  assume 
the  characteristic  slow,  deep  rhythm  of  tracheal  stenosis,  evidently 
because  the  unaffected  side  acts  as  the  pace-maker. 

Conditions  vary  with  the  rapidity  of  devel- 
opment of  a  stenosis.  If  this  be  sudden,  immediate 
asphyxia  may  occur,  but  if  gradual,  the  degree  of  discomfort 
may  be  slight  because  the  individual  learns  to  conserve  his  oxygen 
ration  by  reducing  his  exertions  to  a  minimum.  In  this  way,  indi- 
viduals with  distinctly  reduced  respiratory  capabilities  may  lead 
a  fairly  comfortable  existence — ^how  comfortable  depending  upon 
the  extent  of  the  lesion  and  upon  the  oxygen  need. 

The  large  bronchi  may  be  narrowed  by  many  of 
the  causes  leading  to  tracheal  stenosis,  as,  for  instance,  by  tumors 


204  THE  BASIS  OF  SYMPTOMS 

or  cicatrices  from  within,  or  by  tumors  or  aneurisms  pressing  upon 
them  from  without.  On  account  of  the  large  calibre  of  these  tubes, 
a  swelling  of  the  mucous  membrane  does  not  ordinarily  obstruct 
the  passage  of  air.  In  the  case  of  the  smaller  bronchi,  on  the 
contrary,  the  most  frequent  cause  of  obstruction  is  just  such  an 
inflammation  of  the  lining  mucous  membrane.  If  only  the  larger 
bronchi  are  involved  in  a  bronchitis,  little  effect,  therefore,  is  pro- 
duced upon  the  interchange  of  gases  in  the  lungs ;  whereas  i  f 
the  smaller  tubes  are  affected,  the  results  are  far 
more  serious.  This  is  especially  true  of  children  on  account  of 
the  narrowness  of  their  air-passages,  and  is  also  true  of  those 
with  kyphoscoliosis,  for  their  pulmonary  surface  is  thereby  already 
reduced. 

In  every  severe  bronchitis,  the  breathing  is  superficial  and 
hurried,  the  rate  not  infrequently  rising  to  sixty  or  eighty  per 
minute.  Febrile  types  exhibit  the  most  rapid  rate,  for  fever  per  se 
accelerates  the  breathing.  The  same  respiratory  changes  occur 
also  in  extensive  non-febrile  cases.  The  factors  causing  this 
alteration  in  the  breathing  are  not  understood.  A  mere  retention 
of  carbon  dioxide  in  the  blood — the  normal  respiratory  stimulus  ^^ 
— will  not  produce  this  effect.  The  conception  of  a  peculiar  stimu- 
lation exerted  by  carbon  dioxide  from  diseased  lungs  is  not  satis- 
factory because  it  is  not  known  that  the  gas  actually  does  act  upon 
the  vagus  endings;  nor  would  the  carbon  dioxide  tension  in  the 
alveoli  be  favorable  for  such  a  stimulation.  It  is  possible  that 
the  inflammation  as  such  stimulates  the  vagus  terminations.  In 
conditions  such  as  pneumonia  in  which  an  augmented  respiratory 
volume  is  out  of  the  question,  compensation  can  be  effected  only  by 
an  increase  in  rate.^^  Finally,  we  must  not  lose  sight  of  the  fact 
that  the  respiratory  changes  may  be  due  to  the  products  of  incom- 
plete oxidation,  comparable  to  the  alterations  in  breathing  accom- 
panying muscular  activity.  ^^ 

Bronchial  Asthma. — The  condition  known  as  bronchial 
asthma  ^'^  may  properly  be  considered  here,  because  its  char- 
acteristic paroxysms  are  assumed  to  be  due  to  a  nar- 
rowing of  the  entire  bronchial  tree.  These  attacks  exhibit  an 
extraordinarily  severe  dyspnoea  which  is  independent  of  the  con- 
dition of  the  heart.  Usually  nocturnal  at  first,  they  may  later 
occur  at  any  time  and  last  for  hours  or  days.  Though  both  res- 
piratory phases  are  powerful  and  prolonged,  expiration  is  the  more 


RESPIRATION  205 

labored.  Cyanosis  and  inspiratory  retraction  of  the  soft  parts 
are  rarely  absent.  The  breathing  is  generally  hurried.  During 
the  paroxysm  the  lungs  are  markedly  distended,  and  soon  attain 
the  maximum  inspiratory  position.  Auscultation  yields  profuse 
rhonchi  of  all  types.  Early  in  the  disease  patients  are  comfortable 
in  the  intervals,  but  as  time  goes  on,  bronchial  catarrh,  cough  and 
intermittent  dyspnoea  are  often  present. 

These  asthmatic  paroxysms  occur  particularly  as  phases  of  a 
chronic  exudative  bronchiolitis  (Curschmann).*^ 
The  tough  mucinous  sputum,  Curschmann  spirals  and  Charcot- 
Leyden  crystals  speak  for  a  specific  process,  which  Miiller,^^  on  the 
basis  of  chemical  sputum  analyses,  is  inclined  to  regard  rather  as  a 
disorder  of  secretion  than  as  an  inflammation  in  the  strict  sense. 

The  eosinophilia  in  the  blood  and  sputum  of  asthmatics,  and 
also  in  the  membranous  discharges  of  mucous  colitis,  and  further, 
the  neuropathic  constitution  common  to  both,  have  inclined 
Striimpell  to  the  view  that  both  are  of  similar  origin,  possibly 
an  eosinophilic  diathesis.  Be  this  as  it  may,  asthmatic 
paroxysms  are  practically  pathognomonic  of  bronchiolitis  exu- 
dativa. Similar  paroxysms,  it  is  true,  do  occur  in  emphysema; 
and  it  may  be  difficult  to  determine  whether  the  emphysema  or 
the  asthma  is  primary. 

Diverse  factors  can  apparently  precipitate  an  attack,  for  ex- 
ample, affections  of  the  nasal  mucosa,  possibly  by  reflex  action.  It 
is  conceivable  that  the  mucous  membranes  of  the  bronchi  and  of 
the  nose  are  affected  by  similar  influences,  or  that  simultaneous 
changes  in  both  are  manifestations  of  the  same  (eosinophilic) 
process. 

The  most  unusual  moments  may  bring  on  a  paroxysm,  as,  for 
instance,  a  peculiar  odor,  in  the  asthma  of  hay  fever.  One  thinks 
involuntarily  of  anaphylaxis.  The  tendency  of  many  observers 
to  regard  asthma  as  the  equivalent  of  anaphylactic  sensitization, 
and  to  identify  the  paroxysm  with  anaphylactic  shock, 
rests  upon  a  certain  basis  of  fact.^^  An  unstable  nervous  organ- 
ization is  common  to  both.  In  asthma,  furthermore,  aerogenic 
introduction  of  the  provocative  material  can  occur  only  in  minimal 
amounts,  which  fits  in  well  with  conditions  peculiar  to  sensitization 
and  reinjection  in  anaphylaxis. 

The  dyspnoea  and  the  pulmonary  distention  seen  in  asthma 
must  first  be  explained  before  we  can  understand  the  nature  of 


206  THE  BASIS  OF  SYMPTOMS 

the  paroxysm  itself.  We  have  seen  that  during  inspiration — and 
even  more  during  expiration — there  is  evidence  of  a  marked  ob- 
struction, which  is  of  rapid  onset  and  of  relatively  short  duration, 
and  which  quickly  leads  to  a  pulmonary  distention.  What  con- 
stitutes this  hindrance  to  the  passage  of  air  has  been  variously 
explained.  In  the  bronchiolitic  type  it  is  natural  to  assume  an 
inflammatory  plugging  of  the  finer  tubes.  More  plausible  perhaps 
is  an  acute  non-inflammatory  hypersemia  of  the  medium-sized 
tubes,  in  view  of  the  analogous  condition  of  the  nasal  mucosa; 
for  this  would  not  only  permit  of  a  common  explanation  of  these 
two  conditions  which  seem  to  be  so  intimately  related,  but  would 
also,  regarded  as  a  vasomotor  phenomenon,  be  in  keeping  with 
the  nervous  element  in  asthma.  StriimpelPi  happily  compares 
the  asthmatic  attack  with  an  urticarial  eruption,  which  is  also 
of  short  duration  and  a  secretory  neurosis. 

The  most  acceptable  explanatio n — one  accounting 
for  all  of  the  phenomena  of  the  paroxysm — is  that  of  a 
spasm  of  the  smooth  muscle  of  the  fine  and 
medium-sized  bronchi  superimposed  upon  in- 
flammatory or  vasomotor  swelling  of  the  mu- 
cous membranes.  Experimental  studies  seem  to  indicate 
that  pulmonary  distention  may  unquestionably  be  due  to  such  a 
spasm.  The  predominating  expiratory  dyspnoea  would  then  be 
ascribed  to  the  narrowing  of  the  bronchioles,  with  their  yielding 
walls,  by  the  pressure  exerted  laterally  upon  the  chest  wall  during 
expiration;  though  no  other  explanation  is  needed  than  is  given 
by  the  loss  of  elasticity  consequent  to  the  pulmonary  distention, 
and  by  the  fact  that  the  expiratory  forces  are  naturally  weak. 

Vasomotor  swelling  and  bronchial  spasm,  therefore,  explain 
all  of  the  phenomena  of  asthma.  A  spasm  of  the  diaphragm  is 
inconceivable,  for  the  diaphragm,  unlike  the  involuntary  muscle 
in  the  bronchial  wall,  can  hardly  remain  in  a  state  of  tonic  con- 
traction for  hours  at  a  time  without  tiring  and,  as  radiographic 
studies  have  shown,  does  not  occur.  The  symptoms  of  the 
paroxysm  also  fit  in  well  with  the  conception  of  anaphylactic 
shock,  both  in  the  vasomotor  manifestations  and  in  the  intimate 
association  of  nervous  and  muscular  factors. 

Paralysis  of  the  Respiratory  Muscles. — The  aeration  of  the 
lungs  suffers  if  the  thorax  or  the  lungs  cannot  sufficiently  expand 
and  contract.    A  rigidity  of  the  chest  wall  alone  ordinarily  does 


RESPIRATION  207 

little  harm,  for  the  compensatory  increase  in  the  movements  of 
the  thorax  as  a  whole,  and  of  the  diaphragm,  could  move  the 
lungs  sufficiently  to  keep  them  ventilated. 

More  serious  is  disease  of  the  respiratory  muscles  or  of  the 
nerves  which  supply  them.  The  former  occurs  in  the  muscular 
atrophies  and  in  trichinosis;  the  latter  in  peripheral  neuritis,  or 
in  intracranial  conditions  such  as  inflammation,  tumor  or  hemor- 
rhage. The  diaphragm  and  the  other  muscles  of  respiration  may 
be  paralyzed  together  or  separately.  The  movements  of  the 
diaphragm  may  be  seriously  hampered  by  inflammation  of  its 
pleural  or  peritoneal  surfaces,  and  by  abdominal  distention  whether 
from  fluid,  gas  or  tumor — all  of  which  interfere  with  respiration 
by  forcing  the  diaphragm  up  and  by  offering  an  abnormal  resis- 
tance to  its  inspiratory  descent. 

The  degree  of  disturbance  of  respiratory  function  from  these 
various  causes  is  closely  dependent  upon  the  extent  and  the  loca- 
tion of  the  disease.  Death  quickly  follows  the  simultaneous  in- 
volvement of  all  of  the  inspiratory  muscles.  Of  the  more  limited 
conditions,  equally  fatal  is  bilateral  paralysis  of  the  diaphragm, 
as  occurs  in  disease  of  both  phrenic  nerves.  A  less  serious 
paralysis  may  not  cause  death,  but  merely  interferes  with  the  inter- 
change of  gases  in  the  lungs.  If  the  compensatory  increase  in  the 
movements  of  the  unaffected  muscles  is  not  sufficient,  the  vicarious 
inspiratory  muscles,  previously  referred  to,  are  called  upon,  lead- 
ing to  bizarre  types  of  breathing,  such  as  the  pure  costal  in  a 
man,  etc.  The  rate  may  also  be  increased  in  these  conditions, 
particularly  when  pain  is  a  factor. 

Loss  of  Pulmonary  Elasticity.  Emphysema. — As  has  already 
been  mentioned,  the  elasticity  of  the  lungs  plays  an  important  role 
in  normal  respiration,  for  it  is  one  of  the  main  factors  in  forcing 
the  air  out  during  expiration.  If  the  lungs  are  immoderately 
distended,  or  if  their  elasticity  is  otherwise  diminished,  the  ten- 
dency to  collapse  is  more  or  less  lost.  Such  a  loss  of  elasticity 
of  the  lungs,  as  a  whole  or  in  part,  may  follow  diseases  associated 
with  violent  inspiration  or  coughing,  or  those  in  which  the  egress 
of  air  is  obstructed.  If  a  major  portion  of  the  lungs  has  lost  its 
elasticity  from  overdistention,  respiration  is  handicapped  because 
the  distended  lung  does  not  exhibit  the  normal  tendency  to  collapse 
on  expiration,  and  not  being  fully  collapsed,  cannot  expand  so 
well    on    inspiration.     Volumen    pulmonum    auctum, 


208  THE  BASIS  OF  SYMPTOMS 

therefore,  diminishes  the  functional  capacity  of  the  lung  tissues 
by  rendering  it  less  elastic.  Removal  of  the  cause,  however, 
may  bring  about  a  restoration  of  function  if  the  damage  is  not 
too  great. 

Genuine  emphysema  of  the  lungs  acts  similarly  by 
diminishing  the  pulmonary  elasticity.  It  is  more  serious  than 
mere  overdistention,  because  the  damage  it  causes  is  irreparable, 
and  especially  because  it  leads  also  to  an  actual  loss  of  lung  sub- 
stance. Many  alveolar  septa  disappear,  and  the  respiratory  sur- 
face of  the  lungs  is  markedly  contracted.  The  loss  of  the  septa 
leads  to  an  obliteration  of  many  pulmonary  capillaries,  in  this 
way  increasing  the  resistance  to  the  flow  of  blood  through  the 
lungs.  The  consequence  is  an  hypertrophy  of  the  right  ventricle, 
evidenced  by  the  accentuation  of  the  pulmonary  second  sound. 
Emphysema  does  not,  as  a  rule,  involve  both  lungs  uniformly,  but 
is  most  pronounced  along  the  free  margins  in  front. 

Prominent  among  the  theories  advanced  to  ex- 
plain pulmonary  emphysema ^^  are  the  mechanical 
and  the  toxic-inflammatory.  According  to  the  former, 
the  elastic  tissue  suffers  purely  from  mechanical  interference  with 
the  respiratory  movements ;  while,  in  the  latter,  the  damage  is  the 
result  of  inflammation  and  its  products.  Tendeloo  favors  me- 
chanical factors  because  emphysema  is  most  marked  where  the 
forces  leading  to  overdistention  are  most  active,  and  he  attributes 
variations  in  the  resistance  of  elastic  tissue  both  to  congenital 
inferiority  and  to  acquired  injury. 

Speaking  also  for  mechanical  influences  is  the  fact  that 
although  true  emphysema  is  comparatively  rare,  emphysematous 
changes  secondary  to  long-continued  asthma  may  be  regarded 
almost  as  the  rule. 

Calcification  of  the  first  costal  cartilage  with  a  resultant  rigid 
distention  of  the  thoracic  cage  has  also  been  suggested  as  the  chief 
factor  in  emphysema.^^  Upon  this  view  is  based  a  surgical  treat- 
ment of  the  condition. 2* 

•Experimental  studies  have  explained  the  cause  of  dyspnoea  in 
emphysema  on  the  ground  of  an  unequal  arterialization  of  the 
blood.  As  many  of  the  alveoli  are  rendered  functionally  incapa- 
ble in  emphysema,  oxygenation  in  the  lungs  is  patchy,  so  to  speak, 
the  result  being  a  disturbance  of  the  oxygen  tension  in  the  blood 
as  a  whole.^^ 


RESPIRATION  209 

Respiratory  Changes  of  Nervous  Origin.  Cheyne-Stokes 
Breathing. — Disturbances  of  the  respiratory  centre  may  also  affect 
the  ventilation  of  the  lungs.  With  an  increase  in  intracranial 
pressure,  the  respirations  usually  become  slower  and  deeper, 
and  frequently,  also,  more  irregular.  Anatomical  lesions  that 
injure,  without  destroying,  the  respiratory  centre  may  give  rise 
to  similar  effects. 

The  peculiar  type  of  breathing  known  as  Cheyne-Stokes 
respiration  may  be  considered  in  this  place.^^  In  this  con- 
dition the  respiratory  rhythm  is  broken  by  pauses  of  apnoea. 
After  one  of  these  pauses  the  respirations  are  at  first  weak  and 
superficial,  but  gradually  they  become  stronger  and  stronger,  until 
they  are  exceedingly  labored.  Following  the  extreme  dyspnoea, 
the  respirations  gradually  diminish  in  strength  until  they  cease 
altogether  in  the  period  of  apncea,  and  the  cycle  of  events  is  com- 
pleted. Accompanying  this  anomaly  there  are  frequently  mani- 
festations suggesting  involvement  of  other  parts  of  the  brain. 
The  patient  may  lie  in  a  stupor  during  the  apnoea,  to  awake  during 
the  period  of  dyspnoea  with  oppressive  sensations  of  air-hunger. 
The  pupils  may  be  contracted  and  rigid  during  the  pause  and 
become  dilated  and  mobile  during  the  dyspnoea.  The  pulse  is 
generally  unaffected  though  it  may  exhibit  distinct  variations  in 
frequency  and  tension.  Important  among  the  causes  of 
Cheyne-Stokes  breathing  are  ursemia  and  diseases  of 
the  heart  and  brain. 

The  explanation  of  this  phenomenon  was  be- 
lieved by  Traube  to  reside  in  an  altered  irritability  of  the  res- 
piratory centre.  Filehne,^''^  who  observed  similar  respiratory 
changes  in  rabbits  under  deep  morphin  narcosis,  came  to  the 
conclusion,  on  the  basis  of  comparative  respiratory  and  blood- 
pressure  tracings,  that  the  respiratory  centre  had  become  less  irri- 
table than  the  vasomotor.  As  is  well  known,  blood  with  a  suffi- 
cient carbon  dioxide  tension  furnishes  the  stimulus  to  both.  In 
the  opinion  of  Filehne,  then,  the  blood  is  not  sufficiently  venous 
during  the  pause  to  stimulate  the  respiratory  centre,  but  does 
contain  enough  carbon  dioxide  to  activate  the  vasomotor  centre. 
The  resulting  constriction  of  the  arteries  going  to  the  brain  finally 
renders  the  blood  sufficiently  venous  to  stimulate  the  less  irritable 
respiratory  centre.  The  breathing  then  gradually  deepens  and  the 
blood  becomes  better  aerated.    The  vasomotor  centre,  no  longer 

14 


210  THB  BASIS  OF  SYMPTOMS 

stimulated  by  venous  blood,  allows  the  vessels  to  dilate,  and  in 
this  way  a  fresh  supply  of  arterial  blood  reaches  the  respiratory 
centre.  The  latter  is  thereby  deprived  of  the  necessary  carbon 
dioxide  stimulus  and  the  animal  stops  breathing.  Thus  the  cycle 
is  completed  and  a  new  one  can  begin. 

Rosenbach  ^®  has  vigorously  disputed  this  theory.  In  his  opin- 
ion, certain  portions  of  the  brain,  especially  the  respiratory  centre, 
are  rendered  less  irritable  by  nutritional  disorders,  the  normal 
periodic  exhaustion  being  simultaneously  increased.  He  attached 
no  importance,  therefore,  to  variations  in  the  gas  content  of  the 
blood.  Douglas  and  Haldane^®  have  recently  shown  that  by 
artificially  causing  an  oxygen  deficit  in  the  blood,  a  periodic  res- 
piratory rhythm  could  be  produced,  and  that  this  periodicity  was 
attributable  to  changes  in  the  gas  tension.  How  far  their  results 
go  in  explaining  Cheyne-Stokes  breathing  in  man,  it  is  difficult  to 
say.  Pembrey  and  Allen  ^*^  showed  that  the  pauses  in  this  phe- 
nomenon could  be  eliminated  not  only  by  an  inspiratory  air  rich 
in  carbon  dioxide,  but  also  by  one  with  a  high  oxygen  content, 
and  further  by  a  stimulation  of  sensory  nerves. 

It  is  impossible  to  discuss  the  various  explanations  given  for 
this  type  of  breathing,  mainly  because  so  few  of  the  facts  are 
known.  It  should  be  remembered,  however,  that  even  healthy 
individuals  often  show  a  tendency  to  periodic  breathing,  as,  for 
example,  in  sleep ;  and  that  many  animals  normally  show  this  type 
of  breathing.  For  this  reason,  the  conception  that  Cheyne-Stokes 
breathing  is  due  to  some  disturbance  in  the  nervous  connection 
between  the  cerebral  cortex  and  the  respiratory  centre  in  the 
medulla,  seems  especially  noteworthy  and  fruitful.^* 

Changes  in  the  respiratory  centre  are  probably 
responsible  for  the  abnormal  breathing  seen  in  certain  intoxica- 
tions— ^such,  for  example,  as  the  spasmodic  breathing 
of  hydrocyanic  acid  poisoing,  or  the  deep  res- 
pirations of  diabetes,  uraemia  and  other  condi- 
tions— some  autointoxications,  others  acidoses.^^  The  latter 
are  characterized  by  frequent  and  extraordinarily  deep  breathing 
(air-hunger)  occurring  without  demonstrable  pulmonary 
changes.  The  cause  of  air-hunger  is  supposed  by  some  to  reside 
in  the  increased  irritability  of  the  respiratory  centre  to  such  acids 
as  carbonic  and  lactic.^^ 

The    frequent   and    superficial    respirations    of    salicylic 


RESPIRATION  211 

acid  poisoning,  and  the  various  forms  of  dyspnoea  which 
may  be  present  in  hysteria,  also  seem  to  be  due  to  nervous 
influences.  And  finally,  the  respiratory  centre  may  be  affected 
by  reflexes  from  various  parts  of  the  body,  especially  from  the 
abdominal  organs.  The  conditions  known  as  asthma  dys- 
pepticum,  asthma  uterinum,  etc.,  are  of  this  nature.^* 

Pleural  Effusions.  Pneumothorax. — Even  though  the  move- 
ments of  the  chest  are  normal,  and  the  air  can  reach  the  alveoli, 
respiratory  difficulties  may  arise  from  a  diminution  of  the 
total  functionating  pulmonary  surface.  Such  a 
diminution  may  be  caused  by  various  diseases,  either  because  they 
fill  the  alveoli  with  inflammatory  products,  as  happens  in  pneu- 
monia, or  because  they  obliterate  them  by  pressure  from  without, 
as  happens  in  large  pleural  effusions. 

When  fluid  collects  in  the  pleural  cavity,  the 
lung  at  first  retracts  by  virtue  of  its  elasticity ;  but  as  the  effusion 
grows,  retraction  is  succeeded  by  complete  collapse.  As  pointed 
out  by  Gerhardt,  however,  the  mechanism  is  not  as  clear  as  was 
formerly  supposed.  The  tension  residing  in  a  pleural  exudate 
is  not  commensurate  with  the  size  of  the  latter,  for  in  the  most 
massive  exudates,  Gerhardt  ^^  found  a  more  pronounced  negative 
pressure  than  in  the  intact  pleural  cavity.  That  is  to  say,  the 
lungs  may  suffer  compression,  but  the  mere  fact  that  they  are 
airless  is  not  necessarily  the  result  of  such  compression.  More 
evidence  is  needed  to  explain  the  factors  present  here,  especially 
those  active  in  the  expansion  or  collapse  of  the  lung  bases. 

A  pleural  effusion  does  harm  in  several  ways. 
In  the  first  place,  the  retraction  and  compression  of 
the  lung  on  the  side  of  the  fluid  naturally  diminish  the 
surface  available  for  the  interchange  of  gases. 
Further,  since  the  pressure  in  the  affected  cavity  is  higher  than 
that  in  the  healthy  pleural  cavity,  the  mediastinum  is  dis- 
located toward  the  sound  side,  thus  embarrassing  the  healthy 
lung  as  well.  The  circulation  is  also  materially 
affected,  for  the  negative  pressure  normally  present  in  the 
thorax  is  diminished,  and  the  venous  flow  from  the  periphery 
toward  the  heart  is  consequently  retarded.  Large  exudates  may 
even  compress  or  kink  the  inferior  vena  cava.  Finally,  the  in- 
creased pressure  upon  the  capillaries  of  the  lungs  raises  the 


212  THE  BASIS  OF  SYMPTOMS 

resistance  in  the  pulmonary  circulation,  thus  in- 
creasing the  work  of  the  right  ventricle  (see  p.  19). 

If  air  penetrates  the  pleural  cavity  through  a  wound  in  the 
chest  wall,  or  through  an  opening  in  a  lung  produced  by  such 
causes  as  tuberculosis,  abscess,  gangrene  or  injury,  it  gives  rise 
to  many  of  the  same  results  as  does  an  effusion.  When  such  a 
pneximothorax  communicates  freely  with  the  external  air,  the 
pressure  in  the  affected  cavity  will  be  the  atmospheric  pressure. 
If,  however,  the  perforation  closes,  a  portion  of  the  air  is  absorbed 
and  the  pressure,  though  less  than  that  of  the  atmosphere,  remains 
greater  than  that  on  the  unaffected  side.  If,  finally,  the  opening 
be  of  a  valvular  nature,  permitting  air  to  enter  the  pleural  cavity, 
but  preventing  its  exit,  the  pressure  within  will  exceed  the  atmos- 
pheric, at  least  during  rest  and  expiration,  and  not  only  the  lung 
of  the  affected  side,  but  that  of  the  other  also  will  be  subjected 
to  considerable  pressure. 

The  seriousness  of  a  pneumothorarx,  depends 
mainly  upon  the  functional  capacity  of  the 
healthy  lung.  If  this  can  functionate  without  interference, 
all  the  demands  of  the  resting  body  may  be  met,  even  though  the 
pneumothorax  should  have  developed  suddenly.  Unfortunately, 
the  healthy  lung  is  often  encroached  upon  by  the  mediastinum, 
because  the  latter  is  thrust  past  the  median  line  by  the  high 
pressure  in  the  affected  cavity.^®  When  the  opening  into  the 
pleural  cavity  is  a  large  one,  and  admits  of  free  communication 
with  the  external  air,  each  inspiration  dislocates  the  mediastinum 
toward  the  healthy  side  and  the  air  cannot  enter  the  sound  lung 
as  well  as  normally.  The  consequences  are  less  severe  if  the 
mediastinum  is  very  rigid  or  the  abnormal  opening  small.  The 
severe  collapse  which  sometimes  follows  a  large  perforation  into 
the  pleural  cavity  may  be  prevented  experimentally  by  checking 
the  displacement  of  the  mediastinum.  In  general,  a  right-sided 
pneumothorax  is  more  serious  than  one  on  the  left  side,  because  of 
the  greater  capacity  of  the  former. 

If  the  abnormal  opening  is  small  enough  to  prevent  any  con- 
siderable passage  of  air,  the  air  in  the  pneumothorax  becomes 
rarefied  during  inspiration,  the  lungs  expand  and  pull  upon  the 
mediastinum,  and  the  patient  may  experience  practically  no  dis- 
comfort. 

These  variations  in  the  size  of  the  perforation 


RESPIRATION  213 

and  in  the  degree  of  mediastinal  dislocation  ex- 
plain the  extraordinary  differences  in  the  clinical  picture  of 
pneumothorax,  and  also  why,  in  surgically  produced  pneumo- 
thorax, the  dyspnoea  may  be  relieved  by  suturing  the  lung  into 
the  opening  in  the  chest  wall.  The  dyspnoea  in  this  condition  is 
clearly  the  result  of  the  to  and  fro  displacement  of  the  mediastinum 
and  the  consequent  imperfect  ventilation  of  the  still  functionating 
respiratory  surfaces.^'^ 

Modern  pulmonary  surgery  has  considerably  increased  our 
understanding  of  pneumothorax.  We  now  know  that  the  all- 
important  factor  is  the  tension  in  the  abnormal  pleural  cavity. 
The  recent  studies  on  artificial  respiration,  however,  have  shown 
— and  this  physiologists  have  long  known — that  respiratory  move- 
ments are  essential  only  to  a  certain  degree  for  the  ventilation 
of  the  lungs;  indeed  they  are  quite  unnecessary  if  an  animal  be 
allowed  to  breathe  pure  oxygen.^^  This  throws  considerable  light 
also  upon  the  transportation  of  air  from  the  medium-sized  bronchi 
to  the  alveoli  in  normal  respiration. 

Bruns  found  an  hypertrophy  of  the  right  ventricle  in  experi- 
mental pneumothorax;  and  his  studies,  and  those  of  Brauer,  indi- 
cate that  the  collapsed  lung  receives  less  blood  than  the  other. 

If  one  of  the  larger  bronchi  perforates  directly  into  the 
mediastinum,  air  rushes  not  only  into  the  latter,  but  also  into  the 
subcutaneous  tissues  of  the  entire  body,  and  a  severe  cardiac 
insufficiency  may  follow. 

(It  may  not  be  out  of  place  merely  to  mention  the  fact  that 
with  an  increasing  knowledge  of  intrapleural  pressure  conditions, 
the  field  of  pulmonary  surgery  has  recently  developed  apace,  con- 
firming the  prediction  of  Billroth,  made  half  a  century  ago,  that 
"what  is  now  medical  will  tend  to  become  surgical."  The  revival 
of  artificial  pneumothorax  for  certain  types  of  pul- 
monary tuberculosis;  the  methods  of  surgical  collapse  of 
a  diseased  lung,  particularly  those  of  Wilms  and  Sauer- 
bruch,  and  even  complete  resection  of  an  affected 
lobe — all  of  these  attest  to  the  foresightedness  of  the  master, 
at  least  in  the  realm  of  pulmonary  disease. — Ed.) 

Atelectasis. — An  inflammation  of  the  smaller 
bronchi  may  decrease  the  respiratory  surface  of  the  lungs, 
for  the  oedema  of  the  mucosa  easily  occludes  their  lumina,  render- 
ing useless  the  corresponding  alveoli.    If  the  occlusion  persists  for 


214  THE  BASIS  OF  SYMPTOMS 

any  length  of  time,  the  air  in  these  alveoH  is  soon  absorbed  and 
the  condition  of  atelectasis  is  established.  The  oxygen  and  car- 
bon dioxide  are  rapidly  absorbed,  the  nitrogen  more  slowly.  The 
gases  are  absorbed  because  the  alveoli  tend  to  contract,  thereby 
keeping  the  partial  pressure  of  the  different  gases  within  them 
at  a  higher  level  than  the  tension  of  these  same  gases  in  the  blood. 

Atelectasis  may  also  be  caused  by  compression  of  the 
lungs,  as  from  large  pleural  effusions  or  pneumothorax.  In- 
deed, the  alveoli  may  become  atelectatic  without  bronchial  occlu- 
sion or  compression  from  without.  For  example,  the  portion  of 
the  lung  which  dips  into  the  fluid  of  a  small  pleural  exudate  is  not 
subjected  to  a  positive  pressure,  and  yet  it  is  usually  found  to  be 
airless.  Interference  with  the  movements  of  the 
diaphragm,  it  would  seem,  may  also  produce  atelectases  of 
this  type.  The  importance  of  the  last,  following  operation  upon 
the  abdominal  organs,  has  probably  received  too  little  attention, 
for  to  it  may  be  attributed  many  of  the  transient  so-called  pneu- 
monias and  hypostatic  conditions,  which  in  reality  are  probably 
localized  atelectases  of  the  lung  bases.  An  added  factor  in  these 
conditions  is  the  lowering  of  the  general  resistance  such  as  fol- 
lows prolonged  anaesthesia,  or  severe  operations  even  without 
anaesthesia. 

The  Effects  of  an  Obliteration  of  the  Air-Spaces.— -The 
disturbances  produced  by  a  d  iminution  of  the 
functioning  surface  of  the  lungs  depend  upon 
several  factors,  viz . ,  the  amount  of  pulmonary 
surface  thrown  out  of  function,  the  rapidity 
with  which  this  occurs,  the  demands  of  the 
body  for  fresh  oxygen  and  the  degree  to  which 
an  increase  in  the  respiratory  movements  can 
compensate  for  the  disabled  tissue. 

The  respiratory  movements  in  conditions  of  atelectasis  are 
generally  deef>er  and  often  more  rapid,  particularly  in  febrile 
cases,  for  the  heated  blood  seems  to  stimulate  the  respiratory 
centre  not  only  directly,  but  through  reflexes  from  the  skin.  The 
breathing  may  be  hurried,  however,  even  in  the  absence  of  fever. 
The  explanation  of  this  goes  back  to  the  deeper  inspirations 
observed  in  atelectasis,  which  are  in  turn  probably  due  to  the 
stimulation  of  the  respiratory  centre  by  the  carbon  dioxide  re- 
tained in  the  blood.     The  more  prolonged  inspiratory  movements 


RESPIRATION  215 

enlarge  the  chest  cavity,  and,  since  many  of  the  collapsed  alveoli 
do  not  expand,  the  functioning  ones  must  expand  all  the  more. 
This  excessive  distention  of  certain  alveoli  probably  stimulates 
the  vagus  endings,  thus  ending  inspiration,  as  we  have  seen,  and 
rendering  the  succeeding  expirations  prompt  and  forcible,  and 
thus  perhaps  increasing  the  respiratory  rate.  Accurate  analyses 
of  the  blood  gases  or  of  the  alveolar  air  would  furnish  a  more 
satisfactory  foundation  for  this  theory.  Sensory  stimuli  arising 
in  the  lungs  may  also  play  a  part  in  accelerating  the  respiratory 
rate. 

A  diminished  respiratory  surface  may  sometimes  cause  a  super- 
ficial and  rapid  type  of  breathing.  This  is  likely  to  occur  in  such 
conditions  as  dry  pleurisy  or  peritonitis  localized  about  the  dia- 
phragm, in  which  inspiration  is  curtailed  by  painful  reflexes.  The 
irritability  of  the  respiratory  centre  is  not  dissipated  thereby,  so 
that  a  new  inspiration  follows  immediately.  Hence  the  breathing 
is  both  shallow  and  hurried. 

In  the  last  analysis,  respiratory  efficiency  depends  upon  the 
uniformity  with  which  the  air  is  distributed  to  the  alveoli. ^^  In 
emphysema  and  in  cardiac  dyspnoea,  the  distribution  is  far  less 
uniform  than  in  health.  As  the  partial  pressure  of  carbon  dioxide 
in  the  inspired  air  is  low  in  these  conditions,  the  expired  air  is 
also  relatively  poor  in  this  gas.  Hence  to  bring  the  carbon  dioxide 
output  per  unit  volume  of  air  up  to  a  normal  level,  the  amount  of 
air  taken  in  and  given  out  in  a  given  time-unit  must  be  increased ; 
and  this  is  synonymous  with  dyspnoea. 

Disturbances  in  the  interchange  of  gases  in  the  lungs  may 
arise  from  changes  in  the  chemical  or  physical  character  of  the 
alveolar  membranes,  even  though  this  interchange  has  been  shown 
to  be  merely  one  of  diffusion.  The  dyspnoea  of  patients  with 
chronic  passive  hyperaemia  consequent  to  heart  disease  is  probably 
of  this  nature. 

The  Effects  of  Atmospheric  Pressure  Upon  Respiration. — 
Variations  in  the  composition  of  the  air  must  produce  certain 
effects  upon  the  animal  organism,  for  the  passage  of  the  gases 
through  the  alveolar  membranes  depends  primarily  upon  the  rela- 
tion existing  between  the  partial  pressure  of  these  gases  in  the 
blood  and  in  the  air-cells.  The  partial  pressure  of  the  oxygen  in 
ithe  lungs  may  be  diminished  either  by  diminishing  the  atmos- 
pheric pressure  as  a  whole,  or  by  reducing  the  relative  proportion 


216  THE  BASIS  OF  SYMPTOMS 

of  oxygen  in  ordinary  air.  Practically,  the  latter  is  seen  only 
when  an  animal  is  allowed  to  breathe  in  a  small  air-tight  space 
until  the  oxygen  is  reduced.  The  symptoms  produced  are  those  of 
asphyxia  and  will  be  spoken  of  in  that  connection  (p.  222), 

The  effects  of  low  atmospheric  pressure^*'  are  frequently  seen 
especially  in  those  who  make  balloon  ascensions,  and  in  those 
who  reach  great  heights  in  mountain  climbing.  The  symp- 
toms may  be  merely  unpleasant  at  first,  but  at  higher  eleva- 
tions they  become  actually  dangerous.  The  height  at  which 
symptoms  develop  varies  for  different  individuals  and  under  dif- 
ferent conditions.  Dyspnoea,  headache,  prostration,  paralysis  of 
the  extremities,  and  finally  complete  unconsciousness  may  occur 
during  a  balloon  ascension;  and  a  similar  set  of  symptoms,  vis., 
fatigue,  headache,  sleepiness,  palpitation,  nausea,  rapid  pulse  and 
respiration,  and  especially  dyspnoea,  are  characteristic  of 
mountain-sickness.  In  neither  case  are  the  symptoms 
caused  by  the  mere  reduction  of  atmospheric  pressure,  but  are 
due  in  part  to  the  cold,  the  wind,  the  dazzling  light  and  the 
bodily  and  mental  strain.  That  the  rarefied  air,  however,  is  the 
main  cause  of  the  disturbances,  even  in  mountain  climbing,  is  evi- 
dent from  the  fact  that  symptoms  may  appear  in  individuals  who 
do  not  climb,  but  are  carried  up  the  mountain. 

A  considerable  rarefaction  of  the  respired  air  may  occasion 
no  disturbance  in  the  interchange  of  gases  in  the  lungs.  Most 
animals  and  men  will  endure,  without  serious  consequences,  a 
reduction  of  the  atmospheric  pressure  from  the  normal  of  760  mm. 
down  to  450  or  400  mm.  of  mercury;  and  some  can  withstand 
a  reduction  to  half  an  atmosphere  or  less.  The  manner  in  which 
the  individual  breathes  is  of  great  importance  in  determining  his 
ability  to  withstand  these  reductions  of  pressure.  Those  accus- 
tomed to  keeping  their  lungs  well  ventilated  resist  a  lowering  of 
pressure  comparatively  well,  for  they  know  how  to  keep  the  par- 
tial pressure  of  oxygen  in  the  alveoH  at  a  relatively  high  level. 
Anything  that  acts  unfavorably  upon  the  mechanics  of  respira- 
tion, such  as  cold,  wind,  loss  of  sleep,  etc.,  renders  the  individual 
more  susceptible  to  a  diminution  in  atmospheric  pressure.  For 
these  reasons  there  are  great  individual  variations  in  the  ability 
to  withstand  rarefied  air,  and  animals,  as  well  as  men,  living  at 
high  altitudes  gradually  learn  to  breathe  deeply  so  that  the  par- 
tial pressure  of  oxygen  in  their  alveoli  shall  be  sufficiently  high. 


RESPIRATION  217 

This  explains  the  apparently  paradoxical  observation  that  deep 
breathing,  though  it  adds  the  factor  of  muscular  exertion,  tends 
to  diminish  the  dyspnoea  at  high  altitudes.  A  sudden  change  to  an 
atmosphere  of  low  barometric  pressure  is  not  so  easily  borne,  hence 
the  symptoms  in  the  first  mountain  climb  or  balloon  ascension. 

According  to  certain  observers,^ ^  the  interchange  of  gases 
in  the  lungs  is  not  affected  until  the  pressure  of  the  external  air 
reaches  about  half  an  atmosphere.  If  the  pressure  be  reduced 
below  this,  the  elimination  of  carbon  dioxide  is  markedly  in- 
creased, and  the  absorption  of  oxygen  is  also  somewhat  increased, 
though  relatively  less  so,  at  least  in  the  early  stages. 

Observations  by  Zuntz,  however,  extending  over  several  weeks, 
upon  persons  near  the  summit  of  Monte  Rosa  (elevation  4500 
metres)  showed  in  most  cases  a  considerable  increase  in  the  con- 
sumption of  oxygen  and  in  the  respiratory  rate.  More  recent 
studies  of  the  same  observer ^^  indicate,  nevertheless,  that  this 
increase,  both  with  the  individual  at  rest  and  at  work,  is  not  so 
great  as  was  formerly  believed.  The  persons  subjected  to  these 
experiments  did  not  seem  to  become  acclimated  to  the  changed 
conditions  within  the  period  of  several  weeks  that  they  spent  in 
the  high  altitude. 

The  oxygen-carrying  capacity  of  the  haemo- 
globin does  not  diminish  at  the  same  rate  as 
does  the  partial  pressure  of  the  oxygen  to  which 
it  is  exposed.  Thus  Hiifner*^  has  shown  that  with  the 
partial  pressure  of  oxygen  at  124  mm. — corresponding  to  an  ele- 
vation of  2000  metres — ninety  per  cent,  of  the  haemoglobin  re- 
mains undissociated ;  at  a  partial  pressure  corresponding  to  an 
elevation  of  4000  metres,  eighty-eight  per  cent. ;  and  at  one  corre- 
sponding to  6000  metres,  eighty-five  per  cent.  The  decomposition 
of  oxyhsemoglobin  may,  therefore,  be  relatively  slight  at  these 
high  altitudes,  which  accounts  for  the  considerable  ability  of  the 
animal  body  to  resist  reductions  of  pressure.  It  is  only  on  the 
basis  of  such  observations  that  we  can  account  for  the  ability 
of  balloonists  to  ascend  to  elevations  of  10,000  metres  and  more. 

It  must  be  borne  in  mind,  however,  that  the  partial  pressure 
of  the  oxygen  in  the  lungs  may  be  considerably  lower  even  than  is 
its  partial  pressure  in  the  outside  air.  As  the  blood  becomes 
insufficiently  aerated,  the  respiratory  movements  are  increased  and 
the  partial  pressure  of  the  oxygen  in  the  alveoli  is  raised.    This 


218  THE  BASIS  OF  SYMPTOMS 

constitutes  a  most  important  mechanism  whereby  the  body  is  able 
to  compensate  for  reductions  in  the  atmospheric  pressure.  Mus- 
cular exercise  sometimes  relieves  the  unpleasant  symptoms  of  a 
rarefied  atmosphere,  probably  by  stimulating  the  respiratory 
movements. 

In  conclusion,  we  may  say  that  the  effects  of  a  high 
altitude  are  due  mainly  to  a  diminution  in  the 
tension  of  the  oxygen,  and,  to  a  lesser  extent,  to  other 
causes.  The  conditions  are  very  complicated,  and  it  must  be 
acknowledged  that  various  factors,  such  as  circulatory  disturb- 
ances, may  contribute  to  the  production  of  symptoms.  In  my 
opinion,  however,  the  lack  of  oxygen  is  the  essential  cause,  a  view 
that  is  supported  especially  by  the  fact  that  the  symptoms  of 
those  who  ascend  to  great  elevations  in  balloons  are  often  promptly 
relieved  by  inhalations  of  oxygen. 

Increasing  the  density  of  the  air  up  to  twice  the  normal 
pressure  is,  according  to  recent  observations,  without  any  effect 
upon  the  "quality  or  quantity"  of  the  respiratory  interchange 
of  gases.  The  increased  appetite  and  the  emaciation  that  are 
seen  in  individuals  subjected  to  high  pressures  cannot,  therefore, 
be  ascribed  to  anomalies  of  respiration. 

(An  interesting  condition  is  that  seen  in  caisson  workers, 
divers  and  miners,  and  which  is  known  as  caisson  disease  or  com- 
pressed-air disease.*^  Here,  unlike  the  conditions  enumerated 
above,  the  nitrogen  of  the  air  seems  to  play  the  chief  role.  Dur- 
ing compression,  this  gas  is  absorbed  under  great  pressure,  rapidly 
saturating  the  tissues.  Saturation  takes  place  quickly,  the  reverse 
much  more  slowly.  The  danger  in  this  disease  resides,  therefore, 
in  a  too  rapid  decompression,  which  leads  to  the  formation  of 
nitrogen  bubbles,  especially  in  the  venous  blood  and  fatty  tissue, 
and  to  a  dissemination  of  nitrogen  emboli.  These  emboli  lodge 
chiefly  in  the  spinal  cord ;  hence  the  prominence  of  cord  symptoms, 
paraplegia,  pains  in  the  legs,  etc.,  in  the  clinical  picture.  Pressures 
of  several  atmospheres  lead  to  no  untoward  results  if  decompres- 
sion is  allowed  to  take  place  slowly. — Ed.) 

The  Inhalation  of  Poisonous  Gases.— -The  atmospheric  air  may 
contain  substances  which  are  poisonous  to  the  body.  A  certain 
protection  against  these  poisonous  admixtures  is  furnished  by 
our  sense  of  smell,  which  warns  against  such  gases  as  ammonia 


RESPIRATION  219 

and  sulphuretted  hydrogen.  In  the  case  of  hydrocyanic  acid,  the 
odor  may  be  perceived  only  after  the  ix)ison  has  exerted  its  deadly 
action. 

Carbon  monoxide,  as  usually  inhaled,  is  mixed  with 
gases,  e.g.,  illuminating  gas,  which  possess  an  odor.  Carbon 
monoxide  poisoning  is  of  especial  importance  because  of  the 
marked  affinity  it  possesses  for  haemoglobin.^^  When  the  air 
contains  about  one  part  in  a  thousand  of  carbon  monoxide,  the 
latter  passes  into  the  blood  where  it  unites  with  a  portion  of  the 
haemoglobin  in  such  a  manner  that  the  latter  can  no  longer  com- 
bine with  oxygen  to  form  oxyhaemoglobin.  If  only  a  small 
amount  of  haemoglobin  is  thus  rendered  functionless,  the  damage 
is  slight,  the  patient  experiencing  only  a  few  symptoms,  such  as 
headache,  etc.  If  he  then  breathes  good  air,  the  carbon  monoxide 
haemoglobin  is  either  excreted  as  such,  or  the  combination  is  grad- 
ually broken  up  by  the  mass  action  of  fresh  oxygen.  In  severe 
cases  of  poisoning,  on  the  contrary,  the  blood  can  no  longer  fur- 
nish the  necessary  oxygen  to  the  body. 

Under  such  circumstances,  the  carbon  dioxide  is  excreted 
through  the  lungs  as  usual,  but  the  supply  of  oxygen  is  diminished : 
this  becomes  dangerous  when  about  one-half  of  the  total  haemo- 
globin is  decomposed.  In  rabbits  killed  by  monoxide,  only  twenty 
to  thirty  per  cent,  of  the  normal  amount  of  oxygen  was  found  in 
the  blood  at  the  time  of  death.  Part  of  the  carbon  monoxide 
in  the  blood  passes  into  the  tissues  and  there  exerts  its  anaesthetic 
action.  The  respiratory  centre  soon  becomes  unresponsive,  so 
that  respiration  ceases  entirely:  the  picture  is  quite  different, 
therefore,  from  that  of  acute  asphyxia.  If  the  individual  be 
placed  in  an  atmosphere  of  ordinary  air,  or,  better  still,  be  allowed 
to  breathe  pure  oxygen,  the  carbon  monoxide  haemoglobin  is  grad- 
ually dissociated  and  a  recovery  may  be  effected.  Considerable 
light  has  been  thrown  upon  this  subject  by  improved  methods 
for  the  determination  of  the  total  blood-mass  by  means  of  carbon 
monoxide  inhalations.*^ 

The  Effects  of  Anasmia  upon  Respiration. — The  supply  of 
oxygen  to  the  tissues  may  be  influenced  by  a  reduction  of  haemo- 
globin. If  the  quantity  of  this  pigment  in  the  circulating  blood 
be  too  small,  or  if  it  be  replaced  by  some  useless  combination, 
such  as  carbon  monoxide-  or  methaemoglobin,  the  cells  may  receive 
insufficient  oxygen.    In  acute  hemorrhage,  death  results  from  this 


220  THE  BASIS  OF  SYMPTOMS 

cause  when  about  seventy  per  cent,  of  the  total  haemoglobin  bulk 
is  lost. 

If  the  loss  of  haemoglobin  or  of  blood  be  very  gradual,  the 
body  can  accustom  itself  to  the  changed  conditions,  so  that  a 
much  greater  reduction  is  possible.  We  do  not  know  to  what 
limits  such  a  gradual  reduction  of  the  haemoglobin  may  go, 
because  our  clinical  methods  unfortunately  do  not  determine 
the  total  amount  of  the  pigment  itself,  but  only  the  content  of 
the  blood  per  unit  volume.  This  much  may  be  said,  however, 
that  a  gradual  diminution  to  one-tenth  of  its  normal  bulk  can  still 
be  endured. 

The  manner  in  which  the  organism  accommo- 
dates itself  to  a  gradual  loss  of  haemoglobin  is  not 
well  understood.^^  It  has  been  suggested  that  in  anaemic  states 
the  haemoglobin  undergoes  some  change  whereby  it  is  enabled 
to  transport  more  oxygen.  This  view,  however,  seems  scarcely 
tenable.  Furthermore,  the  total  amount  of  oxygen  absorbed  and 
of  carbon  dioxide  eliminated  during  rest  is  little,  if  any,  below  the 
normal  limits,  even  though  the  anaemia  be  severe.  Such  patients 
learn  to  restrict  their  movements  as  much  as  possible,  and  so  to 
lessen  their  need  for  oxygen;  and  although  the  amount  of  oxygen 
which  they  consume  during  rest  is  the  same  as  that  used  by  a 
healthy  individual,  their  gaseous  interchange  during  exercise  is 
much  less  than  normal.  Then  it  is  that  their  lessened  ability  to 
transport  oxygen  is  most  noticeable;  and  every  physician  knows 
how  incapable  of  exertion  anaemic  persons  are. 

Since,  in  an  anaemic  person,  a  small  amount  of  haemoglobin 
must  supply  the  tissues  with  the  usual  amount  of  oxygen,  at  least 
during  rest,  it  follows  that  either  the  haemoglobin  present  makes 
more  frequent  journeys  from  the  lungs  to  the  tissues,  or  that  it 
gives  up  more  oxygen  to  the  cells  at  each  journey.  Apparently 
both  of  these  methods  of  compensation  are  used.  Certain  it  is 
that  the  circulatory  rate  is  increased,  for  the  heart  throws  out 
more  blood  at  each  beat  and  the  number  of  beats  per  minute  is 
increased.  Of  less  importance  is  the  fact  that  the  oxyhaemoglobin 
is  generally  more  fully  utilized.  This  theory  of  a  more  complete 
utilization  of  the  oxygen  supplied  to  the  cells  assumes  the  truth 
of  the  current  view — and  none  more  satisfactory  has  as  yet  been 
offered — that  oxidation  up  to  the  end-products  of  metabolism 
occurs  in  the  tissues  themselves. 


RESPIRATION  221 

The  Effect  of  Circulatory  Changes  upon  Respiration. — If  the 

cells  are  to  receive  a  proper  supply  of  oxygen,  it  is  not  only  neces- 
sary that  there  should  be  sufficient  air  in  the  lungs  and  sufficient 
haemoglobin  in  the  blood,  but  that  there  be  also  a  sufficiently  rapid 
blood-stream.  The  haemoglobin  takes  up  oxygen  from  the  alveolar 
surfaces  very  rapidly,  and  no  advantage,  therefore,  is  derived 
from  a  slowing  of  the  blood-current  through  the  lungs.  When  the 
blood-current  is  so  retarded,  however,  that  the  respiratory  centre 
is  insufficiently  aerated,  the  cells  in  the  medulla  are  stimulated 
and  the  respiratory  movements  are  deepened.  This  respiratory 
compensation  is  of  special  value  in  circulatory  disturbances,  be- 
cause it  not  only  maintains  the  oxygen  tension  in  the  alveoli  at  a 
higher  level,  but  also  directly  assists  the  flow  of  blood. 

Respiratory  Compensation. — It  is  evident,  therefore,  that  con- 
ditions which  injure  external  respiration  set  in  motion  a  com- 
pensatory mechanism  which  is  designed  to  guard  against  the  harm- 
ful effects  of  a  lessened  internal  respiration.  The  degree 
to  which  such  compensation  is  possible  depends 
first  upon  the  magnitude  of  the  disturbance: 
should  an  aortic  aneurism,  for  instance,  rupture  into  the  lungs, 
filling  the  alveoli  with  blood,  no  increase,  however  great,  in  the 
depth  of  respiration  can  undo  the  damage.  Compensation  depends 
further  upon  the  efficiency  of  the  tools  designed  for  the  purpose, 
viz.,  a  movable  chest  wall,  good  respiratory  mus- 
cles and  a  strong  heart;  and  these  in  turn  depend  upon 
the  age  of  the  individual,  his  constitution  and  the  soundness  of  his 
organs  in  general.  The  respiratory  needs  of  the  body 
also  influence  the  extent  to  which  compensation  is  possible;  thus 
the  demand  for  oxygen  when  the  body  is  at  rest  is  less  than 
during  exercise  or  digestion.  And  finally,  of  importance  is  the 
rapidity  with  which  the  changes  have  become 
established;  a  gradual  development  favors  good  compensa- 
tion, for  persons  with  disturbances  of  respiration  learn  in  time 
to  minimize  their  need  of  oxygen. 

Mention  has  already  been  made  of  the  efficiency  of  this  com- 
pensatory mechanism  in  anaemia.  Studies  have  also  been  made 
of  the  gas  interchange  in  other  pathological  conditions.  It  has 
been  shown,  for  example,  that  in  rabbits  a  pleural  effusion  or  a 
closed  pneumothorax  of  moderate  grade  does  not  influence  to  any 
marked  degree  the  quantity  of  oxygen  absorbed  or  of  carbon 


222  THE  BASIS  OF  SYMPTOMS 

dioxide  eliminated  by  the  lungs.  An  open  pneumothorax  of  one 
side  produces  equally  little  disturbance  in  rabbits  and  dogs.  In 
man  also,  the  effect  of  various  diseases  upon  the  interchange  of 
gases  has  been  studied  by  accurate  methods.  In  emphysema,  bron- 
chitis, tuberculosis,  pneumonia  and  pleurisy,  even  when  marked 
dyspnoea  was  present,  the  interchange  between  the  lungs  and  the 
external  air  was  found  to  be  approximately  normal.  Yet  when 
there  is  dyspnoea,  additional  oxygen  is  used  up  by  the  increased 
respiratory  movements,  and,  if  this  were  deducted  from  the  total 
amount  of  oxygen  consumed  by  such  patients,  there  might  prove 
to  be  some  reduction,  after  all,  in  their  exchange  of  gases.  The 
latter  seems  all  the  more  probable  in  view  of  the  fact  that  the 
respiratory  interchange  of  gases  in  the  above  conditions  tends  to 
diminish  as  the  hindrance  to  the  entrance  of  air  increases. 

It  must  not  be  assumed,  however,  that  because  the  ventilation 
of  the  lungs  remains  practically  normal,  internal  respiration  is 
also  unaffected;  for  it  is  possible  that  the  tension  of  the  oxygen 
in  the  blood  might  be  abnormally  low  or  that  of  the  carbon  dioxide 
abnormally  high.  Either  would  influence  the  interchange  of  gases 
between  the  blood  and  the  tissues.  Dyspnoea,  indeed,  is  usually 
caused  by  just  such  changes  in  the  blood  going  to  the  medulla. 

Asphyxia. — W^hen  disturbances  of  external  respiration  be- 
come considerably  greater  than  can  be  met  by  the  compensatory 
mechanism,  asphyxia  is  produced.  The  symptoms  of  asphyxia  vary 
with  the  rapidity  of  its  onset,  being  milder  and  less  characteristic 
in  gradually  progressive  cases.  Hand  in  hand  with  the  reduced 
oxygen  content  of  the  blood  goes  an  increased  carbon  dioxide 
volume.  The  latter  exerts  some  anaesthetic  effect  and  when  active 
over  a  long  period  of  time,  as  in  chronic  asphyxia,  diminishes  the 
irritability  of  the  respiratory  centre  to  a  point  incompatible  with 
life.  Effects  of  lack  of  oxygen,  therefore,  do  not  become  apparent, 
because  the  medulla  has  been  narcotized  by  the  carbon  dioxide. 

Acute  asphyxia  is  produced  by  suddenly  cutting  off 
the  oxygen  supply  to  a  brain  which  is  still  irritable.  Practically, 
this  does  not  happen  very  often,  but  it  may  result  from  a  filling 
of  the  lungs  with  fluid,  from  the  collapse  of  a  diseased  trachea  or 
from  a  rapidly  fatal  hemorrhage.  The  lack  of  oxygen  causes 
first  an  increase  in  the  depth  and  strength  of  respiration,  which 
is  followed  by  characteristic  changes  in  the  circulation.  The 
vasomotor  centre  is  powerfully  stimulated,  and  this  causes  the 


RESPIRATION  223 

splanchnic  vessels  to  contract,  the  cutaneous  vessels  to  dilate,  and 
produces  a  marked  rise  in  the  general  arterial  pressure.  As  the 
vagus  is  also  stimulated,  the  heart  is  slowed.  These  changes  are 
designed  to  furnish  the  brain  with  the  greatest  possible  amount 
of  blood,  and,  thereby,  oxygen.  In  the  later  stages  of  acute 
asphyxia,  generalized  tonic  and  clonic  convulsions  occur,  and 
finally,  after  a  brief  period  of  paralysis,  death  supervenes. 

Internal  Respiration. — The  internal  respiration  has  necessarily 
entered  at  many  points  into  our  discussion  of  the  disorders  of 
external  respiration,  for  the  two  are  intimately  interdependent. 
Thus  we  have  emphasized  how  changes  in  the  internal  respiration 
of  the  respiratory  centre  may  cause  a  compensatory  increase  in 
the  movements  of  the  chest. 

The  effect  of  disturbances  of  external  res- 
piration upon  the  interchange  of  gases  in  other 
tissues  remains  to  be  considered.  The  need  of  the  cells  for 
oxygen  is  determined  primarily  by  their  functional  activity;  it 
must  be  emphasized,  however,  that  the  supply  must  be  sufficient  if 
they  are  to  use  all  the  oxygen  that  they  require.  It  is  indeed 
true  that  for  a  time  the  cells  can  do  without  oxygen,^^  because  they 
are  still  able  to  fall  back  upon  their  intramolecular  supply,  yet  this 
is  of  little  practical  importance. 

Normally,  the  blood  carries  much  more  oxygen  than  is  needed 
by  the  tissues,  and  when  it  leaves  them  its  supply  is  by  no  means 
exhausted.  We  have  evidence  that  this  excess  of  oxygen  is  not 
a  useless  luxury,  but  that  it  is  beneficial,  and  that  a  relative  scarcity 
of  the  gas  in  the  tissues  is  directly  harmful.  It  has  been  shown, 
at  any  rate,  that  in  dyspnceic  dogs  the  proteid  decomposition  is 
increased;  and  although  the  same  has  not  regularly  been  proved 
for  man,  it  suggests  the  harm  which  may  follow  an  insufficient 
aeration  of  the  blood.^^  According  to  Rosenquist,  severe  anaemias 
exhibit  periodic  increases  in  the  nitrogen  output  (p.  319),  but 
whether  this  is  due  to  the  anaemia  itself,  or  to  the  underlying  cause 
of  the  anaemia,  is  problematical.  It  has  been  shown  also  that  glu- 
cose and  lactic  acid  may  appear  in  the  urine  of  dyspnoeic  animals, 
and  that  lactic  acid  may  be  present  in  the  urine  of  dyspnoeic  men. 
Finally,  the  respiratory  quotient  becomes  greater  than  the  normal 
if  the  oxygen  supply  is  restricted.  Though  the  explanation  of 
these  various  findings  is  uncertain,  they  tend  to  show  that  a  dimin- 


224  THE  BASIS  OF  SYMPTOMS 

ished  tension  of  oxygen  in  the  tissues  leads  to  an  abnormal 
metabolism. 

In  order  to  estimate  the  oxygen  supply  to  the  tissues,  it  is 
necessary  to  know  the  amount  of  this  gas  in  the  blood.^®  Unfor- 
tunately we  possess  but  little  information  bearing  directly  upon 
this  point.  In  animals  with  an  open  pneumothorax,  the  quantity 
of  oxygen  is  much  diminished  in  the  arterial  blood,  and  it  is  this 
diminution  that  stimulates  the  medullary  centres,  causing  such 
fMDwerful  respirations  that  one  lung  is  able  to  do  the  work  of  two. 
We  possess  no  other  data  as  to  the  gases  in  the  blood  in  respiratory 
diseases.  The  mere  fact  that  the  alveolar  interchange  of  gases 
does  not  vary  from  the  normal  proves  nothing,  for  this  might 
be  true  even  though  the  absolute  amount  of  each  gas  in  the  blood 
varied  greatly.  The  cyanosis  of  many  patients  with  respiratory 
diseases  would  lead  one  to  the  belief  that  their  blood  is  rich  in 
reduced  haemoglobin ;  in  some  cases  this  is  undoubtedly  true,  while 
in  others  practically  normal  conditions  are  found. 

Internal  respiration  may  also  be  primarily 
disturbed,  i.e.,  by  changes  in  the  parenchyma  cells  or  in  the 
tissue  fluids.  A  retarded  blood-flow  or  a  lack  of  functionating 
haemoglobin  interferes  not  only  with  the  interchange  of  gases  in 
the  lung,  but  also  with  the  interchange  in  the  tissues.  Primary 
disorders  of  the  internal  respiration  may  arise  when  arterio- 
sclerotic changes,  thrombosis  or  embolism  interfere  with  the 
circulation  of  a  limited  area.  Compensation  is  possible  here 
only  by  the  establishment  of  a  collateral  circulation.  If  the  cere- 
bral arteries  are  blocked,  the  resulting  anaemia  of  the  brain  pro- 
duces the  symptoms  of  acute  asphyxia.  Finally,  the  displacement 
of  oxyhaemoglobin  by  carbon  monoxide-  or  methaemoglobin  causes 
a  primary  disturbance  of  internal,  as  well  as  of  external,  respira- 
tion. 

The  transportation  of  carbon  dioxide  may  be 
affected  by  changes  in  the  blood,  especially  those 
produced  by  an  acid  intoxication.  The  additional  acid  in  aci- 
dosis is  partly  neutralized  by  an  increased  formation  of 
ammonia  (see  p.  327),  and  partly  by  some  of  the  fixed  alkalies 
of  the  blood.  This  diminishes  the  free  alkali  in  the  blood  avail- 
able for  carbon  dioxide  transportation.  In  rabbits  with  severe 
acidosis,  the  carbon  dioxide  content  of  the  blood  was  found  to 
be  reduced  from  the  normal  twenty-five  per  cent,  by  volume  down 


RESPIRATION  2f25 

to  two  per  cent.  Under  such  conditions,  the  plasma  quickly  be- 
comes saturated  with  carbonic  acid  gas,  and  some  of  the  latter 
accumulates  in  the  tissues.  Observers  ^^  have  found,  neverthe- 
less, that  the  blood  in  severe  cases  of  diabetic  acidosis,  if  under 
ordinary  carbon  dioxide  tension,  can  still  absorb  considerable 
amounts  of  the  gas — in  these  cases,  at  least,  invalidating  the 
assumption  that  there  is  a  disorder  of  carbon  dioxide  transporta- 
tion. Conditions  are  further  complicated  by  the  presence,  in 
human  diabetes,  of  a  number  of  other  grave  manifestations  which 
dominate  the  picture.  In  the  acid  intoxication  of  rabbits,  the 
oxidative  processes  in  the  body  are  also  considerably  diminished, 
for  both  the  absorption  of  oxygen  from  the  blood  and  the  elimina- 
tion of  carbon  dioxide  are  reduced.  Since  the  amount  of  oxygen 
in  the  blood  is  not  decreased,  the  lowered  oxidations  in  the  tis- 
sues must  be  referred  to  changes  in  the  cells,  induced  perhaps  by 
the  toxic  action  of  the  retained  carbon  dioxide.  In  the  acidosis 
of  rabbits,  therefore,  the  retention  of  carbonic  acid  gas  in  the 
tissues  affects  both  internal  and  external  respiration. 

In  dogs,  and  in  carnivora  in  general,  much  larger  amounts 
of  acid  are  tolerated,  for,  owing  to  the  relatively  high  proteid 
metabolism,  much  more  ammonia  is  available  for  the  neutraliza- 
tion of  any  acid  present,  and  for  the  protection  of  the  fixed  alkalies 
of  the  blood.  Men  and  carnivora  in  general,  therefore,  can  resist 
a  considerable  amount  of  acid,  disposing  of  really  enormous 
quantities  in  some  pathological  conditions. 

Internal  respiration  finally  may  be  altered  by  changes  in 
the  parenchyma  cells,  either  physiological,  as  by  rest 
and  activity,  and  by  cold  and  heat,  or  pathological,  as  by  the 
various  metabolic  diseases.  In  phosphorus  and  hydrocyanic  acid 
poisoning  many  of  the  cells  lose,  to  a  variable  degree,  their  ability 
to  take  up  oxygen  and  to  form  carbon  dioxide.  Though  the 
external  respiration  and  the  gases  of  the  blood  are  both  normal, 
the  interchange  of  gases  in  the  tissues  is  much  reduced,  because 
the  cells  are  poisoned.  The  animal  dies  of  internal  asphyxia; 
and  in  prussic  acid  poisoning  the  most  violent  respiratory  convul- 
sive movements  may  result  from  the  asphyxia  of  the  medullary 
centre. 

Respiratory  Sensations. — The  most  important  abnormal  sen- 
sation associated  with  respiration  is  that  known  as  dyspnoea. 
The  term  has  been  used  by  some  to  designate  disturbances  in 

15 


226  THE  BASIS  OF  SYI^IPTOMS 

the  respiratory  act  itself,  but  we  prefer  to  limit  its  use  to  the 
subjective  sensation  of  an  air-hunger.  Dyspnoea,  in  this 
sense,  is  always  produced  by  an  insufficient  gas  interchange  in  the 
tissues,  and  especially  by  a  diminution  in  the  supply  of  oxygen  to 
certain  parts  of  the  brain.  The  associated  retention  of  carbon 
dioxide  is  apparently  not  at  fault,  for  it  may  be  breathed  in  large 
quantities  without  any  such  effect.  Frequently  the  respiratory 
movements  are  increased  without  any  sensation  of  dyspnoea;  in 
such  cases  the  retention  of  carbon  dioxide  would  seem  to  be  the 
important  factor  in  producing  the  more  marked  respiratory  move- 
ments. 

How  the  oxygen  is  prevented  from  reaching  the  brain  is 
immaterial,  so  far  as  the  dyspnoea  is  concerned.  The  respiratory 
surface  of  the  lungs  may  be  diminished,  the  blood  may  flow 
slowly,  or  the  red  corpuscles  or  the  tissue  cells  may  have  lost 
their  ability  to  take  up  oxygen.  Dyspnoea  depends  rather  upon 
the  functional  activity  of  the  cells  and  the  degree  to  which  their 
demand  for  oxygen  is  answered ;  many  patients,  therefore,  experi- 
ence no  discomfort  as  long  as  they  are  quiet.  Furthermore,  they 
gradually  learn  to  do  their  work  with  a  minimum  expenditure  of 
energy,  thus  reducing  their  need  of  oxygen,  and,  in  turn,  their 
dyspnoea. 

Actual  pain  may  also  arise  in  respiratory  diseases.  It 
is  generally  believed  that  the  lungs  themselves  contain  no  sensory 
fibres,  and  that  what  seems  to  be  pulmonary  pain  is  really  due  to 
an  associated  disease  of  the  pleura  or  chest  wall.  Severe  pain  is 
frequently  present  in  dry  pleurisy,  and  as  the  latter  often  accom- 
panies disease  of  the  lungs,  it  lies  close  at  hand  to  attribute  the 
pain  to  the  pleural  involvement.  I  am  not  entirely  convinced, 
however,  that  this  is  always  the  case,  for  pain  may  be  present 
in  diseases  of  the  lungs  unaccompanied  by  pleurisy. 

LITERATURE 

*•  Consult  A.   Fraenkel,  Diagnostik  u.    Symptomatologie   der   Lungenkrank- 
heiten,  i8go,  for  a  general  text  on  the  pathology  of  respiration. 
Lommel:  Arch.  f.  klin.  Med.,  xciv,  365. 
F.  Miiller:  Miinch.  med.  Wochenschft.,  1897,  No.  49. 
*  Naunyn :  Arch,  f .  klin.  Med.,  xxiii,  423. 

*Edlefsen:  Arch.  f.  klin.  Med.  xxvi,  200.    For  a  discussion  of  this  subject, 
see  A.  Fraenkel,  Diagnostik  u.  Symptomatologie  der  Lungenkrankheiten,  90. 
Barthel:  Zentralbl.  f.  Bakteriol.,  xxiv,  Pt.  I,  401,  576. 
Diirck :  Arch,  f .  klin.  Med.,  Iviii,  368 ;  Zentralbl.  f .  Bakt.,  xlii,  Ft.  I,  574. 
For  a  more  recent  description  of  pertussis,  see  Sticker,  in  the  NoUinagel 
System. 


I 


RESPIRATION  227 

•  Morawitz  and  Siebeck :  Arch,  f .  klin.  Med.,  xcvii,  219. 

"Breuer:  Wiener  Sitzungsber.,  Ivii,  11,  909;  Rosenthal,  in  Hermann's  Hand- 
buch,  iv,  II ;  Gad,  in  Gad  and  Heyman's  Lehrbuch  d.  Physiol.,  Berlin, 
1892 ;  Head,  Jour,  of  Physiology,  x,  i,  279. 

"  Boothby  and  Berry :  Amer.  Jour.  Physiol.,  xxxvii,  433 ;  see  also  Boothby  and 
Shamoff,  ibid.,  418. 

"  Liebermeister :  Deutsch.  med.  Wochenschft,  1908,  No.  39;  Siebeck,  Arch.  f. 
klin.  Med.,  xcvii,  219;  Forschbach  and  Bittorf,  Miinch.  med.  Wochen- 
schft, 1910,  No.  25;  Bruns,  Zeitschft.  f.  exp.  Path.  u.  Then,  vii,  494. 

"  Kohler :  Arch.  f.  exp.  Path.,  vii,  i. 

"  Haldane  and  Priestley :  Jour,  of  Physiol.,  xxxii,  225 ;  Schenk,  in  Asher- 
Spiro,  1908,  vii,  71. 

"  Siebeck :  Arch,  f .  klin,  Med.,  c,  204. 

"  Haldane  et  al. :  Jour,  of  Physiology,  xxxii,  xxxvii,  et  seq. 

"F.  A.  Hoffmann,  in  the  Nothnagel  System;  A.  Schmidt,  Das  Bronchial- 
asthma,  Wiirzburger  Abhand.  Ill,  7. 

"Kongress  f.  inn.  Med.,  1858,  237,  371  (discussion  and  literature);  Riegel, 
ibid.,  257 ;  Hack,  ibid.,  70. 

"  Sitzber.  d.  Gesell.  zur  Bef  or.  der  ges.  Naturwissensch.,  Marburg,  1896, 
No.  6. 

*°  See  Meltzer :  Jour.  Am.  Med.  Assoc,  1910,  No.  12. 

**Mediz.  Klinik,  1908,  No.  i. 

"  Tendeloo :  Die  Ursachen.  d.  Lungenkrankheiten,  Wiesbaden,  1902 ;  A.  Hoff- 
mann, in  the  Nothnagel  System;  Loeschke,  Deutsch.  med.  Wochenschft., 
191 1,  No.  20. 

**  W.  A.  Freund :  "Qber  primare  Thoraxanomalien,  Berlin,  1906. 

•*Friedrich:  Marburger  naturforschende  Gesellschaft,  1908. 

"  Siebeck:  Arch.  f.  klin.  Med.,  1911,  cii,  390. 

"  Traube :  Beitr.,  ii,  882,  and  iii,  103 ;  Sokolow  and  Luchinger,  Pfliiger's  Arch., 
xxiii,  283;  Lowit,  Prag.  med.  Wochenschft,  1880,  Nos.  47-50;  Unverricht, 
Kongr.  f.  inn.  Med.,  1892,  399. 

"  Arch.  f.  exp.  Path.,  x,  242,  and  xi,  45 ;  Zeitschft  f.  klin.  Med.,  ii,  255. 

"Zeitschft  f.  klin.  Med.,  i,  583,  and  ii,  713. 

*"  Jour,  of  Physiol.,  xxxviii,  401 ;  Douglas,  ibid.,  xl,  454. 

•"Jour,  of  Physiol.,  xxxii  (Proc.  Physiol.  Soc).  Consult  also  Pembrey, 
Beddard  and  French,  Jour,  of  Physiol.  (Proc.  Physiol.  Soc),  xxxiv; 
Pembrey,  Jour,  of  Path,  and  Bact.,  xii,  258,  and  xiv,  409;  Y.  Henderson, 
Amer.  Jour,  of  Physiol.,  xxv. 

■^  Unverricht :  Kongr.  f.  inn.  Med.,  1892,  399. 

"  Kussmaul :  Arch,  f .  klin.  Med.,  xiv,  I ;  Senator,  Zeitschft.  f .  klin.  Med., 
vii,  235. 

** Beddard,  Pembrey  and  Spriggs:  Jour,  of  Physiol.,  xxxi  (Proc.  of  Royal 
Soc). 

"Boas:  Arch.  f.  Verdauungskrankh.,  ii,  345. 

"Arch.  f.  exp.  Path.  (Festschrift),  1908,  228. 

••  See  Garre-Quincke :  Grundriss  d.  Lungenchirurgie,  Jena,  1903,  40 ;  Friedrich, 
Arch.  f.  klin.  Chin,  Ixxxii,  1147,  and  Marburger  Sitzungsber.,  1908,  No.  6; 
Sauerbruch,  Bruns'  Beitrage,  Ix,  450. 

"  See  Brauer :  Uber  Pneumothorax,  Marburger  Programm,  1906 ;  Beitr.  z. 
Klinik  d.  Tuberk.,  xii,  49. 

'*Volhard:  Miinch.  med.  Wochenschft,  1908,  No.  5. 

"Siebeck:  Zeitschft.  f.  Biol.,  xl,  267;  Arch.  f.  klin.  Med.,  cii,  390;  Versamm. 
d.  Naturf.  u.  Arzte  (Karlsruhe),  1911. 

*'For  a  comprehensive  study  of  this  subject,  see  Douglas  et  al. :  Physiolog. 
Observations  made  on  Pike's  Peak,  Philosoph.  Trans.,  London,  1913, 
B.  203,  185  (lit.)  ;  also  Cohnheim,  Physiol,  des  Alpinismus,  in  Asher- 
Spiro,  Ergeb,  ii,  I,  612;  Zuntz,  Muller  and  Caspari,  Hohenklima  u. 
Bergwanderungen  in  ihrer  Wirkung  auf  den  Menschen,  1906. 

*Fraenkel  and  Geppert:  Ubcr  d.  Wirkungen  d.  verdiinn.  Luft  auf  d.  Organ- 
ismus,  Berlin;  Loewy,  Unters.  ii.  Resp.  und  Circ,  etc,  Berlin,  1895. 


228  THE  BASIS  OF  SYMPTOMS 

**  Durig  and  Zuntz :  Engelmann's  Archiv,  1904,  Suppl.,  135,  417. 

**Hufner:  Engelmann's  Archiv.,  1901,  187. 

**  Hill  and  Greenwood :  Caisson  Sickness,  1912 ;  Silberstein,  in  Weyl's  Handb. 
d.  Arbeiterkrankheiten,  1908;  Thompson,  Occupational  Diseases,  1914, 
467;  Bassoe,  in  a  Report  on  Compressed  Air  Disease  (111.  State  Commis- 
sion on  Occupational  Disease),  191 1. 

*"  Hiif ner :  Arch,  f .  exp.  Path.,  xlviii,  87 ;  Mosso,  Die  Atmung  in  den  Tunnels 
u.  d.  Wirkung  d.  Kohlenoxyds,  quoted  from  Jahresber.  f.  Tierchemie, 
XXX,  576;  Haldane,  Jour,  of  Phys.,  xviii,  201;  see  also  Douglas,  Haldane 
and  J.  B.  S.  Haldane,  ibid.,  1912,  xliv,  75. 

*•  Haldane  and  Smith:  Jour,  of  Phys.,  xxv,  334.  For  the  improved  technic 
of  Douglas  and  Haldane,  see  Jour,  of  Phys.,  1912,  xliv,  305. 

*'Hiifner:  Engelmann's  Arch.,  1903,  217;  Morawitz  and  Rohmer,  Arch.  f. 
klin.  Med.,  xciv;  Masing  and  Siebeck,  ibid.,  xcix,  130;  Douglas,  Jour,  of 
Phys.,  xxxix,  453;  Plesch,  Hamodynamische  Studien,  Berlin,  1909. 

*  Lesser :  Das  Leben  ohne  Sauerstoff,  Ergeb.  d.  Phys.,  1909,  viii,  742. 

•See  V.  Noorden:  Path.  d.  Stoffwechsels,  ist  edit.  318,  and  the  chapter 
on  Metabolism  (Metabolism  and  Pract.  Medicine). 

•"For  recent  collected  studies  on  the  g^ses  of  the  blood  see  Barcroft:  Ergeb. 
d.  Phys.,  1908,  viii,  699,  and  Loewy  in  the  Handb.  d.  Biochem.  (Oppenr 
heimer),  1908,  iv,  10,  et  seq. 

"  Beddard,  Pembrey  and  Spriggs,  Jour,  of  Phys.,  xxxvii  (Proc.  of  the  Physiol. 
Soc). 


CHAPTER  V 
DIGESTION 

The  Mouth  and  (Esophagus. — Digestion  includes  ail' of  the 
processes  which  assist  in  preparing  the  food  for  use  in  the  body. 
Disturbances  of  digestion  begin,  therefore,  in  the  mouth.  Here 
the  food  is  seized  by  the  teeth  and  is  ground  up  so  that  it  shall 
present  a  greater  surface  to  the  action  of  the  digestive  juices. 
Serious  disturbances  may  follow  improper  trituration  of  the  food, 
whether  this  results  from  diseases  of  the  teeth,  the  maxillary 
bones  or  the  temporomaxillary  joints,  or  from  weakness  of  the 
muscles  which  move  the  food  about  within  the  mouth.  If  the 
facial  nerves  are  paralyzed,  the  food  collects  in  the  cheeks  and 
cannot  be  forced  back  into  the  mouth,  A  paralysis  of  the  tongue 
interferes  not  only  with  chewing,  but  with  the  passage  of  food 
into  the  throat.  When  chewing  becomes  a  painful  procedure, 
malnutrition  may  be  a  consequence ;  for  many  patients  with  ulcera- 
tions in  the  mouth,  or  with  inflammations  of  the  tonsils,  throat 
or  parotid  glands,  would  rather  suffer  from  hunger  than  from 
the  pain  which  is  caused  by  the  taking  of  food.  Both  the  intensity 
and  the  duration  of  such  diseases  influence  the  amount  of  disturb- 
ance which  they  produce. 

Stomatitis. — The  causes  of  stomatitis*  are  various.  If  par- 
ticles of  food  are  retained  in  the  mouth,  they  decompose,  and 
the  products  of  decomposition,  acting  as  irritants,  may  pave  the 
way  for  the  invasion  of  micro-organisms.  Inflammations  are 
especially  apt  to  occur  when  the  growth  of  bacteria  is  favored 
by  carious  teeth,  or  when,  as  the  result  of  severe  illnesses,  but 
little  saliva  is  secreted,  and  the  mouth  is  allowed  to  become  foul 
owing  to  the  stuporous  condition  of  the  patient.  The  stomatitis 
which  so  often  accompanies  severe  diabetes  is  greatly 
favored  by  the  caries  of  the  teeth  and  by  the  organic  acids, 
both  of  which  are  frequently  present  in  the  mouths  of  these 
patients.  The  oidium  of  thrush  produces  acids,  and  these  un- 
doubtedly irritate  the  mucous  membrane  directly  and  favor  sec- 
ondary infections.  Acids  and  alkalies  introduced  into  the  mouth 
may  destroy  its  coverings  and  so  cause  inflammations.  The 
stomatitis  of  scurvy  seems  to  be  of   a  different   character 

229 


230  THE  BASIS  OF  SYMPTOMS 

from  that  caused  by  other  infectious  diseases,  for  it  develops 
early  in  the  disease,  and  is  particularly  severe.  The  scor- 
butic gingivitis  appears  to  be  a  specific  effect  of  the  disease, 
though  its  true  cause  is  as  little  understood  as  is  that  of  the  other 
scorbutic  manifestations.  (An  ulcerative,  even  gangrenous, 
stomatitis  is  a  very  frequent  and  diagnostically  important  mani- 
festation of  the  acute  leukaemias;  in  this  case,  the  ne- 
crosis probably  occurs  in  the  areas  of  hemorrhagic  infiltration. — 
Ed.) 

Stomatitis  endangers  the  health  of  the  patient,  first  of  all,  by 
diminishing  the  ingestion  of  food — this  diminution  resulting 
partly  from  the  tenderness  of  the  mucous  membrane,  and  partly 
from  the  loss  of  appetite  caused  by  the  disagreeable  taste  in  the 
mouth.  In  the  second  place,  the  number  of  bacteria  in  the  mouth 
is  enormously  increased,  and  vast  numbers  are  swallowed.  The 
ability  of  the  stomach  to  destroy  this  material  is  naturally  limited, 
its  disinfecting  power  often  being  most  reduced  in  the  very  dis- 
eases with  which  the  stomatitis  is  associated. 

The  Saliva. — The  different  salivary  glands  produce  secretions 
of  variable  composition,  and  each  is  dependent  upon  specific 
stimuli  for  its  activity.  We  are  not  familiar,  however,  with  these 
different  factors,  and  for  that  reason  speak  of  saliva  as  the  sum 
of  the  several  secretions.  The  saliva,  in  addition  to  its  digestive 
function,  lubricates  the  food  bolus  for  its  passage  down  the 
oesophagus,  and  also,  by  diluting  irritating  and  corrosive  fluids, 
helps  to  protect  the  stomach  and  oesophagus  from  injury. 

Diminished  Secretion  of  Saliva. — The  quantity  of  saliva  is 
diminished  in  certain  infectious  diseases,  such  as  pneumonia  and 
typhoid  fever ;  in  certain  poisonings,  as  by  atropin ;  in  all  diseases 
which  are  accompanied  by  great  losses  of  water,  such  as  cholera, 
diabetes  and  interstitial  nephritis ;  and,  finally,  in  those  paralyses 
of  the  facial  nerve  that  involve  the  chorda  tympani,  A  diminution 
of  the  saliva  is  always  accompanied  by  a  reduction  in  the  activity 
of  the  buccal  mucous  glands.  The  resulting  dryness  of  the  mouth 
not  only  interferes  with  the  cleansing  of  the  mouth,  but  also  with 
the  acts  of  chewing,  swallowing  and  speaking. 

To  what  degree  a  lack  of  ptyalin  is  injurious  has  not  been 
definitely  settled.  It  was  formerly  considered  that  this  ferment 
played  an  insignificant  part  in  the  processes  of  digestion ;  but  we 
now  know  that  large  quantities  of  starch  are  converted  into  dex- 


DIGESTION  231 

trin  ^  in  the  mouth  and  in  the  stomach  by  the  action  of  this  fer- 
ment. The  conversion  continues  in  the  stomach  even  after  a 
considerable  grade  of  acidity  is  present,  particularly  within  the 
larger  particles  of  food,  of  which  only  the  surfaces  are  acted 
upon  by  the  gastric  juice.  In  addition,  saliva  can  exert  a  further 
effect  in  the  intestines  where  it  is  reactivated  by  the  pancreatic 
juice.^ 

Ptyalism. — ^An  increase  in  the  secretion  of  saliva,  so-called 
ptyalism,  may  result  from  an  irritation  of  the  chorda  tympani 
nerve  as  it  passes  through  the  middle  ear.  Impressionable  persons 
frequently  have  a  marked  flow  of  saliva  when  they  think  about 
food,  or  even  when  they  imagine  that  they  have  taken  calomel. 
Ptyalism  also  accompanies  all  irritative  conditions  of  the  mucous 
membrane  of  the  mouth,  such  as  may  result,  for  example,  from 
stomatitis.  The  ptyalism  of  mercurial  poisoning  is  due 
in  all  probability  to  a  central  or  peripheral  stimulation  of  the 
nervous  connections  of  the  salivary  glands.  It  is  possible  also 
that  the  parenchyma  cells  are  directly  affected  by  the  poison. 
Mercurial  stomatitis  usually  follows  the  ptyalism  and  is  due  to 
some  irritating  mercurial  compound  present  in  the  saliva.  This 
stomatitis  will,  in  turn,  increase  the  salivation,  thus  establishing 
a  vicious  circle. 

There  is  a  remarkable  increase  in  the  amount  of  saliva  in 
certain  chronic  diseases  of  the  medulla  oblongata,  particularly  in 
bulbar  paralysis.  This  has  been  compared  by  some  ob- 
servers to  the  paralytic  secretion  which  appears  in  animals  after 
all  the  salivary  nerves  have  been  cut.  The  latter  begins  about 
twenty-four  hours  after  the  operation,  lasts  about  one  week,  and 
gradually  ceases  on  account  of  the  degeneration  of  the  secreting 
cells.  In  both  conditions,  furthermore,  atropin  will  inhibit  the 
secretion.  The  two  differ,  however,  in  the  length  of  time  over 
which  the  salivation  lasts  and  in  the  amount  of  saliva  secreted, 
the  quantity  being  much  greater  in  the  case  of  bulbar  paralysis. 
It  seems  to  me  very  probable  that  the  ptyalism  of  bulbar  paralysis 
is  not  a  paralytic  secretion,  but  is  due  to  an  irritation  of  the  cells 
of  the  medulla,  which  occurs  as  they  degenerate.  It  is  compara- 
ble, therefore,  to  the  fibrillary  muscular  twitchings  so  often  seen 
when  the  large  motor  cells  of  the  cord  are  undergoing  degenera- 
tion. Certain  it  is  that  the  saliva  is  really  increased  in  these  cases 
of  bulbar  paralysis,  and  that  the  condition  is  not  merely  a  loss  of 


232  THE  BASIS  OF  SYMPTOMS 

normal  saliva  occasioned  by  a  paralysis  of  the  muscles  of  the 
mouth;  indeed,  the  salivation  is  frequently  present  even  before 
the  muscles  have  become  markedly  weakened. 

An  increased  flow  of  saliva  may  be  caused  finally  by  reflexes 
from  other  parts  of  the  body,  as  from  an  ulcer  of  the  stomach, 
from  the  uterus  during  pregnancy,  from  the  trigeminal  nerve  in 
cases  of  trifacial  neuralgia,  etc.,  and  by  an  increased  irritability 
of  the  nervous  system,  as  in  neurasthenia  and  hysteria. 

In  all  these  conditions  the  saliva  presents  the  characteristics 
of  that  obtained  by  stimulation  of  the  chorda  tympani,  i.e.,  it  is 
increased  in  amount,  but  poor  in  solids. 

An  increased  secretion  of  saliva  is  especially  unpleasant  when 
it  drips  from  the  mouth,  as  happens  in  cases  of  bulbar  paralysis. 
Even  when  it  is  swallowed  it  may  be  disadvantageous,  for  the 
large  quantity  of  alkaline,  mucous  fluid,  rich  in  bacteria,  is  inju- 
rious to  gastric  digestion. 

Composition  and  Reaction  of  the  Saliva. — ^The  saliva  may  con- 
tain abnormal  constituents,  such,  for  example,  as  the  compounds 
of  iodin  and  bromin,  when  the  latter  have  been  administered. 
Whether  other  substances  pass  into  the  saliva  or  not  depends 
largely  upon  the  amount  present  in  the  plasma.  Urea  is  thus 
excreted  only  in  those  pathological  conditions  which  increase  its 
concentration  in  the  blood,  as  in  severe  nephritis.  Other  con- 
stituents of  the  blood,  such  as  sugar,  rarely  pass  into  the  salivary 
secretion.  It  is  unnecessary  to  enumerate  the  various  substances 
which  sometimes  appear  in  the  saliva,  for  the  subject  has  but  little 
pathological  significance. 

The  reaction  of  the  saliva  varies  in  the  healthy  individual 
'during  the  process  of  digestion.  In  the  fasting  condition  it  is 
usually  weakly  acid,  but  after  taking  food  it  becomes  alkaline. 
On  the  other  hand,  in  diabetes,  in  fever  and  in  dyspeptic  individ- 
uals, it  is  not  infrequently  constantly  acid,  in  some  instances  owing 
to  the  presence  of  the  products  of  bacterial  decomposition.  The 
pure  parotid  saliva  is  said  to  be  acid  in  severe  diabetes,  but  the 
cause  of  the  acidity  is  not  known ;  and  some  observers  have  found 
it  to  be  alkaline  even  in  severe  forms  of  the  disease. 

Swallowing. — ^The  passage  of  food  from  the  mouth  into  the 
oesophagus  is  accompanied  by  special  dangers,  for  it  must  cross 
the  respiratory  tract  in  the  pharynx.  The  trachea  must  be  closed 
off  below  by  the  epiglottis,  and  the  nasal  passage  above  by  the 


DIGESTION  233 

soft  palate  and  the  superior  constrictors  of  the  pharynx.  This 
intricate  mechanism  is  controlled  by  reflexes  through  the  trigem- 
inal and  vagus  nerves.  The  centripetal  impulses  arise  from  the 
mucous  membrane  of  the  throat;  and  the  centre  which  presides 
over  swallowing  is  situated  in  the  medulla. 

Disturbances  of  the  act  of  swallowing  may  be 
caused  by  a  diminished  irritability  either  of  the  cen- 
tre or  of  the  sensory  nerves.  This  is  seen  in  certain 
intoxications,  notably  in  those  due  to  morphin,  chloroform  and 
chloral,  in  diabetic  coma  and  ursemic  coma,  as  well  as  in  some 
diseases  of  the  nerves.  Disturbances  of  swallowing  may  also 
arise  from  a  paralysis  of  the  necessary  muscles, 
caused  either  by  a  disease  of  the  motor  nuclei  in  the  medulla,  as 
in  bulbar  paralysis  or  medullary  tumors,  or  by  a  neuritis  itself, 
such  as  is  seen  so  frequently  after  diphtheria.  Furthermore, 
difficulty  in  swallowing  may  arise  not  from  a  paralysis,  but  from 
aspasmofthenecessarymuscles,  as  occurs  in  hydro- 
phobia, tetanus  and  hysteria.  Finally,  defects  in  the 
palate,  usually  caused  by  syphilitic  ulcerations,  interfere  with 
the  act  of  swallowing. 

In  these  conditions,  the  food  may  pass  either  into  the  nose  or 
into  the  trachea.  The  latter  is  the  more  serious,  for  if  the  food 
with  its  many  bacteria  enters  the  lungs,  pneumonia,  and  not  infre- 
quently gangrene,  result.  The  entrance  of  food  into  the  nasal 
cavity  is  less  dangerous.  Coughing  and  sneezing  are  the  usual 
results.  Yet  these  may  cause  the  patient  such  great  discomfort 
that  he  refrains  from  eating;  and  it  is  even  possible  that  a  large 
portion  of  his  nourishment  may  be  lost  through  the  nose.  When 
swallowing  causes  pain,  the  patient  may  take  insufficient  nourish- 
ment, just  as  is  the  case  when  chewing  is  painful. 

CEsophageal  Stenosis. — Diseases  of  the  oesophagus^  usually 
produce  symptoms  by  obstructing  the  passage  of  food.  This 
obstruction  may  be  due,  in  the  first  place,  to  a  muscular 
spasm,  as  in  hydrophobia  and  hysteria  (globus  hystericus). 
Such  a  condition  is  rarely  very  serious,  because  in  the  case  of 
hysteria  it  is  usually  finally  overcome,  and  in  hydrophobia  there 
are  other  more  immediate  dangers.  Occasionally,  however,  a 
spasm  of  the  lower  end  of  the  oesophagus,  particularly  at  the 
cardia  (cardiospasm),  may  produce  symptoms  very  like  those 
of  a  mechanical  stenosis.    Still,  it  is  not  certain  that  cardiospasm 


I 


234  THE  BASIS  OF  SYMPTOMS 

is  not  the  result  of  some  disorder  of  the  nerve  supply,  particularly 
of  the  vagus. 

Of  greater  importance  are  permanent  obstructions,  such  as 
may  be  caused  by  the  contraction  of  scar  tissue,  by 
tumors  or  by  pressure  from  without.  The  milder 
stenoses  interfere  only  with  the  swallowing  of  the  coarser  foods ; 
the  more  severe  ones  may  stop  even  fluids.  Normally,  we  do  not 
feel  our  food  after  it  has  once  passed  the  pharynx ;  but  the  patient 
with  an  obstruction  often  complains  that  he  can  feel  the  food 
stop  in  a  definite  place.  Above  the  point  of  obstruction  the  oesopha- 
gus usually  becomes  dilated,  owing  to  the  stasis  of  material; 
and  the  muscular  tissue  surrounding  the  dilatation  undergoes 
hypertrophy.  Some  of  the  food  which  cannot  be  forced  through 
the  narrowed  passage  stagnates  in  situ,  undergoing  decomposition. 
The  remainder  is  immediately  returned  into  the  mouth.  This 
regurgitation  of  food  is  quite  different  from  vomiting,  and  the 
patient  himself  usually  appreciates  the  difference;  for  the  food 
swallowed  appears  to  return  of  itself,  the  individual  experiences 
no  nausea,  and  his  abdominal  muscles  are  not  brought  into  action. 
'Apparently  the  obstruction  to  the  passage  of  food  increases  the 
contractions  of  the  muscular  tissues  of  the  oesophagus.  Many 
believe  that  the  increased  pressure  on  the  food  simply  forces  it 
upward,  and  that  there  is  no  true  antiperistalsis  in  these  cases. 
Personally,  however,  I  see  no  reason  to  exclude  the  possibility 
that  antiperistaltic  movements  do  play  a  part  in  the  regurgitation 
of  food.  (The  probability  of  an  antiperistaltic  factor  is  strength- 
ened by  the  undoubted  occurrence,  as  shown  by  radiographic 
methods,  of  similar  waves  in  pyloric  and  intestinal  obstruction, 
while  in  the  colon,  antiperistalsis  is  normal. — Ed.  ) 

Pressure  Diverticula. — The  so-called  pressure  diverticula^ 
usually  spring  from  the  upper  and  posterior  part  of  the  oesophagus. 
They  seem  to  originate  from  a  primary  weakness  of 
the  oesophageal  wall,  produced  by  such  causes  as  foreign 
bodies,  traumatism  or  possibly  congenital  defects  in  the  muscle. 
The  wall  of  the  diverticulum  is  composed  of  the  mucous  mem- 
brane, the  submucosa  and  a  thin  layer  of  muscle.  As  the  sac 
becomes  larger,  a  part  of  the  food  passes  into  it  instead  of 
going  down  the  oesophagus.  This  food  is  in  part  immediately 
regurgitated,  but  enough  may  remain  in  the  diverticulum  to  press 
upon  the  oesophagus  and  so  to  occlude  it ;  and  it  is  only  after  the 


DIGESTION  235 

sac  has  been  emptied  of  its  contents  that  a  free  passage  is  again 
opened  into  the  stomach.  The  symptoms  caused  by  such 
a  diverticulum  vary  greatly,  depending,  for  the  most  part,  upon 
the  ease  with  which  the  sac  is  filled  and  emptied.  The  food  which 
stagnates  in  the  sac  may  decompose  and  cause  ulcerations  of  the 
mucous  membrane,  and  these  in  turn  may  give  rise  to  very  severe 
pain.  A  pressure  diverticulum  is,  therefore,  a  considerable  men- 
ace to  the  health  of  the  patient,  and  it  is  fortunate  that  the 
condition  is  a  rare  one. 

Primary  Dilatation  of  the  (Esophagus. — Difficulties  in  swal- 
lowing may  be  caused  by  a  diffuse  or  localized  oesophageal  dilata- 
tion, unaccompanied  by  any  demonstrable  anatomical  obstruction.^ 
It  is  very  likely  that  in  many  of  these  cases  the  dilatation  is  due 
to  a  functional  stenosis  originating  in  aspasmofthemus- 
cle  at  the  lower  end  of  the  oesophagus.  Such  spasms 
may  be  primary,  or  they  may  be  reflexly  caused  by  ulcerations  of 
the  mucous  membrane.  In  some  instances  the  dilatation  has  a 
congenital  origin.  The  symptoms  of  such  dilata- 
tions are  very  similar  to  those  of  ordinary  stenoses,  vi:3.,  obstruc- 
tion to  the  passage  of  food,  stasis  in  the  dilated  sac  and  regurgi- 
tation. When  there  is  a  partial  anatomical  stenosis,  or  a  func- 
tional stenosis  from  spasm  of  the  cardia,  the  symptoms  may  per- 
sist for  many  years  with  intervals  of  perfect  health.  The  picture 
sometimes  resembles  that  of  rumination,  especially  if  the  dila- 
tation affects  that  portion  of  the  lower  oesophagus  which  lies  be- 
tween the  diaphragm  and  the  cardiac  orifice  of  the  stomach. 

In  another  class  of  cases,  the  course  of  the  disease  is  exceed- 
ingly rapid,  and  autopsy  discloses  an  oesophagus  widely  dilated, 
filled  with  food  and  yet  without  demonstrable  stenosis.  A  con- 
dition similar  to  this  may  be  produced  experimentally  by  cutting 
both  vagi  in  the  neck  of  a  dog.  This  operation  causes  a  paralysis 
of  the  oesophageal  musculature,  so  that  even  though  the  cardia 
apparently  remains  open,  food  does  not  pass  into  the  stomach, 
but  accumulates  in  the  oesophagus,  decomposes  and  causes  death. 
The  cases  of  acute  oesophageal  dilatation  in  man, 
above  referred  to,  are  probably  due  to  a  similar  primary  paralysis 
of  the  muscles;  and  Kraus  has  described  a  patient  who  died  of 
this  condition,  in  whom  at  autopsy  both  vagi  were  found  to  be 
diseased. 

Painful  sensations  rarely  originate   in  the  oesopha- 


236  THE  BASIS  OF  SYMPTOMS 

gus,  first,  because  painful  affections,  such  as  ulcer,  are  rare  in  this 
portion  of  the  digestive  tract,  and  secondly,  because  this  is  a 
comparatively  insensitive  organ.  Yet,  as  we  have  already  men- 
tioned, diverticula  may  occasion  great  pain,  as  may  also  spasm 
of  the  oesophageal  muscles. 

Rupture  of  the  oesophagus  is  very  rare.  It  is 
usually  a  complication  of  some  definite  lesion  of  the  v^rall,  such  as 
carcinoma  or  erosion  from  acids  or  alkalies.  It  may,  however, 
occur  in  apparently  healthy  individuals,  though  the  cause  in  such 
cases  is  unknown. 

The  Stomach. — The  stomach '^  acts  as  a  reservoir  for  the 
large  quantities  of  food  which  are  ingested  at  each  meal.  Some 
of  this  food  is  absorbed  in  the  stomach,  but  most  of  it,  including 
practically  all  the  water,  is  gradually  passed  on  into  the  duodenum, 
after  having  been  acted  upon  by  the  gastric  juice.  Strangely 
enough,  the  opinion  has  become  current  that  the  stomach  is  a 
superfluous  organ.  It  is,  indeed,  true  that  animals  as  well  as  men 
have  continued  to  live  after  a  practically  complete  gastrectomy, 
and  that  life  may  be  maintained  by  artificially  introducing  food 
into  the  intestines  below  the  stomach.  Indeed,  a  dog  without  a 
stomach  may  live  on  quite  a  varied  diet,  even  though  it  include 
decomposing  meat.  Notwithstanding  these  facts,  it  remains  true 
that  the  less  cause  a  man  has  to  consider  his  digestion,  the  better 
is  his  health,  and  the  stomach  stands  as  a  most  important  prepara- 
tory organ,  which  receives  the  varying  kinds  and  quantities  of 
food,  and  shields  the  more  delicate  intestines  from  the  harm  which 
these  foods  might  produce  if  directly  introduced.  (An  example 
of  the  importance  of  the  stomach  in  this  respect  is  seen  in  the 
so-called  gastrogenous  diarrhoeas,  occurring  in  certain  cases  of 
gastric  achylia  and  attributed  to  the  entrance  of  coarse  food 
particles,  especially  connective  tissue,  into  the  intestines,  the  lining 
of  which  is  thereby  mechanically  irritated. — Ed.) 

It  is  possible  to  obtain  pure  gastric  juice  from  animals,^  but 
from  man  we  are  able  ordinarily  to  obtain  only  mixtures  contain- 
ing both  gastric  juice  and  food.  In  a  number  of  appropriate  cases, 
however,  we  have  been  able  to  study  pure  gastric  juice 
also  in  man ;  these  observations  have  shown  the  secretion  to  have 
an  acidity  approximately  the  same  as  that  in  the  dog,  vis.,  o .  4 
to  0.5  per  cent,   hydrochloric  acid^  (see  p.  240). 

At  the  height  of  digestion,  the  hydrochloric  acid  is  present 


DIGESTION  2S7 

in  the  stomach  in  various  combinations.  In  the  first  place,  some  has 
imited  with  the  inorganic  bases  or  basic  salts  of  the  food,  or  has 
even  decomposed  salts  of  the  weaker  acids.  Secondly,  a  portion 
of  the  hydrochloric  acid  combines  with  certain  basic  organic  com- 
pounds. Of  these,  the  most  important  practically  are  the  com- 
binations between  the  hydrochloric  acid  and  the  various  proteids 
of  the  gastric  contents.  These  combinations  are  dissociated  by 
hydrolysis.  The  generally  accepted  view  is  that  this  loose  union 
of  acid  and  proteid  is  the  essential  substratum  of  what  is  known 
as  the  combined  hydrochloric  acid.^^  In  all  proba- 
bility, however,  more  complex  conditions  are  influential  here. 

Finally,  a  certain  amount  of  free,  un combined  hy- 
drochloric acid  is  usually  present  in  the  gastric  contents. 
Yet  this  may  be  absent,  even  at  the  height  of  digestion  in  some 
individuals,  and  it  is  questionable  whether  such  an  absence  is 
always  pathological  or  not,  for  some  of  these  individuals  appear 
to  be  in  a  state  of  perfect  health.  Organic  acids  may  be  intro- 
duced in  the  food,  but  they  are  not  formed  in  the  healthy  stomach ; 
and  lactic  acid,  for  example,  is  never  a  product  of  normal  gastric 
digestion. 

The  total  amount  of  acid  secreted  depends  mainly 
upon  the  quantity  and  quality  of  the  food  taken.  The  secretion 
apparently  continues  until  the  free  and  combined  hydrochloric 
acid  in  the  gastric  contents  reaches  a  certain  percentage.  Pre- 
cisely to  what  degree  the  secretion  of  acid  depends  upon  the  char- 
acter of  the  nourishment,  and  to  what  degree  it  is  subject  to 
individual  variations,  has  not  been  completely  worked  out.^^ 

The  Disturbances  of  Gastric  Secretion. — The  mucous  mem- 
brane of  the  stomach  usually  continues  to  manufacture  the  zymo- 
gens of  pepsin  and  rennin,  even  though  the  secretion  of  hydro- 
chloric acid  has  partly  or  wholly  ceased.  Only  in  the  most  ad- 
vanced changes  of  the  mucosa  are  these  ferments  much  diminished 
or  altogether  absent.  Such  a  lack  of  ferments,  constituting  the 
so-called  achylia  gastrica,  may  be  seen  in  advanced 
atrophic  gastritis,  in  carcinoma  of  the  stomach  and  in  certain 
neuroses. 

There  is  no  immediate  relation,  however,  between  the  secre- 
tion of  gastric  ferments  and  of  hydrochloric  acid,  for  even  in 
the  complete  absence  of  the  latter,  there  are  considerable  varia- 
tions in  the  amount  of  zymogens  in  the  gastric  juice.    Hence,  the 


238  THE  BASIS  OF  SYMPTOMS 

clinical  picture  of  achylia  gastrica  is  by  no  means  well  defined ;  ^^ 
though  it  may  occur  in  any  of  the  conditions  already  enumerated, 
it  is  often  the  chief  manifestation  in  individuals  who  possess 
simply  an  irritable  digestive  tract. 

No  symptoms  are  necessarily  produced  by  a  mere  absence  of 
gastric  juice  so  long  as  the  motility  of  the  stomach  remains  good, 
and  it  is  a  remarkable  fact  that  this  motility  is  often  increased  in 
cases  of  achylia.  We  know  little  of  the  anatomical  changes  in 
the  mucous  membrane  which  lead  to  a  cessation  of  secretion,  and 
we  are  especially  ignorant  as  to  the  role  which  nervous  influences 
play  in  producing  this  condition.  The  secretion  of  rennin  (lab 
ferment)  parallels  that  of  pepsin. ^^  (And  the  quantitative  de- 
termination of  the  former  affords  a  rough  clinical  index,  likewise, 
of  the  amount  of  pepsin  secreted. — Ed.) 

What  furnishes  the  normal  stimulus  to  gastric 
secretion?  Pawlow  has  shown  that  the  most  important  factor 
in  dogs  is  the  appetite,  which  is  stimulated  by  sensory  influences 
travelling  along  the  first,  second,  fifth  and  ninth  cranial  nerves. 
The  term  "psychic"  as  applied  to  this  secretion  in  dogs  is  an 
unfortimate  one,  because  it  is  not  strictly  such,  or  at  least  need  not 
be.  Whether  the  appetite  plays  an  equal  role  in  man  is  still 
undetermined.^*  At  any  rate,  there  is  considerable  evidence  to 
show  that  an  active  gastric  juice  is  secreted  when  there  are 
certain  types  of  food  in  the  stomach— or  more  correctly 
in  the  pars  pylorica — and  in  the  intestines,  and  further  in  response 
to  reflexes  from  other  parts  of  the  body.  Among  substances 
having  this  stimulating  power  are  the  meat  extractives,  milk 
and  probably  the  saliva.  Mechanical  irritation  of  the 
gastric  mucous  membrane  also  seems  to  be  a  factor.^  ° 

Just  how  important  in  man  the  appetite  is  in  stimulating  the 
flow  of  gastric  juice  must  be  left  in  abeyance.  It  is  my  opinion 
that  other  factors  are  more  significant,  vis.,  ordinary  sensory 
stimuli,  the  act  of  chewing  and  chemical  stimula- 
tion of  the  stomach  lining.^®  Furthermore,  the  importance  of 
habi  t  in  this  regard,  as  emphasized  by  Schiile,  seems  to  me  vital. 
In  general,  I  should  say  that  in  man  purely  psychic  factors  are 
not  of  first  importance, ^''^  but  rather  physical  processes  with  a 
psychic  component.  This  approaches  closely  the  physiological 
reflex. 

It  is  possible,  too,  that  some  substance  secreted  by  the  buccal 


DIGESTION  239 

mucosa  and  analogous  to  secretin,  plays  a  part  in  the  stimulation 
of  the  gastric  juice.^^  The  saliva  and  the  chewing  of  the 
food  are  also  seemingly  of  importance. 

Hypersecretion  of  Gastric  Juice. — We  are  better  informed  in 
the  matter  of  variations  in  the  hydrochloric  acid  content  of  the 
gastric  juice,  though  even  here,  for  reasons  already  mentioned, 
there  are  many  things  that  are  by  no  means  clear.  Most  accessible 
to  study  are  the  conditions  associated  with  pathological  hyper- 
secretions of  the  gastric  juice. 

The  stomach  of  a  healthy  fasting  man  is 
either  empty  or  it  contains  a  small  amount  of 
fluid,  which  may  or  may  not  show  free  acid.  Some  obser- 
vers believe  that  the  fasting  stomach  is  always  empty, ^^  while 
others  hold  that  it  usually  contains  active  gastric  juice  which 
sometimes  amounts  to  fifty  or  one  hundred  cubic  centimetres.^** 
In  our  experience,  it  has  been  found  empty  in  some  cases,  while 
in  others  it  has  contained  a  small  quantity  of  secretion,  possibly 
caused  by  material  (saliva)  swallowed. 

(In  the  past  few  years,  there  have  appeared  many  studies 
devoted  to  conditions  governing  the  secretion  and  com- 
position of  gastric  juice  in  man.  The  observations 
referred  to  have  been  made  upon  individuals  with 
oesophageal  stenoses  and  gastric  fistulae. 

Carlson,  in  a  recent  report,^^  has  given  the  results  of 
his  studies  in  a  young  man  upon  whom  a  gastrostomy  was  per- 
formed because  of  a  complete  cicatricial  stenosis  of  the  oesopha- 
gus. Confirming,  in  general,  the  observations  in  normal  individ- 
uals, he  found  that  the  fasting  stomach  contained  on  an  average 
twenty  c.c.  of  fluid — the  range  being  from  eight  to  fifty  c.c. 
This  fluid  was  made  up  in  part  of  the  secretion  of  the  gastric 
glands  and  also  of  material  that  had  regurgitated  from  the  duo- 
denum. The  daily  and  seasonal  variations  noted,  he  has  attrib- 
uted to  differences  in  tonicity  of  the  empty  stomach,  which  allow 
a  varying  amount  of  duodenal  contents  to  flow  back. 

Furthermore,  differing  with  Pawlow,  and,  in  the  main,  agree- 
ing with  Boldyreff,  in  their  animal  studies,  Carlson  has 
found  that  the  gastric  glands  in  man  are  in  a 
state  of  continuous  secretion,  the  juice  being  poor 
in  hydrochloric  acid — especially  when  the  rate  of  secretion  is 
slow — and  rich  in  pepsin.    This  continuous  secretion  varied  from 


240  THE  BASIS  OF  SYMPTOMS 

two  to  fifty  c.c.  per  hour  and  seemed  to  depend  upon  several 
possible  factors,  such  as  the  vagus  secretory  tonus,  and  the  action 
of  products  of  the  auto-digestion  of  the  gastric  juice  itself.  Carl- 
son, on  the  basis  of  his  own  observations  and  those  of  others 
working  under  similar  conditions,  has  estimated  that  a  normal 
adult  secretes  an  average  of  fifteen  hundred  c.c.  gas- 
tric juice  in  the  course  of  a  day. 

The  seeing,  smelling  and  thinking  of  food  caused  only  a  slight 
secretion  of  gastric  juice  in  Carlson's  subject;  this  he  has  attrib- 
uted to  the  fact  that  he  had  to  do  with  an  individual  for  whom 
the  taste  of  food  was  essential.  Pawlow  has  also  observed  con- 
siderable individual  variations  in  dogs  in  this  respect. 

The  pure  gastric  juice  obtained  from  these  patients 
with  fistulae,  by  different  investigators,  contained  from  0.35 
to  0,5  per  cent,  of  hydrochloric  acid.  This  percen- 
tage, though  considerably  higher  than  that  usually  given  for 
human  gastric  juice,  has  been  rather  constant  in  different  individ- 
uals, and  in  the  same  individual  under  different  circumstances; 
so  much  so  that  Bickel  believes  that  what  is  usually  designated 
as  hyperacidity  in  man  is  in  reality  a  hypersecretion.  The  ex- 
cessive production  of  gastric  juice  merely  raises  the  percentage 
of  acid  in  the  mixture  of  juice  and  food  which  is  subjected  to 
the  ordinary  clinical  analysis.  Even  in  the  most  marked  in- 
stances of  "hyperacidity"  the  total  acid  in  the  gastric  contents 
does  not  exceed  that  of  normal  pure  gastric  juice. 

Of  other  factors  which  influence  gastric  secretion  may  be 
mentioned  anger,  which  decreases  the  secretion  in  both  man  and 
dogs.  Furthermore,  as  necessary  conditions  of  secretion,  the 
body  must  contain  sufficient  water  and  sufficient  chlorids.  A 
deficiency  in  either  causes  less  gastric  juice  to  be  secreted,  without, 
however,  influencing  its  strength. — Ed.) 

Pathologically,  the  stomach  may  contain  large  amounts  of 
fluid,  even  when  the  individual  is  fasting.  The  percentage  of 
hydrochloric  acid  in  this  abnormal  secretion  may  be  low,  or  it 
may  equal  that  of  pure  gastric  juice  (circa  0.5  per  cent).  At 
the  height  of  digestion,  such  patients  also  exhibit  a  variably  acid 
secretion. 

Hypersecretion^  may  occur  as  a  continuous,  or 
— and  this  is  the  more  frequent — as  a  periodic  condition 
in  certain  general  disturbances  of  the  nervous  system,  such  as 


DIGESTION  241 

fever,  hysteria,  migraine  and  neurasthenia,  or  as  evidence  of  a 
local  lesion,  notably  gastric  ulcer.  Occasionally,  the  gastric  dis- 
order associated  with  hypersecretion  appears,  in  a  sense,  to  be 
primary  (dyspepsia  acida).  In  some  cases,  the 
amount  of  juice  poured  out  seems  to  be  particularly  large  when 
digestion  is  at  its  height  (digestive  hypersecretion). 

The  cause  of  the  hypersecretion  appears  to  be  an  increased 
irritability  either  of  the  mucous  membrane  of  the  stomach  or  of 
its  secretory  nerves.  In  many  cases,  even  after  a  long  period 
of  hypersecretion  and  hyperacidity,  no  anatomical  changes 
are  demonstrable  in  the  gastric  mucous  membrane,^^  which 
would  seem  to  indicate  that,  in  these  cases  at  least,  the  condi- 
tion is  of  nervous  origin.  It  is  possible  that  a  hypersecretion 
is  sometimes  caused  by  a  stimulation  of  the  secretory  centres  in 
the  brain,  and  when  this  is  so  the  condition  may  be  comparable 
to  the  salivation  that  is  so  often  present  in  progressive  bulbar 
paralysis. 

Hyperacidity.  Ulcer  of  the  Stomach. — In  still  other  cases,^  the 
stomach  in  the  fasting  state  is  normal,  but  at  the  height  of  digestion 
exhibits  a  percentage  of  .acid  as  high  as  that  of  pure  gastric  juice, 
i.e.,  0.4  to  0.5  per  cent.  This  condition  of  simple  hyperacidity 
probably  arises  in  different  ways.  It  might  be  looked  upon,  for 
example,  as  the  result  of  the  secretion  of  an  abnormally  acid 
gastric  juice;  while,  on  the  other  hand,  the  conception  of  an 
increased  secretion  of  normal  acidity,  especially  if  combined  with 
motor  insufficiency,  would  explain  conditions  no  less  satisfac- 
torily. 

Attention  has  already  been  called  to  the  very  frequent 
association  of  hypersecretion  and  hyperacid- 
ity. In  gastric  ulcer,  however,  a  pure  hyperacidity  is  not  in- 
frequently met  with.  The  relation  between  the  two  is  of  par- 
ticular interest,  because  some  observers  look  upon  the  hyperacid 
condition  as  the  cause  of  the  ulcer.  In  animals,  tissue  defects 
of  the  gastric  mucosa,  produced  by  trauma  or  otherwise,  nearly 
always  heal  rapidly.^^  The  wall  of  the  stomach  opposite  the 
point  of  injury  contracts,  thereby  protecting  the  abrasion,  to  a 
certain  extent,  from  the  action  of  the  gastric  juice  and  enabling 
the  epithelium  rapidly  to  bridge  over  the  defect.  In  man,  on  the 
contrary,  gastric  ulcer  is  characterized  by  its  extraordinary 
chronicity. 

16 


242  THE  BASIS  OF  SYMPTOMS 

A  double  etiological  relation  seems  to  exist  between  hyper- 
acidity and  round  ulcer  of  the  stomach.  On  the  one  hand,  the 
irritation  of  the  nerves  at  the  base  of  the  ulcer  apparently  in- 
creases the  secretion  of  gastric  juice ;  while,  on  the  other,  a  hyper- 
acidity would  interfere  with  the  healing  of  any  defect  in  the 
mucous  membrane,  and  an  anatomical  lesion  would,  therefore,  be 
more  apt  to  lead  to  a  chronic  ulceration.  Chronicity  would  also  be 
favored  by  local  vascular  disease,  in  particular  by  thrombosis  of 
the  smaller  gastric  arteries,^®  by  vasomotor  irritability  and  by  con- 
stitutional disorders,  such  as  anaemia.  The  greater  the  hyper- 
acidity, the  more  readily  would  abrasions  go  over  into  chronic 
ulcer.  The  excess  of  acid  acts  not  by  digesting  the  injured  area, 
but  by  interfering  with  the  formation  of  granulations.  Healing 
naturally  becomes  more  difficult  if  the  defect  has  existed  for 
some  time,  and  induration  of  the  margins  and  base  has  occurred. 
The  view  that  an  absence  of  antipepsin  plays  a  role  in  the  etiology 
of  round  ulcer  still  lacks  confirmation. 

Certain  recent  observations ^^  have  emphasized  the  role  of 
infectious  processes  in  the  production  of  gastric 
ulcer.  Mycotic  necroses  of  the  gastric  mucosa  do  indeed  occur, 
and  it  is  conceivable  that  these  are  transformed  into  genuine 
ulcers  by  the  joint  action  of  the  bacteria  and  the  gastric  juice. 
(Rosenow,  among  others,  has  produced  ulcer  of  the  stomach  by 
the  injection  of  streptococci.^® — Ed.) 

The  etiology  of  gastric  ulcer  is  far  from  clear. 
Not  infrequently,  for  example,  hyperacidity  is  not  present,  and 
on  the  other  hand  a  high  degree  of  acidity  is  often  unaccom- 
panied by  ulcer.  (The  cause  of  the  original  tissue  defect  is  per- 
haps more  readily  understood  than  is  the  reason  for  its  failure 
to  heal.  Chronic  ulcers  have  been  produced  in  rabbits  by  section 
of  the  vagi,^*  though  in  what  way  is  not  known.  In  dogs,  the 
feeding  of  colon  bacilli^**  has  likewise  proved  successful.  The 
action  of  the  acid  gastric  juice  probably  plays  an  important  part, 
either  directly  by  its  corrosive  effect  upon  the  ulcer,  or  indirectly 
by  causing  a  spasm  of  the  pylorus,  delayed  emptying  and  further 
accumulation  of  acid  material.^^ — Ed.) 

Effects  of  Hypersecretion  and  H)rperacidity. — In  discussing 
the  effects  of  an  excessive  secretion  of  hydrochloric  acid,  it  is 
possible  to  consider  hyperacidity  and  hypersecretion  together. 
Disturbances  are  produced  by  the  excess  of  acid ;  and  these  occur 


DIGESTION  249 

during  digestion  in  cases  of  pure  hyperacidity,  during  fasting  in 
cases  of  hypersecretion,  and  during  both  states  when  the  two  are 
combined.  As  Riegel  has  said,  the  results  in  all  cases  are  due 
rather  to  the  profuse  secretion  than  to  the  high  acidity  of  the 
juice  secreted.  In  the  presence  of  an  excess  of  acid,  the  diges- 
tion of  starch  in  the  stomach  ceases  altogether.  The 
proteids  are  digested,  but  whether  normally  or  not  is  not 
known.  The  patient  frequently  suffers  from  severe  pain  and 
from  vomiting,  for  both  of  which  the  hyperacidity  is  usually 
directly  responsible,  for  they  are  generally  relieved  by  the  ad- 
ministration of  substances  which  will  combine  with  acids,  such  as 
alkalies  and  proteids. 

The  effect  of  an  increased  secretion  upon  the  gastric  motility 
will  be  discussed  in  another  place,  though  we  may  mention  here 
that  not  infrequently  a  hypersecretion  is  followed  by  dilata- 
tion of  the  stomach  (Riegel).  What  effect  the  hyper- 
acid gastric  contents  exert  upon  the  intestines  and  upon 
the  intestinal  digestion  is  not  definitely  known.  Pos- 
sibly the  poor  nutrition  of  many  patients  with  hyperacidity  is 
due  to  the  difficulty  in  neutralizing  the  hyperacid  material  which 
reaches  the  intestines  and  to  a  consequent  insufficient  absorption 
of  nourishment.  But,  as  a  rule,  this  is  not  the  only  cause  of  their 
poor  nutrition ;  the  pain,  the  partial  starvation  caused  by  the  fear 
that  food  will  cause  pain,  and  the  loss  of  material  by  vomiting, 
all  tend  to  produce  emaciation.  Constipation  is  also  fre- 
quently associated  with  hyperacidity. 

The  symptoms  of  gastric  ulcer  are,  in  part,  those 
of  hyperacidity;  yet  the  pain  is  usually  more  intense,  probably 
because  the  base  of  the  ulcer  is  especially  sensitive.  The  pain 
may  be  very  severe,  however,  even  though  there  be  hypochlor- 
hydria.  Then,  too,  a  series  of  complications  may  follow  in  the 
train  of  the  ulcer.  Arteries  may  be  eroded  and  hemorrhage 
ensue ;  the  gastric  wall  may  be  perforated  with  resultant  adhesions, 
abscesses  or  peritonitis.  The  number  of  such  complications  is 
unfortunately  a  large  one. 

Subacidity  and  Anacidity. — A  diminution  of  gastric  acidity 
is  met  with  distinctly  more  often  than  is  an  increase.  A  certain 
caution,  however,  is  indicated  in  the  interpretation  of  diminished 
acidity,  for  the  causative  factors  are  complex.  The  amount  of 
free  hydrochloric  acid  may  be  lowered,  or  free  acid  may  be  en- 


S44  THE  BASIS  OF  SYMPTOMS 

tirely  absent ;  in  either  case  the  total  acidity  may  be  low,  or  normal 
or  even  higher  than  normal.  The  absence  of  free  acid  does  not 
necessarily  mean  that  none  is  being  secreted;  for  acid  poured 
out  in  normal  amount  may  combine  with  unusual  avidity,  particu- 
larly with  proteids.  We  can  form  no  idea  of  the  total  amount 
of  acid  secreted,  because  of  the  intimate  relation  in  man  between 
the  quantity  secreted,  reabsorbed  and  propelled  into  the  intestines. 

Free  hydrochloric  acid  is  absent  in  many 
acute  gastric  disturbances,  functional  as  well  as  ana- 
tomical, notably  in  those  associated  with  the  acute  infectious 
diseases.  Anacidity  is  seen  more  frequently,  however,  in 
chronic  diseases  of  the  stomach,  as  in  atrophy  or 
amyloid  degeneration  of  the  mucous  membrane,  and  espe- 
cially in  carcinoma.  Diseases  of  other  abdom- 
inal organs — of  the  liver,  for  example — may  also  inhibit  the 
gastric  secretion ;  and  general  conditions  such  as  per- 
nicious anaemia,  advanced  tuberculosis  and  cachexia  may  all  be 
associated  with  an  absence  of  free  hydrochloric  acid  in  the  gas- 
tric contents.  A  complete  anacidity,  however,  does  not  develop 
rapidly,  but  is  the  result  of  a  gradual  fall  from  the  practically 
constant  and  not  inconsiderable  degree  of  free  acidity  seen  in 
health,  under  fixed  external  conditions.  This  gradual  approach 
to  total  anacidity  is  common  in  the  chronic  dyspepsias. 

We  have  already  emphasized  that  a  decrease  both  in  free 
and  combined  acid  may  be  the  result  of  diverse  factors.  As  the 
secretory  conditions  in  a  healthy  individual  who  leads  an  even 
and  regular  Hfe  are  fairly  constant ^^ — and  incidentally  different 
from  those  under  which  pure  gastric  juice  is  obtained — we  must 
assume  that  there  is  some  regulating  mechanism  at  work,  the 
action  of  which  is  easily  and  often  disturbed  in  pathological  con- 
ditions, and  not  infrequently  even  in  health,  when  the  routine  of  a 
regular  existence  is  upset. 

The  two  conditions  adduced  in  explanation  of  an 
acid  reduction  have  already  been  alluded  to,  viz.,  an  actual 
diminution  in  the  amount  of  gastric  juice  se- 
creted— whether  there  is  a  pure  secretion  containing  less  acid 
is  not  known — and  secondly,  the  production  in  consid- 
erable amount  of  substances  which  combine  with 
free  acid.^^  The  last  is,  undoubtedly,  true  in  carcinoma  of 
the  stomach,  for  hydrochloric  acid  continues  to  be  secreted  in 


DIGESTION  245 

this  condition;  while  the  amount  of  combined  chlorid  may  not 
only  equal,  but  exceed  the  normal,  ^^ 

Clinical  experience  speaks  also  for  this  second  hypothesis. 
Thus  free  acid  may  be  present  in  carcinoma;  this  is  the  rule,  in 
fact,  in  the  early  stages,  particularly  when  the  carcinoma  has  de- 
veloped upon  the  site  of  an  old  ulcer.^^  It  is  more  difficult  to 
understand  the  anacidity  associated  with  malignancy  of  neighbor- 
ing communicating  structures,  as,  for  example,  the  oesophagus 
and  gall-bladder. 

When  the  hydrochloric  acid  in  the  gastric  contents  is  reduced, 
theptyalinis  able  to  act  for  a  long  time  upon  the  food,  unless 
its  activity  is  interfered  with  by  the  presence  of  organic  acids. 
Digestion  of  the  proteids  is  usually  diminished  or 
absent,  according  to  the  reduction  in  the  amount  of  hydrochloric 
acid.^^  (A  carcinoma  of  the  stomach,  however,  apparently  pro- 
duces ferments  capable  of  causing  an  even  deeper  cleavage  of 
proteids  than  does  pepsin.^^  The  use  of  one  of  these  ferments, 
which  will  split  glycyltryptophan,  has  been  suggested 
by  Neubauer  and  Fischer  ^^  in  the  diagnosis  of  gastric  cancer. 
The  test  as  originally  employed,  and  some  of  its  modifications, 
seem  to  have  a  certain  value,  when  disturbing  factors  such  as  the 
regurgitation  of  the  duodenal  contents  can  be  eliminated. — Ed.) 
A  diminished  proteid  digestion  in  the  stomach  does  not  neces- 
sarily mean  a  loss  of  food  material  to  the  body,  for  with  a  proper 
dietary  the  intestinal  digestion  can  compensate  for  the  inefficiency 
of  the  stomach,  and  the  nitrogenous  material  in  the  body  may 
not  only  be  maintained  at  the  old  level,  but  in  some  cases  the  store 
may  be  actually  increased  (v.  Noorden).  And  I  am  convinced 
that  nitrogen  equilibrium  may  be  conserved  even  with 
individuals  on  ordinary  diet,  for  many  such,  despite  the  anacid- 
ity, are  quite  free  from  symptoms. 

Bacterial  Action  in  the  Stomach. — The  normal  gastric  juice 
possesses  decided  antiseptic  properties,  owing  principally  to  its 
acidity.  Whether  the  pepsin  is  of  great  importance  or  not  in 
this  respect  is  still  a  matter  of  dispute.  Cells  are  usually  digestible 
only  when  they  are  dead ;  yet,  in  the  opinion  of  some,  pepsin  plays 
an  important  part  in  limiting  bacterial  growth,  more  especially 
the  growth  of  those  organisms  which  give  rise  to  lactic  acid  fer- 
mentation. An  acidity  of  0.2  per  cent,  in  a  test-tube  will,  after 
a  long  time,  destroy  many  bacteria,  such,  for  example,  as  the 


246  THE  BASIS  OF  SYMPTOMS 

typhoid  bacillus,  the  cholera  vibrio  and  the  bacteria  of  decom- 
position and  fermentation;  whereas  other  organisms,  and  espe- 
cially spores,  are  not  greatly  injured  by  this  amount  of  acid. 
Yet  conditions  in  the  test-tube  are  not  the  same  as  those  in  the 
stomach.  Many  parts  of  the  food  do  not  come  into  intimate  con- 
tact with  the  gastric  juice  at  all,  either  because  they  are  quickly 
passed  on  into  the  intestines,  or  because  they  lie  in  the  centres 
of  large  particles  which  are  not  broken  up  in  the  stomach. 
Furthermore,  a  large  part  of  the  hydrochloric  acid  secreted  is 
immediately  bound  by  the  proteids,  etc.,  and  these  combinations 
are  known  to  be  less  antiseptic  than  is  free  hydrochloric  acid, 
though  even  they  may  kill  cholera  bacilli.  It  is  evident,  there- 
fore, that  the  bactericidal  powers  of  the  gastric 
secretion  are  limited,  and  that  numbers  of  micro- 
organisms are  constantly  being  passed  on  into  the  intestines. 

On  the  other  hand,  an  abundant  multiplication  of  bacteria 
within  the  stomach  is  prevented  mainly  by  the  normal  evacuation 
of  its  contents.  Even  though  hydrochloric  acid  is  absent, 
no  bacterial  decomposition  ordinarily  takes 
place  so  long  as  the  motility  of  the  stomach  re- 
mains good  and  its  contents  are  regularly  passed  on  into  the 
intestines  before  the  bacteria  have  time  to  multiply.  The  con- 
dition most  favorable  to  bacterial  decomposition  is  the  stagnation 
of  material  in  the  stomach;  when  this  last  is  present,  the  grade 
of  acidity  plays  a  most  important  part  in  the  determination  of  the 
variety  of  micro-organisms  which  shall  multiply,  and  this  in 
turn  determines  the' character  of  the  decompositions  that  shall' 
take  place. 

If  free  and  abundant  hydrochloric  acid  be  present  in  stagnated 
gastric  contents,  the  ordinary  putrefactive  decomposi- 
tions of  proteid  material  rarely  take  place.  The  fer- 
mentation of  carbohydrates,  however,  does  occur: 
sugar  is  transformed  into  alcohol  and  carbon  dioxide,  alcohol  into 
acetic  acid,  dextrose  into  lactic  acid,  butyric  acid,  carbon  dioxide 
and  hydrogen,  etc.  The  gases  which  ordinarily  result  from 
these  fermentations  are  carbon  dioxide,  hydrogen  and  traces  of 
methane.  These,  together  with  swallowed  air,  usually  make  up 
the  bulk  of  the  gases  present  in  the  stomach  during  gastric  fer- 
mentations. Each  of  these  fermentations  may  be  carried  on  by 
a  number  of  micro-organisms  that  will  resist  an  acid  reaction 


DIGESTION  247 

of  not  too  high  a  grade  ;^^  but  yeasts  and  sarcinae  are  those  most 
commonly  found.  Occasionally,  similar  fermentative  processes 
occur  even  though  the  gastric  acidity  is  very  high.  Here,  possi- 
bly, the  products  of  fermentation  cause  a  reflex  flow  of  gastric 
juice.^° 

If  the  stagnation  is  accompanied  by  a  diminu- 
tion or  absence  of  hydrochloric  acid,  then  oppor- 
tunity is  given  for  the  multiplication  of  a  greater  variety  of 
micro-organisms.  These  may  even  cause  putrefaction  of  proteid 
material.  More  frequently,  however,  they  give  rise  to  fermen- 
tative processes  similar  to  those  just  described.  Yet  there  is  a 
special  tendency  to  the  production  of  lactic,  butyric  and  other 
volatile  organic  acids. ^^  Lactic  acid  fermentation 
is  particularly  characteristic  of  gastric  stagnation  in  the  absence 
of  hydrochloric  acid;  and  if  this  be  present  in  sufficiently  large 
quantities  it  tends  to  inhibit  the  growth  of  many  bacteria  which 
would  otherwise  give  rise  to  putrefactive  processes.  A  special 
lactic  acid  bacillus  (Oppler-Boas  bacillus)  is  then 
frequently  present  in  enormous  numbers  in  the  gastric  contents. 

From  a  consideration  of  these  facts,  it  will  be  seen  that  no 
one  kind  of  bacterial  decomposition  is  pathognomonic  of  any  par- 
ticular clinical  condition.  The  decomposition  depends  rather 
upon  the  varieties  of  micro-organisms  which  have  been  intro- 
duced into  the  stomach,  upon  the  opportunity  which  they  have 
had  to  multiply  and  upon  the  kind  of  food  which  is  subjected 
to  their  activities.  The  relation  between  carcinoma  of  the 
stomach  and  lactic  acid  fermentation  must  be 
judged  from  such  a  general  stand-point.  The  two  frequently 
occur  together,  but  this  depends  upon  the  fact  that  stagnation, 
absence  of  free  hydrochloric  acid  and  diminution  in  the  ferments 
— the  very  conditions  which  favor  the  development  of  lactic  acid 
fermentation — are  most  frequently  present  in  cancer  of  the 
stomach.  If,  as  rarely  happens,  the  combination  of  a  gastric 
stagnation  and  an  absence  of  free  hydrochloric  acid  is  caused  by 
some  condition  other  than  carcinoma,  lactic  acid  fermentation 
might  occur ;  though  some  maintain  that  lactic  acid  is  formed  only 
in  the  presence  of  a  ferment-like  body,  which  is  found  in  cancer 
tissue,  blood-serum,  etc.^^  Very  remarkable  decompositions  have 
been  observed  in  some  stomachs,  for  example,  the  production  of 
sulphuretted  hydrogen,  when  free  hydrochloric  acid  was  absent. 


248  THE  BASIS  OF  SYMPTOMS 

The  acidity  of  the  gastric  contents  exerts  no  small  influence 
upon  the  chemical  processes  in  the  intestines, ^^  and 
we  may  say  here  that,  in  general,  as  the  acidity  in  the  stomach 
diminishes,  the  putrefaction  in  the  intestines  tends  to  increase. 
This  subject  will  be  more  fully  considered  below. 

It  sometimes  happens  that  fermentation  occurs  in  the  gastric 
contents,  even  though  there  is  no  diminution  either  in  the  secre- 
tion of  acid  or  in  the  motility  of  the  stomach.  In  such  cases  it 
is  possible  that  the  condition  is  due  to  the  introduction  of 
excessive  amounts  of  fermentable  material,  to- 
gether with  the  agents  which  cause  the  fermentation.**  The  lat- 
ter would  in  turn  affect  the  gastric  motility,  and  a  disturbed 
motility  would  favor  further  fermentation. 

Abnormal  fermentative  processes  do  harm  to 
the  stomach  in  various  ways.  The  products  of  fer- 
mentation may  irritate  and  injure  the  gastric  mu- 
cosa, producing  loss  of  appetite,  pain,  vomiting  and  possibly 
spasmodic  closure  of  the  pylorus  with  diminished  gastric  motility. 
Gases  may  be  produced  in  large  quantities,  causing  abnormal 
distention  and  belching.  The  abnormal  secretion  of  fluid  by  the 
stomach,  together  with  the  distention  by  gases,  would  favor  the 
development  ofgastricdilatation.  At  times,  toxicsub- 
stances  are  produced  in  gastric  fermentations,  and  these  may 
give  rise  to  a  varied  category  of  general  symptoms  (see  p.  255). 

We  know  very  little  about  the  function  of  the 
mucus  secreted  by  the  stomach,  which  is  unfortunate,  be- 
cause it  is  quite  probable  that  this  may  exert  some  protective 
influence  in  certain  pathological  conditions.  The  amount  of 
mucus  secreted  in  diseased  conditions  varies  greatly;  and  it  is 
present  in  different  forms,* ^  depending  upon  the  action  of  hydro- 
chloric acid.  At  times,  possibly,  there  may  occur  a  hypersecretion 
of  mucus  on  a  nervous  basis,*®  similar  to  a  hypersecretion  of 
gastric  juice, 

The  Disturbances  of  Gastric  Motility 
The  normal  movements  of  the  different  parts  of  the  stomach 
are  fairly  well  known.*"^  The  fundus  acts  as  a  reservoir  for  the 
food.  Its  wall  shows  peristaltic  movements,  but  the  pressure 
within  it  is  comparatively  low.  The  antrum  pyloricum  contracts 
periodically,  several  times  a  minute,  although  it  may  at  times 


DIGESTION  249 

contract  irregularly.  During  a  contraction,  the  pressure  exerted 
upon  its  contents  is  considerable,  being  over  a  half  metre  of  water 
in  man.  Since  its  cavity  is  shut  off  from  the  fundus  by  the 
sphincter-Hke  action  of  its  proximal  portion,  its  contents  may  be 
propelled  into  the  intestines  only  when  this  muscular  ring  relaxes. 
(The  opening  and  closing  of  the  pylorus  is  in  part,  at  least,  de- 
pendent upon  the  so-called  acid-reflex  ( Hirsch,  Serd- 
jukow,  Cannon). ^^  Relaxation  of  the  pylorus  occurs  when  free 
hydrochloric  acid  appears;  and  when  the  acid  contents  thus  re- 
leased reach  the  duodenum,  they  not  only  initiate  a  reflex  which 
closes  the  pylorus  behind  them,  but  also  stimulate  the  flow  of  the 
alkaline  pancreatic  secretions.  The  latter,  in  turn,  gradually 
neutralize  the  acid  material  which  has  reached  the  intestines,  and 
thus  permit  of  another  pyloric  relaxation,  and  the  repetition  of 
the  cycle. 

Other  factors,  however,  seem  to  be  influential  in  this  mechan- 
ism.*^ Thus  in  dogs,  the  mechanical  irritation  of  coarse  food 
particles  keeps  the  pylorus  in  a  contracted  state ;  and  infiltrations 
of  the  gastric  wall,  even  though  at  a  distance  from  the  pyloric 
end,  affect  its  opening  and  closure.  An  illustration  of  this  last 
is  the  pylorospasm  of  gastric  ulcer  without  hyperacidity.  On  the 
other  hand,  a  carcinoma  not  situated  at  the  pylorus  may,  with 
normal  conditions  of  acidity,  be  associated  with  a  permanent 
pyloric  insufficiency.  And,  finally,  pyloric  insufficiency,  and  par- 
ticularly pylorospasm,  may  exist  in  the  complete  absence  of  gastric 
and  duodenal  changes.  This  nervous  type  of  spasm  may  be  pro- 
voked by  morphin,  physostygmin  and  cold,  and  ended  by  means 
of  atropin  and  papaverin. 

The  pyloric  play,  so-called,  is  therefore  of  a  more 
complex  nature  probably  than  has  heretofore  been  supposed. 
Possibly  innervation  factors  as  yet  little  understood  play  an  im- 
portant part. — Ed.)  The  antrum  pyloricum  seems  to  pick  the 
fluid  and  finely  divided  portion  of  the  gastric  contents  out  of  the 
fundus,  and  in  this  manner  to  regulate  still  further  the  emptying 
of  the  stomach. 

The  cause  of  the  gastric  movements  is  very  un- 
certain. In  the  first  place,  like  all  other  unstriated  muscles,  the' 
stomach  has  periods  of  rest  alternating  with  periods  of  activity. 
Some  have  believed  that  the  acidity  exerts  a  great  influence 
upon  the  gastric  movements,  yet  we  know  that  under  pathological 


250  THE  BASIS  OF  SYMPTOMS 

conditions  at  least,  no  definite  relation  exists  between  the  motility 
of  the  stomach  and  the  acidity  of  its  contents.  The  delayed 
emptying  seen  so  often  in  cases  of  hyperacidity  may  be  ascribed 
to  an  increased  activity  of  the  duodenal  reflex  mentioned  above; 
while  the  rapid  emptying,  on  the  other  hand,  associated  with 
diminished  and  absent  acidity,  is  probably  due  to  the  weakness 
of  the  pyloric  reflex,  and  may  be  regarded  as  the  rule  in  achylia 
gastrica.  The  consistencyof  the  contents  certainly  in- 
fluences gastric  motility.  Large  solid  particles  are  thrust  back 
into  the  fundus  by  the  antrum,  whereas  soft  masses  are  allowed 
to  pass  through  into  the  intestines.  Warm  material  tends 
to  increase  the  peristalsis  and  to  relax  the  pyloric  sphincter.^® 
Although  careful  studies  have  been  made  as  to  the  length  of 
time  that  certain  foods  remain  in  the  stomach,®^  more  work  is 
needed  upon  abundant  mixed  diets. 

(Cannon,  in  his  work  on  cats,  has  carefully  studied  the 
effects  of  different  foods,  singly  and  combined,  upon  the  activity 
of  the  pylorus.  Carbohydrates,  which  make  little  demand  upon 
the  gastric  acidity,  pass  quickly  into  the  duodenum.  The  proteid 
curve  is  a  gradual  one  because  this  food  unites  with  the  first  acid 
secreted,  and  thus  delays  the  appearance  of  sufficient  free  acid 
to  provoke  the  pyloric  reflex.  Fats  likewise  remain  for  a  long 
period  in  the  stomach  because  of  their  known  inhibitory  effect 
upon  the  secretion  of  acid.  Cannon  has  also  elaborated  the  action 
of  combinations  of  these  foods. — Ed.  ) 

Increased  Peristalsis  and  Increased  Gastric  Motility. — At 
times  the  peristaltic  movements  of  the  stomach  are  increased, 
and  its  contents  are  emptied  more  rapidly  than  normal.  Yet 
this  rapid  emptying  does  not  necessarily  occur;  for,  when  a  hin- 
drance to  the  exit  of  food  is  present,  the  powerful  contractions 
of  the  muscle  may  be  unable  to  expel  the  food  even  within  the 
normal  period  of  time.  Frequently  the  patient  is  rendered  ex- 
tremely uncomfortable  by  the  excessive  gastric  peristalsis,  and  the 
movements  of  the  stomach  may  be  plainly  visible  through  the 
abdominal  wall.  In  some  cases  this  condition  of  "peristaltic 
unrest "  is  dependent  upon  a  primary  pyloric  stenosis ;  in  others, 
it  is  probably  caused  by  an  excessive  irritability  of  the  nervous 
connections  of  the  stomach,  and  it  is  then  frequently  accompanied 
by  violent  peristalsis  of  the  intestines.  As  we  have  already  said, 
the  stomach  may  empty  itself  with  unusual  rapidity  in  achylia 


DIGESTION  «61 

gastrica,  though  in  this  case  there  are  usually  no  associated  sen- 
sations of  increased  peristalsis.  We  must  be  cautious,  however, 
in  linking  a  rapid  emptying  with  any  particular  secretory  anomaly, 
for  hypermotility  may  occur  also  with  hypersecretion.^^ 

Motor  Insufficiency  and  Gastric  Dilatation. — Much  more  fre- 
quent than  an  increased  is  a  diminished  gastric  motility,  and  a 
consequent  delayed  or  incomplete  emptying  of  the  organ.  This 
is  seen,  among  other  conditions,  in  acute  and  chronic 
gastritis,  and  particularly  in  carcinoma.  Cancer  may 
act  in  this  way  not  only  when  it  causes  an  anatomical  pyloric 
stenosis,  but  also  when  it  is  situated  in  regions  the  involvement 
of  which  has  no  relation,  necessarily,  to  the  emptying  of  the 
stomach.  In  this  case,  the  disturbance  of  motility  is  associated 
with  anomalies  of  secretion ;  the  interaction  of  the  two,  however, 
is  not  understood.  Either  may  be  the  consequence  of  the  ana- 
tomical lesion,  or  the  secretory  disorder  may  lead  to  the  motor 
insufficiency.  Yet  the  latter  not  infrequently  occurs  primarily, 
the  secretory  conditions  being  quite  normal. 

We  are  as  yet  unacquainted  with  those  factors,  a  knowledge 
of  which  would  be  most  instructive,  vi^.^  what  lesions  of  the 
nervous  apparatus  and  of  the  musculature  underlie  these  motor 
disorders,  and  to  what  extent  is  the  muscle  of  the  antrum  and 
of  the  fundus  crippled.  Possibly  Moritz's  method  of  estimating 
the  pressure  in  the  different  parts  of  the  stomach  will  prove  of 
value  in  this  regard.^^ 

The  motility  of  the  antrum,  and  particularly  of  the  pylorus, 
is  obviously  intimately  influenced  by  what  would  seem  to  be  in- 
significant factors,  not  only  under  pathological  conditions,  but 
even  in  health.^*  I  am  of  the  opinion,  indeed,  that  gastric  pathol- 
ogy is  much  more  a  matter  of  motor  than  of  secretory  disturb- 
ances. The  prominence  of  the  latter  in  diseases  of  the  stomach 
is  due  to  the  fact  that  our  methods  of  estimating  motor  disorders 
are  too  little  refined.  Even  roentgenoscopy  is  not  entirely  satis- 
factory, because  it  carries  with  it  the  use  of  an  abnormal  meal 
which  in  itself  may  affect  gastric  motility. 

The  effect  of  a  motor  insufficiency  is  that  the 
stomach  does  not  empty  itself  as  quickly  as  a  normal  organ  under 
the  same  conditions.  So  long  as  the  degree  of  insufficiency  is 
slight,  this  is  the  only  consequence.  If,  on  the  contrary,  there 
is  a  considerable  stagnation  of  food,  which  in  decomposing  builds 


262  THE  BASIS  OF  SYMPTOMS 

substances  such  as  gases  which  distend  the  stomach,  or  such  as 
fatty  acids,  which  injure  the  mucosa;  and  if,  further,  secretory 
anomaHes  exist  which  favor  the  decomposition  of  the  stagnant 
material,  then  the  motor  insufficiency  leads  to  dilatation. 
The  secretion  of  fluids  in  large  amount  also  predisposes  strongly 
to  dilatation  in  view  of  the  insignificant  power  of  the  stomach  to 
absorb  them.  That  food  stagnation  may  produce  secretory  dis- 
turbances is  indicated  by  the  studies  of  Kausch,  in  which  a  change 
in  secretion  was  observed  after  a  successful  gastro-enterostomy.^' 

Causes  of  Dilatation, — Dilatation  may  result  from  a  variety 
of  causes.  In  the  first  place,  it  may  follow  a  mechanical 
stenosis  of  the  pylorus,  such  as  may  be  caused  by 
tumors,  contracted  scars  or  pressure  from  without.  It  is  quite 
probable  also  that  it  may  follow  a  spastic  contraction 
of  the  pyloric  muscle,  which  arises  from  reflexes 
from  ulcers,  from  sensitive  spots  on  the  mucosa  or  perhaps  from 
the  irritation  of  a  normal  mucous  membrane  by  caustic  sub- 
stances or  even  by  hyperacid  secretions.  In  the  latter  case,  it 
is  the  duodenal  mucosa  and  not  the  gastric,  as  formerly  sup- 
posed, that  seems  to  initiate  the  reflex.^*  In  infants,  a  primary 
pylorospasm  is  not  infrequently  observed.^'^ 

Every  stenosis  of  the  pylorus  increases  the  work  of  the 
muscle  in  the  antrum  pyloricum.  This  additional  work  causes 
the  muscle  to  hypertrophy  just  as  additional  work  elsewhere  will 
lead  to  an  hypertrophy  of  the  corresponding  muscle.  The  more 
powerful  contractions  of  the  hypertrophied  gastric  muscle  may 
for  a  time  neutralize  the  effects  of  even  a  considerable  stenosis. 
To  what  extent  this  is  possible  depends  upon  the  strength  of  the 
hypertrophied  muscle.  Ultimately  the  hindrance  to  the  exit  of 
food  may  exceed  the  compensatory  power  of  the  antrum,  and  the 
stomach  will  no  longer  be  able  to  empty  itself  completely.  Dila- 
tation then  begins,  and  this  is  frequently  favored  by  a  concomitant 
weakening  of  the  antrum  caused  by  a  degeneration  of  its  smooth 
muscle-fibres. 

Anomalies  in  the  form  and  position  of  the 
stomach  may  also  lead  to  dilatation. °*  Our  former  ideas  as 
to  the  position  of  the  organ  have  undergone  complete  revision  as 
a  result  of  radiographic  methods  of  examination.^*  As  a  rule 
it  lies  p)erpendicularly  with  an  upward  kinking  at  the  pyloric 
antrum  (siphon  form  of  Groedel).     Changes  in  its  im- 


DIGESTION  258 

mediate  surroundings,  tight  lacing,  enteroptosis — all  of  these  exer- 
cise a  most  pronounced  influence  upon  the  ability  of  the  stomach 
to  empty  itself.  Such  conditions  may  cause,  in  the  first  place, 
an  actual  narrowing  of  the  gastric  outlet,  as  happens,  for  example, 
when  an  abnormally  low  stomach  presses  upon  or  kinks  the  duo- 
denum. Then,  too,  the  low  position  of  the  fundus  in  gastroptosis 
increases  the  difference  in  the  level  between  it  and  the  pylorus, 
and  renders  a  greater  amount  of  work  necessary  to  lift  the  con- 
tents out  of  the  stomach.  Very  remarkable  dilata- 
tions sometimes  follow  laparotomy  or  develop  in 
the  course  of  acute  infectious  diseases.^^  The  stomach  becomes 
enormously  distended  within  the  course  of  a  few  hours.  In  some 
of  these  cases  the  dilatation  apparently  results  from  an  acute 
obstruction  in  the  duodenum,  due  to  a  kinking  as  noted  above, 
and  the  motor  insufficiency  is  especially  apt  to  occur  if  the 
gastric  wall  has  previously  been  diseased.  Anomalies  in  the 
position  of  the  stomach  may  also  play  a  role. 

(According  to  Mayo  Robson®^  acute  dilatation  of 
the  stomach  is  due  to  a  paralytic  condition  of  its  wall  which 
leads  to  an  overdistention  with  gases  and  with  excessive  secretion, 
this  in  turn  producing  a  kinking  at  the  pylorus  or  at  the  duodeno- 
jejunal flexure.  This  is  comparable  to  the  intestinal  obstruction 
occurring  in  a  loop  of  paralyzed  bowel  which  becomes  distended 
with  fluids  and  gases,  and  by  its  very  weight  causes  a  kinking 
of  the  intestine  just  below. — Ed.) 

In  other  cases  of  gastric  dilatation,  no  hindrance  to  the  exit 
of  food  is  apparent.  Such  dilatations  have  been  met  with  in 
chronic  gastritis,  ulcer  and  carcinoma,  in  cases  of  hyperacidity  and 
hypersecretion,  and  finally  in  association  with  enteroptosis,  neuras- 
thenia and  diseases  of  the  spinal  cord.  Possibly,  certain  cases  of 
ulcer  and  hyperacidity  occupy  a  peculiar  position  in  the  produc- 
tion of  dilatation,  in  that  the  stenosis  is  functional  and  due  to  a 
pylorospasm. 

The  so-called  atonic  type  of  dilatation  would  pre- 
sent no  interpretative  difficulties  were  it  not  for  the  fact  that 
dilatation  is  not  always  accompanied  by  a  delayed  emptying  of 
the  organ ;  on  the  contrary,  indeed,  the  stomach  may  empty  itself 
very  slowly  even  though  such  a  dilatation  is  absent,  and  conversely 
a  dilatation  may  have  no  effect  upon  gastric  motility.  Conditions 
here  are  very  similar  to  those  observed  in  the  varying  behavior 


254  THE  BASIS  OF  SYMPTOMS 

of  cardiac  dilatation  and  cardiac  efficiency.  It  is  important  to 
remember  that  an  apparent  dilatation  does  not  necessarily  mean 
an  actual  enlargement,  for  in  conditions  such  as  enteroptosis,  it 
is  difficult  to  estimate  the  size  of  the  stomach.  Nevertheless, 
gastric  dilatation  may  occur  with  a  normal  emptying  time,^^  in 
which  case  the  only  explanation  possible  seems  to  reside  in  a  pri- 
marily lowered  tonus  of  the  fundus  musculature,  while  the  con- 
tractions occurring  during  digestion  remain  of  normal  strength. 
This  condition  is  known  as  gastric  atony. 

Finally,  gastric  fermentation  may  cause  a  dila- 
tation of  the  stomach.  Fermentation  is,  of  course,  a  com- 
mon sequel  to  dilatation,  yet  in  some  instances  it  is  primary.  In 
Naunyn's  cases,®^  dilatation  and  disturbances  of  gastric  motility 
resulted  from  the  introduction  of  large  numbers  of  micro-organ- 
isms, together  with  easily  decomposable  food ;  and  the  dilatation 
disappeared  as  soon  as  the  gastric  contents  were  removed.  The 
abnormal  fermentation  gives  rise  to  large  amounts  of  gas,  which 
would,  undoubtedly,  interfere  with  the  movements  of  the  stomach. 
Possibly,  also,  the  acid  products  of  fermentation  lead  to  a  reflex 
spasm  of  the  pylorus,  comparable  to  that  occurring  with  a  hyper- 
secretion of  hydrochloric  acid. 

Effects  of  Motor  Insufficiency. — The  results  of  a  motor  insuffi- 
ciency of  the  stomach  may  be  very  serious.  In  the  first  place, 
if  the  obstruction  at  the  pylorus  is  nearly  complete,  the  patient 
will  die  from  lack  of  nourishment  unless  a  communi- 
cation be  established  by  operative  means  between  the  stomach 
and  the  intestines.  If  the  obstruction  is  incomplete,  but  sufficient 
to  cause  considerable  stagnation,  favorable  conditions  are  present 
for  the  growth  of  micro-organisms,  and  the  development  of 
various  abnormal  decompositions.  The  presence  or 
absence  of  free  hydrochloric  acid  in  the  stagnated  contents  is 
an  important  factor  in  determining  which  micro-organisms  shall 
develop  and  what  shall  be  the  character  of  the  abnormal  decom- 
positions. As  a  rule,  an  atonic  stomach  absorbs  material  poorly, 
and  the  retention  of  digestive  products  (albumoses, 
etc.)  in  the  gastric  contents  will  interfere,  to  a  certain  extent,  with 
the  further  progress  of  digestion.  Possibly,  also,  abnormal  quan- 
tities of  true  peptones  are  formed  when  the  food  remains 
in  the  stomach,  and  these  cause  a  direct  irritation  of  the  gastric 
mucous  membrane.     Lastly,  decomposed  material  and 


DIGESTION  255 

large  numbers  of  bacteria  are  passed  on  into  the 
intestines,  where  they  may  irritate  the  more  delicate  mem- 
brane and  initiate  further  abnormal  decompositions. 

Very  remarkable  nervous  symptoms  sometimes  develop  as  a 
result  of  gastric  dilatation.^^  Of  these  we  may  name  the  fully 
developed  and  rudimentary  forms  of  tetany,  epileptiform  con- 
vulsions, tonic  muscular  contractions  resembling  tetanus,  and, 
finally,  symptoms  of  general  depression  and  collapse.  These 
symptoms  usually  occur  in  cases  in  which  dilatation  is  associated 
with  a  hyperacid  secretion,  but  the  latter  is  not  absolutely  neces- 
sary. The  cause  or  causes  of  these  nervous  symp- 
toms are  not  well  understood.  One  is  tempted  to  assume  that 
toxic  substances  are  formed  in  the  abnormal  fermentations,  and 
that  these  produce  the  symptoms  by  their  action  upon  the  nervous 
system.  Indeed,  French  observers  have  prepared  extracts  from 
the  stomach  contents  and  have  shown  that  they  may  give  rise 
in  animals  to  somewhat  similar  nervous  disturbances.  Yet  these 
experiments  need  careful  confirmation  before  much  weight  is  to 
be  attached  to  them.  In  some  patients,  no  such  poisons  could  be 
found;  and  Fleiner  is  of  the  opinion  that  mechanical  causes,  such 
as  an  overfilling  of  the  stomach  with  a  stretching  of  its  parts,  or 
perhaps  the  loss  of  fluids  from  the  body,  may  play  a  more  important 
role  in  the  production  of  these  symptoms. 

Belching  and  Vomiting. — In  addition  to  the  normal  move- 
ments of  the  stomach,  others  rriay  occur  which  tend  to  empty  its 
contents  in  the  direction  of  the  oesophagus.  Waves  of  anti- 
peristalsis  have  been  directly  observed  in  cases  of  gastric 
dilatation.  (With  the  adaptation  of  the  X-ray  to  gastric  pathol- 
ogy, antiperistalsis  has  assumed  an  important  place  in  the  diag- 
nosis of  pyloric  stenosis.®^ — Ed.) 

By  belching,  we  understand  an  expulsion  of  gas  from 
the  digestive  tract  through  the  mouth.  Air  in  the  oesophagus  is 
easily  expelled,  for  a  powerful  inspiratory  movement  with  a  closed 
epiglottis  will  draw  air  into  the  oesophagus  which  may  afterwards 
be  expelled  during  expiration.  The  gases  may,  however,  come 
from  the  stomach,  and  they  then  consist  either  of  air  which  has 
been  swallowed,  or  of  gases  which  have  arisen  from  abnormal 
fermentations,  vis.,  carbon  dioxide,  hydrogen  and  methane.  The 
gas  frequently  carries  with  it  small  amounts  of  liquid  into  the 
throat;  and  if  this  contains  fatty  acids,  as  it  frequently  does  in 


^6  THE  BASIS  OF  SYMPTOMS 

gastric  fermentation,  it  gives  rise  to  the  burning  sensation  known 
as  pyrosis.  Hydrochloric  acid  itself  may  also  be  carried  up 
and  likewise  produce  unpleasant  acid  sensations. 

The  combination  of  movements  by  which  the  gas  is  expelled 
consists,  on  the  one  hand,  of  a  relaxation  of  the  sphincter  at  the 
cardiac  end  of  the  stomach,  and,  on  the  other,  of  a  contraction 
of  the  abdominal  muscles  and  diaphragm,  whereby  the  intra- 
abdominal pressure  is  increased.  Possibly,  in  some  cases,  the 
stomach  also  assists  by  contracting  upon  its  contents.  This  com- 
plicated mechanism  is  most  frequently  set  in  motion  by  reflexes 
from  the  stomach  or  peritoneum. 

In  certain  cases  the  same  movements  take  the  form  of  a  clonic 
spasm,  and  this  produces  the  condition  known  as  hiccough- 
ing. Hiccoughing  is  also  incited  by  reflexes  from  the  stomach 
and  peritoneum,  but  it  may  furthermore  arise  from  causes  situated 
in  the  central  nervous  system,  as  is  the  case  in  the  hiccoughing 
of  hysteria  and  of  severe  lesions  of  the  medulla. 

Vomiting^®  is  produced  by  a  series  of  movements  of  the 
respiratory,  abdominal  and  gastric  muscles,  which  follow  each 
other  in  a  certain  definite  sequence,  and  which  culminate  in  the 
expulsion  of  the  contents  of  the  stomach  through  the  mouth. 
Vomiting  is  initiated  by  a  deep  inspiration,  followed  by  a  spas- 
modic contraction  of  the  abdominal  expiratory  muscles,  during 
which  the  glottis  is  closed  and  the  diaphragm  is  held  in  a  low 
position.  The  pyloric  orifice  is  tightly  contracted,  the  cardia  is 
relaxed,  and  the  stomach  itself,  though  usually  relaxed,  may  pos- 
sibly perform  antiperistaltic  movements.  During  the  primary 
deep  inspiration  some  of  the  gastric  contents  are  probably  aspir- 
ated into  the  oesophagus,  for  the  circular  muscles  of  this  tube  are 
relaxed  and  its  longitudinal  muscles  are  contracted.  When, 
finally,  the  abdominal  muscles  contract,  the  intra-abdominal  pres- 
sure is  greatly  raised,  and  the  contents  of  the  stomach  and  of  the 
oesophagus  are  expelled  through  the  mouth. 

This  complicated  mechanism  is  governed  by  a  special  centre 
in  the  medulla,  situated  not  far  from  the  respiratory  centre.  The 
"vomiting  centre"  may  be  acted  upon  directly  by 
intracranial  diseases  and  by  poisons,  or  it  may  be 
stimulated  reflexly  through  the  vagus  fibres  from 
the  stomach,  especially  from  the  terminations  of  those  which 
supply  the  neighborhood  of  the  cardiac  orifice.     Vomiting  may 


DIGESTION  «57 

also  be  caused  by  reflexes  from  other  organs,  espe- 
cially from  the  peritoneum,  uterus,  etc. 

The  act  of  vomiting  not  only  affects  the  stomach,  but  also 
to  a  marked  degree  the  general  blood-pressure  and  the  intra- 
thoracic pressure.  Traube  has  shown  that  at  the  beginning  of 
the  act  the  blood-pressure  falls,  and  that  the  slow  pulse  is  due 
to  a  vagus  stimulation.  Toward  the  end  of  the  act  both  the 
blood-pressure  and  the  pulse-rate  are  greatly  increased.  The  sali- 
vation and  the  sweating  which  occur  at  the  beginning  of  vomiting 
demonstrate  how  wide-spread  are  the  changes  incident  to  this  act. 

Sensations  Arising  from  the  Stomach. — A  healthy  man  is  not 
conscious  of  his  stomach  except  when  he  is  hungry  or  when  the 
organ  is  overfilled.  The  sensation  of  hunger^^  is  undoubt- 
edly dependent  to  a  great  extent  upon  the  condition  of  the  stomach, 
though  we  do  not  know  the  exact  changes  which  give  rise  to  this 
sensation.  It  seems  probable  that  the  intestines  also  influence 
the  sense  of  hunger,  for  patients  with  intestinal  fistulse  have  been 
observed  whose  hunger  was  not  fully  satisfied  when  food  was 
put  into  the  stomach,  but  was  appeased  if  food  material  was 
also  introduced  into  the  intestines.  The  mental  condition  likewise 
influences  the  sensation  of  hunger,  as  is  well  known.  To  what 
extent  the  needs  of  the  body  for  new  material  influence  the  sensa- 
tion is  still  uncertain;  yet  these  needs  do  seem  to  exprt  some 
influence,  and  the  hunger  of  diabetes  as  well  as  that  following 
muscular  exertion  seem  to  be  examples  of  "  tissue  hunger."  Of 
all  these  various  factors  that  may  influence  hunger  the  condition 
of  the  stomach  is  the  most  important. 

(Certain  observers,  Howell®^  among  others,  believe  that  no 
appreciable  distinction  can  be  made  between  hunger  and 
appetite.  Others,  however,  draw  a  sharp  line  between  the 
two,  defining  hunger  as  the  primitive,  uneducated  call  for  food, 
and  appetite  as  the  desire  for  food  based  upon  previous  pleasurable 
experience.  According  to  Pawlow,^^  they  differ  also  in  their 
effect  upon  the  secretion  of  gastric  juice,  hunger  inhibiting  the 
flow  and  appetite  increasing  it. 

It  is  generally  agreed  that  hunger  is  the  psychic  counterpart 
of  a  physical  phenomenon  evidenced  by  the  so-called  hun- 
ger contraction  waves  of  the  stomach.  Boldyreff, 
who  first  recorded  these  in  dogs,  and  Cannon  and  Washburn, 
who  observed  them  in  man,  have  described  them  as  of  periodic 
17 


258  THE  BASIS  OF  SYMPTOMS 

occurrence  with  intervals  of  complete  quiescence.  C  a  r  1  s  o  n  7** 
on  the  contrary,  believes  that  the  stomach  is  never 
quiet  and  that  the  small,  continuously  occurring  contractions 
increase  in  size  and  even  become  tetanic  when  the  hunger  state 
begins.  These  contractions  may  be  recorded  graphically  by  means 
of  appropriate  apparatus  in  individuals  with  gastric  fistulse,  and 
in  normal  individuals  during  a  period  of  fasting  (Carlson) . — Ed.) 

Abnormally  increased  hunger  is  sometimes  seen 
in  patients  with  gastric  ulcer  or  in  those  with  hyperacidity,  espe- 
cially when  there  is  an  accompanying  hypermotility  of  the 
stomach. 

As  a  rule,  however,  gastric  disturbances  diminish  the  sensation 
of  hunger,  and  the  patient  then  has  less  inclination  to  take  food 
(loss  of  appetite).  Diminished  hunger  and  loss  of  appetite 
are  not  precisely  synonymous,  for  a  person  may  say  that  he  is 
hungry,  and  yet  he  will  not  eat,  because  he  "  has  no  appetite  "  for 
the  food  set  before  him.  Loss  of  appetite  accompanies  many 
disturbances  both  of  the  gastric  secretion  and  of  gastric  motility, 
btit  its  exact  cause  is  not  known. 

The  sensations  of  fulness  and  pressure,  which  the 
healthy  person  experiences  only  after  a  full  meal,  become  patho- 
logical if  they  are  present  when  the  stomach  is  not  much  distended. 
These  sensations  are  produced  more  readily  when  the  distention 
takes  place  rapidly  than  when  it  occurs  gradually.  This  would 
seem  to  indicate  that  an  increased  tension  of  the  stomach  wall 
is  an  important  factor  in  their  production. 

Gastric  pain  is  frequently  due  to  ulcerations  of  the 
wall  of  the  stomach,  whether  these  be  rotmd  ulcers  or  are  pro- 
duced by  carcinomata  or  by  the  action  of  corrosive  poisons.  It 
seems  very  probable  that  the  pain  in  such  cases  is  caused  by  the 
irritating  action  of  the  acid  gastric  contents  upon  the  exposed  base 
of  the  ulcer.  Indeed,  we  know  the  acid  may  cause  most  intense 
pain,  even  when  there  is  no  ulceration.  In  such  cases  the  pain 
may  possibly  result  from  a  direct  irritation  of  the  terminals  of  the 
sensory  nerves  in  the  stomach  wall ;  yet  it  seems  more  likely  that, 
in  most  cases,  it  is  due  to  a  muscular  spasm,  more  especially  of 
the  pyloric  or  the  cardiac  orifices.  The  sensation  popularly  known 
ascrampsinthestomach  may,  therefore,  in  some  instances 
be  actually  due  to  spasm  of  the  gastric  muscula- 
ture.    As  we  have  said,  such  cramps  are  frequently  caused  by 


DIGESTION  259 

hyperacid  secretions,  or  by  ulcerations.  Gastric  pains  may,  how- 
ever, be  of  a  neuralgic  character;  in  this  category  belong  some 
of  the  conditions  called  cardialgia.  We  are  as  ignorant 
concerning  the  nature  of  these  as  we  are  of  neuralgias  in  general. 
The  terrible  pains  which  accompany  the  gastric  crises  of 
tabes  and  of  other  spinal  affections  are  perhaps  due  to  irrita- 
tive-degenerative processes  in  the  pneumogastric  nerve.  ( In  the 
tabetic  cases,  beneficial  results  have  been  reported  following  the 
severance  of  the  sensory  roots  of  the  seventh  to  tenth  dorsal 
nerves.''^^ — Ed.) 

Disturbances  of  the  stomach  may  lead  to  a  great  variety  of 
symptoms  in  other  parts  of  the  body.  We  have  already  men- 
tioned the  attacks  of  tetany  and  related  symptoms.  There  may 
also  be  various  vasomotor  disorders,  parsesthesias,  neuralgias,  mi- 
graine and  vertigo,  as  well  as  disturbances  in  the  innervation  of 
the  heart  (irregular  action)  and  of  the  lungs  (cough).  Some  of 
these  symptoms  are  of  a  reflex  nature;  others  are  probably  due 
to  poisons  absorbed  from  the  stomach.  The  investigation  of  this 
latter  class  of  cases  promises  interesting  results  in  the  future. 

(Another  type  of  painful  sensation  that  may  properly  be 
spoken  of  here  is  that  called  abdominal  angina, "^^  analo- 
gous, etiologically,  to  angina  pectoris  and  to  intermittent  claudi- 
cation. In  this  condition,  the  abdominal  aorta  and  its  branches 
are  the  seat  of  sclerosis,  added  to  which  there  is  usually  the  factor 
of  vascular  spasm.  In  addition  to  severe  abdominal  pain,  these 
cases  exhibit  sudden  and  marked  tympanites,  constipation  and 
sometimes  renal  disorders. — Ed.) 

It  is  especially  characteristic  of  the  stomach  that  disturbances 
of  its  functions  are  combined  in  the  most  varied  manner,  and  that 
one  disturbance  tends  to  bring  others  in  its  train.  In  certain 
cases  it  is  possible  to  determine  which  of  these  is  primary  and 
which  are  secondary;  in  other  cases,  we  cannot  make  such  a 
separation. 

Functional  disturbances  of  the  stomach  are 
not  accompanied  by  constant  anatomical  changes,  and  the  con- 
dition known  as  gastric  catarrh  is  especially  destitute  of  any  well- 
defined  pathological-anatomical  basis.  The  relation  between  func- 
tional and  anatomical  changes  in  the  stomach  is  not  easily  studied, 
because  so  few  gastric  disorders  are  fatal  and  because  the  stomach 
changes  so  rapidly  after  death.    For  these  reasons  we  know  com- 


260  THE  BASIS  OF  SYMPTOMS 

paratively  little  about  the  relation  between  functional  and  ana- 
tomical changes  in  the  stomach. 

Not  infrequently  patients  complain  of  loss  of  appetite,  nausea 
and  sensations  of  pressure  in  the  abdomen,  and  yet  the  most  care- 
ful investigations  fail  to  reveal  any  secretory  or  motor  changes. 
In  a  certain  proportion  of  these  cases  it  is  possible  that  an 
unusual  sensitiveness  of  the  stomach  exists,  and 
that  if  the  patients  are  careful  in  their  diet  they  are  relieved  of 
the  discomfort.  In  other  cases,  however,  the  symptoms  seem  to 
occur  quite  independently  of  the  quantity  and  quality  of  the 
nourishment,  and  to  depend  rather  upon  the  psychic  state 
of  the  individual.  To  this  class  of  cases  Leube  has  given  the 
name  of  nervous  dyspepsias.  The  frequency  of  the 
latter  increases  as  the  resistance  of  people  to  the  unpleasant  things 
of  life  diminishes.  We  all  know  the  great  influence  the  mind 
exerts  upon  the  digestion,  and  it  is  easy  to  conceive  that  this  in- 
fluence might  be  pathologically  intensified  in  neurotic  individuals. 
Indeed,  secretory  and  possibly  even  motor  functions  of  the  stom- 
ach may  be  thus  affected.  Striimpell  has  termed  such  cases 
psychic  dyspepsias.  Dreyfuss,'^^  who  has  given  this  sub- 
ject especial  attention,  has  found  the  chief  predisposing  conditions 
to  be  an  inherited  or  acquired  neuropathic  disposition,  epilepsy, 
hysteria  and  circular  insanity, 

Disturbances  in  the  Secretion  of  Bile^* 

We  know  little  of  the  variations  which  diseases  cause  in  the 
amount  and  composition  of  the  bile.  Physiological  experiments 
would  seem  to  indicate  that  the  amount  is  diminished  in  all  those 
conditions  in  which  but  little  food  is  taken.  This  diminution 
affects  especially  the  water  and  the  bile  salts ;  but  we  are  less  cer- 
tain as  to  the  effect  of  inanition  upon  the  bile  pigments,  for  con- 
siderable variations  in  these  occur  normally. 

Substances  not  ordinarily  present  may  appear  in  the  bile. 
Thus  when  the  sugar  in  the  blood  exceeds  0.3  per  cent,  it  is  ex- 
creted by  the  liver,  and  the  same  is  true  of  other  substances,  among 
which  the  antiseptics  may  prove  of  practical  significance.  Albu- 
min api>ears  in  the  bile  at  times,  e.g.,  after  the  use  of  alcohol. 
The  secretion  of  pigments  may  be  diminished,  as  happens  in 
some  instances  of  degeneration  of  the  hepatic  cells  during  infec- 
tious diseases.    The  pigment  content  is  high  in  passive  hyperaemia 


DIGESTION  261 

of  the  liver ;  while  in  numerous  conditions  it  undergoes  consider- 
able variations. 

It  is  possible  to  affect  the  composition  of  the  bile  through 
changes  in  the  blood.  When  large  numbers  of  red 
blood-corpuscles  are  destroyed,  the  liberated  pig- 
ment is  taken  up  by  the  various  organs,  especially  by  the  liver 
(p.  1 1 6).  This  directly  influences  the  bile.  Its  quantity  is  at  first 
diminished,  the  formation  of  the  pigments  from  the  haemoglobin 
is  increased,  and  the  bile  salts  are  either  normal  or  are  diminished. 
Not  infrequently  the  oxy haemoglobin  itself  passes  into  the  bile, 
even  long  before  it  appears  in  the  urine. 

The  composition  of  the  bile  is  affected  also  by  certain 
poisons,  among  which  are  toluylendiamin,  arseniuretted  hy- 
drogen and  phosphorus.  The  first  two  destroy  the  red  corpuscles 
of  the  blood,  but  phosphorus  does  not  do  so  in  mammals.  In  the 
earlier  stages  of  intoxications  with  these  compounds,  the  total 
quantity  of  the  bile  is  usually  diminished,  the  pigments  are  in- 
creased, and  the  bile  salts  only  slightly  increased  or  even  consider- 
ably diminished.  Owing  to  an  increase  in  its  content  of  nucleo- 
proteids,  the  bile  becomes  thick  and  viscid.  In  the  later  stages 
of  these  intoxications,  the  bile  increases  in  quantity,  its  composi- 
tion varying  in  different  ways.  These  quantitative  and  qualitative 
changes  are  produced  in  part  by  the  destructive  action  of  certain 
of  these  poisons  upon  the  red  blood-corpuscles.  Yet  this  is  not 
the  only  cause  of  the  biliary  changes.  The  main  factor  seems 
rather  to  be  a  stimulation  of  the  liver  cells  to  the  production  of 
an  abnormal  secretion. 

Gail-Stones. — Gall-stones'^^  usually  originate  in  the  gall-blad- 
der. At  times  only  one  stone  is  found ;  more  frequently,  however, 
several  or  many  are  present.  The  numerous  calculi  so  frequently 
found  in  the  gall-bladder  at  autopsy  are  in  many  instances  all  of 
about  the  same  size.  In  other  cases,  they  occur  in  groups  as,  for 
example,  one  or  two  large,  ten  or  twelve  medium-sized  and  fifty 
or  more  tiny  stones.  Such  have  been  termed  generations  of  gall- 
stones. The  explanation  for  this  grouping  of  stones  seems  to  be 
that  during  some  pathological  process  in  the  past  several  nuclei 
originated,  and  that  when  once  started  the  stones  tended  to  act 
as  centres  about  which  the  bile  constituents  were  deposited.  This 
continued  until  some  change  in  the  conditions  in  the  bladder 
allowed  a  fresh  set  of  stones  to  start. 


262  THE  BASIS  OF  SYMPTOMS 

Gall-stones  are  composed,  for  the  most  part,  of  chol- 
esterin  and  of  the  calcium  salt  of  bilirubin.  Both 
these  substances  usually  enter  into  the  composition  of  the  stone, 
but  some  stones  are  formed  entirely  of  one  or  the  other  of 
them.  Other  materials  which  may  be  present  in  biliary  calculi 
are  calcium  carbonate,  salts  of  the  heavy  metals,  pure  bile  pig- 
ments and  derivatives  of  these  pigments. 

The  calcium  salts  probably  arise,  for  the  most  part,  from  the 
epithelial  cells  of  the  biliary  passages,  their  amount  being  inde- 
pendent of  the  diet.  This  is  true  also  of  the  cholesterin,  which 
is  dissolved  in  the  bile  through  the  agency  of  cholates,  soaps  and 
fats.  These  solvents  may  hold  far  greater  amounts  of  cholesterin 
in  solution  than  ever  occur  in  the  bile. 

Under  certain  conditions,  nevertheless,  bile  preserved 
aseptically  may  spontaneously  precipitate 
cholesterin  crystals.  It  is  possible  that  desquamated 
epithelium  favors  this  process.  There  is  no  difficulty,  therefore, 
in  understanding  how  cholesterin  stones  may  arise  if  conditions, 
such  as  tight-lacing,  pregnancy,  etc.,  are  present,  which  predispose 
to  the  stasis  of  bile.  According  to  Aschoff  the  cholesterin  stone 
showing  radiating  lines  is  the  result  of  a  sterile  breaking  up  of 
bile.  This  concrement  usually  occurs  singly,  grows  slowly  and 
has  an  uneven  surface  corresponding  to  veins  of  crystallization 
of  varying  length.  Its  chemical  structure  speaks  for  a  normal 
bile,  not  for  one  changed  by  inflammatory  processes.  A 1 1 
other  types  of  stone — and  these  comprise  the  majority — 
arise  on  an  infectious  basis. 

The  normal  bile  of  a  healthy  individual  is  generally 
sterile,  despite  the  free  communication  between  the  biliary 
and  intestinal  tracts."^*  This  is  to  be  attributed  to  the  constant 
movement  of  the  bile  which  sweeps  before  it  all  alien  bodies,  even 
micro-organisms  which  have  been  artificially  introduced.^'^  Liga- 
tion of  the  common  duct,  however,  and  the  consequent  bile  stag- 
nation, permit  of  a  ready  growth  of  bacteria.  Indeed,  in  animal 
experiment,  the  mere  ligation  of  the  duct  will  cause  infection  of  the 
bile.  In  this  case,  the  micro-organisms  probably  enter  the  biliary 
tract  from  the  intestines,  despite  the  ligature. 

In  certain  infections,  notably  typhoid  fever  and 
pneumonia,  the  bile  frequently  contains  micro-organisms.'^* 
It  is  probable  that  in  the  case  of  the  colon  bacillus,  infection  has 


DIGESTION  263 

occurred  via  the  bowel ;  while  with  the  typhoid  bacillus,  particu- 
larly, the  source  is  hsematogenous.  French  observers  pointed  out 
many  years  ago  the  frequency  of  cholangitis  and  cholecystitis  as 
sequelae  of  typhoid  and  paratyphoid  infections,  and  to  this  we 
fully  subscribe. 

The  bacterial  infection  produces  an  inflam- 
mation of  the  mucous  membrane  and  a  desqua- 
mation of  its  epithelial  cells.  These  latter  contain 
undissolved  cholesterin.  They  likewise  contain  calcium  salts,  and 
these  probably  react  to  form  the  insoluble  calcium  salt  of  bili- 
rubin. From  this  salt,  as  well  as  from  the  amorphous  cholesterin 
in  the  cells,  the  biliary  calculus  takes  its  origin.  Its  further  growth 
is  carried  on  by  the  deposition  and  recrystallization  of  new  mate- 
rial, especially  of  cholesterin. 

Several  facts  favor  the  view  that  gall-stones  result  from  in- 
fectious catarrhs  of  the  biliary  passages.  Thus,  bacteria  may  be 
recovered  from  the  centres  of  gall-stones,  although  this  is  possible 
only  in  the  minority  of  cases.  Gall-stones  have  also  been  produced 
experimentally  by  causing  biliary  stasis  and  by  infecting  the  bile- 
passages  with  bacteria  of  low  virulence.'''^  As  we  have  already 
stated,  groups  of  stones  in  a  gall-bladder  are  frequently  of  about 
the  same  size  and  presumably  of  the  same  age,  and  it  may  be  in- 
ferred that  they  have  all  originated  at  about  the  same  time  from 
a  common  cause.  Infection  of  the  bile-passages  is  by  no  means  an 
infrequent  event  after  certain  infectious  diseases,  especially  after 
typhoid  fever,  and  it  is  quite  conceivable  that  this  furnished  the 
common  cause  for  the  formation  of  a  number  of  stones,  and  that 
afterwards  the  bacteria  died  out  of  the  bile  and  no  new  stones 
were  formed.  In  other  cases,  typhoid  bacilli  live  for  years  in  the 
gall-bladder  and  pass  thence  at  periods  into  the  intestines,  to  leave 
the  body  along  with  the  faeces.  Here  the  conditions  for  a  con- 
tinued new  formation  of  stones  are  present. 

Cholelithiasis  frequently  produces  no  symptoms;  and 
especially  is  this  so  when  the  calculi  lie  quietly  in  the  gall-bladder 
without  occluding  any  of  the  ducts.  Gall-stones  may,  however, 
give  rise  to  severe  pains,  as  well  as  to  inflammations,  peritoneal 
adhesions,  perforations  and  septic  infections  of  the  liver.  All  of 
these  evil  consequences  are  initiated  by  an  inflammation  of  the 
gall-bladder  containing  the  stones.  Riedel  believes  that  this  in- 
flammation may  be  induced  merely  by  the  presence  of  the  stone, 


264  THE  BASIS  OF  SYMPTOMS 

which  acts  as  a  foreign  body,  but  that  in  some  cases,  at  least,  it  is 
started  by  a  traumatism.  The  cystic  duct  is  then  likely  to  become 
occluded  either  by  the  extension  of  the  inflammation  to  its  mucous 
membrane  or  by  the  lodgement  of  a  stone  within  it.  Hydrops 
of  the  gall-bladder  ensues.  Its  original  contents  of  bile 
become  modified  by  interchange  with  the  lymphatic  fluids.  The 
chelates  early  disappear,  the  pigments  follow  them,  and  finally  a 
clear  fluid  is  left,  which  contains  salts,  cholesterin,  nucleo-albumin 
and  characteristic  proteids.  If  bacteria  are  present  they  may  cause 
suppuration.  The  inflamed  wall  of  the  gall-bladder  may  ulcerate, 
it  may  become  adherent  to  surrounding  structures  or  it  may  per- 
forate. Not  infrequently  the  stone  passes  through  the  cystic  duct 
and  occludes  the  common  duct.  It  may  then  produce  a  variety 
of  inflammatory  processes  in  the  liver,  the  peritoneum,  the  stomach 
and  the  intestines. 

The  stagnation  of  bile  and  the  injury  to  the  walls  of  the 
biliary  passages — ^both  common  results  of  gall-stones — greatly 
favor  the  development  of  secondary  infections,  both  enterogenous 
and  hsematogenous,  via  the  portal  vein.  The  obstruction  caused 
by  the  stones  is  conducive  to  the  multiplication  of  bacteria  which 
have  thus  entered  the  bile,  and  inflammatory  processes  of  all  kinds 
result. 

Carcinoma t a  sometimes  complicate  gall-stones,  and  in 
such  cases  it  is  supposed  that  they  are  caused  by  the  irritation 
of  the  mucous  membrane.  Indeed,  carcinoma  of  the  bile-passages 
arises  almost  exclusively  on  the  basis  of  cholelithiasis. 

Biliary  colic  is  the  most  feared  manifestation  of  gall-stones. 
It  is  characterized  by  attacks  of  violent  pain  in  the  region  of  the 
liver  and  is  usually  accompanied  by  vomiting  and  fever  and  some- 
times by  jaundice.  The  paroxysm  may  last  for  hours  or  days. 
The  colicky  pains  are  caused  by  the  inflammation  and  distention  of 
the  tract  and  by  the  spasmodic  contractions  of  the  muscle  in  the 
gall-bladder  and  ducts.  In  a  certain  number  of  cases  the  attack 
is  precipitated  by  the  passage  of  a  small  stone  from  a  wide  into 
a  narrow  passage,  as  happens  at  the  exit  from  the  gall-bladder,  or 
just  before  the  entrance  into  the  duodenum.  Yet  such  is  not 
always  the  case.  A  gall-bladder  which  contains  large  stones,  and 
which  is  isolated  by  an  old  occlusion  of  its  duct,  is  not  infrequently 
the  seat  of  colic.  Indeed,  colic  may  come  from  a  gall- 
bladder   which    contains    no    stones    and    which    is 


DIGESTION  265 

merely  shrunken  and  surrounded  by  adhesions.  The  immediate 
cause  of  the  paroxysm  of  biHary  colic,  not  only  in  these  excej)- 
tional  cases,  but  possibly  in  all,  is  an  inflammation  of  the  bile- 
passages.  This  may  either  drive  the  stone  into  a  narrower  portion 
of  the  duct,  or  it  may  cause  the  mucous  membrane  to  swell  about 
the  stone,  thus  occluding  the  passage.  The  fever  and  jaundice 
that  so  often  accompany  biliary  colic  will  be  discussed  in  another 
place  (p.  266), 

The  Exclusion  of  Bile  from  the  Intestines. — The  bile  may  be 
excluded  from  the  intestines  by  gall-stones  lodged  in  the 
common  or  hepatic  ducts,  by  tumors  growing  within  them 
or  pressing  upon  them  from  without,  or  finally  by  catarrhal 
inflammations  which  cause  a  swelling  of  the  mucous  mem- 
brane, and  so  occlude  the  narrower  portions  of  the  passages, 
especially  the  exit  of  the  common  duct  at  the  papilla  of  Vater  and 
the  smaller  bile  capillaries  within  the  liver. 

The  effect  of  an  occlusion  of  the  common 
duct  varies  with  the  site  of  the  obstruction.  If  the  latter  be 
seated  high  up,  bile  alone  is  excluded  from  the  intestines ;  whereas, 
if  it  be  at  the  papilla  of  Vater,  the  pancreatic  juice  may  also  in 
part  or  altogether  be  shut  off.  Experiments  upon  dogs  have 
shown  that  when  no  bile  can  enter  the  intestines  the  diges- 
tion and  absorption  of  proteids  and  carbohy- 
drates proceeds  approximately  in  a  normal  manner,  whereas 
the  absorption  of  fats  is  seriously  interfered  with;  only 
about  forty  per  cent,  of  the  fat  taken  in  the  food  being  absorbed, 
as  compared  with  the  normal  of  ninety  per  cent.  Fr.  Muller^^ 
has  shown  that  the  same  relations  hold  good  for  man.  If  bile  be 
excluded  from  the  intestines,  the  absorption  of  carbohydrates  is 
not  affected  and  the  absorption  of  proteids  is  only  slightly  les- 
sened; while,  on  the  other  hand,  from  sixty  to  eighty  per  cent,  of 
the  fat  taken  in  the  food  escapes  absorption  as  compared  with 
the  normal  of  from  seven  to  eleven  per  cent.  The  "clay 
color"  of  the  stools  in  these  cases  is  caused  partly  by 
the  absence  of  bile  pigments  and  partly  by  the  presence  of  ex- 
cessive quantities  of  fat.  It  is  difficult  to  explain  the  cause  of 
this  diminished  absorption  of  fat  on  the  theory  that  the  latter 
is  taken  up  from  the  lumen  of  the  intestines  as  fine  particles.  If, 
however,  we  assume  that  it  is  absorbed  in  a  state  of  solution  after 
having  undergone  hydrolytic  cleavage,®^  then  the  important  role 


266  THE  BASIS  OF  SYMPTOMS 

played  by  the  bile  might  in  part  be  explained  by  the  fact  that 
the  chelates  are  capable  of  holding  large  quantities  of  fatty  acids 
in  solution.®^ 

(Hewlett®^  has  shown  that  the  bile  may  assist  the  digestion 
and  absorption  of  fats  in  other  ways.  In  the  first  place,  the  emulsi- 
fication  of  fats  is  favored  by  the  presence  of  bile;  and  in  the 
second,  the  bile  accelerates  the  fat-splitting  action  of  the  pancreatic 
juice  eightfold  and  even  more.  There  appears,  therefore,  to  be  a 
sufficient  physiological  explanation  for  the  effect  which  follows  an 
exclusion  of  the  bile  from  the  intestines. — Ed.  ) 

Even  though  the  bile  be  excluded  from  the  intestinal  tract, 
it  is  possible  to  maintain  nutrition  by  paying  sufficient  attention 
to  the  diet,  which  should,  under  these  circum- 
stances, consist  mainly  of  proteids  and  carbo- 
hydrates. If  the  food  contains  much  fat,  the  latter  under- 
goes excessive  cleavage  through  the  action  of  the  pancreatic  juice 
and  of  the  intestinal  bacteria.  The  products  of  this  decomposition 
irritate  the  intestinal  mucous  membrane  and  may  lead  to  dis- 
turbances of  its  functions.  For  this  reason  the  administration  of 
fats  to  patients  with  biliary  obstruction  is  not  only  useless  but 
frequently  injurious.  We  are  not  yet  certain  what  effect  the 
absence  of  bile  exerts  upon  the  bacterial  decomposi- 
tions which  normally  take  place  in  the  intestines.  The  putre- 
faction of  proteids^*  has  been  found  to  be  increased  in  some 
instances,  while  in  others  it  has  been  diminished.  It  is  very 
doubtful  if  the  bile  exerts  any  antiseptic  action  upon  the  growth 
of  micro-organisms  in  the  intestines,  for  Strasburger^^  found 
no  increase,  and  even  a  diminution,  in  the  number  of  bacteria 
in  the  faeces  in  cases  of  complete  biliary  obstruction.  Possibly, 
however,  the  absence  of  bile  allows  the  intestinal  decompositions 
to  pursue  an  abnormal  course. 

Jaundice. — If  the  lumen  of  the  common  duct  be  obstructed, 
and  if  the  liver  cells  continue  to  secrete  bile,  the  gall-bladder  and 
the  bile-passages  become  filled  with  the  secretion,  the  pressure 
of  the  bile  within  them  increases,  the  liver  cells  are  forced  apart, 
and  the  bile  is  absorbed  into  the  lymphatic  system  or  directly  into 
the  blood.^*  It  thus  enters  the  general  circulation  and  permeates 
all  the  organs  of  the  body.  The  liver  cells  may,  indeed,  resecrete 
some  of  the  constituents  out  of  the  blood ;  yet  this  has  little  effect, 


DIGESTION  267 

for,  the  passage  into  the  intestines  being  obstructed,  these  con- 
stituents are  again  reabsorbed. 

In  jaundice,  the  bile  pigments  are  deposited  in  various  tissues, 
and  the  skin  assumes  a  color  which  varies  from  a  light  yellow 
to  a  dark  green  or  brown.  Whether  these  different  shades  are 
due  to  a  blending  of  varying  amounts  of  bile  pigments  with  the 
color  of  the  skin,  or  whether  they  arise  from  a  conversion  of 
bilirubin  into  other  pigments,  has  not  been  decided.  The  jaundice 
may  be  visible  within  a  few  hours  after  the  obstruction  has  taken 
place,  though  usually  it  does  not  appear  for  from  one  to  three 
days.  The  retained  bile  pigments  are  excreted  by  the  kidneys 
and  by  the  sweat-glands ;  but  they  do  not,  as  a  rule,  appear  in  the 
tears,  the  saliva  or  the  gastric  juice. 

Of  the  constituents  of  the  bile  which  pass  into  the  lymph  and 
the  blood,  the  bile  salts  are  of  especial  interest  on  account 
of  their  known  toxic  properties.  During  the  first  few  days  of 
jaundice  they  can  frequently  be  detected  in  the  urine,  but  in  the 
later  stages  they  are  usually  absent.  Concerning  the  quantitative 
relations  of  other  constituents  of  the  bile — to  what  extent  they 
are  formed,  to  what  extent  eliminated  in  the  various  secretions, 
and  to  what  degree  destroyed  in  the  body — we  know  but  little. 

Jaundice  may  arise  not  only  from  an  obstruction  to  the  flow 
of  bile  through  the  larger  passages,  but  from  obstructions 
located  in  the  smaller  biliary  capillaries.  These 
produce  the  jaundice  which  may  accompany  various  diseases  of 
the  liver,  such  as  cirrhosis,  carcinoma,  cholangitis  and  calculi  of 
the  finer  ducts.  The  "biliary  thrombi"  described  by 
Eppinger  are  a  fruitful  cause  of  such  obstructions.  The  develop- 
ment of  jaundice  is  dependent  less  upon  the  nature  of  the  disease 
than  upon  its  location,  the  essential  factor  being  an  obstruction  to 
the  exit  of  bile.  The  jaundice  that  so  frequently  accompanies 
gall-stones  may  be  due  to  the  lodgement  of  a  stone  in  the  common 
or  hepatic  ducts,  or  to  an  associated  inflammation  of  the  mucous 
membrane.  According  to  Riedel,  the  latter  is  the  more  common.^^ 
Closure  of  the  cystic  duct  does  not  ordinarily  cause  jaundice. 

The  resorption  of  the  stagnating  bile  is  influenced  not  only 
by  the  degree  of  mechanical  obstruction,  but  also  by  the  consis- 
tency of  the  secretion.  A  thick  viscid  bile,  rich  in  pigments,  may 
be  reabsorbed  even  when  the  obstruction  is  a  comparatively  slight 
one,  such  as  might  be  caused,  for  example,  by  a  catarrh  of  the 


268  THE  BASIS  OF  SYMPTOMS 

bile-passages,  by  a  biliary  thrombus  or  by  the  swelling  of  liver 
cells  which  have  undergone  fatty  degeneration.  The  icterus 
of  phosphorous  and  of  toluy lendiamin  poison- 
ings is  usually  produced  in  this  manner ,^^  as  is  that  which 
may  accompany  snake-bites,  pneumonia,  pyaemia, 
septicaemia  and  various  other  intoxications  and 
infections.  In  none  of  these  can  a  marked  obstruction  to 
the  outflow  of  bile  be  demonstrated.  This  fact  gave  rise  to  the 
theory  that  the  jaundice  in  such  cases  does  not  depend  upon  the 
changes  in  the  liver,  but  upon  the  formation  of  biliary  pigments 
in  other  parts  of  the  body.  It  is,  indeed,  possible  for  bilirubin 
to  be  formed  outside  of  the  liver,  for  this  happens  in  old  blood- 
clots  ;  yet  the  amount  thus  formed  is  very  small  and  never  produces 
jaundice.  Indeed,  we  may  say  that,  so  far  as  we  know,  jaun- 
dice is  always  of  hepatic  origin,  and  that  we  have  no 
proof  that  a  haematogenous  type  can  occur. 

Conditions  are  particularly  favorable  for  the  resorption  of 
bile  when  the  biliary  capillaries  are  narrowed  by  catarrh.  Thrombi 
in  the  bile-passages,  upon  which  Eppinger  has  laid  emphasis,  are 
especially  prone  to  occur  when  the  composition  of  the  bile  is 
altered  by  abnormal  conditions  of  secretion.  Such  an  alteration 
is  frequent ;  indeed,  even  fibrinogen  may  appear  in  the  bile-ducts. 
The  occurrence  of  these  thrombi  may  well  explain,  on  a  mechanical 
basis,  some  of  those  difficult  cases  of  icterus — in  phosphorous 
poisoning,  haemolytic  conditions  and  in  the  infectious  diseases — 
which  give  no  evidence  of  a  gross  obstruction  to  the  flow  of  the 
bile.  It  must  be  admitted,  however,'  that  this  conception  of  a 
mechanical  obstruction  is  in  some  cases  based  upon  purely  hypo- 
thetical considerations.  The  question  here  resolves  itself  into  a 
study  of  the  conditions  under  which  the  liver  cells  might  pour  their 
secretions  directly  into  the  blood  or  lymphatic  systems,  rather  than 
into  the  bile  capillaries.*^  A  better  understanding  of  the  part 
the  parenchyma  cells  play  in  these  processes  would  possibly  throw 
considerable  light  upon  this  vexed  problem. 

The  etiology  of  the  so-called  catarrhal  ictenis  is  but  little 
understood.  The  view  formerly  held  was  that  of  Virchow,  who 
looked  upon  the  duodenal  catarrh  with  an  occlusion  of  the  papilla 
of  Vater  by  a  mucus  plug  as  the  underlying  cause.  But  the 
observation  of  Eppinger  ®° — the  occlusion  of  the  common  duct 
as  a  result  of  the  swelling  of  its  lymphoid  tissues — shows  what 


DIGESTION  269 

variable  factors  may  be  present.  My  clinical  experience  has  led 
me  to  believe  more  and  more  that  this  form  of  jaundice  is  gener- 
ally due  to  changes  in  the  liver  cells,  rather  than  in  the  bile- 
passages,  in  other  words  that  we  have  to  do  with  ahepatitis. 

The  cause  of  icterus  neonatorum  which  occurs  in  about  sixty 
per  cent,  of  all  new-born  children  is  not  well  understood.^^  This 
much  is  certain,  that  it  results  from  the  resorption  of  bile ;  for  not 
only  the  pigments,  but  the  bile  salts  as  well,  are  found  in  the 
various  body  fluids.  It  seems  probable  also  that  icterus  neona- 
torum is  associated  with  a  destruction  of  the  red 
blood-corpuscles,  for  it  is  especially  apt  to  develop  in 
those  infants  who  have  had  the  cord  tied  late  and  who  have  re- 
ceived, therefore,  a  larger  amount  of  blood  from  the  placenta. 
We  know  that  jaundice  frequently  accompanies  an  increased  de- 
struction of  red  blood-corpuscles,  as  happens  in  paroxysmal 
hsemoglobinuria,  but  the  attempts  to  produce  it  experimentally 
by  the  introduction  of  haemoglobin  have  hitherto  failed.  There 
seems,  therefore,  to  be  some  other  factor  present  than  the  mere 
destruction  of  the  erythrocytes.  Possibly,  as  Quincke  believed, 
the  jaundice  of  the  new-born  is  due  to  the  resorption  of 
bile  from  the  intestines.  This  theory  receives  some 
support  from  the  fact  that  for  several  days  after  birth  the  blood 
from  the  intestines  may  not  go  through  the  liver,  but  may  pass 
directly  into  the  general  circulation  from  the  portal  vein  by  way 
of  the  ductus  venosus.  An  infectious  origin  has  also 
been  suggested  (Czerny  and  Keller). 

(Considerable  attention  has  lately  been  devoted  to  another 
form  of  icterus,  the  so-called  hsemolytic  icterus.^ ^  Two  types  are 
recognized,  the  congenital  and  the  acquired.  In  both 
there  is  an  acholuric  jaundice  with  urobilinuria 
and  splenomegaly.  A  striking  feature  of  the  congenital 
type  is  the  evidence  of  a  diminished  resistance  of  the 
erythrocytes  to  hypotonic  salt  solutions;  while  in  the 
acquired  form  the  fragility  of  the  (unwashed)  corpuscles  does 
not  vary  greatly  from  the  normal.  The  blood-picture  of  the 
acquired  type  may  in  some  cases  closely  resemble  that  of  per- 
nicious anaemia.  This  form  of  jaundice  is  of  particular  interest 
in  view  of  the  therapeutic  success,  reported  by  many  observers,^^ 
of  splenectomy. — Ed.) 

Effects  of  Jaundice. — The  obstruction  to  the  flow  of  bile  may 


270  THE  BASIS  OF  SYMPTOMS 

cut  off  this  secretion  from  the  intestines  with  the  results  which 
have  already  been  described  (p.  266).  On  the  other  side,  the 
liver  cells  are  affected.  They  become  compressed  and 
separated ;  and,  though  for  a  time  they  may  continue  to  perform 
their  functions  normally,  nevertheless,  after  a  while,  they  suffer 
both  in  structure  and  in  function.  Areas  of  necrosis  and  inflam- 
mation may  appear.  These  are  due  in  part  to  the  toxic  action  of 
the  bile  itself,  and,  in  part,  to  the  infections  that  are  so  prone 
to  appear  in  stagnating  bile.  It  is  impossible  to  apply  the  experi- 
mental data  upon  this  subject  to  man,  because  the  various  animals 
differ  so  greatly  in  the  effect  produced  by  a  stasis  of  bile  upon 
the  liver. 

It  is  difficult  to  decide  which  constituents  of  the  bile  produce 
each  of  the  varied  general  symptoms  of  jaundice.  The  cholates 
seem  to  be  the  most  toxic  in  their  action,  although  recently  atten- 
tion has  been  directed  to  the  poisonous  properties  of  the  biliary 
pigments.**  The  itching  of  the  skin  so  frequently  pres- 
ent is  apparently  due  to  the  deposit  of  pigment  in  the  skin.  In 
the  early  stages  of  jaundice  the  heart's  action  may  be- 
come slow  and  irregular,  both  in  force  and  frequency,  and  the 
blood-pressure  may  fall  (see  p.  60).  These  symptoms  seem  to 
be  due  to  the  action  of  the  bile  salts,  for  even  small  doses  of 
sodium  cholate  stimulate  the  central  endings  of  the  vag^s  nerve, 
and  larger  doses  act  upon  the  heart  itself.  The  convul- 
sions that  very  rarely  occur  in  the  beginning  of  jaundice  are 
also  possibly  due  to  the  action  of  the  bile  salts,  for  the  injection 
of  very  large  amounts  of  cholates  will  produce  convulsions.  True 
cholate  intoxication  occurs  in  man  only  when  the  obstruction 
to  the  outflow  of  bile  is  complete  or  nearly  so,  and  when  the 
formation  of  these  salts  is  not  materially  interfered  with.  It 
may^  accompany  catarrhal  jaundice,  cholelithiasis  and  carcino- 
matous obstruction.  Yet  the  cholate  symptoms  are  by  no  means 
always  present  in  jaundice,  and  often  they  last  only  a  short  time; 
for  the  quantity  of  bile  salts  in  the  blood  varies  enormously  and 
it  is  usually  small  in  the  later  stages  of  an  obstruction.*^  This 
is  due  apparently  to  the  fact  that  the  hepatic  cells  may  lose  their 
ability  more  or  less  to  produce  the  bile  salts,  as  well  as  to  the 
constant  endeavor  on  the  part  of  the  liver  to  remove  bile  salts 
from  the  blood.  For  these  reasons  there  are  frequently  no  signs 
of  cholate  intoxication  even  when  the  jaundice  is  most  profound. 


DIGESTION  271 

Other  Hepatic  Toxasmias. — At  times  serious  toxic  disturl> 
ances  develop  in  the  later  stages  of  liver  disease,  and  these  may  or 
may  not  be  accompanied  by  jaundice.  The  patient  becomes  stupor- 
ous and  delirious,  and  after  a  few  days  of  high  fever  and  perhaps 
convulsions,  death  usually  closes  the  scene.  The  condition  resem- 
bles the  termination  of  certain  other  metabolic  diseases,  such  as 
the  coma  of  diabetes  and  the  uraemia  of  nephritis.  It  is  very 
improbable  that  these  late  toxic  symptoms  are  in  any  way  caused 
by  a  resorption  of  bile,  for,  in  the  first  place,  the  picture  differs 
from  a  cholate  intoxication  in  the  high  fever  and  in  the  frequency 
of  general  convulsions;  and  in  the  second  place,  diseases  of  the 
liver  may  terminate  in  this  manner  even  though  hardly  any 
jaundice  is  present,  and  even  though,  furthermore,  on  account  of 
the  extensive  destruction  of  hepatic  cells,  it  is  probable  that  only 
very  small  quantities  of  the  bile  salts  are  manufactured. 

A  wide-spread  degeneration  of  the  liver  cells  seems  to  be  the 
underlying  cause  of  these  toxaemias.  The  hepatic  cells  are  known 
to  perform  very  important  metabolic  functions,  such  as  the  storing 
of  carbohydrates,  the  formation  of  urea  out  of  ammonium  salts, 
the  conversion  of  toxic  aromatic  compounds  into  the  comparatively 
harmless  ethereal  sulphates,  and  the  disposal  of  various  other 
poisons  absorbed  from  the  intestines.  It  may,  therefore,  be  easily 
understood  how  seriously  the  metabolism  might  suffer  when  the 
liver  is  thrown  out  of  function.  Possibly  the  above  toxaemias  are 
caused  by  poisonous  compounds  which  would  normally  be  ren- 
dered non-toxic  in  the  liver.  Of  great  interest  in  this  connection 
is  the  fact  that  geese  will  frequently  die  of  convulsions  after 
extirpation  of  the  liver,  if  they  are  fed  on  a  rich  nitrogenous 
diet.®'  The  same  holds  true  for  dogs  if  an  Eck  fistula  between 
the  portal  vein  and  the  inferior  vena  cava  permits  the  blood  to 
flow  from  the  intestines  directly  into  the  general  circulation  with- 
out traversing  the  liver,  under  which  circumstances  the  liver  cells 
gradually  degenerate.  Certain  symptoms  presented  by  these  ani- 
mals would  seem  to  be  due  to  the  action  of  the  carbamic  acid.  If 
ammonium  carbamate  be  injected  into  the  portal  blood  of  normal 
animals,  it  is  converted  into  urea  in  the  liver.  In  animals  from 
which  the  liver  has  been  extirpated  or  thrown  out  of  function  this 
does  not  occur,  and  in  them  the  carbamic  compounds  would  be  free 
to  produce  toxic  symptoms. 

The  toxaemia  associated  with  extensive  hepatic  disease  may 


272  THE  BASIS  OF  SYMPTOMS 

also  possibly  be  due  to  the  formation  of  poisonous  compounds 
from  the  disintegrating  liver  cells.  Finally,  some  of  these  intoxi- 
cations are  undoubtedly  of  infectious  origin,  as  is  probably  the 
case  in  acute  yellow  atrophy  and  in  the  not  infrequent  infections 
of  the  biliary  passages  which  follow  chronic  obstruction. 

Considerable  attention  has  been  given  in  recent  years  to  the 
factors  governing  the  appearance  of  urobilin  (hydrobilirubin) 
and  its  forerunner,  urobilinogen,  in  the  urine  and  in 
the  fseces.^''^  Urobilinogen  is  derived  from  bilirubin  by  the  reduc- 
ing action  of  the  intestinal  flora.  In  man,  urobilinogen  and  urobilin 
are  formed  exclusively — or  at  least  predominantly — in  the  intes- 
tinal tract;  whether  they  may  arise  in  the  liver  also,  as  in  dogs, 
is  not  improbable,  though  not  confirmed.  From  the  intestines, 
hydrobilirubin  passes  into  the  circulation  and  is  excreted  in  part 
by  the  kidneys  as  urobilin.  Normally,  then,  urobilin  and  uro- 
bilinogen occur  in  the  urine,  but  in  negligibly  small  amounts.  The 
greater  part  of  the  urobilin  thus  absorbed  from  the  intestines  is 
returned  to  the  liver,  and  passing  once  more  into  the  bile,  again 
reaches  the  bowel. 

In  many  hepatic  disorders,  this  intermediate  urobilin 
circulation  is  disturbed.  The  urobilin  returning  to  the 
injured  liver  cells  is  no  longer  excreted  by  them  into  the  bile, 
but  is  thrown  into  the  lymph  and  blood  and  is  then  excreted 
by  the  kidneys  in  large  amount.  Urobilinuria  may,  therefore,  be 
regarded  as  the  best  and  most  constant  clinical  index  of  a  dis- 
turbed liver  function.  (Unlike  alimentary  galactosuria,  however, 
it  is  not  significant  of  particular  hepatic  derangements — cirrhoses, 
catarrhal  icterus — ^but  may  occur  in  any  condition  deleteriously 
affecting  the  liver  function,  e.g.,  cirrhosis,  passive  hyperaemia, 
malignancy  and  even  parenchymatous  degeneration  accompanying 
the  acute  infections  ( Bauer ).^® 

It  is  evident  from  what  has  been  said  concerning  the  forma- 
tion and  circulation  of  urobilin,  that  in  complete  closure 
of  the  common  duct,  no  urobilin  can  be  formed 
because  no  bilirubin  reaches  the  bowel.  In  these 
cases,  the  absence  of  the  former  in  the  urine  and  faeces  speaks 
for  a  complete,  as  against  an  incomplete,  occlusion  of  the  duct. 

The  same  is  true  in  practically  every  respect  of  urobilinogen, 
which  is  readily  oxidized  into  urobilin  by  a  brief  exposure  to  light 
and  air  and  is,  therefore,  not  so  accessible  to  study,    In  hepatic 


DIGESTION  278 

insufficiency — when  the  common  duct  is  patent — it  may  be  demon- 
strated in  freshly  voided  urine  by  the  Ehrlich  aldehyde 
reaction  or  by  means  of  the  spectroscope. — Ed.  ) 

The  Pancreatic  Juice 

The  complete  exclusion  of  the  pancreatic  juice  from  the  intes- 
tines without  a  concomitant  exclusion  of  bile  is  extremely  rare, 
for  the  gland  usually  possesses  two  functioning  ducts.^^  A  clos- 
ure of  both  of  these  is  uncommon;  and  a  total  degeneration  of 
the  secreting  glandular  parenchyma  is  likewise  very  exceptional. 
By  far  the  most  frequent  site  of  a  pancreatic  obstruction  is  the 
papilla  of  Vater,  and  here  not  only  the  duct  of  Wirsung,  but 
the  common  bile-duct  would  be  closed.  One  can  never  be  certain 
to  what  extent  the  pancreatic  juice  is  diminished  when  the  duct 
of  Wirsung  alone  is  occluded,  because  the  secretion  still  finds  an 
exit  via  the  duct  of  Santorini. 

For  these  reasons  we  are  insufficiently  acquainted  with  the 
results  of  a  simple  exclusion  of  the  pancreatic  juice 
from  the  intestines.  F.  Miiller ^°^  studied  the  faeces  of 
several  patients  who  had  extensive  pancreatic  degeneration,  and 
found  that  the  absorption  of  carbohydrates  in  the 
digestive  tract  was  not  at  all  affected  by  the  disease,  that  the 
absorption  of  the  proteids  was  only  slightly  affected, 
and  that  the  total  quantity  of  fats  absorbed  was  like- 
wise not  far  from  the  normal.  The  cleavage  of  fats  in 
the  intestines,  however,  was  considerably  diminished;  for, 
of  the  fat  in  the  faeces,  only  forty  per  cent,  was  found  to  be 
split  into  fatty  acids  and  soaps,  as  against  the  normal  of  about 
eighty-four  per  cent.  These  figures  correspond  well  with  those 
obtained  in  animals  with  ligated  ducts.  (Other  observers,  how- 
ever, have  come  to  different  conclusions  both  as  to  amount  of  fat 
absorbed  from  the  intestines  in  pancreatic  disease  and  as  to  the 
extent  of  cleavage.  The  variations  in  observations  relative  to 
cleavage  are  due  probably  to  differences  in  the  type  of  fat  in- 
gested— whether  emulsified  or  not — and  to  individual  differences 
in  the  fat-splitting  jx)wer  of  the  stomach.^^^ — Ed.)  Miiller's 
results,  too,  would  be  more  significant,  had  he  been  able  to  make 
more  extended  observations  on  the  amount  of  fat  utilized,  par- 
ticularly when  larger  amounts  of  fatty  food  were  ingested. 

(A  greater  part  of  the  pancreas  may  be  rendered  functionless, 
18 


274  THE  BASIS  OF  SYMPTOMS 

experimentally,  or  by  such  conditions  as  extensive  cirrhosis,  car- 
cinoma, softening  or  even  by  an  apparently  complete  closure  of 
the  main  excretory  duct  by  stones,  without  the  appearance  of 
digestive  anomalies.  This  is  due  in  all  probability  to  the 
vicarious  action  of  the  succus  entericus,  the 
bile  and  the  gastric  juice,  and  to  the  patency  of 
the  accessory  pancreatic  duct.  But  when  the  loss  of 
function  is  complete,  certain  changes  in  the  faeces  manifest  them- 
selves which  have  a  practical  value  in  diagnosis.  Thus,  char- 
acteristic of  severe  pancreatic  lesions  are  large 
fatty  stools — not  acholic,  however,  as  in  complete  biliary 
obstruction;  further,  the  predominance,  as  a  rule,  of  neutral 
fat  in  these  stools;  the  presence  of  large  amounts  of  undi- 
gested muscle  fibres,  only  about  one-half  of  the  ingested 
proteid  being  utilized ;  the  persistence  of  the  nuclei  in 
muscle  fibres  taken  in  the  food,  the  gastric  juice  not  hav- 
ing the  power  to  digest  nuclei;  and  finally,  the  evidence  of 
putrefaction  and  sometimes  of  f ermentation.^^^ — 
Ed.) 

The  experimental  studies  of  Abelmann  have  demonstrated  the 
serious  impairment  of  absorption  which  follows 
the  extirpation  of  the  pancreas  of  animals. 
About  fifty-six  per  cent,  of  the  ingested  proteids,  twenty  to  forty 
per  cent,  of  the  carbohydrates  and  all  of  the  non-emulsified  fats 
appeared  in  the  faeces.  Of  the  latter,  from  thirty  to  eighty-five 
per  cent,  had  undergone  cleavage  into  fatty  acids  and  soaps.  If 
the  fat  were  introduced  in  the  form  of  a  natural  emulsion,  such 
as  milk,  a  considerably  larger  proportion — about  thirty  to  fifty 
per  cent. — was  absorbed  by  the  intestines.  Other  experimenters 
have  obtained  quite  different  results  ;^®^  in  many  cases  the  fat 
was  not  absorbed  at  all,  and  in  others  up  to  eighty  per  cent,  was 
absorbed.  It  seems  to  me  that  the  results  of  these  experiments 
cannot  be  applied  directly  to  human  pathology,  for  extirpation  of 
the  pancreas  is  attended  with  considerable  shock  to  the  animal 
and  we  have  no  data  as  to  how  the  secretion  of  bile  is  influenced 
by  these  operations.  Furthermore,  the  internal  secretion  of  the 
pancreas  plays  a  significant  part  in  these  processes,  particularly  in 
that  of  fat  absorption.  Possibly  the  entire  resorptive  power  of  the 
intestinal  mucosa  is  regulated  by  this  secretion  ^^^  (see  chap.  VII ) . 

Fat  Necroses. — Attention  must  be  directed  further  to  a  severe 


DIGESTION  275 

picture  which  may  result  from  the  extravasation  of  pancreatic 
juice  into  the  peritoneal  cavity.  This  may  be  due  to  trauma; 
while  in  other  cases  there  is  no  evidence  of  injury,  but  instead  a 
back  flow  of  bile  into  the  duct  of  Wirsung,  such  as  occurs,  for 
example,  when  the  papilla  of  Vater  is  blocked  by  a  stone.  The 
pancreatic  juice  activated  by  the  bile  or  intestinal  secretions  causes 
an  auto-digestion  and  necrosis  of  the  gland,  and  leads  to  a  de- 
struction of  the  fatty  tissue,  not  only  about  the  pancreas,  but 
often  in  the  entire  abdominal  cavity  and  even  in  the  pleural 
cavities.  This  condition  was  first  described  by  Balser^^°  under 
the  name  of  fat  necrosis. 

The  fat  in  the  neighborhood  of  the  pancreas  assumes  a  peculiar 
light,  opaque  appearance  due  to  its  decomposition  into  free  fatty 
acids  and  fatty  acid  salts,  particularly  those  of  calcium. ^°®  These 
necrobiotic  changes  lead  in  turn  to  a  melting  away  of  the  tissue, 
and  to  the  formation  of  abscess-cavities  which  are  filled  with 
necrotic  material. 

'  Fat  necroses  may  be  produced  experiment- 
ally by  plugging  the  pancreatic  arteries,  by  the  injection  of 
oil,  bile  or  intestinal  juice  into  the  pancreatic  ducts,  by  the  intro- 
duction of  activated  trypsin  into  the  ducts,  by  the  implantation  of 
a  normal  pancreas  into  the  abdominal  cavity  of  a  healthy  animal 
and  finally  by  allowing  the  pancreatic  duct  to  pour  its  contents 
into  the  free  abdominal  cavity.  Both  the  necroses  and  fatal  out- 
come in  the  implantation  experiments  may  be  prevented,  however, 
by  a  preliminary  immunization  of  the  animal  with  trypsin.^*'^ 

The  clinical  picture  in  animal  experiments  involves  complex 
factors.  Fischler^^®  showed  the  important  role  of  the  liver  in 
these  particulars.  Animals  with  an  Eck  fistula,  for  example,  are 
extremely  sensitive  to  lesions  of  the  pancreas ;  a  mere  handling  of, 
or  pulling  upon,  the  gland,  which  ordinarily  have  the  effect  of 
producing  only  slight  areas  of  necroses,  and  are  borne  with 
impunity  by  a  healthy  animal,  cause  in  those  with  the  fistula 
a  severe  set  of  disturbances.  A  very  characteristic  central 
necrosis  of  the  liver  lobules  occurs  coincident  with  the  appearance 
of  the  lime  salts  of  the  fatty  acids  in  the  liver  cells.  The  animal 
dies  in  twelve  to  thirty-six  hours  with  severe  nervous  manifes- 
tations. On  the  other  hand,  if  there  has  been  a  previous  immu- 
nization with  trypsin,  these  liver  changes  do  not  appear  and  the 


276  THE  BASIS  OF  SYMPTOMS 

animal  survives.    This  is  further  evidence  of  the  chemical  rela- 
tionship existing  between  the  liver  and  the  pancreas. 

The  clinical  manifestations  are  variously  explained  on  the  basis 
of  an  intoxication  with  trypsin,  with  the  substances  arising  in  the 
necrosis  of  the  pancreas,  with  soaps  and  with  the  split-products 
of  the  ferments  set  free  in  the  process. ^^® 

The  Processes  in  the  Intestines 

The  Effect  of  Poisons  Upon  the  Intestines. — ^The  intestines 
may  be  injured  by  various  substances,  such  as  the  fatty  acids, 
the  metallic  salts,  aromatic  compounds,  etc.  Many  of  these  are 
used  therapeutically,  while  others  may  be  taken  in  the  food.  It 
is  not  easy  to  separate  those  which  are  toxic  from  those  which  are 
not,  for  the  susceptibility  of  different  individuals  varies  enor- 
mously in  this  respect.  Even  such  a  marked  poison  as  arsenious 
acid,  which  in  most  men  causes  a  violent  enteritis,  may  become 
comparatively  harmless  through  habituation ;  and  quantities  may 
then  be  borne  which  would  ordinarily  be  almost  immediately 
fatal. 

Toxic  substances  may  be  elaborated  outside  the  body  by  the 
action  of  bacteria.  These  include  the  so-called  ptomains,^^" 
many  of  which,  such  as  neurin,  mydalein  and  mytilotoxin,  are 
extremely  poisonous.  Since  such  compounds  are  formed  only 
in  the  later  stages  of  putrefaction,  an  intoxication  from  this  source 
is  most  apt  to  follow  the  ingestion  of  decomposed  food.  Specific 
toxins,  formed  by  specific  bacteria,  e.g.,  the  anaerobic  ba- 
cillus botulinus,  may  also  be  introduced  with  the  food. 
Some  of  these  poisonous  substances  injure  the  wall  of  the  intes- 
tines, producing  anatomical  and  functional  disturbances,  while 
others  are  absorbed  and  produce  more  general  symptoms.  It  is 
often  difficult  to  determine  whether  a  certain  intoxication  resulted 
from  poisons  introduced  with  the  food,  or  whether  it  arose  from 
toxins  which  were  produced  within  the  intestines  by  the  abnormal 
action  of  bacteria;  yet  in  some  instances  the  former  is  by  far  the 
more  probable,  for  the  symptoms  appear  almost  immediately  after 
the  ingestion  of  the  decomposed  food.  The  same  is  also  true 
when  the  intoxication  is  caused  by  material  which  has  been  cooked, 
such  as  meat,  fish,  sausage,  oysters  and  eggs,  for  it  is  then  very 
improbable  that  any  living  organisms  other  than  spores  were 
introduced. 


DIGESTION  277 

Abnormal  Bacterial  Processes  within  the  Gastro-Intestinal 
Tract. — Numerous  bacteria  are  regularly  carried  into  the  stomach 
with  the  food.  A  portion  of  these  are  there  destroyed,  some  are 
reduced  in  virulence,  and  a  part  pass  on  but  slightly  injured  into 
the  duodenum.  Of  these,  some  decompose  the  carbohydrates  and 
split  the  fats,  thus  producing  organic  acids,  such  as  acetic,  lactic 
and  succinic  acids,  even  in  the  small  intestines.  In  the  lower 
ileum,  and  especially  in  the  colon,  the  bacterial  decompositions 
normally  become  more  marked,  and  here  the  putrefaction  of  the 
proteids  is  a  normal  process. 

The  number  of  bacteria  in  the  human  intes- 
tines varies  greatly. ^^^  The  dried  faeces  of  a  healthy  man  are 
made  up  of  one-eighth  to  one- fourth,  by  weight,  of  bacteria.  Yet 
the  upper  small  intestines  in  fasting  animals,  at  least,  are  almost 
free  from  micro-organisms,  which  would  seem  to  indicate  that 
they  regulate  their  bacterial  flora  to  a  marked  degree. ^^^ 

Certain  factors  apparently  inhibit  bacterial 
growth  in  the  small  intestines.  As  we  have  seen, 
the  hydrochloric  acid  of  the  stomach  diminishes  the  number  of 
bacteria  present  in  the  food,  and  it  is  probable  that  the  bile  acids, 
the  fatty  acids  produced  by  cleavage  of  the  fats,  and  the  intestinal 
secretions  exert  a  certain  antiseptic  action  in  the  upper  intestines. 
The  living  epithelium  itself  possesses  bactericidal  power ;  while, 
according  to  certain  observers,  the  feebly  bactericidal  succus  en- 
tericus  is  rendered  more  potent,  in  vitro  at  least,  by  the  pancreatic 
juice.  Of  greater  importance,  however,  is  the  rapid  tran- 
sit of  material  through  the  duodenum  and 
ileum,  for  the  few  hours  that  food  remains  there  do  not 
allow  sufficient  time  for  the  bacteria  to  multiply.  Fortunately, 
in  the  large  intestines,  where  the  transit  is  slower  and  where  the 
bacterial  action  is  most  marked,  the  greater  portion  of  nutritive 
material  has  already  been  absorbed,  and  the  bacteria  find  less  to 
decompose. 

Another  protection  against  the  growth  of  strange  bacteria 
in  the  intestines  is  the  inhibitory  action  which  the 
normal  flora  seems  to  exert  upon  the  growth  of 
outsiders. ^^^  For  this  reason,  the  normal  flora  of  the  in- 
testines is  probably  very  useful.  Whether  it  is  absolutely  neces- 
sary or  not,  is  a  question  that  has  received  different,  though  not 
irreconcilable,  answers  from  different  investigators.^^*     Guinea- 


878  THE  BASIS  OF  SYMPTOMS 

pigs  may  be  reared  upon  sterilized  milk ;  whereas  chickens  do  not 
thrive  on  bacteria-free  food — an  observation  which  would  appear 
to  supi>ort  the  view  that  the  presence  of  micro-organisms  in  the 
gastro-intestinal  tract  is  necessary  during  extrafetal  life.  In 
man,  at  least,  the  intestinal  bacteria  are  important  in  the  digestion 
of  cellulose,  upon  which  the  ordinary  enzymes  do  not  act. 

Whatever  the  importance  may  be  of  the  intestinal  flora  in  the 
digestion  and  absorption  of  food,  it  is  probable  that  these  micro- 
organisms are  of  great,  perhaps  vital,  significance  as  protective 
forces  against  the  invasion  of  alien  bacteria.  To  this  we  have 
already  referred  (p.  156). 

The  kind  of  micro-organisms  in  the  intes- 
tines depends  partly  upon  the  food  taken,  and  partly  upon 
the  condition  under  which  the  individual  lives.*  *^  The  intestinal 
contents  of  a  new-born  infant  are  sterile,  but  after  birth  they 
quickly  become  infected,  and  at  the  end  of  the  fourth  day  a  fully 
developed  intestinal  flora  is  present.  The  latter  varies  with  the 
kind  of  food  used — whether  mother's  or  cow's  milk — and  further 
with  each  change  in  the  food  in  later  life.  Upon  this  phenomenon 
are  based  the  attempts  that  have  been  made  to  expel  certain  flora 
from  the  bowel  by  altering  the  diet.**^ 

So  long  as  the  epithelium  remains  intact  and  healthy,  the  body 
is  fairly  well  protected  from  invasion  by  the  bacteria  which  hap- 
pens to  be  present  in  the  intestines.*"  The  epithelial  cells  form 
a  protective  bulkhead,  their  antibacterial  action  being  attributed 
by  some  authors  to  their  content  of  nucleinic  acid  and  its  com- 
binations, substances  which  are  acid  in  reaction  and  will  cause  a 
precipitation  of  proteids.**^  Yet  the  protection  afforded  to  the 
body  by  the  intestinal  mucosa  is  not  an  absolute  one.  Apparently 
the  tubercle  bacillus  may  penetrate  the  intact  mucous  membrane, 
and  slight  lesions  will  certainly  render  the  epithelium  permeable 
to  many  bacteria.**® 

The  soluble  products  of  bacterial  action  frequently  pass 
through  the  normal  mucosa  and  in  so  doing  they  may  possibly 
render  an  important  service  to  the  individual  by  immunizing  him 
against  the  action  of  the  bacteria  from  which  they  are  derived. 
These  toxins,  which  are  of  a  proteid  nature,  may  in  many  cases 
be  digested  in  the  intestines,  just  as  are  other  proteids;  yet  it 
would  appear  that  this  does  not  occur  in  the  intestines  of  in- 


DIGESTION  «70 

f ants.*  ^  Antitoxins  penetrate  the  epithelium  only  when  dissolved 
in  homologous  milk.*^* 

Many  intestinal  diseases,  perhaps  the  majority  of 
them,  are  due  to  abnormal  bacterial  action  within 
the  intestines.  The  bacteria  ordinarily  present  may  in- 
crease in  number  or  in  virulence,  or  bacteria  that  are  not  usually 
present  may  give  rise  to  pathological  changes.  Such  foreign 
micro-organisms  must,  of  course,  be  introduced  from  without; 
thus  it  is  manifestly  impossible,  for  example,  to  acquire  cholera 
at  a  time  when  no  cholera  bacilli  are  about.  Yet  it  is  often 
extremely  difficult  to  be  certain  of  the  absence  of  pathogenic 
germs  in  a  certain  locality,  for  individuals,  not  themselves  ill, 
may  harbor  and  distribute  virulent  bacilli  {e.g.,  from  chronic 
typhoid  infections  of  the  bile-passages  or  urinary  bladder).  The 
mere  introduction  of  pathogenic  bacteria  does  not  necessarily  do 
any  harm;  for  just  as  large  numbers  of  harmless  bacteria  daily 
enter  the  gastro-intestinal  canal  and  there  disappear,  so  may 
pathogenic  organisms  be  destroyed  without  their  producing  any 
ill  effect.  They  succumb  to  the  various  protective  agencies  in 
the  stomach  and  intestines  that  have  already  been  described.  In 
some  cases,  however,  the  bacteria  introduced  are  so  numerous 
or  so  virulent  that  they  cause  the  disease  in  practically  every  indi- 
vidual in  whom  they  enter,  as  is  illustrated  by  the  fact  that  every 
person  who  has  partaken  of  a  particular  dish  may  become  ill. 
Possibly,  aggressin-like  bodies  are  present  in  an  infected  food. 

It  is  often  impossible  to  say  in  what  manner  the  infection 
has  taken  place,  whether  it  is  by  overcoming  the  normal  inhabitants 
of  the  intestines,  or  by  causing  a  lesion  of  the  mucosa,  etc.  Appar- 
ently different  factors  enter  into  consideration  in  different  infec- 
tions. We  know,  for  example,  that  the  cholera  vibrio  is  extremely 
sensitive  to  the  acid  reaction  of  the  gastric  juice;  and  clinical 
experience  has  shown  that  the  disease  is  especially  apt  to  attack 
individuals  who  have  presumably  a  lessened  gastric  acidity,  caused 
either  by  some  slight  digestive  disturbance  or  by  great  fear  of 
contracting  the  disease. 

Intestinal  indigestion  is  apt  to  be  produced 
in  some  individuals  by  certain  articles  of  diet, 
and  it  is  quite  possible  that  these  articles  allow  the  bacteria  nor- 
mally present  in  the  intestines  to  proliferate  with  abnormal  rapid- 
ity, or  that  they  reduce  the  resistance  which  the  flora  of  the  intes- 


280  THE  BASIS  OF  SYMPTOMS 

tines  normally  exerts  against  foreign  invaders.  In  some  cases, 
however,  they  cause  the  indigestion  by  directly  influencing  the 
secretions  poured  into  the  intestinal  canal.  The  first  of  these 
possibilities  seems  to  be  exemplified  in  the  case  of  infants,  for 
in  them  some  very  slight  qualitative  or  quantitative  change  in  the 
food  may  induce  a  dangerous  proliferation  of  bacteria,  quite 
independently  of  the  bacterial  contents  of  the  food  ingested. 

The  evidence  would  indicate  that  this  applies  also  to  adults. ^^^ 
A  severe  colitis,  for  example,  may  be  caused  to  disappear  by  the 
giving  of  proteids  in  place  of  carbohydrates.  In  my  opinion, 
abnormal  bacterial  activity  occupies  the  foreground  even  in  diges- 
tive disturbances  produced  by  errors  of  diet. 

On  the  other  hand,  the  abnormal  bacterial  growth  may  follow 
changes  in  the  secretory  or  motor  functions  of  the  intestines.  The 
normal  emptying  of  the  faeces  is  one  of  the  most  important  means 
by  which  abnormal  bacterial  growths  are  limited;  and  changes  in 
the  secretions  are  perhaps  of  equal  importance. 

How  frequently  the  normal  inhabitants  of  the  intestinal  tract 
produce  disease  has  not  yet  been  fully  determined.  It  is  certain 
that  they  may  give  rise  to  a  peritonitis  when  the  bowel  ruptures 
or  when  its  wall  becomes  abnormally  permeable,  as  happens  in 
strangulation.  Local  infections  may  take  place  when  the  intes- 
tinal wall  is  injured,  and  this  is  the  probable  cause  of  many  cases 
of  colon  bacillus  cystitis.  Beyond  this  we  know  little  about  such 
enterogenous  auto-infections.  (Generalized  infections  with  the 
colon  bacillus  have,  however,  been  frequently  demonstrated  by 
blood-cultures. — Ed.)  Possibly  some  of  the  infantile  diarrhoeas 
are  caused  by  a  change  in  virulence  in  the  normal  intestinal  flora. 

(The  factors  concerned  in  the  causation  of  infantile  diarrhcEas 
seem  to  be  considerably  more  complex  than  was  at  first  supposed, 
and  have  recently  received  a  great  deal  of  attention.  A  dysentery 
bacillus  similar  in  many  ways  to  the  Shiga  organism  has  been  iso- 
lated in  a  large  number  of  cases.^^^  In  others,  the  colon  bacillus, 
the  bacterium  lactis  aerogenes  and  the  ordinary  pyogenic  cocci 
seem  to  have  played  a  prominent  part,  either  alone  or  associated 
with  the  dysentery  bacillus.  It  is  possible  that  the  bacterial  role 
has  been  overestimated  and  that  other  conditions,  such  as  an 
increased  permeability  of  the  intestinal  wall,  allowing  an  aug- 
mented absorption  of  toxic  materials,  bacterial  or  metabolic,  are 
also  of  great  moment.     Such  an  increased  absorptive  tendency, 


DIGESTION  281 

it  would   seem,  may  be  caused  by   the  intense   summer 
heat.i24_ED) 

An  abnormal  growth  of  bacteria  in  the  intes- 
tinesmayharmthebodyinseveralways.  Either  the 
poisons  formed  may  be  absorbed  and  cause  a  general  toxaemia, 
or  they  may  act  directly  upon  the  mucosa  itself  and  so  interfere 
with  its  functions.  Frequently  the  mucosa  undergoes  anatomical 
alterations,  such  as  degenerations  of  the  epithelium,  inflammations 
and  ulcerations.  These  latter  are  important,  for  when  they  occur, 
the  barriers  to  invasion  are  let  down  and  bacteria  may  penetrate 
the  mucosa  and  cause  a  general  infection. 

Various  toxic  compounds  result  from  bacterial  decompositions 
in  the  bowel.  Of  these,  some,  such  as  lactic  acid,  butyric  acid 
and  acetic  acid,  have  already  been  mentioned  in  speaking  of  the 
abnormal  fermentative  processes  in  the  stomach.  These  acids 
are  regularly  produced  in  the  small  intestines;  but  under  patho- 
logical conditions,  the  quantity  so  formed  may  be  enormously 
increased.  They  irritate  the  intestines,  increase  the  peristaltic 
movements  and  may  cause  lesions  of  the  epithelium.  This  is 
particularly  the  case  in  infants  because  of  the  greater  suscepti- 
bility to  injury  of  their  intestinal  lining.  Gases,  such  as  hydro- 
gen, carbon  dioxide  and  methane,  likewise  may  be  produced  in 
excessive  quantity  and  cause  tympanites  and  intestinal  colic. 

An  excessive  proteid  decomposition  in  the 
intestines  gives  rise  to  all  the  various  products  of  putrefaction, 
among  them  indol,  skatol,  phenol  and  other  compounds  belonging 
to  the  aromatic  series  of  compounds.  Many  of  these 
are  rendered  non-toxic  after  absorption,  through  combination 
with  sulphuric  acid,  glycocoll,  glycuronic  acid,  etc.  These  com- 
binations apparently  take  place  in  the  liver, ^^^  and  the  com- 
pounds thus  produced  are  excreted  by  the  kidneys.  These  aro- 
matic bodies  are  normally  formed  almost  exclusively  in  the  large 
intestines.  Their  amount  depends  upon  a  variety  of  factors, 
of  which  the  most  important  are  the  quantity  of  material  in  the 
chyme  that  can  undergo  putrefaction,  the  amount  of  substances 
present  which  will  exert  an  antiseptic  action,  the  varieties  of 
bacteria  present  and  the  rapidity  with  which  the  material  passes 
through  the  intestines. 

(Our  best  index  of  the  amount  of  putrefaction 
which  is  taking  place  in  the  intestines  is  the  quantitative  deter- 


282  THE  BASIS  OF  SYMPTOMS 

mination  of  the  ethereal  or  aromatic  sulphates  in 
the  urine; ^^®  for,  as  has  been  said,  the  aromatic  products 
of  putrefaction  are  largely  eliminated  as  such  sulphates,  when 
once  they  have  been  absorbed  from  the  intestines;  while  the 
quantity  of  these  substances  arising  in  the  metabolic  processes  is 
negligible.  An  increased  output  of  these  bodies  in  the  urine  speaks 
particularly  for  intestinal  stasis.  Ordinary  constipation  is  often 
associated  with  a  more  or  less  marked  increase,  and  intestinal 
obstruction  is  regularly  associated  with  the  elimination  of  large 
quantities  of  ethereal  sulphates  in  the  urine. 

We  do  not  know  how  serious  the  absorption  of  these  aromatic 
bodies  from  the  intestines  is.  Indol,  when  administered  by  mouth, 
is  only  moderately  toxic,  and  individuals  vary  considerably  in  their 
susceptibility  to  its  action.  Small  doses  are  liable  to  produce 
frontal  headaches  and  a  condition  of  nervous  irritability  and  rest- 
lessness ;  larger  doses  may  cause  diarrhoea,  or  marked  irritability, 
insomnia  and  mental  restlessness.  The  continued  administration 
of  enough  indol  to  cause  a  constant  and  decided  reaction 
for  indican  in  the  urine  is  capable  of  inducing  neuras- 
thenic symptoms.  It  is  very  probable,  therefore,  that  the 
neurasthenia  which  is  so  often  seen  in  cases  of  chronic  intestinal 
indigestion  is  in  part  due  to  the  absorption  of  the  aromatic 
products  of  putrefaction. — Ed.) 

It  is  also  possible  that  the  nephritis  which  so  frequently  follows 
intestinal  obstruction  is  caused  by  the  products  of  intestinal 
decomposition.  ^^'^ 

Many  disturbances  in  the  function  of  the  intestines  have 
been  ascribed  to  the  action  of  protozoa,  though  their  etiological 
relationship  has  been  well  established  for  only  one  disease — en- 
demic dysentery.^^^  The  virulence  of  the  ameba  of  dysentery 
for  cats  leaves  us  in  no  doubt  as  to  its  pathogenicity.  Yet  not 
all  cases  clinically  classified  as  dysentery  are  due  to  the  action  of 
this  amoeba. 

The  Pathology  of  Absorption. — ^Absorption  takes  place 
throughout  the  small  intestines,  being  more  rapid  for  organic 
substances  at  least,  in  the  upper  than  in  the  lower  portion.  Ac- 
cording to  the  most  trustworthy  observations,  but  little  nutritive 
material  is  absorbed  by  the  large  intestines. 

The  manner  in  which  many  diseases  of  the  intestines  affect 
the  absorption  of  food  is  not  fully  known.     Those  circulatory 


DIGESTION  283 

disturbances  that  produce  a  slower  blood-current  lead  to  a  diminu- 
tion in  the  absorption  of  fats,  but  do  not  affect  that  of  sugars 
and  proteids.^^^  Fat  absorption  is  also  reduced  whenever 
the  lymphatic  vessels  that  drain  the  intestines  are  obstructed,  as 
may  happen  in  tuberculosis  of  the  mesenteric  lymph-nodes.  The 
diseases  that  affect  the  intestines  only  in  isolated  areas,  such 
as  typhoid  fever,  have  almost  no  influence  upon  absorption.  On 
the  other  hand,  wide-spread  diffuse  diseases  of  the  mucosa,  such 
as  enteritis  and  amyloid  degeneration,  as  well  as  caseation  of  the 
mesenteric  lymphatic  nodes,  will  diminish  the  fat  absorption  if 
they  are  moderately  severe,  and  will  reduce  the  absorption  of  all 
kinds  of  food  if  they  are  very  severe.  This  loss  of  material  is 
caused  partly  by  the  changes  in  the  mucosa  itself  and  partly  by 
the  rapid  passage  of  the  food  through  the  intestinal  tract,  though 
diarrhoea  alone  does  not  necessarily  diminish  absorption.  ^^®  On 
the  whole,  our  knowledge  of  this  important  field  is  extremely 
limited,  particularly  with  respect  to  disturbances  of  absorption  in 
the  individual  intestinal,  and  also  systemic,  disorders.  In  tuber- 
culosis, without  bowel  involvement,  Plesch^^^  has  found  that  the 
absorption  of  all  types  of  food  material  is  reduced  by  one-half. 

In  the  healthy  individual,  the  greater  part  of  the  water  in 
the  food  is  absorbed  in  the  upper  small  intestines.^^^  If  the 
amount  of  water  in  the  intestinal  contents  be  increased,  this  may 
arise,  first,  from  a  diminished  absorption  of  water  from  the  food, 
due  either  to  the  presence  of  salts  or  other  bodies  which  raise  the 
osmotic  tension  of  the  intestinal  contents,  or  to  a  too  rapid  passage 
of  the  chyme  through  the  intestines.  A  rapid  transit  of  material 
through  the  large  intestines  always  diminishes  the  absorption  of 
water.  Drinking  large  amounts,  on  the  other  hand,  frequently  has 
no  effect  upon  the  faeces. 

In  the  second  place,  an  increase  in  the  amount  of 
water  in  the  faeces  may  result  from  excessive  secretion. 
We  know  that  the  stomach  secretes  water  readily,  and  there  is 
abundant  reason  to  believe  that  the  intestines  may  likewise  furnish 
large  quantities  of  fluid  to  their  contents,  either  by  the  process 
of  transudation  or  by  that  of  secretion.  The  most  remarkable 
example  of  watery  faeces  is  furnished  by  the  "rice-water" 
stools  of  Asiatic  cholera.  These  contain  only  a  trace 
of  albumin,  an  amylolytic  enzyme  and  hardly  any  salt  except 
sodium  chlorid.    Their  composition  approaches  that  of  the  nor- 


284  THE  BASIS  OF  SYMPTOMS 

mal  intestinal  secretion,  differing  from  an  ordinary  inflammatory 
exudate  in  the  low  proportion  of  proteids  present  and  in  the 
amylolytic  ferment.^^^  Cohnheim  believed,  therefore,  that  the 
rice-water  stools  of  cholera  were  caused  by  an  increase  in  the 
intestinal  secretions,  rather  than  by  an  inflammatory  exudation. 
Yet  later  researches  have  shown  that  the  essential  pathological 
process  in  cholera  is  an  intense  inflammation  of  the  mucous  mem- 
brane, so  that  the  question  as  to  the  inflammatory  or  secretory 
nature  of  the  fluid  still  remains  unsettled. 

(The  theory  of  MacCallum^^^  that  saline  cathartics 
produce  a  watery  stool  purely  by  their  stimulation  of  the  intes- 
tinal secretions  has  not  been  confirmed  by  the  more  recent  work 
of  Frankl  and  of  Auer,^^^  who  found  that  these  concentrated 
salts  act  principally  by  virtue  of  their  power  to  absorb  and  to 
hold  water,  and  that  their  stimulative  effect  is  of  subordinate 
importance.  They  found  further  that  the  subcutaneous  and  intra- 
venous injections  of  the  salines  do  not  cause  diarrhoea;  in  concen- 
trated solution,  indeed,  they  may  cause  constipation  by  inducing 
diuresis  and  loss  of  water  from  the  blood  and  tissues. — Ed.) 

Disturbances  in  the  Intestinal  Movements. — In  discussing 
this  subject,  it  is  necessary  to  consider  separately  the  small  and 
the  large  intestines,  for  the  peristaltic  movements  in  each  are 
quite  different.  During  a  complete  fast,  rest  prevails  throughout 
the  entire  gastro-enteric  tract,  whereas  digestion  leads  to 
peristaltic  movements  of  the  small  intestines. 
These  consist,  in  the  first  place,  of  progressive  waves  of 
contraction  which  affect  the  circular  muscle 
over  a  limited  area,  and  which  travel  forward,  tending  to 
carry  the  chyme  with  them.  The  second  form  of  movement  is 
produced  by  a  simultaneous  contraction  of  the  cir- 
cular and  longitudinal  fibres,  and  this  results  in  a 
twisting  of  the  intestinal  coils,  which  tends  to  bring  different 
parts  of  the  chyme  into  contact  with  the  mucosa.  (Meltzer  and 
Auer  ^^°  have  described  a  third  movement  of  the  small  intestines 
— the  so-called  peristaltic  rush,  which  consists  of  a  rapid 
peristaltic  contraction,  following  a  relaxation  of  a  considera- 
ble part  of  the  small  bowel — ^which  may  even  pass  uninterruptedly 
from  the  duodenum  to  the  ileocsecal  valve.  Rhythmic 
segmentation  (Cannon)  is  another  type  of  movement  ob- 
served in  the  small  intestines.    In  cats  fed  with  food  containing 


DIGESTION  285 

bismuth,  the  Rontgen  rays  show  a  rhythmic  breaking  up  of  the 
food  column  into  small  segments,  which  are  then  joined  together 
again.  The  process  occurs  at  the  rate  of  thirty  times  a  minute 
in  the  cat.  This  movement  serves  to  mix  the  contents  of  the 
bowel  and  not  to  further  their  progress,  which  depends  rather  upon 
an  associated  peristalsis.  Antiperistalsis,  finally,  may 
be  observed  in  cases  of  obstruction  in  the  small  bowel. — Ed.) 

According  to  Holzknecht,"'^  the  colon  of  the  healthy  in- 
dividual exhibits  rhythmic  propulsive  waves,  which  impel  the 
faeces  onward  for  a  considerable  distance  and  then  cease  for 
several  seconds.  Three  or  four  such  waves  serve  to  drive  the 
faecal  column  through  the  entire  large  bowel.  Other  observers, 
however,  deny  the  existence  of  this  peristaltic  movement.  It 
would  appear,  furthermore,  that  a  kind  of  contraction  ring  is 
situated  half-way  along  the  transverse  colon,  at  which  point  the 
formation  of  the  stool  begins.  Proximal  to  this  ring,  the  chyme 
remains  relatively  motionless;  when  it  tends  to  move  forward, 
it  is  forced  back  into  the  caecum  by  antiperistaltic 
waves.  By  this  means  the  contents  of  the  large  bowel  are 
thoroughly  mixed  and  absorption  is  not  hurried. 

Ziilzer  ^^^  has  described  substances  which  arise  in  the  stomach 
wall  during  the  process  of  digestion,  and  which,  if  injected  into 
rabbits,  cause  a  lively  peristalsis  extending  throughout  the  intes- 
tinal tract.  This  same  body — called  by  him  ''peristaltic 
hormone' ' — occurs  also  in  other  organs,  particularly  in  the 
spleen.  The  physiological  significance  of  this  hormone  in  the 
initiation  of  intestinal  peristalsis  is  not  known ;  practically,  how- 
ever, it  has  proved  of  value  in  the  treatment  of  certain  cases  of 
constipation. 

Diarrhoea. — Defecation  is  a  partly  voluntary,  partly  reflex  act, 
which  is  initiated  by  the  presence  of  more  or  less  faeces  in  the 
rectum.  In  many  individuals  defecation  occurs  regularly  at  the 
same  time  each  day,  while  in  others  it  occurs  very  irregularly. 
In  diarrhoea,  the  large  intestines  fill  rapidly  and  frequently  with 
fluid  contents,  and  their  peristaltic  movements  are  increased. 
Added  to  this  is  an  inhibition  of  the  antiperistaltic  waves  already 
referred  to,  which  normally  tend  to  hold  the  faeces  back  until 
properly  constituted.  The  small  intestines,  however,  may  or  may 
not  be  affected.  The  milder  and  more  transitory  diarrhoeas  usually 
do  not  involve  the  small  intestines,  as  may  be  inferred  from  the 


286  THE  BASIS  OF  SYMPTOMS 

character  of  the  faeces.  On  the  other  hand,  in  many  conditions, 
such  as  typhoid  fever,  the  small  intestines  are  affected  and  the 
stools  contain  undecomposed  biliary  pigments  and  abnormal  quan- 
tities of  unabsorbed  food  material.  This  difference  in  the  be- 
havior of  the  large  and  small  bowel  is  not  well  understood.  It  is 
possible  that  a  given  stimulus  produces  a  lively  peristalsis  in  the 
one  and  has  little  or  no  effect  upon  the  other. 

Nervous  Diarrhoeas. — The  cause  of  the  diarrhoea  may  lie 
outside  of  the  intestines.  In  many  individuals  a  mere  cooling  of 
the  skin  or  a  feeling  of  nervousness  will  produce  diarrhoea  without 
necessarily  disturbing  the  general  health.  A  gradual  transition 
may  be  seen  in  such  cases  from  the  physiological  to  the  patho- 
logical ;  in  the  one,  a  pronounced  stimulus  is  necessary  to  produce 
any  effect,  whereas,  in  the  other,  a  little  excitement  or  even  the 
fear  of  a  diarrhoea  may  be  enough  to  bring  it  on.  Such  individ- 
uals often  show  other  neurasthenic  or  hysterical 
stigmata.  It  seems  probable  that  their  central  nervous  sys- 
tem affects  the  peristalsis  of  the  intestines  through  the  vagus  and 
splanchnic  nerves.  Even  normally,  the  peristaltic  movements 
are  influenced  to  a  certain  extent  by  the  central  nervous  system, 
while  in  these  pathological  conditions  this  influence  is  greatly 
exaggerated.  In  some  of  these  cases,  however,  the  irritability 
of  the  intestines  themselves  may  possibly  be  increased  so  that  they 
respond  excessively  to  normal  stimuli. 

Diarrhoeas  may  also  accompany  anatomical  diseases 
of  the  nervous  system,  as  happens,  for  example,  in  the 
intestinal  crises  of  tabes.  It  is  quite  certain  that  in  these  cases 
the  diarrhoeas  are  dependent  upon  changes  either  in  the  nerves 
or  in  the  central  nervous  system,  yet  definite  proof  of  this  is 
wanting.  The  watery  character  of  the  faeces  in  nervous  diar- 
rhoeas may  be  due,  in  part,  to  the  rapid  transit  of  material  through 
the  intestines,  though  it  seems  probable  that  it  is  more  often 
caused  by  a  nervous  hypersecretion  from  the  intestinal  mucosa, 
a  condition  which  would  find  an  analogy  in  the  well-known  in- 
stances of  nervous  secretion  of  saliva,  gastric  juice  and  urine. 

In  hysterical  girls,  the  small  intestines  are  frequently  the  seat 
of  increased  peristalsis,  often  giving  rise  to  constant  gurgling 
sounds,  without,  however,  causing  diarrhoea.  That  these  peri- 
staltic movements  are  dependent  upon  mental  influences  is  sup- 


\ 


DIGESTION  287 

ported  by  the  fact  that  they  are  most  liable  to  occur  at  the  very 
times  at  which  the  patient  wishes  to  suppress  them. 

When  the  hypersecretion  affects  the  large  intestines,  the  mucus 
and  proteids  in  the  secretion  may  form  tubular  and  membranous 
casts,  which  are  afterwards  passed  in  the  faeces.  This  disease, 
known  as  colica  mucosa  (memfbranous  colitis),  has, 
in  most  instances  at  least,  nothing  whatever  to  do  with  an  in- 
flammation of  the  mucous  membrane,^^^  but  is  a  pure  secretory 
neurosis.  It  usually  occurs  in  nervous  women,  and  may  be  accom- 
panied by  the  most  violent  paroxysms  of  colic.  At  times,  how- 
ever, very  similar  membranous  structures  may  result  from  true 
inflammatory  processes  in  the  intestines,  for  example,  in  con- 
valescence from  typhoid  fever. 

Diarrhoeas  in  General  Diseases. — Intermediate  between  these 
diarrhoeas  of  nervous  origin  and  those  due  to  causes  situated 
within  the  intestines,  is  a  second  group,  viz.,  those  that  accompany 
general  diseases.  Several  possibilities  suggest  themselves  as  to 
the  cause  of  this  class  of  diarrhoeas.  In  the  first  place,  the  general 
disease  may  so  weaken  the  resistance  of  the  intes- 
tinal mucosa  that  the  latter  falls  a  prey  to  the  normal  flora 
of  the  intestines  or  to  bacteria  which  are  introduced  into  the 
gastro-intestinal  canal,  either  by  mouth,  or  by  the  secretions  from 
the  infected  body.  In  the  second  place,  toxins  produced  by 
the  general  disease  may  directly  cause  the  diarrhoea,  just  as  do 
other  poisons.  Some  infectious  diseases,  such  as  pneumonia, 
rarely  cause  diarrhoea ;  whereas  others,  such  as  measles,  frequently 
do  so.    Diarrhoea  not  infrequently  complicates  chronic  nephritis. 

DiarrhcEas  of  Intestinal  Origin. — The  third  and  most  import- 
ant class  of  diarrhoeas  is  that  caused  by  the  excessive  stimulation 
of  the  intestinal  mucosa  by  the  intestinal  contents.  The  materials 
which  act  as  stimulants  are  in  the  first  place  coarse,  hard 
food  remnants,  especially  cellulose,  which  resist  the  action 
of  the  intestinal  secretions  and  bacteria.  In  the  second  place,  and 
more  commonly,  the  peristalsis  is  excited  by  chemical 
irritants,  which  may  either  be  introduced  from  without  or 
be  produced  within  the  intestinal  canal.  Of  these,  we  shall  name 
only  the  organic  acids  and  the  gases  which  result  from  fermen- 
tation.^^^  These  are  of  the  greatest  importance  in  the  production 
of  many  diarrhoeas.  Whether  or  not  water  alone  will  in- 
crease the  peristalsis  has  not  been  definitely  settled.    We  know. 


288  THE  BASIS  OF  SYMPTOMS 

however,  that  diseases  which  interfere  with  the  absorption  of 
water  by  the  small  intestines  may  lead  to  diarrhcea,  as  is  the  case 
with  amyloid  degeneration  of  the  intestines. 

Diarrhoea  is  favored  by  an  increased  irritability  of  the  intes- 
tinal mucous  membrane,  muscle  or  nerves,  for  normal  stimuli 
then  give  rise  to  excessive  responses.  Such  an  increased  irrita- 
bility of  the  intestines  is  probably  present  in  most  acute  inflam- 
mations of  the  mucous  membrane.  In  acute  enteritis, 
for  example,  the  diarrhoea  is  due  to  the  combination  of  two  causes 
— increased  intestinal  irritability  and  increased  stimulation  of  the 
intestines  by  the  products  of  abnormal  fermentations.  In 
chronic  enteritis  there  is  frequently  no  increase  in  the 
irritability  of  the  mucous  membrane.  Even  in  intestinal  ulcera- 
tions, the  irritability  may  not  be  increased,  this  being  especially 
true  of  the  chronic  ulcerations. 

The  effect  of  diarrhoea  upon  the  body  depends 
to  a  great  extent  upon  its  cause.  If  the  food  is  hurried  through 
the  upper  part  of  the  small  intestines,  its  absorption  may  be  seri- 
ously interfered  with  and  the  patient  may  suffer  from  malnu- 
trition. On  the  other  hand,  when  the  diarrhoea  is  due  entirely 
to  an  increased  peristalsis  of  the  large  intestines,  it  is  often  sur- 
prisingly well  borne,  for  the  most  nourishing  part  of  the  food  has 
already  been  absorbed  before  the  large  bowel  was  reached. 

Constipation. — In  constipation,  the  chyme  remains  in  the  large 
intestines  for  an  abnormally  long  time,  and  more  water  is  absorbed 
from  it  than  usual,  with  the  result  that  the  faeces  become  hard 
and  are  passed  less  frequently  than  usual. ^^^  It  is  impossible 
to  draw  any  sharp  line  here  between  what  is  pathological  and  what 
is  physiological.  We  may  say  in  general,  however,  that  infrequent 
defecation  can  only  be  regarded  as  pathological  when  it  gives  rise 
to  symptoms.  Constipation  is  undoubtedly  caused  by  abnormali- 
ties of  the  large  intestines;  yet  it  is  unprofitable  to  speculate  on 
the  exact  nature  of  these  abnormalities  so  long  as  we  do  not  even 
know  why  the  normal  intestines  empty  themselves  so  infrequently. 

Causes  of  Constipation. — In  a  certain  proportion  of  cases  the 
constipation  is  caused  by  improper  food.  We  have  stated 
that  the  material  in  the  bowels  furnishes  the  normal  stimulus  to 
intestinal  peristalsis.  Every  animal  must  take  food  that  furnishes 
the  necessary  amount  of  stimulus.  Thus  an  herbivore  will  die  of 
constipation  if  it  be  totally  deprived  of  the  cellulose  which  nor- 


DIGESTION  289 

mally  excites  its  peristalsis,  and  even  carnivorous  animals  may 
suffer  seriously  from  constipation  if  fed  solely  on  such  easily 
absorbable  material  as  milk,  eggs  and  meat,  A  certain  number 
of  men  place  themselves  on  just  such  a  diet.  Though  their  intes- 
tines possess  a  normal  irritability,  the  stimulus  to  peristalsis  is 
lacking  and  they  suffer  from  constipation.  If  they  take  foods 
which  stimulate  the  intestines  either  by  reason  of  their  coarse, 
indigestible  character,  or  because  of  their  content  of  chemical 
irritants,  such  as  the  organic  acids,  then  the  constipation  is  cured. 
A  lack  of  water  in  the  chyme  may  also  lead  to  constipation. 
This  is  probably  the  cause  of  the  form  which  so  frequently 
accompanies  dilatation  of  the  stomach,  with  hypersecretion  and 
the  vomiting  of  large  quantities  of  fluid. 

In  other  cases  of  constipation,  the  normal  irritabil- 
ity of  the  intestines  is  reduced  more  or  less,  and 
consequently  the  normal  stimuli  are  not  followed  by  the  customary 
response.  This  is  apparently  the  cause  of  the  constipation  which 
sometimes  accompanies  chronic  catarrh  and  atrophy  of  the  mucous 
membrane  of  the  large  intestines. 

It  is  evident  that  no  irritation  will  prove  of  any  value  when 
the  muscular  coat  of  the  intestines  is  greatly  weakened  by  mus- 
cular paralysis  or  atrophy.^^^  Such  a  muscular 
atrophy  may  or  may  not  be  associated  with  atrophy  of  the 
mucous  membrane.  Peritonitis  is  frequently  accompanied  by 
constipation  and  even  by  total  paralysis  of  the  intestines. 

Although  the  ganglia  and  their  nervous  connections  within 
the  intestinal  walls  are  now  believed  to  control  peristalsis,^^^ 
nevertheless  the  exact  effect  of  disease  of  these  structures  is  not 
known.  Degeneration  of  this  nervous  apparatus  has 
been  described  in  cases  of  lead  poisoning  and  of  chronic  consti- 
pation, yet  similar  changes  have  been  observed  in  other  con- 
ditions. 

Constipation  may  be  associated  with  diseases  of  the 
central  nervous  system,  such  as  neurasthenia,  melan- 
cholia and  many  organic  changes.  The  cause  of  this  constipation 
is  not  always  clear.  The  view  that  it  is  due  to  a  spastic  con- 
dition of  the  muscle  of  the  large  bowel  is  scarcely  tenable,  not 
only  because  tonic  contractions  of  smooth  muscle  can  scarcely 
persist  for  months  and  even  years,  but  also  because  the  clinical 
picture  is  quite  different  from  that  of  spastic  constipation. 

19 


£90  THE  BASIS  OF  SYMPTOMS 

Thus  we  see  that  many  causes  may  lead  to  constipation.  Im- 
proper food,  reduced  irritability  of  the  intestines,  weakness  of 
the  intestinal  musculature,  abnormal  nervous  influences — all  may 
act  independently  or  in  combination.  Some  cases  of  constipation 
are  cured  by  exercise,  although  we  do  not  know  how  it  is  effected. 

The  act  of  defecation  is  often  assisted  by  the  con- 
tractions of  the  abdominal  muscles,  although  in  the  perfectly 
healthy  man  this  is  not  necessary,  and  the  peristalsis  of  the  large 
intestines  suffices  to  empty  them.  In  most  cases  of  constipation, 
the  intestinal  peristalsis  is  primarily  at  fault  and  it  is  rare  to 
find  the  rectum  filled  with  unexpelled  faeces.  If  such  be  the  case, 
however,  then  either  the  presence  of  the  faeces  in  this  locality  fails 
to  produce  the  normal  stimulus  to  defecation,  or  the  abdominal 
muscles  do  not  furnish  the  help  which  may  be  necessary  to  expel 
the  accumulated  material. 

.Finally,  there  is  a  form  of  constipation  which  is  due  to  a  tonic 
spasm  of  the  smooth  muscle  of  the  intestine.^**  Such  a  spasm 
may  be  produced  by  the  action  of  lead  and  by  meningitis;  and 
the  condition  may  also  occur  in  association  with  neurasthenia 
and  hypochondriacal  conditions.  In  spastic  constipa- 
tion, certain  |X)rtions  of  the  intestines,  especially  of  the  colon, 
are  firmly  contracted  and  do  not  propel  the  chyme.  Antiperi- 
stalsis  is  possibly  an  additional  factor.^*^  These  contracted  in- 
testines may  sometimes  be  felt  through  the  abdominal  wall  as 
round,  hard,  somewhat  sensitive  cords.  The  spasm  of  the  intes- 
tines frequently  causes  colic,  and  the  faeces  are  often  hard  and 
of  small  calibre,  the  latter  the  result  of  the  spasm. 

Effects  of  Constipation. — The  effects  of  constipation  are  for 
the  most  part  subjective,  and  the  general  nutrition  of  the  patient 
rarely  suffers.  Defecation  is  often  extremely  difficult,  and  the 
worry  about  this  tends  to  upset  the  nervous  equilibrium  of  the 
patient.  Immediately  after  defecation  he  feels  brighter  and  his 
head  feels  freer.  These  sensations  are  partly  suggestive,  as  is 
evidenced  by  the  fact  that  they  are  most  pronounced  in  individuals 
who  worry  most  about  their  condition. 

Yet  they  are  not  entirely  suggestive,  for  leaving  out  of  con- 
sideration the  ill-defined  and  much-abused  application  of  the  term 
auto-intoxication,  we  meet  with  cases  of  constipation  exhibiting 
albumin  and  casts  in  the  urine,  both  of  which  disap- 
pear after  a  thorough  evacuation  of  the  bowels.^**     And  the  same 


DIGESTION  291 

urinary  anomalies  may  appear  in  cases  of  constipation  produced 
by  opium  or  tannalbin.  We  must  not  lose  sight,  therefore,  of  the 
possibility  of  the  absorption  of  toxic  materials. 

Intestinal  Obstruction. — ^Two  degrees  of  intestinal  obstruction 
are  recognized — the  incomplete  and  the  complete. 
Among  the  factors  leading  to  delay  or  complete 
blocking  of  the  progress  of  the  intestinal  con- 
tents are  inflammatory  and  malignant  strictures,  foreign  bod- 
ies, gall-stones,  invagination,  kinks  in  the  bowel,  compression  from 
without  and  strangulation  in  hernial  openings  and  by  fibrous 
bands.  The  view  that  paralysis  of  a  short  portion  of  the  bowel 
may  be  equivalent  to  a  stenosis  is  no  longer  tenable ;  for  the  chyme 
suffers  no  delay  in  passing  through  a  section  of  intestine  made 
inactive  by  a  sarcomatous  infiltration  of  its  walls.  When  stenosis 
does  occur  in  a  paralyzed  loop,  it  is  due  to  a  kinking  in  the  latter, 
the  result  in  turn  of  its  lack  of  tone  and  of  the  torsion  which  it 
undergoes  in  its  overfilled  state.  This  is  a  frequent  mechanism 
in  postoperative  ileus. 

Pocket  s — either  congenital  or  formed  by  inflammatory 
bands — are  of  common  occurrence  in  the  peritoneal  cavity ;  among 
such  are  the  bursa  omentalis  and  those  formed  by  inflammatory 
adhesions  about  the  caecum  and  in  the  pelvis.  Into  these  openings 
slips  a  loop  of  bowel,  not  as  a  result  of  peristaltic  movements,  but 
by  virtue  of  the  combined  action  of  gravity  and  the  contractions 
of  the  abdominal  muscles.  Here  the  loop  may  be  merely  fixed, 
or  incarcerated  by  the  elastic  recoil  of  the  distended  hernial  ring. 
In  external  hernias  this  mechanism  is  especially  well  illustrated. 
In  consequence  of  the  constriction,  there  occurs  a  rapid  venous 
stasis  in  the  affected  loop  of  the  bowel,  followed  by  oedema,  an 
increase  in  volume  of  the  loop,  and  finally,  when  the  hernial  ring 
can  no  longer  accommodate  the  swollen  bowel,  an  obstruction 
to  the  faecal  movement. 

In  cases  in  which  the  stasis  and  oedema  are  less  marked  and 
the  portion  of  intestines  is  firmly  fixed  but  not  incarcerated,  the 
loop  may  increase  in  size  by  another  mechanism,  as  pointed  out 
by  Wilms.^*'^  Here,  peristalsis  impels  the  contents  of  the  her- 
niated bowel  toward  the  hernial  opening,  where  a  further  move- 
ment is  hindered  by  the  greater  or  less  obstruction  existing  at  the 
ring.  As  a  result,  the  impeded  contents  distend  the  bowel  at  this 
point,  the  distention  serving  to  pull  upon  the  g^t  behind  it.    To 


292  THE  BASIS  OF  SYMPTOMS 

this  pulling  is  added  the  tensile  force  of  the  rapidly  accumulating 
contents,  as  incarceration  proceeds  at  the  hernial  ring. 

No  adequate  explanation  has  yet  been  given 
for  the  sudden  obstruction  that  sometimes  de- 
velops in  hernias  which  have  existed  for  a  long 
time  without  producing  symptoms.  Experiments 
on  the  cadaver  have,  indeed,  demonstrated  that  when  the  intes- 
tinal coils  are  overfilled  it  is  difficult  to  empty  them,  for  they  tend 
to  become  kinked,  and  the  mucous  membrane  often  slides  over  the 
muscularis,  so  that  it  lies  in  folds  at  the  neck  of  the  sac.  Yet  these 
exj>eriments  do  not  explain  why,  at  a  particular  time,  the  intestines 
should  become  overfilled;  and,  furthermore,  the  neck  of  the  sac 
may  not  be  especially  narrow  in  these  chronic  cases.  It  seems  to 
me  that  insufficient  attention  has  been  paid  to  the  possibility  that 
there  may  be  a  primary  paralysis  of  the  muscularis  in  these  cases, 
which  would  allow  the  intestinal  contents  to  accumulate  at  one 
spot.  This  hypothesis  may  possibly  serve  to  explain  many  cases 
in  which  no  mechanical  cause  can  be  found  for  the  obstruction. 
The  question  cannot  be  finally  answered,  however,  until  we  possess 
more  evidence  from  clinical  and  experimental  sources. 

If  a  piece  of  intestine  possesses  a  long  mesentery  with  a  short 
attachment  to  the  posterior  abdominal  wall,  as  is  the  case,  for 
example,  with  the  sigmoid  flexure,  it  is  liable  to  become  twisted 
about  its  pedicle,  thus  producing  the  condition  known  as  vol- 
vulus. The  rapid  distention  with  gas  that  follows  the  volvulus 
interferes  with  the  movements  of  the  intestines  and  prevents  them 
from  untwisting,  and  the  lumen  of  the  canal  is  obliterated  at  the 
point  of  twisting. 

Intestinal  obstruction  may  result  finally  if  a  portion  of  the 
intestines  is  carried  downward  toward  the  anus  within  the  portion 
immediately  succeeding  it.  The  cause  of  such  an  intussus- 
ception is  somewhat  obscure.^^*  It  cannot  be  reproduced 
experimentally  by  the  mere  paralysis  of  an  intestinal  loop.  It 
would  appear  rather  as  if  one  portion  of  intestines  drew  itself 
over  another  that  was  tetanically  contracted,  and  that  the  invagina- 
tion increased  by  the  successive  inclusion  of  freshly  contracted 
portions.  A  similar  process  is  frequently  seen  in  the  normal 
intestines,  but  the  invagination  is  then  neither  extensive  nor  per- 
manent. We  do  not  know  what  interferes  with  a  straightening 
out  of  the  canal  in  the  pathological  cases.     When  the  invagination 


DIGESTION  293 

has  once  passed  beyond  a  certain  limit,  the  circulation  of  the 
enclosed  intestines  is  interfered  with,  and  oedema  follows. 

In  all  these  obstructions  the  symptoms  depend 
mainly  upon  the  degree  of  stenosis  and  the  ra- 
pidity with  which  it  develops.  If  the  lumen  of  the 
bowel  is  only  partially  and  gradually  encroached  upon,  the  intes- 
tines lying  immediately  above  the  obstruction  contract  more 
forcibly  than  usual  and  their  muscular  tissue  undergoes  hyper- 
trophy.^*^ The  cause  of  these  increased  contractions  resides 
essentially  in  the  greater  work  demanded  of  the  hyp>ertrophied 
muscles.  A  moderate  stenosis  may  last  for  months  without  giv- 
ing rise  to  any  symptoms  other  than  slight  constipation  whenever 
the  food  is  not  properly  chosen.  When  the  hypertrophy  can  no 
longer  keep  pace  with  the  amount  of  work  demanded,  the  mani- 
festations of  stenosis  appear.  This  occurs  sooner  in  the  large 
than  in  the  small  bowel,  as  is  most  clearly  seen  in  old  age. 

If  the  lumen  of  the  bowel  is  totally  occluded,  the  resulting 
symptoms  are  entirely  different  from  those  of  a  gradual  and  par- 
tial obstruction.  A  total  occlusion  may  develop  acutely,  or  it 
may  come  on  during  the  course  of  a  chronic  obstruction,  owing 
to  the  inability  of  the  muscle  to  force  material  past  the  partial 
stenosis.  In  either  case  the  intestinal  contents  stagnate  above  the 
point  of  obstruction.  The  bacteria  then  multiply  rapidly,  for 
their  growth  is  no  longer  held  in  check  by  the  onward  movement 
of  the  chyme.  The  resulting  decompositions  are  of  various 
kinds,  depending  partly  upon  the  bacteria  present  and  partly  upon 
the  material  subjected  to  their  action.  When  the  obstruction 
affects  the  lower  part  of  the  small  intestines,  large  quantities  of 
unabsorbed  food  material  stagnate,  and  putrefaction  is  very 
marked;  whereas,  if  the  large  intestines  are  affected,  some  time 
may  pass  before  any  abnormal  decomjxDsition  is  apparent,  because 
most  of  the  nourishment  has  already  been  extracted  from  the 
chyme.  When  putrefaction  occurs,  all  its  varied  products  are 
formed,  and  often  in  large  amounts.  Of  these,  the  aromatic  com- 
pounds, such  as  indol  and  phenol,  combine  in  the  body  with 
sulphuric  acid  to  form  the  comparatively  harmless  ethereal 
sulphates.  As  a  result  there  is  often  a  marked  increase  in  the 
quantity  of  indican  and  of  ethereal  sulphates  in  the  urine  (see 
p.  281).  It  is  possible,  however,  that  some  of  the  poisonous  com- 
pounds resulting  from  the  intestinal  decomposition  may  escape 


294  THE  BASIS  OF  SYMPTOMS 

neutralization,  and  that  they  are  responsible  for  many  of  the 
general  symptoms  of  intestinal  obstruction.  For  example,  the 
complicating  nephritis  is  possibly  of  such  a  toxic  origin. 

The  most  frequent  symptom  of  intestinal  obstruction  is 
obstinate  constipation.  Yet  in  certain  forms  of  ob- 
struction, especially  in  intussusception,  there  may  be  d  i  a  r  - 
rhoeal  discharges,  composed  not  of  faeces,  but  of  inflam- 
matory or  secretory  products  of  the  mucous  membrane  at  and 
below  the  obstruction. 

As  a  rule,  however,  the  portion  of  the  intestines  below  the 
obstruction  is  totally  paralyzed,  and  not  even  flatus  escapes  through 
the  anus.  Gases  collect  above  the  obstruction  and  gradually  back 
up  in  the  direction  of  the  stomach.  The  intestines  which  are 
thus  distended  contract  vigorously,  peristaltic  and  tetanic  contrac- 
tions alternating  with  each  other.  These  can  be  frequently 
observed  through  the  abdominal  wall,  especially  if  the  obstruction 
is  an  old  one  and  the  muscularis  has  had  time  to  hypertrophy. 
These  muscular  contractions,  especially  the  tonic  ones,  frequently 
give  rise  to  the  most  violent  colic.  The  patient  begins  to 
vomit  soon  after  the  obstruction  sets  in.  At  first,  the  vomitus 
consists  merely  of  the  gastric  contents  mixed  with  bile-stained 
material  from  the  duodenum.  If  the  vomiting  continues, 
however,  thin,  greenish-yellow  material,  of  a  faecal  odor,  may 
appear. ^^^  This  material  undoubtedly  comes  from  the  intestines, 
and  is  composed  in  part  of  unabsorbed,  decomposed  food,  and  in 
part  of  the  products  of  intestinal  secretion. 

The  mechanism  by  which  this  material  reaches  the  stomach 
is  not  perfectly  clear.  One's  first  thought  would  be  that  anti- 
peristaltic movements  play  an  important  part,^^^  for 
these  occur  in  other  conditions,  and,  even  though  they  have  not 
been  directly  observed  in  intestinal  obstruction,  no  reason  exists 
a  priori  why  they  should  not  be  present.  Indeed,  since  we  have 
learned  that  antiperistalsis  is  normal  in  the  colon,  we  are  more 
than  ever  inclined  to  assume  that  a  similar  mechanism  is  present 
in  the  small  intestines.  (And,  indeed,  fluoroscopy  has  made  us 
familiar  with  antiperistaltic  waves  in  cases  of  stenosis  in  the 
small  bowel  and  at  the  pylorus. — Ed.) 

As  the  obstruction  continues,  the  patient  loses  in  weight  and 
strength  rapidly.  The  period  of  increased  peristalsis  is  later  fol- 
lowed by  one  of  paralysis  of  the  intestines.     At  first,  this  cessation 


DIGESTION  295 

of  intestinal  movements  is  caused  merely  by  the  overdistention 
of  the  intestines;  for  it  has  been  shown,  experimentally,  that 
greatly  distended  intestines  cease  to  contract,  but  that  they  will 
begin  to  do  so  again  as  soon  as  the  tension  is  diminished.  In  the 
later  stages  of  obstruction,  however,  the  intestinal  par- 
alysis is  absolute;  and,  experimentally  at  least,  no  move- 
ments can  be  elicited.  This  entire  absence  of  peristaltic  movements 
in  intestinal  obstruction  indicates  an  exceedingly  grave  condition, 
and  if  help  is  not  forthcoming,  the  patient  dies  in  collapse. 

Though  it  is  generally  agreed  that  a  period  of  increased  peri- 
stalsis always  precedes  the  period  of  paralysis  in  chronic  obstruc- 
tion, some  consider  that  this  primary  period  may  be  absent  in 
acute  obstruction.  Yet  it  seems  to  me  that  a  primary  period 
of  increased  peristalsis  is  present  even  in  these  patients.  When 
this  is  of  short  duration  or  apparently  altogether  absent,  the 
cessation  of  intestinal  movements  is,  in  my  opinion,  usually  due  to 
an  inflammation  of  the  intestinal  wall. 

Strangulation. — The  severity  of  the  symptoms  varies  greatly 
in  different  cases  of  obstruction.  In  some,  the  meteorism,  faecal 
vomiting  and  collapse  do  not  occur  for  days;  whereas  in  others 
these  symptoms  develop  within  a  few  hours  after  the  obstruction 
takes  place.  These  variations  depend  largely  upon  the  nature  of 
the  occlusion.  A  simple  closure  of  the  lumen  of  the  intestines  is 
much  less  dangerous  than  a  so-called  strangulation,  which  may 
accompany  any  of  the  different  forms  of  intestinal  obstruction. ^^^ 
In  this  latter  condition  the  blood-supply  of  the  intestines  is  affected. 
The  mesenteric  and  intestinal  veins  are  pressed  upon  and  occluded, 
the  arteries  continue  to  send  blood  into  the  intestines,  and  cedema 
results.  These  vascular  changes,  together  with  injuries  to  the 
nerves  of  the  peritoneum,  are  apparently  responsible  for  the  rapid 
and  alarming  symptoms  which  ensue.  The  walls  of  the  intestines 
become  infiltrated  with  fluid,  and  bacterial  decomposition  proceeds 
with  excessive  rapidity  within  the  lumen  of  the  strangulated 
bowel.  The  products  of  this  bacterial  activity  injure  the  intes- 
tinal walls,  so  that  they  no  longer  oppose  the  normal  resistance  to 
the  gases  which  are  formed.  Consequently  the  strangulated  piece 
of  intestine  becomes  enormously  distended  (local  meteorism). 
The  violent  peristaltic  movements  produce  the  most  intense  pain, 
and  vomiting  becomes  uncontrollable.  Added  to  these  are  certain 
systemic  manifestations,  such  as  the  general  circulatory  changes, 


296  THE  BASIS  OF  SYMPTOMS 

the  collapse  and  the  rapid  loss  of  strength.  The  circulatory  dis- 
turbances are  caused,  in  the  first  place,  by  reflexes  from  the  peri- 
toneum that  act  upon  the  heart  and  vessels,  but  especially  by  those 
that  influence  the  splanchnic  vascular  area.  In  the  second  place, 
they  are  probably  produced  directly  by  the  toxic  action  of  putre- 
factive products  absorbed  from  the  intestines. 

Meteorism. — The  intestines  of  healthy  individuals  contain 
gases  ^^^  composed  in  part  of  swallowed  air  and  in  part  of  thos? 
which  arise  from  the  decomposition  of  the  intestinal  contents  by 
the  digestive  juices,  and  especially  by  bacteria.  When  air  is 
swallowed,  the  oxygen  in  it  is  rapidly  absorbed,  so  that  the  small 
intestines  rarely  contain  this  gas.  The  nitrogen,  however,  remain^ 
in  the  canal  for  a  much  longer  time.  Carbon  dioxide  is  set  free 
by  the  action  of  acids  upon  the  carbonates  in  pancreatic  juice,  bile 
and  succus  entericus,  but  it  is  generated  in  much  larger  quantities 
during  carbohydrate  fermentation.  The  latter  also  yields  hydro- 
gen and  marsh  gas;  and  the  putrefaction  of  proteids  produces 
small  quantities  of  hydrogen  sulphid.  Of  these  various  gases, 
the  carbon  dioxide  is  readily  absorbed  by  the  blood,  the  nitrogen, 
methane  and  hydrogen,  on  the  contrary,  much  more  slowly.  The 
quantity  and  quality  of  the  intestinal  gases  vary  greatly,  even  in 
a  healthy  man;  for  they  depend  largely  upon  the  quality  and 
quantity  of  the  food  taken  and  upon  the  varieties  of  bacteria  that 
happen  to  be  present. 

These  intestinal  gases  may  produce  some  variation  in  the  size 
of  the  abdomen,  but  rarely  does  great  distention  result,  for  the 
normal  intestines  can,  to  a  certain  extent,  dispose  of  the  gases 
they  contain,  either  by  absorption,  or  by  expulsion  through  the 
anus,  both  processes  depending  largely  upon  the  tonus  of  the 
smooth  muscle. 

In  gastro-intestinal  diseases  much  larger  quantities  of  gas 
may  be  formed,  and  those  produced  in  greatest  abundance  are 
usually  the  very  ones  which  are  least  easily  absorbed,  vis.,  methane 
and  hydrogen.  Yet  a  mere  increased  production  of  gas  does  not 
necessarily  cause  meteorism  either  in  a  healthy  individual,  or  even 
in  some  patients  with  intestinal  obstruction.  It  would  appear 
that  a  diminished  muscular  tonus  and  an  insufficient  absorptive 
capacity  are  of  much  greater  importance  in  the  production  of 
tympanites  than  is  an  excessive  formation  of  gases.  For  this 
reason,  meteorism  is  especially  marked  in  peritonitis  and  acute 


DIGESTION  297 

strangulation.  If  the  intestines  once  yield  to  the  pressure  of  gas 
within  them,  a  vicious  circle  is  established,  for  this  very  disten- 
tion embarrasses  their  circulation,  and  so  diminishes  their  ability 
to  absorb  gas. 

Meteorism  tends  to  develop,  therefore,  when- 
ever a  weakness  of  the  intestinal  musculature 
is  associated  with  an  over-production  of  gas 
within  the  intestines.  The  milder  forms  of  tympan- 
ites are  seen  in  connection  with  dyspepsias,  enteritides  and  typhoid 
fever ;  the  more  severe  in  association  with  peritonitis  and  intestinal 
obstruction. 

The  meteorism  that  is  present  at  times  in  hysterical 
patients  has  not  been  satisfactorily  explained,  but  seems  to 
depend  in  part  upon  transitory  paralyses  of  the  muscle,  and  in 
part  upon  the  swallowing  of  large  amounts  of  air.  Hysterical 
paralyses  are  common  enough  in  other  parts  of  the  body,  and  we 
see  no  reason  why  they  should  not  occur  in  the  intestines;  and 
the  fact  seems  well  established  that  many  hysterical  individuals 
swallow  air  in  considerable  quantities.  That  some  cases  may  be 
due  to  a  spasm  of  the  diaphragm  associated  with  a  relaxed  abdom- 
inal wall  is  evidenced  by  the  fact  that  they  disappear  under  anaes- 
thesia. 

Abnormal  Intestinal  Sensations. — ^These  are  various.  In  the 
first  place,  a  distention  of  the  intestines  will  produce  the  sen- 
sation of  fulness  in  the  abdomen,  and  if  the  distention 
be  marked,  dyspnoea  may  result,  owing  to  the  high  position 
of  the  diaphragm. 

Colic  results  from  violent  contractions  of  the  intestines. 
It  has  been  said  that  colic  is  never  produced  by  the  normal  peri- 
staltic movements,  but  only  by  tetanic  states  of  the  intestinal 
musculature.  These  are  liable  to  occur  whenever  the  stimuli  for 
peristaltic  movements  are  especially  strong.  The  most  severe 
forms  of  colic  are  seen  in  connection  with  intestinal  obstruction 
and  lead  poisoning.  Less  severe  is  the  colic  which  may  accompany 
intestinal  catarrah  and  cholera  nostra.  The  pain  of  colic  has 
been  located  by  some  in  the  muscles,  in  which  case  it  would  be 
analogous  to  that  caused  by  cramps  in  voluntary  muscles.  By 
others,  it  has  been  located  in  the  peritoneum,  for  we  know  that, 
like  the  other  serous  membranes,  the  peritoneum  is  an  exceedingly 


298  THE  BASIS  OF  SYMPTOMS 

sensitive  structure,  and  inflammations  in  it  are  always  accompanied 
by  severe  pain. 

The  cause  of  painful  sensations  referred  to  the 
viscera  is  still  unsettled.  It  has  long  been  known  that  the  brain 
is  insensitive  to  pressure  and  to  mechanical  irritation,  and  a 
similar  absence  of  painful  sensations  is  true  also  in  the  case  of 
the  stomach  and  intestines.  Lennander^^^  has  attributed  the 
pain  of  intestinal  colic  to  the  pressure  exerted  by  the  dilated  bowel 
upon  the  sensitive  parietal  peritoneum ;  while  Wilms  ^^^  regards 
the  traction  upon  the  sensory  nerve-containing  mesentery  as  the 
explanation.  Both  are  agreed  that  the  pain  arises  outside  of  the 
stomach  and  bowel ;  yet,  under  certain  conditions,  the  latter  may 
at  times  be  the  seat  of  pain.^^^  At  any  rate,  the  idea  that  local 
anaesthesia  in  intestinal  operations  is  equivalent  to  general,  must 
be  relinquished  in  view  of  the  fact  that  the  bowel  is  insensitive 
even  when  no  anaesthetic  is  employed.  Nevertheless,  I  am  not 
convinced  that  pain  may  not  arise  in  the  internal  organs.  Pos- 
sibly, the  sensitiveness  of  an  organ  is  more  important  than  the 
strength  of  the  irritation ;  or  in  other  words,  that  pain  originates 
in  the  viscera  only  when  the  threshold  of  sensibility  is  lowered 
by  disease. 

The  pain  of  appendicitis  and  ofcholecystitis 
is  due  to  the  inflammation  present.  In  renal  and  biliary 
colic,  the  Hkeliest  explanation  of  the  pain  is  the  pull  exerted 
by  a  distended  renal  pelvis  and  gall-bladder,  respectively,  upon 
the  nerves  in  the  biliary  passages  and  ureter;  it  is  possible,  how- 
ever, that  the  most  important  factor  is  the  dragging  upon  the 
peritoneum,  as  suggested  by  Wilms. 

Still  other  pains  are  unquestionably  to  be  referred  to  the 
peritoneum,  such,  for  example,  as  those  which  accompany  peri- 
toneal adhesions.  These  adhesions  which,  as  a  rule, 
follow  some  previous  inflammation,  often  cause  the  most  annoy- 
ing pain,  which  becomes  worse  when  the  bands  are  dragged 
upon.^^^  The  pain  of  peritoneal  adhesions  is  of  the  greatest  prac- 
tical importance,  for  it  may  harass  the  patient  for  years  after  the 
original  disease  has  subsided. 

A  somewhat  similar  pain  is  often  experienced  by  nervous 
individuals,  and  seems  to  be  of  a  neuralgic  nature,  for  no  anatomi- 
cal basis  can  be  discovered  for  it.  It  will  be  discussed,  therefore, 
in  connection  with  diseases  of  the  nervous  system. 


DIGESTION  299 

Diseases  of  the  anal  orifice  are  often  the  source 
of  severe  pain.  Each  time  that  hard  fasces  pass  over  the  in- 
flamed or  ulcerated  mucosa  the  most  intense  agony  is  experienced. 
Perhaps  even  more  unpleasant  is  the  condition  known  as 
tenesmus,  in  which  a  constant,  violent  desire  to  defecate 
harasses  the  patient.  This  is  especially  liable  to  be  present  in 
diseases  of  the  rectum.  The  inflammatory  changes  of  dysentery 
frequently  cause  this  constant  desire  to  defecate,  but,  owing  to 
the  lack  of  faecal  material  in  the  rectum,  nothing  is  passed  except 
inflammatory  products  and  these  with  most  excruciating  pain. 

LITERATURE 

^For  the  literature  of  stomatitis  and  ptyalism  see  Hoffendahl  and  Brugsch, 

respectively,  in  the  Kraus-Brugsch  System,  1914. 
*J.  Miiller:  Kongr.  f.  inn.  Med.,  1901,  321. 
'Roger  and  Simon:  C.  r.  soc.  biol.,  Ixii,  1070. 

*  Kraus  and  Ridder,  in  the  Nothnagel  System ;  Ridder,  in  the  Kraus-Brugsch 

System,  1914  (lit.). 
"Starck:  Die  Divertikel  u.  Erweitg.  d.  Speiserohre,   191 1;  Die  Osophago- 
skopie,  1905. 

*  Kraus  and  Ridder :  1.  c. ;  Starck,  1.  c. ;  Einhorn,  Am.  Jour.  Med.  Sc,  October, 

1910;  Best,  Arch.  f.  Verdauungskrankh.,  xvi,  464. 
^  For  physiology  of  digestion :  O.  Cohnheim,  D.  Phys.  d.  Verdauung  u.  Ernah- 
rung,  1908;  Fuld,  in  the  Kraus-Brugsch  System;  Bickel,  in  Oppenheimer's 
Handb.  d.  Biochemie;  Tigerstedt,  Lehrb.  d.  Physiologic  d.  Mensch.,  7th 
edit.,  1913  (Chap,  on  Metabolism  and  Nutrition);  Ellenberger  and 
Scheunert,  in  Zuntz-Loewy,  Lehrb.  d.  Phys.,  2nd  edit.,  1913,  Chap,  xvii; 
Starling,  Principles  of  Human  Physiology,  1912.  For  pathology  of  diges- 
tion :  V.  Tabora-Riegel,  in  the  Nothnagel  System ;  Riegel,  Magenkrank- 
heiten ;  Boas,  Magenkrankheiten ;  Pick,  Magenkrankheiten. 

*  Pawlow :  The  Work  of  the  Digestive  Glands,  1903. 

'  Bickel :  Kongr.  f .  inn.  Med.,  1906,  481 ;  Cohnheim,  1.  c.  See  also  Rehf  uss 
and  Hawk,  Jour.  Am.  Med.  Assn.,  1914,  Ixiii,  2088  (lit.). 

"Erb:  Zeitschft.  f.  Biol.,  xli  (lit.)  ;  Castex,  Arch.  f.  klin.  Med.,  c,  148. 

"  Driest :  Untersuch.  ii.  d.  Salzsauregeh.  d.  Mageninhaltes,  Diss.  Greif swald, 
1902;  Kornemann,  Arch.  f.  Verdauungskrankh.,  viii,  369;  Rose,  Arch.  f. 
klin.  Med.,  xcv,  508,  518. 

"  Kuttner :  Zeitschft.  f .  klin.  Med.,  xlv,  i ;  Boas,  Magenkrankheiten,  4th 
edit.,  ii. 

"  Blum  and  Fuld :  Berl.  klin.  Wochenschft.,  1905,  106. 

"  Bickel :  Zeitschft.  f .  physikal.  Ther.,  1907,  325 ;  Umber,  Berl.  klin.  Wochen- 
schft, 1905,  56;  Carlson,  Amer.  Jour,  of  Phys.,  191 5,  xxxvii,  50. 

"  Gross :  Arch,  f .  Verdauungskrankh.,  xii,  507 ;  Maly's  Jahresber.,  1906,  xxxvi, 
chapt.  viii  (lit.)  ;  Fuld,  in  Kraus-Brugsch  (lit.)  ;  Edkins,  Jour,  of  Phys., 
xxxiv,  133;  Wolfsberg,  Zeitschft.  f.  phys.  Chem.,  1914,  xic,  344  (a  recent 
study  devoted  to  the  effect  of  different  foods  on  the  flow  of  gastric  juice), 

"Schiile:  Arch.  f.  klin.  Med.,  Ixxi,  iii;  Umber,  I.  c. ;  Sommerfeld,  Engel- 
mann's  Arch.,  1905,  455  (suppl.). 

"  Cf.  Bickel :  Kongr.  f .  inn.  Med.,  1906,  485. 

"Edkins:  Proc.  Royal.  Soc,  Ixxvi  (B),  376;  Jour.  Physiol.,  xxxiv,  132. 

**  See  Nothnagel's  System  (Dis.  of  the  Stomach);  Ewald,  Klinik  d.  Ver- 
dauungskrankh.; Fleiner,  Lehrbuch,  192. 

*" Martins:  Deutsch.  med.  Wochenschft.,  1894,  No.  32;  Gentgen,  ibid.,  1907, 
1404. 


800  THE  BASIS  OF  SYMPTOMS 

"  Amer.  Jour.  Physiol.,  xxxvii,  50  (lit.  on  the  factors  governing  the  secretion 

of  gastric  juice). 
^Allard:  Arch.  f.  Verdauungskrankh.,  xv,  161  (lit.). 
"  Strauss  and  Bleichroder :  Untersuch.  ii.  d.  Magensaftfluss,  1903. 
'*Bickel:    Biochem.    Zeitschft.,    i,    153;    Bubow,    Arch.    Verdauungskrankh., 

xii,  I. 
'"Matthes:   Ziegler's   Beitrage,   xiii,  309;   Moller,   Ergeb.   d.  inn.   Med.,   vii, 

520  (collective  article). 
""^  Payr :  Deutsch.  med.  Wochenschf t.,  1909,  Nos.  36,  ^y ;  Arch,  f .  klin.  Chir., 

xciii,  436. 
"Matthes:  1.  c. ;  Moller,  1.  c. 
"Jour,  Am.  Med.  Assn.,  1913,  Ixi,  1942. 
*'Orphiils:  Jour.  exp.  Med.,  viii,  181. 
"Turck:  Jour.  Am.  Med.  Assn.,  xlvi,  1753. 
"  Hamburger  and  Friedman :   Arch.  Int.  Med.,  xiv,  722 ;  Jour.  Am.  Med. 

Assn.,  1914,  Ixiii,  380. 
•"Rose:  Arch.  f.  klin.  Med.,  xcv,  508;  Rehfuss  and  Hawk,  Jour.  Am.  Med. 

Assn.,  1914,  Ixiii,  2088. 
**  Emerson:  Arch.  f.  klin.  Med.,  Ixxii,  415. 
"Reissner:  Zeitschft.   f.  klin.  Med.,  xliv,  87. 
"Hauser:  Munch,  med.  Wochenschf t.,  1910,  No.  23- 
■*  Rosenberg :  Zeitschft.  f .  klin.  Med.,  Ivi,  449. 
"Emerson:  Arch.  f.  klin.  Med.,  Ixxii,  415. 
"  Neubauer  and  Fischer :  Arch,  f .  klin.  Med.,  xcvii,  449 ;  Weinstein,  Jour. 

Am.  Med.  Assn.,  Ivii,  1420.     See  also  Sanford  and  Rosenbloom,  Arch. 

Int.  Med.,  ix,  445 ;  Jaque  and  Woodyat,  ibid.,  x,  560. 
*"  Strauss  and  Bialocour :  Zeitschft.  f.  klin.  Med.,  xxviii,  567. 
*•  Minkowski :  Mitth.  a.  d.  med.  Klinik  z.  Konigsberg,  Leipzig,  1888. 
**  Rosenheim  and  Richter :  Zeitschft.  f .  klin.  Med.,  xxviii,  505, 
**  Sick :  Arch,  f .  klin.  Med.,  Ixxxvi,  370. 
^'v.  Tabora:  Arch.  f.  klin.  Med.,  Ixxxvii,  254, 
"  Naunyn :  Arch,  f .  klin.  Med.,  xxxi,  225. 
**  A.  Schmidt :  Arch,  f .  klin.  Med.,  Ivii,  65. 
*•  Dauber:  Arch.  f.  Verdauungskrankh.,  ii,  167. 
*''  Starling,  in  Asher-Spiro,  i.  Part  2,  446 ;  Sick  and  Tedesco,  Arch.  f.  klin. 

Med.,   xcii,    416;    v.    Bergmann,    in   the   Kraus-Brugsch    System    (lit,); 

Cannon,  The  Mechanical  Factors  of  Digestion,  1911,     (This  volume  em- 
braces Dr.   Cannon's  studies  in  this  field  to  191 1   and  contains  a  very 

complete  literature.) 
**  Hirsch,  v,  Mehring  and  Moritz :  Studies  from  Pawlow  Institute ;  Cannon,  1.  c. 
*•  v,  Bergmann :  Die  Rontgenuntersuchung  d.  Magens,  in  the  Kraus-Brugsch 

System,  v,  403. 
"  Schiile :  Zeitschft.  f .  klin,  Med.,  xx,  80. 
"  V.  Leube :  Arch,  f .  klin.  Med.,  xxxv,  i ;  Penzoldt,  ibid.,  Ii,  535 ;  Cannon, 

1.  c,  chaps,  viii,  ix,  and  x. 
"  Forschbach :  Arch,  f .  Verdauungskrankh.,  xv,  182. 
"C/.  Sick:  Arch.  f.  khn.  Med.,  Ixxxviii,  169. 
"  Rose :  Arch,  f .  klin.  Med.,  xcv,  508. 
"Mitth.  a.  d.  Grenzgeb.,  iv,  347. 
"  Rutimeyer :  Arch,  f .  Verdauungskrankh.,  vii,  67. 
"  Ibrahim :  Ergeb.  d.  inn.  Med.  u.  Kinderheilk.,.  i,  208. 
■*  Fleiner :  Verdauungskrankh.,  i,  208. 
"*  Rieder :  Fortschritte  a.  d.  Geb.  d.  Rontgenstrahlen,  viii,   141 ;  Holzknecht, 

Reports  from  his  laboratory,  Fischer.  Jena ;  Groedel,  Arch.  f.  klin.  Med., 

xc,  433  (lit.)  ;  V.  Bergmann,  in  the  Kraus-Brugsch  System  (lit). 
~  Fleiner :  1.  c. ;  Albrecht,  Virch.  Arch.,  clvi,  285. 
"  In  Keen's  Surgery,  iii,  949. 

^  Stiller :  Berl.  klin.  Wochenschft.,  1901,  No.  39. 
*  Arch,  f .  klin.  Med.,  xxxi,  225. 


DIGESTION  301 

*^'  See  Fleiner :  Arch,  f .  Verdauungskrankh.,  i,  243 ;  also  Die  Verdauungs- 
krankheiten  (lit.)  ;  F.  Miiller,  Kongr.  f.  inn.  Med.,  1898,  167. 

^  See  Jonas :  Deutsch.  med.  Wochenschft.,  1906,  No.  23 ;  Franz  Groedel,  in 
Lehmann's  med.  Atlanten,  vii,  198. 

"  See  Magnus,  in  Asher-Spiro,  Biophysik,  1903,  64. 

^  Cannon :  1.  c. ;  Carlson,  many  studies  in  the  Amer.  Jour,  of  Physiology, 
xxxi,  xxxii,  xxxiii,  xxxiv,  xxxvi. 

**  Text-book  of  Physiology,  1913,  284. 

*  Pawlow :  1.  c. 

">  Loc.  cit. 

"  Foerster  and  H.  Kiittner :  Beitr.  z.  klin.  Chir.,  Ixiii,  No.  2. 

"  See  Pal :  Wiener  med.  Wochenschft.,  1904,  Nos.  14  and  15. 

^*Die  nervose  Dyspepsie,  1908. 

"  For  literature,  see  Minkowski,  in  Ergeb.  d.  allg.  Path.,  ii,  696 ;  Quincke 
and  Hoppe-Seyler,  Diseases  of  the  Liver,  in  the  Nothnagel  System. 

"  See  Aschoff  and  Bacmeister :  Die  CholeHthiasis,  1909. 

'"Fraenkel  and  Krause:  Zeitschft.  f.  Hyg.,  xxxii,  97;  Gilbert  and  Lesebomlet, 
C.  r.  soc.  biol.,  1903,  664;  Ehret  and  Stolz,  Mitth.  a.  d.  Grenzgeb.,  vi-viii. 

"  Naunyn :  Klinik  d.  Cholelithiasis. 

"Forster:  Miinch.  med.  Wochenschft.,  1908,  No.  i. 

*'  See  Naunyn,  Proc.  13th  Inter.  Med.  Congr.,  Paris. 

•"  Zeitschft.  f.  klin.  Med.,  xii,  45. 

"Krehl:  His'  Arch.,  1890,  97;  Pfliiger,  Pfliiger's  Arch.,  Ixxxviii,  222,  431; 
xc,  I. 

"Matthes  and  Marquardsen:  Kongr.  f.  inn.  Med.,  1898,  358. 

**  Johns  Hopkins  Hosp.  Bull.,  1905,  xvi,  20. 

•*Brieger:  Zeitschft.  f.  klin.  Med.,  iii,  465;  Miiller,  ibid.,  45. 

"Zeitschft.  f.  klin.  Med.,  xlix,  432. 

"Gerhardt:  Kongr.  f.  inn.  Med.,  1897,  460;  Eppinger's  studies  collected  in 
Ergeb.  d.  inn,  Med.  u.  Kind.,  i,  107. 

"  See  Ehret  and  Stolz,  Mitth.  a.  d.  Grenzgeb.,  x,  150. 

**  Stadelmann :  Der  Ikterus,  1891 ;  Eppinger,  1.  c. 

•* Minkowski:  Ergeb.  d.  Path.,  xcvii.  Part  2,  705;  Zeitschft.  f.  klin.  Med., 
Iv,  34 ;  Mod.  Clin.  Med.,  Digestive  Diseases,  332. 

•"  Wiener  klin.  Wochenschft.,  1908,  No.  14. 

'*  Quincke,  in  the  Nothnagel  System ;  Heubner,  Lehrbuch,  3rd  edit.,  i,  103. 

**  Chauffard :  Semaine  med.,  1907  xxvii,  25 ;  1908,  xxviii,  49 ;  Rolleston,  Clin. 
Journal,  1908;  Tileston  and  Griffin,  Amer.  Jour.  Med.  Sc,  1910,  cxxxix, 
847;  Thayer  and  Morris,  Johns  Hopkins  Hosp.  Bull.,  xxii,  85  (lit); 
Meyerstein,  Ergeb.  d.  inn.  Med.,  1913,  xii. 

"  Klemperer :  Therap.  d.  Gegenwart,  1914,  No.  i ;  Tiirk,  Deutsch.  med. 
Wochenschft.,  1914,  No.  8;  Miihsam,  ibid. 

"  Stadelmann :  Zeitschft.  f.  Biol.,  xxxiv,  57. 

"Yeo  and  Herroun:  Jour,  of  Phys.,  v,  116;  Stadelmann,  1.  c. 

•*  Minkowski:  Arch.  f.  exp.  Path.,  xxi,  41. 

"  Newer  literature :  Fischler,  Das  Urobilin,  etc.,  1906 ;  Kongr.  f .  inn.  Med., 
1908,  544;  Hildebrand,  Miinch.  med.  Wochenschft.,  1909,  Nos.  14  and  15; 
Zeitschft.  f.  klin.  Med.,  lix,  351 ;  Friedr.  Meyer-Betz.,  Ergeb.  d.  inn.  Med., 
xii,  733  (lit.)  ;  Wilbur  and  Addis,  Arch.  Int.  Med.,  1914,  xiii,  235  (lit.). 

'*  Bauer :  Wiener  med.  Wochenschft.,  1906,  xxi,  2537 ;  Deutsch.  med.  Wochen- 
schft., 1908,  No.  35;  Wiener  klin.  Wochenschft.,  1912,  39;  see  also  Hoff- 
mann, Zeitschft.  f.  exp.  Path.,  1914,  xvi,  337. 

"Opie:  Diseases  of  the  Pancreas;  A.  Schmidt,  Deutsch.  med.  Wochenschft., 
1908,  No.  23 ;  Arch,  f .  klin.  Med.,  Ixxxvii,  456. 

'•^Zeitschft.  f.  klin.  Med.,  xii,  45;  Brugsch,  ibid.,  Iviii,  SiQ- 

^•'Ad.  Schmidt:  Die  Funktionspriifg.  d.  Darmes,  1908,  49  (lit.). 

'"^  Schmidt :  1.  c,  50.  See  also  Schmidt-Strasburger,  Die  Fazes  d.  Menschen, 
etc.,  4th  edit.,  191 5. 

"*Oser,  in  the  Nothnagel  System  (lit.). 


302  THE  BASIS  OF  SYMPTOMS 

***  Fleckseder :  Arch,  f .  exp.  Path.,  lix,  407 ;  Lombroso,  ibid.,  Ixvi,  99. 

^*"  Kongr.  f.  inn.  Med.,  1892,  450. 

*°*  Langerhans :  Virch.  Arch.,  cxxii,  252 ;  Benda,  ibid.,  clxi,  194. 

^'"  V.  Bergmann  and  Guleke :  Miinch.  med.  Wochenschft.,  1910,  No.  32 ;  Opie, 
Diseases  of  the  Pancreas,  40;  Johns  Hopkins  Hosp.  Bull.,  xii,  182. 

*°°Fischler:  Arch.  f.  klin.  Med.,  c,  329,  and  ciii,  156. 

*"  See  also  Flexner:  Jour.  exp.  Med.,  ii,  413,  and  Hewlett,  Jour.  Med.  Re- 
search, ix,  277. 

""  See  van  Ermengen,  in  Kolle-Wassermann,  ii,  637. 

"^  Metchnikoff :  Les  microbes  intestinaux.  Bull,  de  I'lnstitut  Pasteur,  1903,  i, 
217,  264;  Strasburger,  Zeitschft.  f.  klin.  Med.,  xlvi,  413;  xlviii,  491; 
Moro,  Arch.  f.  Kinderheilk.,  xliii. 

"*  Kohlbrugge,  ref.  in  Baumgarten's  Jahresber.,  1901,  895 ;  Roily,  Deutsch. 
med.  Wochenschft.,  1906,  No.  43 ;  see  also  Gushing  and  CoUingwood, 
Contributions  to  the  Science  of  Medicine,  Balto.,  1900,  543. 

"*Bienstock:  Die  med.  Wochenschft.,  1901,  Nos.  33  and  34;  Arch.  f.  Hyg., 
xxxix,  390  (Ht.)  ;  Roily  and  Liebermeister,  Arch.  f.  klin.  Med.,  Ixxxiii, 

413- 
"*  Thierf elder  and  Nuttal :  Zeitschft.  f.  phys.  Chem.,  xxi,  109;  xxii,  62;  Schot- 

telius,  Arch.  f.  Hyg.,  xlvii,  177 ;  Metchnikoff,  Ann.  Pasteur,  1901,  631  ; 

Moro,  Verhandl.  d.  Gesellsch.  f .  Kinderheilk.,  1905,  190. 
*"Lit.  in  Baumgarten's  Jahresber.,  in  the  chapter,  Vorkommen  u.  Bedeut.  d. 

Mikroorg.,   etc. ;  Tissier,  Recherches  sur  la  flore  intest.  d.  nourissons, 

1900. 
""Moro:  Miinch.  med.  Wochenschft.,  1908,  No.  31 ;  Combe,  Med.  Klinik.,  1909, 

Nos.  19  and  20;  see  also  Seifert,  Deutsch.  med.  Wochenschft,  191 1,  No.  23. 
"^Schott:  Zentralbl.  f.  Bakt.,  xxix,  i,  239,  291. 
*"  Klemperer :  Deutsch.  med.  Wochenschft.,  1894,  No.  20 ;  H.  and  A.  Kossel, 

Du  Bois'  Arch.,  1894,  200. 
""  Posner  and  Cohn :  Berl.  klin.  Wochenschft.,  1900,  No.  36. 
"•  Behring :  Naturforscherversamm.  zu  Kassel,  1903. 
***  Salge :  Jahrb.  f.  Kinderheilk.,  Ix,  i. 
^  Rosenheim :  Deutsch.  med.  Wochenschft,  1908,  Nos.  7  and  8 ;  Baumstark, 

ibid.,  1911,  No.  16. 
^  Studies  from  the  Rockefeller  Inst,  for  Med.  Research,  ii,  1904. 
^  See,  for  example,  Cameron :  Brit.  Jour,  of  Child.,  1913,  x,  205 ;  E.  Schlesin- 

ger,  Deutsch.   med.  Wochenschft.,   1912,  xxxviii,   558;   Helmholz,  Jour. 

Am.  Med.  Assn.,  1914,  Ixiii,  1371. 
^  Fischler :  Arch,  f .  klin.  Med.,  civ ;  Adrian,  Arch,  f .  Verdauungskrankh.,  i, 

179  (lit). 
"•Herter:  Lectures  on  Chem.  Pathol.,  202;  N.  Y.  Med.  Jour.,  1898,  89;  many 

studies  on  indol  an '  skatol  in  Jour,  of  Biol.  Chem.,  i-v ;  Gerhardt,  Ergeb. 

d.  Physiol.,  1904  (iii,  Part  I),  107  (lit)  ;  EUinger,  ibid.,  1907,  vi,  29  (lit). 
""Frank:   Berl.  klin.   Wochenschft.,   1887,   No.  38.     See  also  Krause,  allg. 

Mikrobiologie,  191 1,  281. 
***  Councilmann  and   Lafleur :   Johns  Hopkins   Hosp.   Rep.,   iii ;   Kartulis,   in 

Kolle-Wassermann,  Handb.,  Suppl.,  i,  347. 
"*Miiller:  Kongr.  f.  inn.  Med.,  1887,  404;  Zeitschft  f.  khn.  Med.,  xii,  45; 

Grassmann,  ibid.,  xv,  183. 
""  Dapper :  Zeitschft.  f.  klin.  Med.,  xxxi,  382. 
^  Zeitschft  f .  Exp.  Path.,  iii,  446. 

^  V.  Mering :  Kongr.  f .  inn.  Med.,  1893,  471 ;  Moritz,  ibid. 
^Kiihne:  Berl.  klin.  Wochenschft,  1868,  170. 
"*  Am.  Jour,  of  Phys.,  x,  loi,  259. 
*"  Franicl :  Arch,  f .  exp.  Path.,  1907,  Ivii,  386 ;  Auer,  Amer.  Jour,  of  Phys., 

1906,  xvii,  15  (lit)  ;  Jour,  of  Biol.  Chem.,  1908,  iv,  197  (lit). 
***  Amer.  Jour,  of  Phys.,  1907,  xx,  266. 
*"  Miinch.  med.  Wochenschft.,  1909,  No.  47.     See  also  Boehm,  Arch.  f.  klin. 

Med.,  cii,  431  (lit),  and  Cannon,  1.  c. 


DIGESTION  303 

^Ziilzer,  Dohrn  and  Marker:  Berl.  klin.  Wochenschft.,  1908,  No.  46;  Kanert, 

Miinch.  med.  Wochenschft.,  1911,  No.  17;  Glitsch,  ibid.,  No.  23. 
"•Nothnagel:  Dis.  of  the  Intestines,  in  his  System  (lit.). 
^"  Bokai :  Arch.  f.  exp.  Path.,  xxiii,  209,  and  xxiv,  153. 
^"  Lohrisch :  Arch,  f .  klin.  Med.,  Ixxix,  383 ;  Tomascewski,  Med.  Klinik.,  1909, 

No.  12. 
^*^  Nothnagel :  Zeitschft.  f.  klin.  Med.,  iv,  422. 

*"  Magnus :  Pfliiger's  Arch.,  cii  and  ciii ;  Jour,  of  Phys.,  xxxiii,  34. 
*■"  Fleiner :  Berl.  klin.  Wochenschft.,   1893,   No.  3 ;   Boas,  Darmkrankh.,  2nd 

edit.,  570. 
***  Boas :  Arch,  f .  Verdauungskrankh.,  xv,  683. 
^^Boehm:  Arch.  f.  klin.  Med.,  cii,  431 ;  Miiller,  Kongr.  f.  inn.  Med.,   1898, 

149;    Combe,    Intestinal    Auto-Intoxication,    1908;    Ebstein,    Berl.    klin. 

Wochenschft.,  1909,  No.  41,  and  Die  chron.  Stuhlverstopfg.,  1901 ;  Robit- 

schek,  Berl.  klin.  Wochenschft.,  1910,  No.  18. 
"'  Der  Ileus,  Deutsch.  Chirurgie,  No.  46  g. 

***  Nothnagel :  Dis.  of  the  Intestines,  in  his  System ;  Wilms,  1.  c. 
^**Herczel:  Zeitschft.  f.  klin.  Med.,  xi,  221. 

""  Leichtenstern  :  Kongr.  f .  inn.  Med.,  1889,  56 ;  Nothnagel,  1.  c. ;  Wilms,  1.  c. 
'"^  Hernmehr :  Arch,  f .  Verdauungskrankh.,  viii,  59. 
"^Kirstein:  Deutsch.  med.  Wochenschft.,  1889,  No.  49;  v.  Mikulicz,  Therap. 

d.  Gegenwart,  1900.     For  more  recent  studies  on  the  causes  of  the  toxic 

manifestations  of  intestinal  obstruction  see  Hartwell,  Jour.  exp.  Med., 

1913,  xviii,  139;  Bunting  and  Jones,  ibid.,  1913,  xvii,  192,  and  xviii,  25; 

Whipple,  Stone  and  Bernheim,  ibid.,  1913,  xvii,  286,  307. 
*"  Cf.  Fries :  Amer.  Jour.  Phys.,  xvi,  468, 
^"  Grenzgebiete,  xv  and  xvi. 
"*  Zeitschft.  f .  Chirurg.,  c,  372. 
"'Ritter:  Zentralbl.  f.  Chir.,  1908,  No.  20  (lit.). 
"'  Riedel :  Arch.  f.  klin.  Chir,,  xlvii,  153 ;  Vogel,  Deutsch.  Zeitschft.  f.  Chir., 

Ixiii,  296. 


CHAPTER  VI 
NUTRITION  AND  METABOLISM 

The  activities  of  the  living  cells  are  associated  with  chemical 
changes  within  them,  and  with  an  interchange  of  food  and  waste 
material  with  their  surroundings.  The  sum  of  all  these 
processes  is  termed  metabolism.  A  discussion  of 
nutrition  and  metabolism  ought  properly  to  deal  with  each  organ 
individually,  for  it  is  obvious  that  different  tissues  require  differ- 
ent food  materials  and  give  rise  to  different  waste  products.  In- 
deed, the  various  organs  are  more  or  less  interdependent  upon 
one  another,  and  one  organ,  for  example,  may  need  material  that 
has  been  elaborated  by  another,  or  may  transform  waste  products 
derived  from  another.  This  interdependence — or  chemical 
correlation,^  as  it  is  known  to-day — predicates  the  activities 
of  hormones,  or  substances  which,  elaborated  by  one  organ, 
exert  a  specific  influence  upon  another.  Though  the  existence  of 
such  substances  has  long  been  assumed,  it  is  only  recently  that  we 
have  acquired  some  knowledge  of  their  origin  and  characteristics. 
They  are  the  products  particularly  of  the  ductless  glands,  though 
it  is  probable  that  every  organ  takes  a  part  in  their  formation. 
The  disorders  of  these  internal  secretions — and  our 
acquaintance  with  these  disorders  is  still  largely  undeveloped — 
we  shall  consider  in  connection  with  the  various  processes  in  which 
they  play  a  role. 

In  the  present  state  of  our  knowledge,  however,  we  are 
unable  to  discuss  metabolism  from  the  standpoint  of  the  individual 
organs,  but  are  obliged  rather  to  consider  the  metabolic  processes 
that  take  place  in  the  body  as  a  whole.  Our  knowledge 
of  these  processes  is  derived  mainly  from  exam- 
inations of  the  food  ingested  and  of  the  various 
waste    products    eliminated. 

The  Quantitative  Variations  in  the  Metabolism  of 
Proteids  and  Fats 

In  order  to  maintain  the  body,  it  is  necessary  to  sui)ply  it  with 
water,  mineral  salts  and  organic  bodies,  i.e.,  proteids,  carbohy- 
drates and  fats.     It  is  not  quite  certain,  however,  that  this  enumer- 

S04 


NUTRITION  AND  METABOLISM  305 

ation  is  complete  and  that  there  are  not  other,  still  undiscovered, 
needs  of  the  body. 

The  Caloric  Needs  of  the  Body. — The  food  ingested  is  utilized 
partly  to  repair  the  tissue  waste,  and  partly  to  furnish  energy 
for  muscular  movements,  bodily  heat  and  for  the  respiratory 
and  circulatory  activities.  For  these  last  purposes,  it  is  practically 
immaterial  in  what  form  the  energy  is  provided — whether  it  be 
as  carbohydrates,  fats  or  proteids — the  essential  point  being  that 
the  quantity  of  food  is  sufficient.  The  energy  contained  in  the 
various  foodstuffs  is  transformed  by  the  body  into  mechanical 
work,  chemical  work  and  especially  into  heat.  Indeed,  Rubner  ^ 
has  shown  that  almost  the  entire  energy  of  the  food  leaves  the 
resting  body  in  the  form  of  heat,  and  that  the  heat  which  results 
from  combustion  in  the  body  is  the  same  as  that  which  would  be 
produced  were  the  foods  burned  outside  to  the  same  waste 
products. 

(The  unit  for  measuring  quantities  of  heat  is  the  large 
calorie,  which  represents  the  amount  of  heat  necessary  to 
raise  the  temperature  of  a  kilogram  of  water  one  centigrade 
degree.  When  equal  weights  of  different  foodstuffs  are  burned 
in  the  body,  different  quantities  of  heat  are  liberated.  Thus  each 
gram  of  fat  produces  about  9.3  calories,  each  gram  of  carbohy- 
drates about  4.1  calories,  and  each  gram  of  proteids  about  4.1 
calories.  It  will  be  seen  from  these  figures  that  the  energy  de- 
rived from  fat  is  relatively  greater  than  that  derived  from  carbo- 
hydrates or  proteids.  Indeed,  one  gram  of  fat  furnishes  about 
the  same  energy  as  do  2.3  grams  of  either  of  the  other  two.  It 
is  possible,  with  certain  limitations,  to  replace  any  constituent  of 
the  diet  by  any  other,  without  disturbing  the  equilibrium  of  metab- 
olism, providing  due  attention  be  paid  the  caloric  value  of  each 
foodstuff.  Each  gram  of  fat  in  the  food,  for  example,  may  be 
replaced  by  2.3  grams  of  carbohydrates,  etc.  It  is  furthermore 
possible  to  calculate  the  total  quantity  of  energy  contained  in  any 
particular  diet  and  in  this  manner  to  estimate  whether  or  not 
this  diet  contains  a  sufficient  amount  of  energy  to  cover  the 
caloric  needs  of  the  individual. 

The  amount  of  energy  that  must  be  supplied  to  the  body  de- 
pends primarily  upon  the  activities  of  the  tissues,  and  is  subject 
to  many  influences.  This  amount  has  been  estimated  empirically 
from  the  mean  quantity  of  food  taken  by  different  individuals. 
20 


306  THE  BASIS  OF  SYMPTOMS 

We  quote   from  Lusk^   the   following   "standard"   die- 
taries for  a  man  of  seventy  kilograms: 

(Weights  in  Grams) 

Light  Work:                                                       Voit  Rubner  Atwater 

Protein 123  100 

Fat    46  * 

Carbohydrates 377  * 

Calories  2445  2700 

Medium  Work: 

Protein  118  127  125 

Fat 56  52  * 

Carbohydrates  500  509  * 

Calories  3055  2868  3400 

Hard  Work: 

Protein    145  165  150 

Fat 100  70  * 

Carbohydrates  500  565  * 

Calories  3574  3362  4150 

*  Carbohydrates  and  fats  to  make  up  the  full  value. — Ed.  ) 

A  small  person  needs  a  relatively  greater  supply  of  energy  per 
kilo  of  weight,  for,  as  is  well  known,  a  small  body  has  a  relatively 
large  surface,  and  consequently  loses  more  heat  in  comparison 
to  its  weight.  This  is  one  reason  why  children  need  more  food 
than  adults  in  proportion  to  their  weight.  On  the  other  hand, 
stout  individuals  need  relatively  less  food;  instead  of  the  normal 
thirty- four  to  forty-five  calories,  they  require  only  about  twenty- 
six  to  thirty-six  calories  per  kilo  of  body  weight.  This  difference 
is  due  to  the  fact  that  a  large  body  has  a  relatively  small  surface; 
that  the  thick  layer  of-  fat  protects  these  persons  from  heat  losses ; 
that  the  fat  itself  is  practically  dead  tissue  in  the  body  and  does 
not  consume  energy;  and,  finally,  that  stout  individuals  usually 
take  a  minimal  amount  of  exercise. 

Not  all  variations  in  the  caloric  needs  of  different  individuals 
are  thus  easily  explained,  and  there  are  reasons  for  assuming  that 
the  cells  of  different  persons  manifest  different  needs  for  energy. 
At  least,  no  other  satisfactory  explanation  can  be  given  for  the 
fact  that  certain  men  seem  to  require  very  much  smaller  quantities 
of  proteids  and  of  energy  than  do  others. 

The  Proteid  Needs  of  the  Body. — ^The  food  must  furnish  the 
body  not  only  with  a  sufficient  amount  of  energy,  but  also  with 
a  certain  minimum  of  proteids,  which  is  utilized  in  part  in  the 


NUTRITION  AND  METABOLISM  307 

repair  of  the  waste  within  the  cells.  In  view  of  the  extensive 
splitting  undergone  by  the  proteids  in  the  intestines,*  it  is  con- 
ceivable that  the  body  might  be  properly  maintained  if,  instead 
of  the  proteids  themselves,  their  split-products  (amino-acids  and 
ammonium  salts)  were  substituted  in  correct  proportion.  And, 
in  fact,  this  has  been  done  with  success,  using  the  products  of  the 
digestion  of  meat  and  milk.  Unpublished  studies  of  Grafe  would 
indicate  that  in  young  undernourished  animals  whose  diet  has 
contained  insufficient  proteids  and  an  excess  of  carbohydrates, 
ammonium  salts  are  indeed  utilized,  if  one  may  judge  from  the 
persistently  high  percentage  of  ammonia  nitrogen  retained. 

The  minimal  amount  of  proteid  ^  necessary 
for  the  needs  of  the  body  varies  with  the  condition  of  proteid 
nutrition  that  is  to  be  maintained,  with  the  kind  of  proteid  given, 
with  the  nature  and  amount  of  other  foods  given  and  with  the 
work  which  the  body  performs.  The  lowest  minimum  recorded " 
is  0.02  gram  nitrogen  per  kilogram  body-weight.  Although  the 
quantity  given  by  Voit  seems  considerable  (one  hundred  and 
eighteen  grams  of  proteid  for  a  man  of  seventy  kilograms),  and 
although  less  (even  twenty-five  to  forty  grams)  is  sufficient  for 
an  individual  when  other  forms  of  food  are  taken  in  great  abund- 
ance,'^ nevertheless  there  is  a  growing  inclination  to  regard  these 
older  figures  as  approximately  correct  for  a  healthy  individual, 
and  to  believe  that  the  capabilities  of  the  body  are  apt  to  be 
diminished  if  less  than  this  amount  of  proteid  food  be  taken.  On 
the  other  hand,  as  Rubner  has  shown,  proteids  in  the  food  should 
not  exceed  a  certain  maximum  proportion,  for  if  they  do,  an 
excessive  amount  of  heat  is  liberated  immediately  after  meals, 
and  this  is  not  only  useless,  but  may  be  directly  harmful  if  the 
heat  regulation  in  the  body  be  imperfect. 

The  cells  are  capable  of  repairing  their  proteid  waste  irre- 
spective of  whether  the  food  contains  a  diversity  of  proteids  or  a 
single  one.  But  in  what  way  the  proteids  are  conveyed  to  the 
cells  is  not  known,  though  it  is  likely  that  the  source  is  the  blood 
plasma.  Nor  is  it  known  whether  the  cells  are  supplied  with  fully 
formed  proteids  or  with  the  split-products  of  the  latter  from  which 
they  synthetize  their  own  proteids.®  That  the  body  may  build 
up  its  nucleins  for  the  most  part  is  known.^ 

Certain  facts  lead  us  to  believe  that  even  the  minimal  proteid 
requirement  is  considerably  in  excess  of  that  needed  to  repair 


308  THE  BASIS  OF  SYMPTOMS 

tissue  waste.  This  excess  enters  into  the  formation  of  energy.  In 
this  second  function,  however,  proteids  may  be  entirely  replaced 
by  carbohydrates  and  almost  completely  by  fats.^^ 

Inanition. — Inanition  may  be  due  to  a  variety  of  causes. 
Of  these  the  most  important  are,  first,  an  insufficient  in- 
gestion of  food — either  from  lack  of  food  or  lack  of  appe- 
tite— and  secondly,  an  insufficient  absorption  of 
material  from  the  gastro-intestinal  canal.  Prac- 
tically, inanition  is  most  frequently  seen  in  connection  with  dis- 
eases of  the  digestive  system. 

It  is  necessary  to  distinguish  an  insufficient  supply  of  food 
as  a  whole — a  caloric  insufficienc y — from  an  insuffi- 
cient supply  of  proteid  material — a  proteid  insuffi- 
ci  ency.  These  two  are  more  or  less  independent  of  each 
other,  it  being  possible,  for  example,  that  a  patient  should  gain 
in  weight,  and  yet  suffer  from  an  insufficiency  of  proteids,  or 
vice  versa. 

If  too  little  food  be  supplied  to  the  body,  the  in- 
dividual must  live  upon  his  own  tissues.  His  glycogen 
and  fats  can  furnish  him  with  energy.  In  addition  to  this, 
however,  he  consumes  a  certain  minimal  quantity  of  pro- 
teids, which  is,  for  the  most  part,  sacrificed  by  the  less  im- 
portant organs  of  his  body.  The  amount  of  proteids  thus  con- 
sumed depends  partly  upon  the  quantity  of  fat  and  glycogen  at 
his  disposal  and  partly  upon  individual  peculiarities,  which,  in  a 
particular  case,  tend  to  maintain  it  at  a  fairly  constant  level. 
During  the  first  few  days  of  an  absolute  fast  the  excretion 
of  nitrogen  is  comparatively  high,  owing  to  proteids  that 
had  been  taken  just  before  the  fast  began.  As  this  excess  of 
nitrogen  is  being  eliminated,  the  quantity  in  the  urine  gradually 
sinks  to  a  minimum;  though  the  fall  is  sometimes  interrupted 
about  the  third  or  fourth  day,  possibly  because  the  glycogen 
in  the  body  is  exhausted.  Toward  the  end  of  the  fast  the  pre- 
mortal rise  of  nitrogen  excretion  occurs,  which  is  due 
to  the  lessened  amount  of  fat  for  consumption  and  to  a  larger 
derivation  of  energy  from  the  proteids  alone. 

During  the  earlier  stages  of  starvation,  therefore,  the  energy 
necessary  for  muscular  movements  and  for  heat  is  supplied  by 
the  combustion  of  the  glycogen  and  fats  stored  up  in  the  body. 
The  more  valuable  proteid  material  is  thus  protected  from  con- 


NUTRITION  AND  METABOLISM  309 

sumption.  When  the  store  of  non-nitrogenous  material  comes 
to  an  end,  however,  the  proteids  themselves  must  be  utilized  to 
supply  the  necessary  energy  to  the  body.^^  The  living  tissues 
then  break  down  rapidly;  yet  a  certain  discrimination  still  takes 
place.  The  more  important  organs  live  at  the  expense  of  the 
less  important;  and  Voit  has  shown  that  the  former  will  retain 
their  normal  weight  practically  unaltered  to  the  end.  The  greatest 
loss  is  sustained  by  the  muscles,  glands  and  fatty  tissues;  while 
the  heart  and  central  nervous  system  are  spared  to  the  very  last.^^ 

Absolute  starvation  is  rarely  seen  by  the  physician,  but  partial 
inanition  is  by  no  means  infrequent,  and  its  treatment  furnishes 
one  of  the  most  important  problems  that  confront  him.  Usually, 
in  these  cases,  both  the  total  caloric  energy  and  the  proteids  in 
the  diet  are  insufficient.  The  amount  of  this  deficiency  may  vary 
up  to  absolute  starvation. 

The  effects  of  starvation  upon  the  individual  de- 
pend, in  the  first  place,  upon  how  complete  it  is.  If  the  body 
consumes  thirty-five  calories  per  kilo  a  day,  and  receives  only 
ten  from  the  food,  it  must  supply  twenty-five  calories  from  its 
own  substance,  and  the  condition  is  naturally  a  much  more  serious 
one  than  if  it  had  received  thirty  calories  in  the  food  and  had 
supplied  only  five  from  its  own  substance.  Furthermore,  star- 
vation is  withstood  much  better  if  the  patient  be  stout,  for  he 
then  has  a  larger  amount  of  fat  that  can  be  utilized  to  supply 
energy.  This  serves  to  postpone  the  time  at  which  the  non- 
nitrogenous  stores  in  the  body  give  out,  and  the  living  tissue  itself 
must  be  consumed  to  supply  energy.  Finally,  the  course  of  inani- 
tion is  influenced  by  the  demands  made  upon  the  energy  within  the 
body ;  thus,  the  condition  is  a  more  serious  one  when  the  individ- 
ual must  work,  or  when  he  is  not  well  protected  by  clothing,  etc., 
from  losses  of  heat. 

In  certain  diseases,  hunger  and  insufficient 
nourishment  are  often  surprisingly  well  borne 
— ^better  indeed  than  they  are  in  health — for  the  body  seems  to 
be  able  to  limit  its  consumption  of  proteids  and  energy.  Aston- 
ishingly low  figures  have  been  found  in  such  cases;  indeed, 
patients  have  often  gained  in  weight  on  a  diet  that  would  be 
entirely  insufficient  for  a  healthy  man.^^  The  amount  of  heat 
produced  in  the  body  during  a  short  fast  is  about  the  same  as 
when  the  individual  is  consuming  moderate  amounts  of  food.    If 


310  THE  BASIS  OF  SYMPTOMS 

the  patient  suffers  from  prolonged  partial  starvation,  however, 
the  amount  of  heat  produced  in  the  body  seems  to  be  lessened ; 
and  it  would  seem  that  the  ability  to  limit  the  expenditure  of 
energy  is  much  greater  in  wasting  diseases,  such  as  diabetes,  for 
example,  than  in  hunger  states  of  short  duration  in  which  no 
opportunity  is  given  for  accommodation  to  the  new  conditions. 

The  Effects  of  an  Oversupply  of  Food. — It  is  necessary  to 
discuss  the  effects  of  increasing  the  nitrogenous  and  the  non- 
nitrogenous  elements  in  the  food  separately,  for  the  laws  govern- 
ing each  are  different.  We  may  say,  in  a  general  sort  of  way, 
that  the  cells  of  the  body  ordinarily  decompose  all  the  p ro- 
te ids  taken  in  the  food.  When  proteids  are  taken  in  abund- 
ance, and  the  total  caloric  energy  of  the  food  is  not  too  greatly 
increased,  there  is  merely  a  slight  retention  of  nitrogenous  mate- 
rial during  the  first  few  days  of  the  new  diet.  Very  soon,  however, 
the  body  reaches  a  condition  in  which  it  is  consuming  all  the 
proteids  furnished  to  it,  and  it  is  then  said  to  be  in  nitrog- 
enous   equilibrium. 

If  the  tissues  happen  to  be  in  need  of  new  material,  as  is  the 
case  during  growth  and  convalescence,  it  is  possible  that  a  con- 
siderable proportion  of  the  extra  supply  of  proteids  may  be 
retained  in  the  body  and  may  be  built  up  into  living  tissue. 

It  is  even  possible  to  cause  a  considerable  retention  of 
nitrogenous  material  in  the  bodies  of  normal  animals 
by  feeding  them  with  large  quantities  of  both  nitrogenous  and 
non-nitrogenous  food.^*  Apparently  the  same  result  may  be 
attained  even  more  easily  in  man.^^  We  do  not  know  certainly 
whether  this  nitrogenous  material  is  retained  in  the  body  as  pro- 
teids or  as  other  compounds.  It  is  interesting  to  note  in  this 
connection  that  when  growing  children  or  convalescents  retain 
nitrogenous  material  in  their  bodies,  they  are  taking  a  diet  that 
contains  an  excessive  amount  of  energy.^® 

The  ingestion  of  fats,  but  especially  of  carbohy- 
drates, in  great  excess  tends  to  diminish  the  excretion  of 
nitrogen  in  the  urine;  or,  in  other  words,  it  tends  to  cause  a 
retention  of  nitrogenous  material  in  the  body.  This  fact  has 
been  variously  interpreted.  E.  Voit  considers  that  the  cells 
utilize  those  foods  which  are  supplied  to  them  in  greatest  abund- 
ance; whereas  Pfluger  and  others  believe  that  the  selection  of 
material  for  consumption  is  a  property  of  the  living  protoplasm, 


I 


NUTRITION  AND  METABOLISM  Sll 

and  as  such  is  almost  independent  of  which  foods  are  supplied 
in  excess.  We  cannot  enter  into  a  discussion  of  this  physiological 
problem,  but  may  state  our  belief  that  the  growth  of  living  tissue 
depends  primarily  upon  the  activities  of  the  cells.  In  virtue  of 
some  unknown  property,  the  cells  grow  and  multiply,  and  their 
growth  and  multiplication  are  especially  excited  by  functional 
activity;  providing,  of  course,  that  a  supply  of  building  material 
is  at  hand.  When  the  physician  wishes  to  increase  the  living 
protoplasm  of  the  body,  therefore,  he  should  remember  that  it  is 
more  important  to  increase  the  functional  activities  of  the  cells 
than  to  furnish  the  body  with  an  oversupply  of  food. 

Among  the  materials  essential  to  the  building  of  the  larger 
proteid  molecule  seem  to  be  certain  intermediate  products  of 
carbohydrate  consumption — t he  keto-acids.  This  explains, 
possibly,  the  favorable  influence  of  carbohydrates  in  the  mainten- 
ance of  nitrogen  equilibrium. 

We  have  seen  that  the  amount  of  energy  needed  by  the  body 
depends  primarily  upon  the  work  performed  and  the  heat  ex- 
pended. A  person  lying  in  a  warm  bed,  for  example,  expends  less 
energy  than  does  one  who  works  hard  eight  or  ten  hours  each  day, 
or  who  is  exposed  to  very  cold  weather.  When  excessive  quanti- 
ties of  non-nitrogenous  food  are  taken  in  the  diet,  a  portion  of 
the  excess  is  decomposed  into  its  end  products,  carbon  dioxide 
and  water;  thus  Rubner  has  shown  that  the  feeding  even  of 
greatly  excessive  amounts  of  fat  leads  to  no  appreciable  increase 
in  heat  production.  So  far  as  man  is  concerned,  what  constitutes 
such  an  excess  is  still  undetermined ;  in  all  probability  individual 
variations  play  an  important  part. 

Stahelin  ^^  has  observed  in  cases  of  tuberculosis  an  enormous 
increase  in  energy  expenditure  following  the  ingestion  of  proteids. 
Certain  individuals  do  not  gain  weight  despite  a  diet  of  extremely 
high  caloric  value.  According  to  Grafe,^^  this  is  due  not  to  a 
deficient  absorption  from  the  intestines,  but  to  a  greatly  augmented 
metabolism  both  in  the  fasting  condition  and  after  the  taking  of 
food. 

Disturbances  in  Fat  Metabolism. — We  have  said  that  if  large 
quantities  of  non-nitrogenous  material  are  taken  in  the  food,  the 
unused  excess  is  stored  up  in  the  body  either  as  glycogen  or  as 
fat.    The  quantity  of  fat  in  the  body  depends,  therefore,  to  a 


812  THE  BASIS  OF  SYMPTOMS 

great  extent  upon  the  relation  that  exists  between  the  supply  of, 
and  the  demand  for,  energy-producing  material. 

Different  classes  of  foodstuffs  produce  dif- 
ferent effects  as  regards  the  tendency  to  accu- 
mulate fat.  For  example,  when  proteids  are  eaten,  the 
general  metabolism  is  accelerated  far  more  than  when  fats  or 
carbohydrates  are  taken,  and  consequently  less  energy  is  left 
for  storage.  The  question  as  to  whether  fat  is  ever  formed 
directly  from  the  proteids  or  not,  has  been  settled  to  the  extent  that 
it  is  known  that  sugar  is  split  off  from  proteids  and  that  fat 
arises  from  sugar.  At  any  rate,  an  excess  of  proteid  material  in 
the  food  would  favor  a  retention  of  fat  in  the  body,  for  the  reason 
that  the  non-nitrogenous  products  of  proteid  cleavage  may  be 
utilized  for  energy.  This  would  spare  the  fats  and  carbohydrates 
and  allow  them  to  be  stored. 

The  carbohydrates  of  the  diet  that  are  not  burned 
immediately  are  deposited  in  the  body  partly  as  glycogen  and 
partly  as  fat.^^  That  carbohydrates  may  give  rise  to  fat  in  the 
body  has  been  demonstrated  repeatedly.  This  transformation 
takes  place  with  the  elimination  of  oxygen,  which  is  subsequently 
used  in  metabolism.  Consequently  more  carbon  dioxide  is  elim- 
inated from  the  lungs  than  corresponds  to  the  oxygen  absorbed. 
The  respiratory  quotient,  or  ratio  of  the  former  to  the  latter,  may 
rise,  therefore,  to  as  high  a  figure  as  1.3  during  this  formation 
of  fat  from  carbohydrates.^^  The  fat  that  is  thus  formed  is  rich 
in  stearin  and  plamitin,  but  poor  in  olein.  In  what  part  of  the 
body  the  transformation  takes  place  is  not  known,  though  there 
is  some  evidence  that  it  occurs  in  the  liver. 

If  fat  is  ingested  in  excessive  quantities,  it  is  deposited 
as  such  in  the  body.  The  composition  of  animal  fat  is,  therefore, 
to  a  certain  degree,  dependent  upon  the  composition  of  the  fats 
taken  by  the  mouth.  In  spite  of  this  fact,  however,  the  body  fat 
in  man  and  in  many  animals  preserves  a  fairly  constant  composi- 
tion. This  may  be  explained  on  the  assumption  that  the  body 
tends  to  pick  certain  fats  out  of  the  food  for  storage,  or  that 
the  food  commonly  taken  is  really  of  a  more  constant  composition 
than  is  ordinarily  believed.  Possibly  the  main  reason  for  this 
uniformity  resides  in  the  fact  that  a  great  part  of  the  body  fat 
arises  from  carbohydrates. 

The  relation  of  the  ingestion  of  fluids  to  fat 


NUTRITION  AND  METABOLISM  313 

metabolism  is  a  much-discussed  and  still  unsettled  subject. 
Many  stout  individuals  drink  a  considerable  quantity  of  liquids, 
especially  of  beer,  and  it  often  happens  that  when  the  latter  is 
stricken  from  the  diet,  a  loss  of  weight  promptly  follows.  This 
result  is  due  in  part  to  the  loss  of  energy  that  would  be  derived 
from  the  alcohol  and  carbohydrates  of  the  beer;  but  it  may  be 
due  in  part  to  the  lessened  quantity  of  fluids  taken.  Small 
amounts  of  other  drinks,  such  as  coffee,  tea,  bouillon  or  light  wine, 
are  often  taken  to  increase  the  appetite,  and  if  these  be  omitted 
the  individual  may  eat  less  and  so  lose  weight  from  this  cause. 
Although  these  facts  are  of  the  greatest  practical  importance, 
they  have  no  theoretical  bearing  on  the  question  as  to  whether  or 
not  fluids  directly  influence  the  storage  or  decomposition  of  fats 
in  the  body.  Though  this  question  has  not  yet  been  satisfactorily 
settled,^ ^  it  seems  worth  while  to  review  some  of  the  evidence 
bearing  upon  it,  and  to  call  attention  to  some  of  the  difficulties 
encountered  in  its  solution. 

It  is  a  surprising  fact  that  while  animals  are  being  fattened 
very  little  water  is  usually  allowed  them,^^  from  which  we  may 
infer  that  a  relatively  dry  diet  certainly  does  not  seriously  inter- 
fere with  the  accumulation  of  fat  in  the  body. 

The  question  as  to  the  effect  of  liquids  upon  the  accumulation 
of  fat  in  man  is  a  difficult  one  to  solve ;  for  in  him  the  only  method 
whereby  we  can  practically  estimate  a  gain  or  loss  of  fat  is  weigh- 
ing, and  a  difference  in  weight  might  equally  well  be  caused  by  a 
change  in  the  quantity  of  proteids,  of  glycogen  or  of  water  in  the 
body.  The  first  two  of  these  may  be  neglected,  practically,  for 
the  variations  that  they  undergo  are  not  great.  The  third,  how- 
ever, is  of  the  utmost  importance  in  a  consideration  of  this  ques- 
tion, and  constitutes  a  considerable  source  of  error  whenever  we 
assume  that  a  gain  or  loss  of  weight  is  necessarily  caused  by  a 
correspondingly  great  gain  or  loss  of  body  fat. 

Stout  persons  ordinarily  drink  large  quantities  of  water,  prob- 
ably because  they  perspire  so  freely,  and  this  water  is  not  all 
immediately  excreted,  but  is  stored  in  part  in  the  body.  If  now 
the  patient  refrains  from  drinking  water,  and  takes  much  exercise, 
he  loses  weight  rapidly.  The  main  cause  of  this  early  loss  of 
weight,  however,  is  the  loss  of  water,  the  result  being  merely  a 
drying-out  of  the  body.^^  Indirectly  this  loss  of  water  may  assist 
in  reducing  the  fat  in  the  body,  for  when  the  weight  of  a  stout  per- 


314  THE  BASIS  OF  SYMPTOMS 

son  is  lessened  by  the  loss  of  fluids,  it  is  possible  that  he  will  take 
more  exercise  and  so  consume  more  fat. 

It  will  be  seen  from  these  considerations  that  different  factors 
render  this  question  a  most  difficult  one  to  solve.  At  present  we 
possess  no  conclusive  evidence  that  the  limitation  of  fluids  directly 
influences  fat  metabolism ;  though  such  a  limitation  may  indirectly 
reduce  the  weight  of  the  body  either  by  removing  water  from  it, 
by  diminishing  the  amount  of  food  taken  or  by  increasing  the 
ability  to  take  exercise. 

Pathological  Accumulations  of  Fat. — No  sharp  distinction 
can  be  made  between  pathological  and  physiological  accumulations 
of  fat,  and  it  is  often  merely  a  matter  of  opinion  as  to  whether 
a  given  person  is  too  stout  or  not.  The  line  separating  the  normal 
from  the  abnormal  should  be  drawn  at  the  point  where  the  general 
health  and  the  capabilities  of  the  individual  begin  to  be  impaired. 
When  these  are  affected,  we  are  justified  in  speaking  of  a  patho- 
logical accumulation  of  fat. 

Fat  tends  to  collect  in  certain  parts  of  the  body,  especially 
in  the  subcutaneous  tissues  and  the  mesentery,  and  about  the 
heart,  the  kidneys  and  the  liver.  In  young  animals  it  may  also 
collect  in  the  muscles  between  the  individual  muscle-fibres,^^ 
whereas  in  older  animals  it  tends  to  accumulate  in  the  above- 
mentioned  situations. 

The  individual  who  suffers  from  excessive  accumulations  of 
fat  gradually  becomes  less  and  less  able  to  work.  This  is  due,  in 
part,  to  the  increased  weight  of  the  body,  for  more  exertion  is 
required  to  execute  the  same  movements.  On  this  account,  fat 
persons  are  inclined  to  avoid  all  unnecessary  exertion.  This  be- 
ing the  case,  their  muscles  tend  to  atrophy  from  disuse,  and  the 
disproportion  between  the  body-weight  and  the  individual's  loco- 
motive power  constantly  increases.  The  patient  avoids  movements 
because  his  body  is  too  heavy;  and  the  lack  of  exercise  weakens 
his  muscles  so  that  he  is  less  able  to  move.  Most  stout  people 
also  perspire  very  readily,  because  their  thick  layer  of  fat  dimin- 
ishes the  amount  of  heat  given  off  from  the  surface  of  the  body 
by  radiation  and  conduction.  This  sweating  is  very  unpleasant, 
and  furnishes  another  excuse  for  their  avoiding  exercise. 

In  Rubner's  laboratory,  the  capabilities  of  lean  and  stout  men 
have  been  carefully  studied  under  different  conditions  of  tempera- 
ture and  humidity,^^  and  it  has  been  shown  that  as  the  temperature 


NUTRITION  AND  METABOLISM  315 

and  humidity  of  the  air  increase  the  ability  of  stout  people  to  work 
diminishes  rapidly,  for  they  quickly  become  overheated  and  per- 
spire profusely.  Their  fat  thus  renders  them  less  able  to  work 
and  soon  causes  unpleasant  subjective  sensations  from  over- 
heating. 

Finally,  very  stout  people  avoid  exertion  because  they  get  out 
of  breath  so  easily.  Their  dyspnoea  is  due,  in  the  first  place,  to  the 
increase  in  abdominal  fat,  which  limits  the  movements  of  the 
diaphragm;  in  the  second  place,  to  the  additional  weight  of  the 
body  which  necessitates  more  actual  work  for  the  accomplishment 
of  the  same  movements ;  in  the  third  place,  to  a  weakness  of  the 
muscles  or  to  an  associated  anaemia;  and  finally,  it  is  due  to  the 
cardiac  disturbances  which  are  so  often  present  in  obese  individ- 
uals and  which  have  already  been  described  (p.  43).  It  is  thus 
apparent  that  excessively  fat  persons  suffer  in  a  variety  of  ways, 
partly  on  account  of  the  presence  of  the  fat  itself  and  partly  on 
account  of  the  weakness  of  the  general  or  cardiac  musculature. 

The  primary  cause  of  obesity  lies  in  a  dispro- 
portion between  the  energy  taken  in  the  food 
and  the  amount  expended  by  the  body.  As  we  have 
just  said,  stout  people  usually  show  a  disinclination  to  exercise, 
and  this,  by  diminishing  the  expenditure  of  energy,  favors  the 
deposition  of  new  fat  in  the  body.  Furthermore,  many  stout 
persons  eat  to  excess,  and  the  carbohydrates  and  fats  in  their  diet 
are  especially  disadvantageous.  In  certain  instances,  the  absorp- 
tion of  proteids  seems  to  be  diminished,  and  the  patient  suffers, 
at  one  and  the  same  time,  from  too  much  fat  and  too  little  pro- 
teid.^*  Alcoholic  beverages  certainly  tend  to  increase  obesity. 
In  the  first  place,  they  furnish  a  not  inconsiderable  amount  of 
energy  in  the  form  of  alcohol,  and  frequently  also  in  the  form  of 
carbohydrates  (beer)  ;  and,  in  the  second  place,  they  tend  to  take 
away  the  energies  of  the  individual  and  so  to  diminish  the  exercise 
that  he  takes. 

These  causes,  singly  or  together,  are  responsible  for  most 
cases  of  obesity.  It  is  merely  a  problem  in  arithmetic.  A  certain 
amount  of  energy  is  taken  in  the  form  of  food,  a  certain  amount 
is  lost  as  heat  and  work,  and  the  remainder  is  stored  up  in  the 
body  mainly  as  fat.  As  soon  as  the  accumulation  of  fat  begins 
to  deter  the  patient  from  taking  active  exercise,  a  vicious  circle  is 
established  and  he  tends  to  increase  in  weight  more  and  more. 


316  THE  BASIS  OF  SYMPTOMS 

The  question  has  been  raised  as  to  whether  all  cases  of  obesity 
can  be  explained  in  this  comparatively  simple  manner.  Physicians 
certainly  have  the  impression  that  not  all  cases  are  due  to  a  simple 
disproportion  between  the  energy  taken  in  and  that  given  out; 
and  it  seems  as  if  many  persons,  in  spite  of  abundant  nourishment 
and  little  exercise,  remain  lean,  whereas  others  become  stout, 
even  though  they  eat  but  little  and  do  considerable  work. 

It  is  extremely  difficult  to  form  a  judgment  on  this  question. 
In  the  first  place,  it  often  happens  that,  although  the  patient  thinks 
he  is  not  eating  to  excess,  he  is  really  doing  so.  Then  we  have  no 
accurate  method  for  determining  the  amount  of  exercise  that  he 
takes.  There  are  the  most  extraordinary  individual  variations 
in  this  respect,  as  can  be  readily  imagined  if  we  compare  a  nervous 
individual,  constantly  in  motion  and  all  his  muscles  tense,  with  a 
phlegmatic  person  who  never  executes  an  unnecessary  movement. 
The  energy  expended  by  each  is  vastly  different,  even  while  they 
are  accomplishing  the  same  task.  Finally,  factors  that  influence 
heat  losses  must  be  considered,  such  as,  for  example,  the  thickness 
of  the  clothing,  the  temperature  of  the  surrounding  air,  its  mois- 
ture, etc.  All  these  influence,  to  some  degree,  the  consumption 
of  energy  in  the  body. 

Yet,  even  allowing  for  all  of  them,  there  still  remains  the 
impression  that  some  men  exhibit  an  unusual  relationship  between 
the  diet,  the  exercise  taken  and  the  fat  deposited.  Some  chil- 
dren,^^  for  example,  show  a  remarkable  tendency  to  become  stout ; 
or  certain  families  are  known  for  the  obesity  of  their  members; 
some  anaemic  persons  tend  to  accumulate  fat,  etc.  To  be  sure,  it 
may  be  answered  that  when  the  parent  eats  to  excess,  the  children 
learn  the  same  habit,  or  that  the  anaemias  tend  to  limit  the  amount 
of  exercise  taken,  etc.  Nevertheless,  the  impression  remains  that, 
for  some  unknown  cause,  certain  individuals  possess  a  peculiar 
tendency  to  lay  on  fat. 

We  should  not,  however,  trust  to  impressions.  The  question 
is  one  that  can  be  solved  only  by  careful  and  exact  experiments, 
and  up  to  the  present  these  have  furnished  no  evidence  which 
would  indicate  that  such  a  constitutional  tendency  to 
obesity,  in  the  sense  of  a  slower  rate  of  metabolism,  actually 
exists.  For  example,  Rubner  has  shown  that,  of  two  brothers, 
one  stout  and  the  other  thin,  the  former  burned  up  even  more 
fat  than  the  latter.     Others  have  demonstrated  that  stout  persons 


NUTRITION  AND  METABOLISM  317 

consume  a  normal  amount  of  oxygen  and  give  off  a  normal 
amount  of  carbonic  acid  gas  during  fasting;  ^^  and,  although  the 
increase  in  heat  production  that  immediately  follows  the  taking 
of  food  is  said  to  be  less  in  stout  than  in  thin  persons,  v/e  are 
hardly  justified  from  this  fact  alone  in  assuming  a  slower  rate 
of  metabolism  in  the  former. 

Recent  studies  have  shown  that  a  slower  rate  of  metabolism 
actually  may  be  present  in  obesity.  The  caloric  needs  in  the  ex- 
periments of  V.  Bergmann  and  Stahelin  ^^  were  so  small  that  one 
must  assume  the  possibility  of  a  constitutional  adiposity.  Graf  e  ^^ 
has  shown  that  a  similar  diminution  of  energy  expenditure  may 
occur  also  in  comatose  conditions. 

The  gain  in  weight  that  so  often  follows  castration  has 
been  cited  as  an  example  of  a  constitutional  change  leading  to 
obesity.  It  is  certain  that  many,  though  not  all,  castrated  animals 
and  men  gain  in  weight.  We  may  question,  however,  whether 
this  gain  is  directly  due  to  the  loss  of  a  hypothetical  accelerating 
influence  of  the  genital  organs  upon  metabolism,  or  whether  the 
gain  is  not  indirectly  due  to  changes  in  the  temperature  of  the 
individual,  in  his  appetite  for  food,  his  desire  to  exercise,  etc. 
Liithje^^  has  made  a  careful  comparative  study  of  the  nitrogen- 
ous metabolism,  and  a  partial  study  of  the  carbon  and  mineral 
metabolisms  of  castrated  and  normal  dogs  over  a  period  of  more 
than  a  year,  and,  finally,  at  the  end  of  this  time,  he  has  determined 
the  total  composition  of  their  bodies.  As  no  differences  could  be 
found  between  the  normal  and  pathological  animals,  we  must  con- 
clude from,  these  experiments  that  castration  does  not  directly 
affect  the  body  metabolism.  Although  other  observers ^^  have 
found  certain  differences  by  other  methods,  nevertheless  it  seems 
to  me  that  Liithje's  experiments  are  the  most  conclusive  we  have. 
Nor  have  studies  on  castrated  women  cast  any  doubt  upon  the 
validity  of  his  results. 

This  much  is  certain,  that  obesity  results  from  a  failure  to 
consume  all  of  the  nourishment  taken ;  but  that  a  lessened  rate  of 
cellular  metabolism  also  plays  an  important  part  in  certain  cases, 
has  been  shown  by  recent  observations.^^ 

The  association  of  obesity  with  anaemia,  with 
gout,  with  arteriosclerosis  and  with  various 
forms  of  calculi,  should  be  mentioned  here,  though  the 
exact  causal  relation  between  these  is  unknown  to  us.     Further- 


318  THE  BASIS  OF  SYMPTOMS 

more,  when  we  compare  the  many  similarities  in  the  picture  of 
myxcedema  and  obesity,  we  need  not  hesitate  in  attrib- 
uting to  a  lessened  activity  of  the  thyroid  gland  a 
part  in  the  abnormal  accumulation  of  fat.  (And,  finally,  various 
types  of  adiposity — adiposis  universalis,  dystrophia  adiposo- 
genitalis,  adiposis  dolorosa — have  come  to  be  regarded  as  mani- 
festations in  many  cases  of  an  insufficiency  of  the  pos- 
terior lobe  of  the  hypophysis,  associated  w'ith 
an  increased  tolerance  for  carbohydrates.  This 
accumulation  of  fat  may  be  due  to  a  primary  hypopituitarism, 
or  it  may  follow  a  period  of  increased  hypophysial  activity,  the 
end  stage  being  called  by  Gushing^*  dyspituitarism. — Ed.) 

Pathological  Changes  in  the  Metabolism  of  Proteids. — As  has 
been  described,  the  growing  child  and  the  convalescent  from  in- 
fectious diseases  are  both  able  to  retain  some  of  the  nitrogen 
taken  in  the  food;  whereas  a  normal  individual  under  like  cir- 
stances  would  soon  come  into  a  condition  of  nitrogenous  equi- 
librium. Even  in  the  above  instances,  however,  a  great  excess 
of  food  is  usually  taken,  for  such  individuals  have  an  enormous 
appetite. 

Pathological  Destruction  of  Proteid  Material. — If,  as  has  been 
said,  the  ingestion  of  proteids  falls  below  a  certain  limit,  or  if  the 
body  has  no  non-nitrogenous  material  at  its  disposal,  and  is  not 
oversupplied  with  proteids  in  the  food,  then  the  living  nitrogenous 
substances  in  the  tissues  must  be  consumed  to  supply  the  body 
needs.  In  the  class  of  cases  which  we  now  wish  to  consider,  how- 
ever, there  is  a  pathological  consumption  of  the  body  substance, 
and  especially  of  its  proteids,^ ^  even  though  an  ordinary  amount 
of  food  be  taken.  If  such  a  patient  fasts,  his  excretion  of  nitrogen 
is  considerably  greater  than  is  that  of  a  normal  individual  of  like 
weight,  etc.  If  an  attempt  be  made  to  bring  him  into  a  condition 
of  nitrogenous  equilibrium,  it  is  often  a  complete  failure,  for  as 
proteids  are  added  to  his  diet  the  consumption  of  nitrogenous 
material  also  increases,  so  that  the  output  of  nitrogen  remains 
constantly  somewhat  greater  than  the  intake.  In  certain  of  these 
cases,  however,  it  is  possible  to  maintain  a  nitrogenous  equi- 
librium by  using  enormous  quantities  of  food. 

We  must  not  lose  sight  of  the  fact,  however,  that  what  we 
call  a  pathological  destruction  may  be  only  a  disturbance  in  the 
power  of  the  body  to  synthetize  proteids — a  process  which  prob- 


NUTRITION  AND  METABOLISM  319 

ably  plays  a  larger  role  in  metabolism  than  is  generally  supposed. 
And  it  is  possible  that  fats  and  carbohydrates  have  an  altered 
influence  upon  proteid  metabolism  in  the  pathological  types  of 
proteid  destruction  we  are  considering.  For  example,  in  certain 
disorders  of  the  liver,  a  considerably  larger  amount  of  carbohy- 
drates than  under  normal  conditions  is  necessary  to  insure  a  proper 
fat  consumption  without  an  associated  destruction  of  the  body 
proteids.^^ 

A  pathological  proteid  destruction  of  this 
character  takes  place  in  all  forms  of  fever,  and  will  be 
referred  to  again  in  that  connection.  It  also  occurs  in  many 
patients  with  carcinomata^^  and  other  malignant  tumors, 
in  many  with  tuberculosis,  even  though  no  fever  is  pres- 
ent, in  severe  anaemias^®  and  in  certain  intoxica- 
tions, as  from  phosphorus. ^^  Possibly,  also,  it  is  pres- 
ent in  other  conditions,  such  as  scleroderma,  lichen  ruber  and 
pemphigus  vegetans.  In  these  conditions,  it  is  not  the  disease 
per  se  which  determines  the  destruction,  but  rather  some  con- 
dition, as  yet  not  understood,  of  the  tissues  themselves. 

In  the  chronic  leukaemias,  even  in  those  without  fever,  metabo- 
lism as  a  whole  is  increased,  though  proteid  destruction  is  appar- 
ently unaffected.*^ 

In  the  conditions  enumerated,  excessive  quantities  of  fat  are 
also  frequently  consumed,  for  the  diet  is  often  an  insufficient  one, 
but  this  consumption  follows  the  ordinary  physiological  laws  of 
inanition;  whereas  the  destruction  of  proteids  is  of  a  pathological 
character.  Which  cells  of  the  body  suffer  most  from  this  con- 
sumption of  proteids  has  never  been  determined,  though  one  would 
be  inclined  to  believe  the  loss  falls  on  the  same  organs  as  it  does 
in  inanition  (see  p.  308). 

Not  all  patients  with  carcinomata,  severe  anaemias  or  tuber- 
culosis suffer  from  this  increased  destruction  of  proteids;  and  it 
would  appear,  therefore,  that  other  factors  are  operative  in  these 
cases.  In  view  of  the  fact  that  certain  poisons,  such  as  phos- 
phorus, may  accelerate  the  destruction  of  proteid  material, 
F.  Miiller  has  advanced  the  hypothesis  that  toxic  sub- 
stances are  also  responsible  for  the  increased 
proteid  destruction  in  certain  cases  of  carcinoma. 
These  toxic  substances  have  never  been  isolated,  yet  there  is 
every  reason  to  believe  that  this  explanation  is  a  correct  one. 


320  THE  BASIS  OF  SYMPTOMS 

Only  when  this  hypothetical  poison  is  produced  does  the  disease 
lead  to  a  destruction  of  proteid  material.  This  theory  is  sup- 
ported by  the  fact  that  in  tuberculosis  and  carcinoma  we  some- 
times see  toxic  symptoms  resembling  those  of  diabetic  coma. 

In  the  light  of  our  present  conception  that  the  body  may  build 
its  own  proteids  from  the  simpler  components  of  the  latter,  it  is 
possible  that  a  patfiological  proteid  destruction  may  be  due  to  a 
toxic  disturbance  of  this  synthetic  process.  As  amino-acids  are 
built  up  from  keto-acids  (an  intermediate  step  in  the  combustion 
of  carbohydrates)  and  ammonium  salts,  it  is  readily  understood 
how  carbohydrates  may  affect  the  elimination  of  nitrogen.*^ 

In  carcinoma,  special  factors  play  a  role  in  the  destruction 
of  proteids.  According  to  Blumenthal,*^  ulceration  of  the  pri- 
mary growth  and  the  formation  of  metastases  have  a  distinct 
influence  upon  the  body  proteids.  Schmidt  ^^  attributes  this  to 
the  formation  of  a  heterolytic  ferment,  which  under  given  con- 
ditions enters  the  circulation.  Though  this  is  still  disputed,** 
Abderhalden  observed  certain  differences  in  the  behavior  of  fer- 
ments from  healthy  and  carcinomatous  tissues  (see  p.  i86). 

A  pathologically  increased  nitrogenous  metabolism  is  most 
serious,  for  it  becomes  impossible  to  maintain  the  patient's  nutri- 
tion, and  the  loss  of  proteids  may  eventually  prove  fatal. 

The  Metabolism  in  Thyroid  Disease. — Many  patients  with 
exophthalmic  goitre  manifest  no  peculiarities  as  regards  their 
metabolism ;  others,  however,  show  periods  of  fair  to  good  nutri- 
tion alternating  with  periods  of  emaciation.  This  emaciation 
may  occur  even  when  the  appetite  is  considerably  increased. 
One  of  F,  Miiller's  patients,*^  for  example,  weighing  only  twenty- 
nine  kilos  (sixty- four  pounds),  lost  both  in  nitrogen  and  general 
weight,  even  though  the  diet  furnished  as  much  as  sixty-eight 
grams  of  proteids  per  day  and  fifty-eight  calories  for  each  kilo 
of  body  weight.  In  such  cases  a  pathological  consumption  of 
both  nitrogenous  and  non-nitrogenous  material  is  undoubtedly 
taking  place  in  the  body.  Steyrer,*^  on  the  contrary,  found  no 
increase  in  nitrogen  elimination  or  in  metabolism  as  a  whole, 
in  cases  of  hyperthyroidism  which  were  given  thyroid  extract. 
Magnus-Levy  *''^  observed  an  increased  oxygen  consumption  in 
hyperthyroidism  whether  the  individual  was  at  rest  or  not,  due 
probably  to  the  marked  motor  unrest.    As  a  rule,  it  is  possible 


NUTRITION  AND  METABOLISM  321 

to  attain  a  nitrogenous  and  caloric  equilibrium  in  these  patients 
by  giving  them  very  large  quantities  of  food.*® 

It  is  very  interesting  that,  in  Matthes's  cases,  the  excessive 
consumption  of  proteid  material  disappeared  after  the  removal 
of  a  large  part  of  the  thyroid  gland,  thus  conclusively  demon- 
strating that  the  pathological  thyroid  function  in- 
creased the  consumption  of  nitrogenous  and 
non-nitrogenous  material  in  the  body.  It  was 
found,  furthermore,  that  when  the  substance  of  the  thyroid  gland 
was  administered  to  these  patients  after  their  operations,  the 
excretion  of  nitrogen  rose  to  what  it  had  been  previously. 

The  amounts  of  oxygen  absorbed  and  of  car- 
bon dioxide  eliminated  by  patients  with  exoph- 
thalmic goitre  are  greater  than  the  normal.*® 
This  is  in  accord  with  the  observation  that  after  the  removal 
of  the  thyroid  gland  from  rabbits,  these  animals  show  an  abnor- 
mally low  "respiratory  interchange  of  gases"  when  fasting; 
and,  if  thyroid  substance  be  then  administered  to  them,  this  inter- 
change returns  to  the  normal.^^  We  see,  therefore,  that  in  cer- 
tain patients  with  exophthalmic  goitre  there  is  an  increased  con- 
sumption not  only  of  proteids  but  also  of  non-nitrogenous  mate- 
rials. In  this  last  feature  the  metabolism  differs  from  the  increased 
proteid  metabolism  of  carcinoma;  and  it  is  possible  that  the  loss 
of  proteids  in  exophthalmic  goitre  is  merely  secondary  to  the  loss 
of  non-nitrogenous  material. °^ 

The  administration  of  the  thyroid  gland  to 
healthy  men  or  animals,  either  by  way  of  the  digestive  tract 
or  by  subcutaneous  injections,  increases  the  bodily  consumption 
of  proteids  and  fats.^^  In  a  certain  proportion  of  cases  this  loss 
may  be  covered  by  an  abundant  diet.  Here  again  it  is  uncertain 
whether  the  destruction  of  proteids  is  secondary  to  the  destruction 
of  fats  or  not,  though  in  general  it  would  appear  that  the  proteids 
are  directly  affected  and  not  because  of  a  deficiency  of  fats. 

Metabolism,  as  a  whole,  is  sometimes  moderately  increased 
after  thyroid  extract  administration,  and  at  other  times  unchanged. 
Hence,  the  loss  in  weight  suffered  by  stout  individuals  who  have 
been  given  thyroid  extract  cannot  be  due  solely  to  a  generally 
augmented  metabolism,  but  must  depend  in  great  part  upon  the 
increased  exercise  which  is  prescribed. 

It  is  not  unlikely  that  a  physiological  func- 

21 


322  THE  BASIS  OF  SYMPTOMS 

tion  of  the  thyroid  gland  is  the  regulation  of  the 
body  metabolism.  At  any  rate,  we  often  meet  with  in- 
dividuals whose  metabolic  processes  exhibit  marked  quantitative 
changes  and  whose  thyroid  glands  suggest  variations  from  the 
normal,  not  in  the  sense  of  an  exophthalmic  goitre.  For  example, 
an  emaciation  often  follows  the  exhibition  of  small  doses  of 
iodin,  which  clinically  bears  a  close  resemblance  to  thyroid 
cachexia.  Peculiar  factors  must  be  at  work  here,  however,  for 
iodin  ordinarily  does  not  augment  metabolism.^^ 

If  the  function  of  the  thyroid  gland  be  dimin- 
ished below  a  certain  point,  nutritional  disturbances  may  de- 
velop in  the  skin,  nails,  bones  and  other  organs. ^^  The  skin 
becomes  thick  and  immobile,  owing  to  a  collection  of  mucin-like 
material  in  the  corium,  the  connective-tissue  fibrils  thicken  and 
the  hair  falls  out.  Weakness  of  the  muscles  and  disturbances  of 
sensation  are  associated  with  a  general  loss  of  intelligence;  and 
if  the  glands  be  removed  from  growing  animals,  the  growth  may 
be  stunted.  Metabolism  in  these  cases  is  gener- 
ally and  markedly  slowed  and  diminished,  both 
as  regards  the  destruction  of  proteids  and  the 
consumption  of  energy  in  general. ^^  After  extir- 
pation of  the  thyroid,  fats  and  carbohydrates  do  not  reduce  proteid 
destruction  to  nearly  as  marked  a  degree  as  they  do  normally. ^^ 
In  general  the  manifestations  of  thyroid  insufficiency  depend 
upon  the  rapidity  with  which  the  changes  in  its  secretion  have 
occurred  and  particularly  upon  the  age  of  the  individual. 

These  symptoms  closely  resemble  those  of  myxcedema 
and  cretinism,^''^  conditions  in  which  the  thyroid  gland  is 
found  to  be  diseased  or  absent.  The  variations  in  symptoms  seen 
in  these  diseases  are  probably  due  to  the  varying  intensity  and 
character  of  the  thyroid  lesion,  as  well  as  to  the  age  of  the  patient 
when  the  disease  began.  The  changes  in  myxcedema  and  cretinism 
are  to  be  attributed,  therefore,  to  an  insufficient  function  on  the 
part  of  the  thyroid  gland.  As  proof  of  this  we  have  the  remark- 
able results  obtained  by  the  administration  of  thyroid  substance 
to  these  patients.^^  It  is  important  to  remember  that  partially 
developed  cases  (formes  frustes)  of  hypothyroidism,  as  well  as  of 
hyperthyroidism,  are  not  uncommon  among  all  peoples. 

Exophthalmic  goitre,  on  the  contrary,  is  probably 
due  to  an  increased  thyroid  function,^*     In  favor  of 


NUTRITION  AND  METABOLISM  323 

this  view  are  the  facts  that  a  partial  extirpation  of  the  thyroid 
has  improved  or  cured  many  patients  with  this  disease,  and  that 
the  administration  of  large  quantities  of  thyroid  substance  to  a 
normal  individual  will  produce  symptoms  resembling,  to  a  certain 
degree,  those  of  exophthalmic  goitre. 

The  picture  of  hyperthyroidism  is  a  variable 
one.*^^  The  individual  case  may  be  mild  or  severe,  and  its  course 
chronic  or  very  rapid.  Of  great  theoretical  importance  is  the 
question  whether  the  manifestations  of  this  disease  are  the  result 
merely  of  a  hypersecretion  of  the  normal  products  of  the  thyroid 
gland  or  whether  there  is  an  associated  chemical  alteration  of  the 
latter.  Though  this  question  is  still  sub  judice,  it  seems  to  me 
that  the  change  is  purely  a  quantitative  one;  speaking  for  this 
are  the  results  of  surgical  interference,  as  well  as  the  production 
of  the  characteristic  symptoms  in  animals  and  in  man  by  feeding 
not  only  extracts  of  the  gland,  but  also  iodin  and  its  compounds.^^ 
Baumann  has  familiarized  us  with  the  role  of  the  thyroid  in  iodin 
economy,  and  has  shown  that  in  certain  individuals — in  those 
particularly  whose  thyroids  are  already  functionally  disturbed — 
the  exhibition  even  of  small  doses  of  iodin  suffices  to  render  the 
thyroid  overactive. 

The  activities  of  the  thyroid  are  also  intimately  bound  up 
with  those  of  the  nervous  system.  Many  cases  of  hy- 
perthyroidism are  of  nervous  origin.  That  the 
nervous  system  directly  or  indirectly  stimulates  the  gland  is  a 
possibility,  for  we  are  still  uncertain  whether  hyperthyroidism 
rests  upon  a  primary  disturbance  of  the  thyroid  gland.  The 
glands  of  internal  secretion  are  all  intimately  de- 
pendent upon  nervous  and  psychic  factors,  and  the  evidence  of 
the  latter  is  almost  a  regular  accompaniment  of  hyperthyroidism. 

The  pathological  substratum  of  Basedow's 
disease  is  not  specific,  despite  the  frequency  of  such  findings 
as  changes  in  the  colloid  and  an  epithelial  hyperplasia,  as  well 
as  lymphoid  infiltration.^^  At  any  rate,  the  clinical  picture  may 
arise  in  association  with  strumas  of  various  types  or  even  in  the 
apparent  absence  of  thyroid  changes. 

The  symptom-complex,  as  we  have  already  empha- 
sized, is  extraordinarily  variable.  Rudimentary  forms 
with  a  few  manifestations  are  extremely  common.  Personally, 
I  am  strongly  convinced  that  from  a  simple  goitre  a  series  of 


324  THE  BASIS  OF  SYMPTOMS 

thyreotoxic  conditions  may  arise,  varying  from  the  mildest  to 
the  most  severe  types.  It  is  advisable  perhaps,  for  clinical  reasons, 
to  distinguish  these  transitional  forms,  such  as  the  K  r  o  p  f  - 
herz,  though  this  represents  merely  one  manifestation  of  the 
many.  On  the  other  hand,  one  of  the  characteristic  evidences  of 
hyperthyroidism — an  augmented  metabolism — ^may  be  absent  even 
in  severe  cases  of  the  disorder. 

The  origin  of  the  various  symptoms  of  Basedow's  disease  is 
not  known.  Certain  factors  point  to  increased  sympathetic  irrita- 
bility. Furthermore,  we  would  call  attention  again  to  the  interre- 
lationship of  the  ductless  glands,  though  the  weighty  observa- 
tions^^ reported  from  the  Gottlieb  institute  relative  to  a  non- 
increase  of  epinephrin  in  the  blood  of  Basedow  patients  suggest 
caution  in  this  respect. 

There  seems  good  reason  to  believe,  despite  the  inherent  com- 
plexity of  the  problem,  that  the  thyreotoxicoses  are  susceptible 
of  clear-cut  classification;  though  I  would  discard  such  vague 
subdivisions  as  vagotropic  and  sympathicotropic,^*  and  also  a 
classification  based  upon  the  poly  valence  of  the  thyroid  substances. 

The  parathyroid  glands  are  functionally  distinct  from 
the  thyroids,  and  their  complete  removal  from  animals  is  followed 
by  tetany. ^^  In  accordance  with  this  experimental  fact  is  the 
experience  that  in  those  clinics  where  the  method  of  extirpation 
of  the  thyroid  involved  a  simultaneous  removal  of  the  parathyroids 
the  patients  showed  a  special  tendency  to  tetany.  The  exact  way 
in  which  the  parathyroids  affect  the  nervous  system  is  not  known. 
(It  would  appear  from  the  studies  of  several  observers®®  that 
the  parathyroids  exert  their  effect,  in  part  at  least,  via  the  sym- 
pathetic nervous  system.  Complete  extirpation  of 
the  glands  in  dogs  leads  to  a  marked  increase  of  vasomotor 
irritability.  That  this  may  be  a  result  of  calcium  deficiency  is 
indicated  by  the  fact  that  subsequent  injections  of  calcium  salts 
tend  to  restore  this  irritability  to  its  normal  level. — Ed.  ) 

The  Qualitative  Changes  in  Metabolism 

Unfortunately,  we  know  but  little  concerning  the  intermediary 
stages  through  which  the  various  constituents  of  the  body  pass 
before  they  are  finally  eliminated  through  the  excretory  organs 
as  highly  oxidized  products.  Though  it  would  be  logical  to 
discuss  the  catabolism  of  each  substance  separately,  and  to  follow 


NUTRITION  AND  METABOLISM  325 

each  to  its  excretion,  this  is  not  possible  with  our  present  limited 
knowledge.  For  this  reason,  therefore,  we  shall  merely  consider, 
first,  certain  facts  concerning  the  proteids,  and,  later,  certain 
abnormal  excretory  products. 

The  proteids  taken  in  the  food  are  split  up  in  the  body 
into  nitrogenous  and  non-nitrogenous  constituents.  The  former 
probably  consist  of  ammonium  compounds;  and  the  greater  part 
of  these  are  synthesized  into  urea,  probably  in  the  liver,  and 
are  then  eliminated  through  the  kidneys.  Nitrogen  is  present  in 
the  urine  in  various  forms,  about  eighty-five  per  cent,  being  urea, 
from  two  to  five  per  cent,  ammonia,  and  the  remaining  ten  per 
cent,  a  variety  of  compounds  of  which  uric  acid  and  the  purin 
bases  form  a  large  part. 

Whether  or  not  the  proteid  catabolism  in  the  body  follows 
the  same  course  as  it  does  in  the  digestive  tract — ^viz.,  albumoses, 
peptones  and  amino-acids — has  not  yet  been  determined.  Patho- 
logically, at  least,  albumoses  and  amino-acids  may  be  formed, 
for  they  are  demonstrable  in  the  urine,  as  will  be  shown  in  dis- 
cussing the  subject  of  autolysis  (p.  326). 

Autolysis. — If  the  organs  of  the  body  are  kept  aseptically  at 
37°  C.  for  some  time,  their  proteids  undergo  hydrolytic 
cleavage,  owing  to  the  action  of  enzymes  that  are  present  in 
the  cells.^^  Albumoses  and  peptones  have  not  been  demonstrated 
as  products  of  this  "autolysis,"  presumably  because  they  are  so  rap- 
idly split  up  into  amino-acids,  basic  substances,  fatty  acids,  hydro- 
gen sulphid,  carbohydrates,  etc.  The  nucleo-proteids  are  decom- 
posed into  proteids  and  the  nucleinic  acids,  and  the  latter  in  turn 
into  phosphoric  acid  and  the  purin  bases.  It  is  an  interesting  fact 
that  the  enzymes  in  any  particular  class  of  cells  will  split  up  the 
proteids  of  those  cells  more  readily  than  they  will  proteids  from 
other  sources.  To  what  extent  the  cleavage  of  proteids  within 
the  normal  body  resembles  autolysis  is  not  known,  for  normally 
the  intermediary  products  of  proteid  catabolism,  such  as  the 
amino-acids,  do  not  appear  in  the  urine.  This  last  is  not 
conclusive,  however,  for  it  is  possible  that  the  normal  organism 
oxidizes  them  so  rapidly  that  their  existence  is  a  short  one.  Speak- 
ing for  this  hypothesis  is  the  fact  that  even  in  conditions  in  which 
large  amounts  of  proteid  are  hydrolyzed  (phosphorus  poisoning, 
acute  yellow  atrophy  of  the  liver)  amino-acids  may  not  appear 
in  the  urine,  or,  if  they  do,  their  amount  is  small.     Albu- 


326  THE  BASIS  OF  SYMPTOMS 

moses^®  have  been  found  by  some  observers  in  the  blood  of 
healthy  individuals,  but  this  has  not  been  generally  confirmed*^ 

(c/.  p.  139). 

The  products  of  a  hydrolytic  cleavage  of  pro- 

teids  are,  however,  excreted  under  pathological 
conditions,  especially  when  dead  cells  or  fibrin  are  left  to 
themselves,  as  occurs  in  abscesses,  in  the  resolving  stage 
of  pneumonia,"^*  in  acute  yellow  atrophy  of  the 
liver  and  in  phosphorus  poisoning.  In  these  condi- 
tions, albumoses  and  even  peptones  may  appear  in  the  urine. 

Since  the  above  conditions  are  caused  by  toxic  or  infectious 
processes,  the  question  naturally  arises  as  to  whether  the  hydro- 
lytic cleavage  of  the  proteids  is  due  directly  to  the  toxins  or  bacteria 
that  cause  the  disease,  or  whether  it  is  due  to  the  action  of  intra- 
cellular enzymes  and  is  of  the  nature  of  an  autolysis.  The  former 
view  seems  rather  improbable,  for  Miiller  has  shown  that  the 
pneumonic  exudate  exhibits  no  tendency  to  undergo  hydrolytic 
cleavage  so  long  as  but  few  leucocytes  are  present,  even  though 
the  bacteria  have  been  constantly  at  hand.  As  has  already  been 
mentioned,  the  tissues,  even  when  free  from  all  bacteria,  contain 
proteolytic  enzymes,  and  it  seems  probable  that  these  are  respon- 
sible for  the  abnormal  decomposition  in  the  above-mentioned 
conditions. 

During  the  involution  of  the  puerperal  uterus 
the  muscle-fibres  also  undergo  autolysis,  and  the  resulting  products 
may  appear  in  the  urine."^^ 

In  many  diseases  of  the  liver  no  abnormal  end- 
products  of  proteid  decomposition  are  excreted.  In  other  more 
serious  and  extensive  hepatic  conditions,  various  pathological 
substances  appear,  and  in  acute  yellow  atrophy  and  phosphorus 
poisoning,  especially,  the  urine  may  contain  albumoses,'^  or  even 
peptones,''^^  as  well  as  leucin,  tyrosin,  para-oxyphenylacetic  acid 
and  lysin."^*  These  substances  appear  to  arise  mainly  from  an 
autolysis  of  the  liver  cells,  but  in  some  cases  the  quantity  in  the 
blood  is  so  great  that  they  could  not  possibly  have  all  originated 
in  this  manner,  and  some  must  have  come  from  other  tissues.'^® 

By  means  of  Emil  Fischer's  improved  technic  for  the  detection 
of  amino-acids,'^^  we  have  learned  that  these  bodies  are  present 
in  not  inconsiderable  amount  in  the  urine  even  of  healthy  indi- 


NUTRITION  AND  METABOLISM  327 

viduals  J^  They  appear  also  in  such  conditions  as  gout,  leukaemia 
and  the  infectious  diseases,  though  not  in  excessive  quantities. 

The  Formation  and  Excretion  of  Ammonia. — Normally, 
from  two  to  five  per  cent,  of  the  total  nitrogen  excreted  appears 
in  the  urine  in  the  form  of  ammonium  salts.  Under  pathological 
conditions,  however,  the  proportion  may  be  greatly  increased; 
and  in  acute  yellow  atrophy,  for  example,  it  may  reach  thirty- 
seven  per  cent.,  and  in  starvation  even  fifty-seven  per  cent. 

An  increased  excretion  of  ammonia  is  not  the  result  of  an 
increased  production  of  this  compound  within  the  body;  for  large 
quantities  of  the  ammonium  salts  of  organic  acids  may  be  taken 
by  the  mouth  with  only  an  insignificant  increase  in  their  elimina- 
tion in  the  urine.'®  The  quantity  of  ammonium 
salts  in  the  urine  is  to  be  regarded  rather  as  an  in- 
dication of  an  excessive  quantity  of  acid  in  the 
body.  The  ammonia  normally  formed  in  metabolism,  instead 
of  being  transformed  into  urea,  combines  with  the  excessive  acids, 
and  is  excreted  by  the  kidneys  as  the  ammonium  salts  of  these 
acids.  The  body  thereby  retains  for  the  most  part  its  fixed  alka- 
lies for  the  transportation  of  carbon  dioxide.  Eppinger"^^  sees 
in  the  differing  behavior  of  herbivora  and  carnivora  in  respect 
to  their  ability  to  neutralize  excessive  acids,  only  the  result  of 
their  dissimilar  foods ;  in  other  words,  he  believes  that  the  am- 
monia employed  in  the  neutralization  of  acids  arises  not  from  the 
body  proteids,  but  from  those  ingested.  Indeed,  the  administration 
of  large  amounts  of  alkalies  may  cause  a  complete  disappearance 
of  the  urinary  ammonia.  Walter®^  found  that,  after  adminis- 
tering hydrochloric  acid  to  dogs,  about  three- fourths  of  it  was 
neutralized  by  ammonia  in  the  body,  while  most  of  the  remainder 
went  to  raise  the  acidity  of  the  urine,  and  a  small  part  apparently 
combined  with  the  fixed  alkalies  of  the  blood.  This  last  effect  is 
serious,  for  the  ability  of  the  blood  to  carry  carbon  dioxide  is 
thereby  diminished  (see  p.  224). 

An  excessive  excretion  of  ammonia  is  indicative,  therefore, 
of  an  excessive  amount  of  acid  in  the  body.  The  amount 
of  ammonia  in  the  urine  is  increased  whenever 
the  proteids  of  the  diet  are  increased  at  the  ex- 
pense of  the  carbohydrates,  for  the  reason  that  pro- 
teids furnish  an  acid  ash.  The  amount  is  increased,  furthermore, 
whenever  there  is  a  pathological  breaking  down  of 


328  THE  BASIS  OF  SYMPTOMS 

the  tissues,  for  this  is  equivalent  to  an  increased  proteid 
catabolism.  In  diabetes,  an  excessive  amount  of  organic 
acids  may  be  formed,  thus  increasing  the  elimination  of  ammo- 
nium salts.  Finally,  an  abnormal  excretion  of  ammonia  is  the 
rule  infebrileconditions^^  and  may  also  accompany  various 
chronic  diseases,  especially  of  the  liver.  In 
phosphorus  poisoning,  the  output  is  both  relatively  and 
absolutely  increased  and  may  reach  seventeen  per  cent. 

That  the  increased  elimination  of  ammonia  is  purely  secondary 
has  been  proved  by  the  fact  that,  if  alkalies  be  administered  to 
patients  who  excrete  excessive  quantities  of  ammonia  in  the  urine, 
the  abnormal  acid  in  the  body  will  be  neutralized,  the  excessive 
excretion  of  ammonium  compounds  diminished  and  the  excretion 
of  urea  correspondingly  increased. 

In  some  instances  the  origin  of  the  abnormal  acid- 
it  y  is  readily  determined.  Mineral  acids  may  have  been 
taken  by  mouth,  either  accidentally  or  with  suicidal  intent.  In 
phosphorus  poisoning,  the  rapid  destruction  of  cellular 
protoplasm  liberates  the  sulphur  and  phosphorus  contained  in 
the  proteid  molecules,  and  these  give  rise  to  sulphuric  and  phos- 
phoric acids  in  considerable  quantities.  In  addition  to  these, 
various  organic  acids,  such  as  lactic  and  aromatic  acids,  are  formed 
in  phosphorus  poisoning,  and  this  excessive  acid  production  is 
sufficient  to  account  for  the  increased  excretion  of  ammonia 
which  takes  place  in  this  condition.  In  many  diseases,  however, 
the  explanation  is  not  so  close  at  hand  and  we  must  assume  that 
organic  acids  are  produced  to  account  for  the  increased  ammonia 
excretion. 

The  Production  of  Organic  Acids. — Organic  acids,  especially 
carbonic  and  carbamic  acids,  are  being  constantly  formed  in  nor- 
mal metabolism.  These  particular  acids,  however,  are  not  elim- 
inated in  ammonia  combinations,  for  the  carbonic  acid  leaves  the 
body,  for  the  most  part,  through  the  lungs,  and  the  ammonium 
salt  of  carbamic  acid  can  be  transformed  into  urea  in  the  liver. 
The  organic  acids  that  are  most  frequently  eliminated  as  ammo- 
nium compouHds  are  beta-oxybutyric  and  diacetic 
acids. 

It  is  remarkable  that  sarcolactic  acid  is  not  more  fre- 
quently found  in  the  urine,  for  we  know  that  it  is  normally  formed 
in  considerable  quantity  during  muscular  activity.     Under  such 


NUTRITION  AND  METABOLISM  329 

circumstances,  however,  it  is  apparently  rapidly  oxidized.  It  prob- 
ably arises  from  the  non-nitrogenous  products  of  proteid  cleavage, 
although  it  is  possible  that  it  may  also  arise  in  part  from  the 
carbohydrates,  in  view  of  the  close  relationship  that  we  now  know 
to  exist  between  the  latter  and  proteids.  Pathologically,^  ^  lactic 
acid  has  been  found  in  the  urine  in  cases  of  phosphorus  poison- 
ing, trichinosis,  pernicious  anaemia,  severe  heart  disease,  acute 
yellow  atrophy  and  in  animals  during  arsenical  poisoning  and  after 
severe  hemorrhage.  Yet  in  none  of  these  conditions,  with  the 
possible  exceptions  of  phosphorus  poisoning  and  acute  yellow 
atrophy,  does  lactic  acid  regularly  appear  in  the  urine.  In  some 
instances,  its  appearance  is  due  to  a  diminution  in  the  oxidative 
processes  within  the  body,®^  especially  in  the  liver,  and,  in  still 
others,  to  unknown  causes.  Ethyliden-lactic  acid  has 
been  found  in  the  urine  in  severe  cases  of  diabetes,  and  at  times 
propionic  and  acetic  acids  have  also  been  found. 

Of  all  the  organic  acids,  beta-oxybutyric  is  the  most 
important  in  this  respect,  for  it  appears  in  the  urine  not  very 
infrequently,  and  is  sometimes  excreted  in  enormous  quantities. 
By  oxidation  of  this  acid,  diacetic  acid  is  formed;  though 
the  process  may  be  reversed — ^beta-oxybutyric  acid  is  formed  from 
diacetic  acid  by  reduction — as  recent  studies  ®*  have  shown.  Ace- 
tone probably  does  not  arise  in  the  cellular  metabolism  proper, 
but  rather  in  the  lungs  and  kidneys,  through  which  it  is  excreted, 
in  the  former  case  giving  to  the  breath  the  characteristic  "  fruity  " 
odor.  The  condition  underlying  the  building  of  these  so-called 
acetone  bodies  is  known  as  acidosis.*^ 

Normally  these  bodies  are  oxidized  to  carbon  dioxide  and 
water  in  the  body,  and  only  traces,  at  most,  of  acetone  are  excreted 
in  the  urine.  Under  various  abnormal  conditions, 
however,  they  may  leave  the  body  unoxidized.  This 
may  occur  during  hunger,^®  after  anaesthesia,  during  a  salt-free 
diet,®^  in  many  cases  of  diabetes,^*  and,  in  general,  in  severe 
states  of  inanition.  Experimentally,  beta-oxybutyric  acid  may 
appear  in  the  urine  of  dogs  after  phlorhizin  poisoning*^  and  after 
extirpation  of  the  pancreas,  though  the  latter  is  rare.  At  times, 
some  one  or  several  of  these  compounds,  but  especially  acetone, 
will  appear  in  the  urine  without  any  apparent  cause.*^  It  is  pos- 
sible in  these  obscure  cases,  that  it  arises  from  the  absorption  of 
toxic  substances  from  the  intestines ;  yet  even  in  the  acid  intoxi- 


830  THE  BASIS  OF  SYMPTOMS 

cations  occurring  especially  in  children,  and  associated  with  pro- 
fuse diarrhoeas,  the  acidosis  is  not  intestinal  in  origin,  but  rather 
the  result  of  a  carbohydrate  deficiency.  It  was  formerly  held  that 
the  acetone  bodies  might  be  formed  within  the  intestinal  canal, 
but  at  present  there  is  but  little  inclination  to  refer  their  origin 
to  this  source.  In  the  majority  of  cases,  at  least,  they  are  pro- 
duced during  the  intermediary  metabolism  within  the  body. 

As  beta-oxybutyric  acid  and  its  derivatives  are  not  of  regular 
occurrence  in  the  conditions  mentioned  above,  we  must  assume 
that  special  factors  are  influential.  Prominent  among  these  is  a 
deficiency  of  carbohydrates,  be  it  that  the  amount 
ingested  is  too  small,  as  in  starvation,  or,  with  a  sufficient 
supply,  that  it  is  improperly  utilized,  as  in  diabetes.  The 
acetone  bodies  occur  promptly  in  man  and  in  the  ape  during  star- 
vation, and  in  dogs,  on  the  contrary,  very  tardily.  This  starva- 
tion acidosis  disappears  forthwith  if  carbohydrates  or  even  pro- 
teids  in  large  amounts  are  ingested.  In  the  latter  case,  the  carbo- 
hydrate arising  from  the  proteid  is  apparently  the  influential 
element. 

Though  the  lack  of  carbohydrates  is,  undoubtedly,  an  im- 
portant factor  in  the  causation  of  acidosis,  it  is  just  as  certainly 
not  the  sole  one  in  all  cases.  In  many  of  these  there  is  an  inter- 
mediate and  as  yet  unknown  anomaly  in  carbohydrate  metabolism 
which  plays  the  determining  role;  though  in  still  others,  the 
utilization  of  carbohydrates  seems  to  be  quite  normal. 

In  no  condition  do  the  acetone  bodies  appear 
in  the  urine  in  such  quantities  as  in  diabetes  mel- 
litus.  Our  knowledge  of  the  conditions  underlying  their 
formation  and  excretion  is  derived  principally  from  studies  of 
exj>erimental  diabetes  in  animals  and  of  the  disease  in  man. 
Acidosis  is  common  and  pronounced  in  phlorhizinized  animals. 
After  pancreas  extirpation,  on  the  contrary,  it  is  decidedly  less 
frequent.  In  human  diabetes  it  may  or  may  not  be  present,  being 
most  likely  to  occur  in  the  very  severe  cases,  i.e.,  those  with  a  low 
sugar  tolerance.  The  transition  from  a  mixed  to  a  strict  meat  diet 
favors  its  appearance  or  intensifies  it  if  it  is  already  present.  A 
diminished  combustion  of  carbohydrates  in  the 
intermediary  metabolism  is,  therefore,  an  import- 
ant factor  in  the  causation  of  diabetic  acidosis, 
though  not  the  only  and  determining  factor.     Nor  does  proteid 


NUTRITION  AND  METABOLISM  331 

destruction  play  this  important  role,  for  Weintraub®^  has  ob- 
served an  acid  intoxication  in  cases  of  nitrogen  equilibrium  and 
indeed  of  nitrogen  retention. 

Though  the  ultimate  cause  of  diabetic  acidosis  is  not  known, 
it  is  probable  that  it  resides  in  an  anomaly  of  the  intermediary 
metabolism  of  certain  cells,  linked,  on  the  one  hand,  with  a  dis- 
turbed carbohydrate  utilization  and,  on  the  other,  with  an  in- 
creased consumption  of  fat. 

The  main  source  of  the  acetone  bodies  is  still  not 
definitely  settled.  In  this  connection,  our  attention  is  focussed 
upon  the  proteids  and  fats,  rather  than  upon  the  carbohydrates 
as  was  formerly  the  case.  We  must  assume  that  in  some  instances, 
at  least,  both  proteids  and  fats  contribute  to  their  formation,  for 
in  cases  of  maximal  beta-oxybutyric  acid  production,  the  nitrogen 
output  is  greatly  below  what  we  should  expect  if  proteids  were 
the  sole  source  of  the  acid.®^ 

Our  knowledge  of  the  origin  of  the  acetone  bodies  has  been 
appreciably  increased  in  recent  years  both  as  a  result  of  animal 
experiments®*  (perfusion,  etc.)  and  of  observations  in  severe 
cases  of  human  diabetes  based  on  the  feeding  of  various  sub- 
stances.®* These  have  shown  that  beta-oxybutyric  acid  represents 
a  point  of  contact  in  the  metabolism  of  two  main  food-stuffs,  viz., 
fats  and  proteids,  in  that  the  catabolism  of  both  occurs  via  this 
acid.  This  is  the  more  interesting  because  there  exists  an  anal- 
ogous point  of  contact  in  the  case  of  proteids  and  carbohydrates 
in  the  next  simpler  oxyacid,  lactic.  Of  the  amino-acids,  leucin, 
ty rosin  and  phenylalanin  build  oxybutyric  acid ;  while  of  the  fatty 
acids,  butyric  and  capronic  acids  and  their  higher  homologues 
with  an  even  number  of  carbon  atoms,  have  a  similar  property. 
Though  these  various  observations  are  of  great  theoretical  interest, 
we  cannot  enter  into  fuller  detail,  except  to  mention  the  fact  that 
certain  fatty  acids  of  the  aliphatic  series — as  well  as  substances 
which  go  over  into  sugars — are  capable  of  strongly  inhibiting 
the  formation  of  beta-oxybutyric  acid,  Of  such  acids,  glutaric 
is  of  particular  interest  ®®  because  its  exhibition  in  phlorhizinized 
dogs — and  occasionally  in  severe  human  diabetes — not  only  checks 
acidosis,  but  also  the  formation  of  sugar  from  proteid. 
'  Attention  has  already  been  called  to  the  fact  that  the  normal 
organism  is  capable  of  oxidizing  considerable  amounts  of  the 


332  THE  BASIS  OF  SYI^IPTOMS 

acetone  bodies,  which  is  not  the  case  in  diabetes.  That  this 
process  may  take  place  in  the  Hver  is  undoubted.^^ 

An  important  question  is  whether  diabetic  acidosis  is  due  not 
only  to  a  deficient  destruction  of  the  acetone  bodies,  but  also 
to  an  increased  formation.  This  question  involves  and  is  identical 
with  another,  viz.,  Does  the  decomposition  of  the  higher  fatty 
acids  normally  go  beyond  oxybutyric  acid  ?  That  this  actually  does 
occur  would  appear  from  the  finding  of  a  diacetic  acid  formation 
in  the  normal  liver.  On  a  mathematical  basis,  it  may  be  conceded 
that  the  split-products  of  fats  and  proteids  are  changed  into  oxy- 
butyric acid;  and  it  is  known  that  the  healthy  body  can  easily 
destroy  large  amounts  of  oxybutyric  and  diacetic  acids.  Despite 
all  of  these  observations,  however,  it  remains  to  be  proved  that 
there  is  a  constant  construction  of  beta-oxybutyric  acid.  Indeed, 
there  are  many  facts  speaking  against  this  hypothesis,  among 
others  that  the  amount  of  this  acid  increases  in  proportion  to  the 
degree  of  acidosis,  or  in  other  words,  with  the  severity  of  the 
metabolic  disturbance. 

The  Effects  of  an  Excessive  Formation  of  Organic  Acids. 
Diabetic  and  Other  Toxic  Comas. — The  specific  action  of  the 
acetone  bodies  is  a  comparatively  slight  one.  Acetone  in 
large  doses  will  produce  a  sort  of  drunkenness,  similar  to  that 
caused  by  alcohol,  and  it  is  possible  that  in  certain  intestinal 
diseases  of  children  it  may  cause  a  feeling  of  fatigue.  The  effect 
produced  by  beta-oxybutyric  and  diacetic  acids  is, 
for  the  most  part,  not  a  specific  toxic  effect  of  these  compounds, 
but  is  due  rather  to  their  acid  properties.  However,  recent  stud- 
ies®^ in  particular  tend  to  emphasize  the  specific  nature  of  the 
intoxication.  In  virtue  of  their  acid  properties,  these  organic 
acids  will  combine  with  basic  substances  in  the  body,  and  tend  to 
carry  them  away  in  the  urine.  In  this  manner  they  produce  the 
symptoms  of  an  acid  intoxication  (see  p.  224). 

In  the  comas  that  accompany  diabetes,  car- 
cinoma and  some  intestinal  diseases,  large  quanti- 
ties of  beta-oxybutyric  acid  are  usually  eliminated  in  the  urine. 
The  patient  becomes  stupid  and  sleepy  or,  at  times,  irritable.  The 
temperature  falls,  the  respirations  become  deep  and  often  more 
frequent,  and  the  heart's  action  becomes  rapid. 

The  immediate  cause  of  diabetic  coma  is  unknown, 
but  it  seems  to  be  precipitated  in  some  instances  by  a  too  rigorous 


I 


NUTRITION  AND  METABOLISM  833 

meat  and  fat  diet,  by  digestive  disturbances,  overwork,  infectious 
diseases,  alcoholic  intoxication,  etc.  The  symptoms  are  certainly 
very  similar  to  those  that  result  from  acid  intoxications  experi- 
mentally produced ;  and  in  no  other  condition  are  such  enormous 
quantities  of  beta-oxybutyric  acid  found  in  the  urine  as  at  the 
onset  of  diabetic  coma.  The  ability  of  the  blood  to  carry  carbon 
dioxide  is  usually  found  to  be  consideraby  diminished  during  dia- 
betic coma,  just  as  it  is  in  experimental  acid  intoxications  (see 
p.  224  ) .   These  facts  indicate  the  acid  character  o f  the  intoxication. 

On  the  other  hand,  in  some  comas  complicating  diabetes,  no 
increased  elimination  of  acids  has  been  found.  Yet  such  cases  are 
quite  rare,  for,  as  a  rule,  the  symptoms  of  diabetic  coma  are 
accompanied  by  an  acid  intoxication.  The  coma  is  preceded  by 
an  increased  formation  of  beta-oxybutyric  acid  in  the  body,  and 
large  quantities  of  this  acid  may  appear  in  the  urine  as  the  ammo- 
nium salt.  During  the  coma,  however,  the  elimination  frequently 
does  not  keep  pace  with  the  acid  formation,  and  consequently 
considerable  amounts  are  retained  in  the  body.  Careful  estima- 
tions of  the  amounts  thus  retained  demonstrate  that  they  are 
sufficient  to  give  rise  to  coma.  In  some  cases,  it  is  possible  to  abort 
the  coma,  partly  or  completely,  by  the  use  of  large  quantities  of 
soda,  which  serves  to  neutralize  the  acid  in  the  body.®* 

Those  rare  cases  of  diabetic  coma  without  increased  acid 
formation  are,  according  to  Naunyn,  produced  by  other  toxic 
substances,  which  act  directly  upon  the  cerebral  cells,  and  especially 
upon  the  cells  of  the  respiratory  centre.  The  exact  nature  of  these 
toxic  substances  is  unknown,  but  from  the  diversity  of  symptoms 
seen  in  diabetic  coma  it  is  readily  conceivable  that  more  than  one 
cause  is  operative. 

The  Relation  between  Hepatic  Disease  and  the  Excretion  of 
Ammonia. — The  greater  portion  of  the  nitrogenous  waste  which 
does  not  serve  to  neutralize  acids  leaves  the  body  in  the  form 
of  urea.  We  know  that  the  liver  can  convert  many  ammonium 
salts,  such  as  the  carbamates,  into  urea,  and  Minkowski's  experi- 
ments on  birds  would  seem  to  indicate  that  this  is  a  portion  of  the 
normal  hepatic  function.®®  On  the  other  hand,  we  are  not  certain 
that  all  the  eliminated  urea  is  thus  formed  in  the  liver,  nor,  indeed, 
that  it  is  all  derived  from  ammonium  salts. 

These  questions  are  of  the  greatest  importance,  for  it  is 
possible  that  some  relation  may  exist  between 


334  THE  BASIS  OF  SYMPTOMS 

hepatic  diseases,  on  the  one  hand,  and  the  amount 
of  urea  formed  out  of  ammonium  salts,  on  the 
other.  Not  infrequently  it  happens  that  the  liver  is  found  to  be 
diseased  when  large  quantities  of  ammonia  have  appeared  in  the 
urine.  We  have  seen  that  one  cause  of  an  increased  excretion 
of  ammonia  is  an  acid  intoxication,  in  which  case  the  ammonia 
serves  merely  to  neutralize  the  excess  of  acid.  Is  it  not  possible, 
however,  that  large  amounts  of  ammonia  may  be  excreted  for  the 
reason  that  the  liver  is  so  diseased  that  it  cannot  form  urea  out 
of  ammonium  salts?  Such  a  serious  loss  of  function  could  only 
result  from  a  most  extensive  destruction  of  liver  cells,  if  we  may 
draw  an  analogy  from  the  corresponding  effects  produced  by 
diseases  of  the  pancreas  and  of  the  thyroid  gland. 

An  increased  excretion  of  ammonium  com- 
poundsattheexpenseof  urea  has  been  observed  in  dif- 
ferent forms  of  hepatic  disease,  such  as  cirrhosis,  tumors 
and  extensive  degenerations,  though  these  urinary 
changes  do  not  accompany  all  serious  diseases  of  the  liver. ^°® 
Weintraub  discovered  that  if  ammonium  salts  were  administered 
to  patients  even  in  the  advanced  stages  of  hepatic  disease,  these 
salts  were  converted  into  urea  just  as  they  are  in  healthy  individ- 
uals, thus  demonstrating  that  these  patients  are  still  able  to  trans- 
form large  quantities  of  ammonium  salts.  Glaessner,^®^  on  the 
other  hand,  found  in  cases  of  extensive  degenerative  changes  in 
the  liver  cells  (cirrhosis,  phosphorus  poisoning,  fatty  liver, 
syphilis  of  the  liver)  that  amino-acids  ingested  were  eliminated 
in  part  as  such,  whereas  the  normal  organ  transforms  them  com- 
pletely into  urea.  The  administration  of  alkalies  in  these  hepatic 
disorders  would  permit  of  a  decision  as  to  whether  the  ammonia 
acts  as  a  neutralizing  agent;  for  were  this  the  case  it  would  be 
appreciably  diminished  after  the  giving  of  soda.  For  the  present, 
therefore,  the  question  must  be  left  in  abeyance  as  to  whether 
the  increased  output  of  ammonia  in  the  urine  in  diseases  of  the 
liver  is  the  consequence  merely  of  an  acid  intoxication. 

Alkaptonuria. — The  tyrosin  and  phenylalanin  groups  of  the 
proteid  molecule  give  rise  at  times  to  the  formation  of  dioxy- 
phenylacetic  acid  (homogentisic  acid).  When  this  acid  is 
excreted  by  the  kidneys,  the  urine  turns  dark  on  standing  or  on  the 
addition  of  alkalies,  and  the  condition  is  termed  alkaptonuria.^®^ 
These  urines  will  reduce  Fehling's  solution,  and  the  condition  may 


NUTRITION  AND  METABOLISM  335 

be  mistaken  for  a  glycosuria.  Though  patients  with  alkaptonuria 
ordinarily  show  no  other  clinical  peculiarities,  attention  hasi" 
recently  been  called  to  manifestations  which  would  indicate  that 
there  exists  a  profound  constitutional  disturbance  similar,  in  a 
sense,  to  that  of  diabetes.  For  example,  wounds  may  heal  slowly 
in  such  patients ;  ^^^  and  further,  it  is  not  unlikely  that  alkapto- 
nuria is  the  forerunner  of  ochronosis *°* — a  congenital  con- 
dition, with,  at  times,  a  family  tendency — and  which  is  associated 
with  changes  in  the  joint  cartilages.  In  this  event,  the  severe 
joint  disturbances  observed  in  some  cases  of  ochronosis  might  be 
regarded  as  due  to  the  metabolic  disturbance  under  consideration 
(arthritis   alkaptonurica). 

Although  it  was  formerly  believed  that  the  substances  giving 
rise  to  the  reaction  for  alkapton  were  produced  in  the  intestines, 
it  now  seems  certain  that  the  oxyacids  concerned  arise  within  the 
body  during  the  intermediary  metabolism,  and  that  they  appear 
in  the  urine  because  the  organism  is  incapable  of 
breaking  down  the  tyrosin  and  alanin  groups  of 
the  proteid  molecule  in  a  normal  manner. 

Interesting  and  extensive  studies  ^^^  have  been  undertaken  to 
determine  what  must  be  the  constitution  of  these  aromatic  oxy- 
acids to  allow  of  their  transformation  into  homogentisic  acid  in 
the  alkaptonuric  individual.  These  studies  point  to  the  existence 
of  certain  steric  arrangements  both  of  the  side  chains  and  of  the 
nucleus  of  the  proteid  molecule. ^^^  The  subject  is  of  particular 
interest  in  the  light  it  throws  on  the  normal  catabolism  of  the 
aromatic  amino-acids  in  warm-blooded  animals.^"^  It  has  an 
immediate  bearing,  therefore,  upon  the  question  as  to  whether 
alkaptonuria  represents  a  qualitative  change  in  intermediary 
metabolism,  or  whether  the  destruction  of  the  aromatic  oxyacids 
proceeds  normally  via  homogentisic  acid,  the  characteristic  feat- 
ure of  the  process  being  merely  a  splitting  of  the  oxy-amino-acids 
without  a  breaking  up  of  the  benzol  ring.  Both  theories  have 
been  espoused.  Speaking  against  the  first  is  the  fact  that  the 
tolerance  to  homogentisic  acid  and  tyrosin  may  not  be  the  same. 

The  amount  of  homogentisic  acid  appearing  in  the  urine  de- 
pends in  general,  therefore,  upon  the  quantity  and  form  of  proteid 
destroyed,  the  tyrosin  content  of  the  latter  being  the  determining 
factor.  We  have  yet  to  learn  in  what  organ  the  transformation 
of  tyrosin  and  phenylalanin  into  alkapton  occurs.    Proteid  metab- 


336  THE  BASIS  OF  SYMPTOMS 

olism,  as  a  whole,  remains  within  normal  bounds;  the  nitrogen 
output  in  particular  is  unchanged.  All  of  this  would  indicate  that 
there  is  no  qualitative  disturbance  of  proteid  metabolism,  but 
rather  that  the  latter  ceases  when  but  half  completed. 

Cystinuria.i*>8 — In  this  anomaly,  there  exists  a  disturbance  in 
the  metabolism  of  the  aliphatic  amino-acids.  Cyst  in,  which 
makes  up  the  greater  part  of  the  unoxidized  sulphur  in  the  pro- 
teid molecule,  is  eliminated  in  the  urine  because  of 
the  inability  of  the  organism  to  utilize  it.  This 
condition  is  remarkable  in  that  the  individuals  affected  can  burn 
cystin  when  administered  as  such,  but  are  unable  to  metabolize 
the  cystin  group  of  the  proteid  molecule.^®^ 

Baumann  and  his  pupils  formerly  believed  that  cystin  was 
formed  in  the  intestines,  because  cystinuria  is  frequently  asso- 
ciated with  the  appearance  in  the  urine  of  diamins  (putrescin 
and  cadaverin),^^^  which  occur  in  the  faeces  both  in  abnormal 
intestinal  conditions  and  even  physiologically  in  small  amount. 
As  diaminuria  does  not  always  accompany  cystinuria,  however, 
it  is  possible  that  the  interdependence  of  the  two  is  slight. 

It  seems  unlikely  that  the  diamins  are  entirely  of  intestinal 
origin.  A  comparison  of  the  metabolic  processes  in  cystinuria 
with  those  concerned  in  the  catabolism  of  the  aromatic  amino- 
acids,  points  to  this  origin  as  being  in  the  intermediary  metab- 
olism, particularly  in  the  liver,  where  cystin  is  normally  converted 
into  taurin.  Recent  studies  show  that  leucin  and  tyrosin  among 
other  amino-acids  may  be  excreted.^  ^^  The  cystinuric  individual 
can  utilize  neither  the  monamino-acids  in  his  food  (tyrosin, 
asparagin),  nor  the  diamino-acids ;  the  latter  he  excretes  as  dia- 
mins. The  degree  of  the  disturbance,  however,  varies  with  dif- 
ferent individuals,  for  some  can  burn  both  the  endogenous  and 
exogenous  amino-acids.^  ^^  Important  accessory  factors,  there- 
fore, are  the  amount  of  amino-acids  occurring  in  the  intermediary 
metabolism,  as  well  as  the  tissue  in  which  the  latter  is  to  occur. 
Cystinuria,  therefore,  would  appear  to  be  a  constitutional  anomaly 
closely  related  essentially,  to  alkaptonuria. 

The  presence  of  cystin  stones  in  the  bladder  may  cause  dis- 
turbances in  such  individuals. 

The  Adrenals.  Addison's  Disease.  Epinephrin. — A  d  d  i  - 
son's  disease  is  generally  associated  with  changes,  primary 
or  secondary,  in  the  adrenal  glands  ;^^®  though,  on  the  one  hand. 


NUTRITION  AND  METABOLISM  337 

cases  are  observed  with  normal  adrenals,  and  on  the  other,  exten- 
sive changes  may  involve  these  organs  without  producing  manifes- 
tations of  the  disease.  I  shall  not  go  into  a  discussion  of  these 
problems,  first,  because  it  would  carry  us  too  far,  and,  further, 
because  our  knowledge  rests  upon  too  insecure  a  footing.  In  my 
opinion,  it  can  only  be  said,  on  the  basis  of  the  best  observations, 
that  the  Addison  symptom-complex  and  disease 
of  the  adrenals  are  intimately  related,  proba- 
bly in  the  way  of  a  diminished  function  of  the 
latter.  It  is  not  a  question  of  a  decreased  activity  of  the 
adrenal  medulla  and  thereby  of  a  lessened  production  of 
epinephrin,  because  the  latter  arises  from  all  parts  of  the  chro- 
mafiEin  system,  v.  Neusser  and  Wiesel,  in  view  of  this  fact, 
regarded  the  disease  as  due  to  a  constitutional  weak- 
ness of  the  entire  chromaffin  system.  This  is  an 
interesting  hypothesis,  explaining  as  it  does  those  cases  of 
Addison's  disease  with  intact  adrenals;  for,  in  view  of  the  close 
relation  existing  between  the  chromaffin  and  the  sympathetic 
nervous  systems,  we  might  assume  that  there  exist  changes  in  the 
chromaffin  cells  outside  of  the  adrenals  or  changes  in  the  secre- 
tory nerves.  In  some  cases  of  Addison's  disease,  however,  the 
entire  chromaffin  system  seems  quite  normal;  and,  furthermore, 
there  are  observers  who  look  upon  changes  in  the  adrenal  cortex 
as  the  cause  of  morbus  Addisonii. 

The  interrelationship  of  the  medullary  and 
cortical  substances  of  these  glands  is  still  un- 
determined despite  the  tremendous  amount  of  study  de- 
voted to  the  subject.  In  my  opinion,  if  one  is  to  hold  fast  to 
the  etiological  significance  of  adrenal  disease  in  the  Addison 
symptom-complex,  he  must  assume  that  the  medulla  and  cortex 
are  both  involved. 

The  function  of  the  cortex  is  not  known.  On  the 
other  hand,  an  epinephrin  deficiency  or  a  diminished  sympathetic 
activity  falls  short  of  explaining  even  the  majority  of  the 
manifestations  of  this  disease.  The  diminished 
arterial  tension  ordinarily  observed  in  these  cases  is  readily  ex- 
plained on  an  epinephrin  deficiency.  But  the  prostration  and 
lethargy,  the  muscular  weakness,  the  anaemia  and  the  gastric 
disturbances  are  in  part,  at  least,  not  due  to  this  cause.  Some 
observers  do  not  look  upon  the  pigmentation  as  an  integral  feature 
22 


338  THE  BASIS  OF  SYMPTOMS 

of  the  condition ;  others  attribute  it  to  changes  in  the  sympathetic 
system.  Biedl's  theory  that  the  mother  substance  of  epinephrin 
is  converted  directly  or  indirectly  into  the  Addison  pigment  is 
an  interesting  possibility. 

(Among  those  who  regard  an  insufficiency  of  the 
adrenal  cortex  as  the  cause  of  the  characteristic  asthenia 
of  this  disease  are  Biedl  and  Loewi.  The  former  bases  his  opin- 
ion upon  extirpation  experiments  in  animals  in  which  the  cortex 
and  medulla  are  separate;  the  latter  upon  cases  of  Addison's 
disease  in  individuals  in  whom  only  the  cortex  was  found  insuffi- 
cient. Crowe  ^^^  has  recently  added  a  convincing  extirpation 
and  ligation  experiment  to  the  evidence. 

The  views  as  to  the  function  of  epinephrin  have 
undergone  a  considerable  change  in  the  past  few  years.  It  is 
generally  agreed,  in  the  first  place,  that  epinephrin  is  a  product  of 
the  medullary  substance  of  the  adrenals;  that  it  acts  only  upon 
structures  possessing  a  sympathetic  innervation,  selectively  stimu- 
lating, in  all  probability,  the  so-called  myoneural  junc- 
tion or  terminal  receptive  substance;  and  that  it 
exerts  its  characteristic  activity  in  very  high  dilutions.  The  most 
recent  studies  ^^^  would  indicate  that  epinephrin  is  not  present  in 
the  blood  under  ordinary  conditions,  but,  on  the  contrary,  is 
poured  out  only  in  periods  of  emergency. 

The  recent  work  of  Cannon  and  his  co-workers  has  given 
us  an  entirely  new  conception  of  the  significance  of  epinephrin. 
According  to  Cannon,  epinephrin  plays  adefi- 
nite  role  in  enabling  the  individual  to  meet  suc- 
cessfully the  emergencies  of  life.  Various  emo- 
tions— ^pain,  fear,  anger,  etc. — cause  a  reflex  secretion  of  epi- 
nephrin and  assist  in  the  execution  of  the  physical  counterparts 
of  the  emotions,  vijs.,  combat,  flight,  and  so  on.  As  the  muscles 
are  chiefly  concerned  in  these  bodily  activities  they  are  assumed 
to  benefit  to  the  greatest  extent  in  the  epinephrin  discharge.  The 
inhibition  of  intestinal  peristalsis  causes  a  shifting  of  blood  from 
the  bowel  to  the  muscles,  as  does  also  the  constriction  of  the 
splanchnic  and  cutaneous  vessels.  The  hyperglycaemia  conse- 
quent upon  epinephrin  discharge  would  furnish  the  muscles  with 
the  needed  additional  food-supply.  More  oxygen  for  the  crisis 
is  supplied  by  a  dilatation  of  the  bronchioles.  Furthermore,  the 
efficiency  of  fatigued  muscle  is  greatly  improved  by  epinephrin; 


NUTRITION  AND  METABOLISM  SS9 

and,  finally,  within  certain  limits,  the  coagulation  time  of  the 
blood  is  diminished. 

In  contrast  with  this  physiological  conception  are  the  experi- 
mental results  due  to  the  injection  of  epinephrin  in  pharmacologi- 
cal doses.  There  are  many  facts,  for  example,  indicating  that  epi- 
nephrin is  not  concerned  with  a  permanent  hypertension 
and  with  arteriosclerosis.^^'^  Among  these  are  the  lim- 
ited capacity  of  the  adrenals  to  manufacture  epinephrin;  the  fact 
that  epinephrin  in  sufficient  amount  to  maintain  an  augmented 
arterial  tension  would  at  the  same  time  paralyze  intestinal  activity ; 
the  fact  that  glycosuria  appears  before  a  rise  in  blood-pressure; 
and,  finally,  that  the  anatomical  changes  observed  in  the  vessel- 
walls  after  repeated  injections  of  epinephrin  differ  in  many  par- 
ticulars from  those  seen  in  arteriosclerotic  conditions  in  man, — 
Ed.) 

LITERATURE 

*Krehl:  Arch.  f.  klin.  Med.,  Ixxxviii,  351;  Biedl,  Innere  Sekretion,  2nfd 
edit.,  1913  (The  Internal  Secretory  Organs,  etc.,  New  York,  1913). 

'Gesetze  d.  Energieverbrauchs ;  also  Physiol,  d.  Nahrung  u.  Ernahr.,  in  v. 
Leyden's  Handb.  d.  Ernahrungstherapie. 

*  Lusk :  Science  of  Nutrition,  2nd  edit.,  222. 

*Abderhalden  et  al. :  Zeitschft.  f.  Physiol.  Chem.,  xlii  toi  Ixviii;  Frank  and 
Schittenhelm,  Munch,  med.  Wochenschft.,  191 1,  No.  24. 

"Rubner:  1.  c. ;  Sitzungsber.  d.  kgl.  preuss.  Akad.  d.  Wissensch.,  1911,  440, 

•Grafe:  Zeitschft.  f.  physiol.  Chem.,  191 1,  Ixv,  29. 

'' Cf.  V.  Noorden:  Path.  d.  Stoffwechsels,  2nd  edit.,  320  (Metabolism  and 
Practical  Medicine,  London,  1907) ;  Chittenden,  Physiol.  Economy  in 
Nutrition,  1904. 

*  See  Abderhalden  and  London :  Zeitschft.  f .  phys.  Chem.,  liv,  80 ;  Freund, 

Zeitschft.  f.  exp.  Path.,  iv,  i;  Rubner,  1.  c.  (Sitzungsber.,  etc.,  chap.  xix). 

For  a  recent  study  of  the  fate  of  the  protein  digestion  products,  see  Van 

Slyke  and  Meyer,  Jour.  Biol.  Chem.,  1913,  xvi,  197. 
•Neumeister:  Phys.  Chemie,  2nd  edit.,  364. 
** Rubner:  Arch.  f.  Hyg.,  1908,  Ixvi,  7. 
"C  Voit:  Physiol,  d.  Stoffwechsels,  93;  E.  Voit,  Zeitschft.  f.  Biol.,  xH,  550; 

Schulz,  Miinch,  med.  Wochenschft.,  1899,  No,  16. 
"  C.  Voit :  Stoffwechsel,  95 ;  Sedelmayer,  Zeitschft.  f.  Biol.,  xxxvii,  35.    For 

the  effect  of  starvation  upon  the  blood,  see  Ash,  Arch.  Int.  Med.,  1914, 

xiv,  8. 
**F.  Miiller:  Zeitschft,  f.  klin.  Med.,  xvi,  496;  Klemperer,  ibid.,  550;  Richter, 

Arch.  f.  exp.  Path.,  xliv,  239;  Magnus-Levy,  Zeitschft.  f.  klm.  Med.,  Ix, 

199. 

"  Pfliiger :  Pfliiger's  Arch.,  Ixxvii,  424.  ^ 

"Liithje:  Zeitschft.  f.  klin.  Med.,  xliv,  22;  Kaufmann,  Zeitschft.  f.  diat. 
Then,  vii,  Nos.  7  and  8  (lit). 

**Camerer:  Zeitschft.  f.  Biol.,  xxxiii,  320;  Heubner,  Zeitschft,  f.  diat.  Then, 
v.  No.  I ;  Liithje  and  Berger,  Arch.  f.  klin.  Med.,  Ixxxi,  278  (lit.)  ;  Rub- 
ner, Arch.  f.  Anat.  u.  Phys.  (Phys.  Section),  191 1. 

"  Zeitschft.  f.  klin.  Med.,  Ixvi,  39,  241. 

"Kongr.  f.  inn.  Med.,  191 1,  546;  Grafe  and  Graham,  Zeitschft,  f.  phys. 
Chem.,  191 1,  Ixxiii,  i;  Grafe  and  Koch,  Arch.  f.  klin.  Med.,  ci,  209. 


340  THE  BASIS  OF  SYMPTOMS 

"C/,  Rosenfeld,  in  Asher-Spiro,  Ergeb.,  i,  I,  651,  and  ii,  I,  50  (lit). 

^Bleibtreu:  Pflugrer's  Arch.,  Ixxxv,  651. 

"Oertel:  Allg.  Then  d.  Kreislaufstor.,  1891,  147;  see  also  Salomon,  Uber 

Durkstkuren,  in  v.  Noorden's  Samml.  klin.  Abhandl.,  No.  6,  1905  (Chap. 

on  Obesity). 
**  Hennenberg :  Kongr.  f.  inn.  Med.,  1885,  46;  Vogel,  Jour.  f.  Landwirtschaft., 

xxxix,  37. 
"Dennig:  Zeitschft.  f.  physikal.  Then,  i,  281;  Zuntz,  Therap.  d.  Gegenwart, 

July,  1901. 
"  Miiller :  Path.  d.  Stoffwechs.,  in  v.  Leyden's  Handb.,  204. 
*•  Schattenf  roh :    Arch,    f .   Hyg.,   xxxviii,   92 ;    Wolpert,   ibid.,   xxxix,   298 ; 

Rubner,  Beitrage  z.  Ernahr.  im  Knabenalter,  1902. 
*■  Rubner :  Beitrage,  1.  c,  68. 
"  Cf.  Hoffmann :  Konstitutionskrankh.,  253. 
"  See  Magnus-Levy :  Zeitschft.  f .  klin.  Med.,  xxxiii,  301   (lit.)  ;  Jaquet  and 

Svenson,  ibid.,  xli,  376;   Zuntz,   1.  c. ;   Brugsch,   in  the   Kraus-Brugsch 

System. 
**v.  Bergmann:  Zeitschft.  f.  exp.  Path.,  v,  646;  Deutsch.  med.  Wochenschft., 

1909,  14;  Stahelin,  Deutsch.  med.  Wochenschft.,  1909,  No.  14;  Zeitschft. 

f.  klin.  Med.,  Ixv,  425. 
•"Arch.  f.  klin.  Med.,  191 1,  cii,  15. 
""  Arch.  f.  exp.  Path.,  xlviii,  184,  and  1,  268. 
•*  Loewy  and  Richter :  Zentralbl.  f .  Phys.,  1902,  No.  17 ;  Loewy,  ibid.,  No.  50 ; 

Loewy,  in  Asher-Spiro,  Ergeb.,  ii,  I  (lit.). 
"  Cf.  Rubner :  Die  Ernahrung,  etc.,  70 ;  see  also  v.  Bergmann,  in  Oppen- 

heimer,  Handb.  d.  Biochem.,  iv,  194. 
■*For  a  discussion  of  this  subject  see  Gushing:  The  Pituitary  Body,  etc., 

1912,  257  (lit.). 
"F.  Miiller,  G.   Klemperer:   Zeitschft.   f.  klin.  Med.,  xvi,  496,  550,   resp.; 

Miiller,  Kongr.  f.  inn.  Med.,  1889,  396. 
"  Tallquist :  Arch,  f .  Hyg.,  Ixv,  39. 
"  Miiller :  1.  c. ;  Klemperer,  1.  c. 
"*  Striimpell :  Arch.  d.  Heilkunde,  xvii,  547 ;  Rosenquist,  Zeitschft.   f.  klin. 

Med.,  xlix,  193. 
**  Fraenkel  and  Rohmann :  Zeitschft.  f .  physiol.  Chem.,  iv,  439. 
*°  Graf  e :  Arch,  f .  klin.  Med.,  cii,  40 ;  see  also  Strauss,  in  v.  Noorden's  Handb. 

d.  Path.  d.  Stoffwechsels,  i,  896. 
*^  Embden  and  Schmitz :  Biochem.  Zeitschft.,  1910,  xxix,  423. 
**  Die  chem.  Vorgange  bei  d.  Krebskrankh.,  1906. 
*'  In  V.  Noorden's  Handbuch,  2nd  edit.,  ii,  373. 
**  See  Kepinow:  Zeitschft.  f.  Krebsforsch.,  vii  (lit). 
*Arch.  f.  klin.  Med.,  Ii,  401. 
*"  Zeitschft.  f.  exp.  Path.,  iv,  720. 
"Zeitschft.  f.  klin.  Med.,  xxxiii,  269;  Berl.  klin.  Wochenschft.,  1895,  No.  30; 

also  in  v  Noorden's  Handb,  ii,  311. 
**  Scholz :  Zentralbl.  f .  klin.  Med.,  1895,  Nos.  43  and  44 ;  Matthes,  Kongr.  f. 

inn.  Med.,  1897,  232. 
**  Magnus-Levy :  1.  c. 
■^Maier:  Beitrage  z.  Kenntniss  d.  Stoffwechsels  thyreoekt.  Kaninchen,  Diss. 

Wiirzburg,  1900. 
"F.  Miiller:  1.  c,  and  Kongr.  f.  inn.  Med.,  1897,  239;  Magnus-Levy,  1.  c. 
"Schondorff:  Pfliiger's  Arch.,  Ixvi,  395;  Voit,  Zentralbl.  f.  Biol.,  xxxv,  116. 
■^Magnus-Levy:  Zeitschft.  f.  klin.  Med.,  Hi,  201. 
"  See  Ewald,  in  the  Nothnagel  System ;  v.  Eiselsberg,  Deutsch.  Chirurgie, 

No.  38 ;  Kraus  and  Kocher,  Kongr.  f .  inn.  Med.,  1906. 
"^  Eppinger,  Falta  and  Rudinger,  Zeitschft.  f .  klin.  Med.,  Ixvii,  380. 
"See  Biedl:  Innere  Sekretion  (lit). 

"  Scholz :  Klin.  u.  anat.  Untersuch.  ii.  d.  Kretinismus,  1906. 
"*  Osier :  Amer.  Jour.  Med.  Sc,  cxiv,  Z77- 
*See  Mobius,  in  the  Nothnagel  System  (lit). 


NUTRITION  AND  I^IETABOLISM  341 

"Verhand.    d.    Karlsruher    Naturforscherversamm.,    191 1;    Deutsche    med. 

Wochenschft.,  191 1,  No.  48. 
"  See  Wiener :  Arch,  f .  exp.  Path.,  Ixi,  297 ;  Oswald,  Chemische  Pathologic, 

1907 ;  Hofmeister's  Beitrage,  ii,  545 ;  Pfliiger's  Arch.,  cxxix. 
"Simmonds:  Karlsruher  Naturforscherversamm.,  191 1,    For  a  recent  mono- 
graph see  Rautmann,  Grenzgebiete,  xxviii,  No.  3;  Wilson,  Am.  Jour. 

Med.  Sci.,  1913,  cxlvi,  781 ;  Plummer,  ibid.,  790. 
"O'Connor:  Munch,  med.  Wochenschft.,  191 1,  No.  27. 
•*  Cf.  Eppinger  and  Hess :  tjber  Vagotonie,  1910. 
*  MacCallum  and  Davidson :  Med.  News,  April  8,  1905. 
"  Hoskins  and  Wheelon :  Am.  Jour,  Phys.,  xxxiv,  263. 
"  Salkowski :  Deutsch.  Klinik,  xi,  147. 

**  v.  Bergmann  and  Langstein :  Hofmeister's  Beitrage,  vi,  27, 
*Abderhalden  and  Oppenheimer:  Zeitschft.  f.  physiol.  Chem.,  xliii,  155. 
™F.  Miiller:  Kongr.  f.  inn.  Med.,  1902,  192;  Simon,  Arch.  f.  klin.  Med.,  Ixx, 

604. 
"Langstein  and  Neubauer:  Miinch.  med.  Wochenschft.,  1902,  1249;  Ehrstrom, 

Arch.  f.  Gyn.,  Ixiii,  695. 
"v.  Jaksch:   Zeitschft.   f.   klin.   Med.,   vi,  413;   Robitschek,   Deutsch.   med. 

Wochenschft.,  1893,  No.  24. 
"  Stadelmann :  Untersuch.  ii.  Peptonurie,  1894,  90 ;  Miura,  Virch.  Arch.,  ci, 

317- 
"  Neuberg  and  Richter :  Deutsch.  med.  Wochenschft,  1904,  No.  14 ;  Abder- 

halden  and  Bergell,  Zeitschft.  f.  phys.  Chem.,  xxxix,  9;  Wohlgemuth, 

ibid.,  xliv,  74. 
"  A  E.  Taylor :  Jour.  Med.  Research,  viii,  424. 
"Fischer  and  Bergell:  Berich.  d.  deutsch.  chem.  Gesell.,  1902,  xxxv  (HI), 

m     3779- 

"Henriques  and  Sorensen;  Zeitschft.  f.  physiol.  Chem.,  Ixiii,  27;  Ixiv,  120; 

Yoshida,  Biochem.  Zeitschft.,  xxiii,  239. 
'*Rumpf:  Kongr.  f.  inn.  Med.,  1896,  509;  Virch.  Arch.,  cxliii,  i;  Zeitschft.  f. 

Biol.,  xxxi. 
'•  Zeitschft.  f .  exp.  Path.,  iii,  530,  and  Wiener  klin.  Wochenschft,  1906,  No.  5. 
""Arch.  f.  exp.  Path.,  vii,  148. 
**Rumpf :  Virch,  Arch.,  cxliii,  i. 
**  See  V.  Noorden's  Handbuch. 

'^  Mandel  and  Lusk :  Jour.  Am,  Med,  Assn.,  xlviii,  1804, 
**Maase:    Phys.   Gesellsch.,   Berlin,   March    13,    1910;    Blum,   Munch,   med, 

Wochenschft.,  1910,  No.  13  (lit.)  ;  Neubauer,  Kongr.  f,  inn.  Med.,  1910, 

566;  Wakeman  and  Dakin,  Jour,  of  Biol,  Chem.,   1909,  vi,  373;   ibid., 

1910,  viii,  105. 

*'See  Baer:  Therapeut,  Monatshefte,   1908;  Blum,  Med,  Klinik,   1908,  No. 

44;  Magnus-Levy,  Ergeb.  d.  inn.  Med.,  i,  352;  Ewing,  Arch.  Int  Med.,  ii, 

330;  Lusk,  ibid.,  iii,  i. 
**  Lehmann,  Muller  et  al. :  Virch.  Arch.,  cxxxi,  Suppl. 
■"Taylor:  Univ.  of  Calif.  Publications,  Pathology. 
**  Stadelmann :  Arch,  f .  exp.  Path.,  xvii,  419 ;   Minkowski,  ibid.,  xviii,  35 ; 

Kiilz,  Zeitschft.  f.  Biol.,  xx,  165, 
*v.  Mehring:  Zeitschft.  f.  klin.  Med.,  xvi,  431;  Minkowski,  Arch.  f.  exp. 

Path.,  xxxi,  85. 
'"Lorenz:  Zeitschft   f.  klin.  Med.,  xix,   18;   Kraus,  Ergeb.  d.  allg.   Path., 

1895,  617. 
^  Arch,  f .  exp.  Path.,  xxxiv,  169. 
"*  See  Magnus-Levy :  Ergeb.  d.  inn.  Med.,  i,  372,  384. 
**  Embden  and  Almagia :  Hofmeister's  Beitrage,  vi,  44 ;  Embden  and  Kal- 

berlah,  ibid.,  viii,  120;  Embden  et  al.,  ibid.,  129. 
"*Baer  and  Blum:  Arch.  f.  exp.  Path.,  Iv,  98;  Ivi,  92;  lix,  321;  Ixv,  i;  Borch- 

ardt  and  Lange,  Hofmeister's  Beitrage,  ix,  116. 
*Baer  and  Blum:  Hofmeister's  Beitrage,  x,  80;  xi,  lor;  Arch,  f,  exp.  Path., 

191 1,  Ixv,  I. 


342  THE  BASIS  OF  SYMPTOMS 

•*  Embden  and  Michaud :  Hof meister's  Beitrage,  xi,  332 ;  Biochem.  Zeitschft, 

xi,  262. 
"  Wilbur :  Jour.  Am.  Med.  Assn.,  1904,  1228 ;  Ehrmann,  Esser  and  Loewy, 

Zeitschft.  f.  klin.  Med.,  Ixxii,  496. 
'^Liithje:  Zeitschft.  f.  klin.  Med.,  xliii,  225;  Marchand,  Munch,  med.  Wochen- 

schft.,  1912,  No.  4. 
•"  Minkowski :  Arch,  f .  exp.  Path.,  xxxi,  214. 

'■^  Weintraub :  Arch.  f.  exp.  Path.,  xxxi,  30 ;  Miinzer,  ibid.,  xxxiii,  180. 
"''Zeitschft.  f.  exp.  Path.,  iv,  336;  Prey,  Zeitschft.  f.  klin.  Med,,  Ixxii,  383. 

As  to  the  role  of  the  liver  in  the  formation  of  urea  from  amino-acids, 

however,  see  Fiske  and  Sumner,  Jour.  Biol.  Chem.,  1914,  xviii,  285. 
*'Samuely:  Zentralbl.  f.  Stoflfwechsel,  vii   (lit.);  Fromherz,  Biochem.  Zen- 

tralbl.,  viii,  i;  Neubauer,  Arch.  f.  klin.  Med.,  xcv,  211;  Abderhalden  and 

Massini,  Zeitschft.  f.  phys.  Chem.,  Ixvi,  140. 
"^  Allard  and  Gross :  Grenzgebiete,  xix,  24. 
*°*Allard  and  Gross:  1.  c. ;  Arch.  f.  exp.  Path.,  lix,  384;  Landois,  Virch. 

Arch.,  cxiii,  275. 
**  Abderhalden,    Bloch    and    Rona:    Zeitschft.    f.    physiol.    Chem.,    lii,    435; 

Neubauer,  Arch.  f.  klin.  Med.,  xcv,  211. 
^'^  Fromherz  :  1.  c. 
^'^  Neubauer :  1.  c. 
"'  See  Neuberg,  in  v.  Noorden's  Handbuch,  2nd  edit.,  II,  464  (Metab.  and 

Practical  Medicine)  ;  Loewy  and  Neuberg,  Biochem.  Zeitschft.  ii,  438. 
'■"Wolf  and  Shaffer:  Jour,  of  Biol.  Chem.,  iv,  439;  William  and  Wolf,  ibid., 

vi,  337- 
"*  Thiele :  Jour,  of  Phys.,  xxxvi,  68. 
*"  Abderhalden   and   Schittenhelm :    Zeitschft.    f.   physiol,   Chem.,   xlv,   468; 

Neuberg  and  Loewy,  ibid.,  xliii,  338. 
"*  Simon :   Zeitschft.   f .  physiol.   Chem.,  xlv,  357 ;   Alsberg  and  Folin,  Am. 

Jour.  Phys.,  xiv,  54. 
"*v.  Neusser  and  Wiesel:  Die  Erkrank.  d.  Nebennieren,  2nd  edit,   1910; 

Bittorf,  Die  Path.  d.  Nebennieren,  1908;   Biedl,  Innere  Sekretion,  2nd 

edit.,   1913    (complete  lit);   Goldzieher,   Die  Nebennieren,   1911;   Falta, 

Die  Blutdriisen,  1914.     (Translated  by  Meyers,  1915.) 
"*  Communication  before  the  Amer.  Soc.  for  Exp.  Path.,  Dec.  30,  1913,  quoted 

from  Hoskins,  Jour.  Amer.  Med.  Assn.,  1914,  Ixii,  1803  (lit). 
"*  Stewart :  Jour.  Exp.  Med.,  xiv,  377 ;  xv,  547. 
"'Cannon:  Am.  Jour,  of  Phys.,  1914,  xxxiii,  356;  Cannon,  Bodily  Changes 

in  Pain,  Hunger,  Fear  and  Rage,  New  York,  191 5. 
*^^For  the  complete  literature  see  Biedl,  2nd  edit.,  1913. 


CHAPTER  VII 

DISTURBANCES  IN   CARBOHYDRATE  METABOLISM. 

DIABETES 

In  this  chapter  we  shall  limit  our  discussion  to  dextrose,  or 
grape-sugar;  for  although  other  sugars,  such  as  Isevulose^  and 
pentoses,^  may  appear  in  the  urine,  the  meaning  of  these  findings 
is  not  yet  sufficiently  clear  to  be  discussed  in  connection  with 
dextrose. 

The  cells  of  the  body  that  use  dextrose,  especially  the  muscle- 
cells,  take  it  out  of  the  blood;  yet  the  amount  in  the  plasma  re- 
mains nearly  constant,  for  whenever  the  percentage  falls  below 
the  normal,  new  sugar  is  supplied  to  the  blood,  mainly  from  the 
glycogen  store  in  the  liver.  The  liver  glycogen  is  derived,  for 
the  most  part,  from  the  carbohydrates,  and,  to  a  lesser  extent, 
from  the  proteids  taken  in  the  food.^  The  sugar  that  is  absorbed 
from  the  intestines  goes  to  the  liver  by  way  of  the  portal  vein, 
where  it  is  converted  into  glycogen  by  a  process  of  dehydration 
and  polymerization.  The  non-nitrogenous  products  of  proteid 
cleavage  may  also  be  converted  into  glycogen,  by  a  synthetic 
process ;  *  and,  as  there  can  no  longer  be  any  doubt  that  a  complete 
splitting  of  the  proteid  molecule  occurs  in  the  intestines,  it  is 
reasonable  to  assume  that  this  synthesis  of  glycogen  likewise  takes 
place  in  the  liver.  The  latter  acts,  therefore,  as  a  store-house  for 
carbohydrate  material,  holding  it  back  when  it  is  present  in  the 
blood  in  excess,  and  giving  it  out  when  the  percentage  falls.  The 
muscles  likewise  are  capable  of  storing  sugar. 

In  a  healthy  man,  the  sugar  in  the  blood  varies  but  little,  the 
quantity  remaining  constantly  in  the  neighborhood  of  o.i  per 
cent.  If,  for  any  reason,  more  than  this  is  present  in  the  general 
circulation  without  being  immediately  consumed,  it  is  eliminated 
by  the  kidneys,  and  the  urine  then  contains  more  than  the  trace  of 
dextrose  normally  present. 

Alimentary  Glycosuria. — As  we  have  said,  the  liver  possesses 
the  property  of  removing  from  the  portal  blood  any  excessive 
quantity  of  sugar  that  may  be  present  there.  If,  for  example, 
a  limited  quantity  of  dextrose  be  injected  into  the  portal  vein, 
the  excess  disappears  from  the  blood;  whereas,  if  the  same  quan- 

343 


344  THE  BASIS  OF  SYMPTOMS 

tity  be  injected  Into  a  systemic  vein,  the  percentage  in  the  general 
circulation  is  increased  and  sugar  is  excreted  by  the  kidneys. 

Yet,  when  very  large  amounts  of  dextrose  are  taken  by  mouth 
and  are  absorbed  from  the  intestinal  canal  within  a  short  space  of 
time,  the  percentage  in  the  blood  may  rise  above  the  normal,  either 
because  the  liver  cannot  hold  all  the  sugar  coming  to  it  through 
the  portal  vein,  or  because  some  sugar  reaches  the  general  circu- 
lation through  the  lymphatics  without  traversing  the  liver.  In 
keeping  with  this  latter  hypothesis  is  the  markedly  lowered  toler- 
ance exhibited  by  dogs  with  an  Eck  fistula.® 

Under  such  circumstances,  dextrose  may  be  excreted  by  the 
kidneys,  a  condition  that  is  spoken  of  as  alimentary  gly- 
cosuria.^ The  quantity  of  sugar  that  must  be  taken  by 
mouth  in  order  to  produce  an  alimentary  glycosuria  varies  in  dif- 
ferent individuals,  though  it  is  apparently  constant  for  the  same 
individual.  It  does  not  necessarily  follow,  however,  that  a  certain 
person  is  in  an  early  stage  of  diabetes  merely  because  he  passes 
dextrose  in  the  urine  after  taking  a  relatively  small  quantity  by 
mouth.  Yet  such  may  be  the  case.  Minkowski  has  shown,  for 
example,  that  whereas  the  removal  of  the  whole  of  the  pancreas 
is  followed  by  a  diabetes,  the  removal  of  a  part  may  cause  merely 
an  inability  to  take  much  sugar  in  the  food  without  having  it 
appear  in  the  urine.  Furthermore,  clinical  experience  has  demon- 
strated that  in  some  cases  a  marked  alimentary 
glycosuria  gradually  passes  over  into  a  true 
diabetes  mellitus.  In  still  others,  on  the  contrary,  it 
would  appear  to  be  quite  without  significance. 

The  occurrence  of  an  alimentary  glycosuria 
in  a  healthy  man  is  greatly  favored  by  alcoholic  drinks, 
and  especially  by  the  ingestion  of  large  quantities  of 
beer.'^  It  is  impossible  to  say  why  this  should  be  so,  and 
whether  the  effect,  in  the  case  of  beer,  is  to  be  attributed  more  to 
its  alcohol  or  to  its  maltose.  Muscular  exertion  and  heating  of 
the  body,  on  the  contrary,  tend  to  diminish  the  excretion  of  sugar 
in  alimentary  glycosuria,  just  as  in  true  diabetes.® 

Lactose  may  also  appear  in  the  urine  after  excessive  quan- 
tities have  been  taken  in  the  food,  but  it  appears  there  more  fre- 
quently because  it  has  been  resorbed  from  the  mammary  glands 
of  nursing  women,  owing  to  a  stasis  of  milk.  Some  special  factor 
seems  to  favor  its  excretion  in  these  cases,  for  the  amount  absorbed 


DIABETES  345 

would  appear  to  be  too  small  to  give  rise  to  an  ordinary  alimentary 
glycosuria. 

Many  studies  have  been  made  relative  to  the  ease  with  which 
an  alimentary  glycosuria  may  be  produced  in  different  diseases. 
These  investigations,  unfortunately,  are  not  based  upon  conditions 
as  found  in  a  normal  individual,  for  the  patient  is  generally  in  the 
fasting  state,  and  is  given  large  amounts  of  pure  dextrose.  De- 
spite this,  such  patients  rarely  exhibit  an  alimentary  glycosuria; 
nor  is  it  generally  true  that  individuals  with  hepatic  dis- 
ease are  especially  prone  to  show  such  a  glycosuria,^  at  least 
when  dextrose  is  given;  though  it  is  a  fact  that  a  laevulo- 
suria  is  more  readily  produced  in  similar  conditions.^^  I 
should  advise  caution,  however,  in  assuming  the  existence  of  a 
disordered  liver  function  from  the  appearance  of  such  a  glycosuria, 
for  we  have  learned,  beyond  question,  that  the  specific  activity  of 
an  organ — and  this  applies  particularly  to  the  liver — ^may  persist 
even  though  the  major  part  of  its  cells  be  destroyed  or  severely 
damaged. 

In  phosphorus  poisoning,  however,  and  thyreo- 
toxic states,  sugar  passes  into  the  urine  with  particular 
case.  Certain  observers  have  interpreted  the  thyreotoxic  form 
as  an  epinephrin  glycosuria  and  as  representing  an  increased 
stimulation  exerted  by  the  thyroid  gland  upon 
the  chromaffin  system. ^^  This  needs  further  confirma- 
tion, however.  Alimentary  glycosuria  occurs,  further,  in  many 
cases  of  hysteria  and  neurasthenia,  in  the  trau- 
matic neuroses  and  in  the  infectious  diseases.  In 
the  latter,  and  also  in  cachectic  states,  the  mere  ingestion  of  starch 
may  lead  to  a  similar  result.  These  various  observations  show 
how  conservative  we  must  be  in  interpreting  such  transitory  and 
etiologically  uncertain  glycosurias. 

Phlorhizin  Glycosuria.^^ — phlorhizin  is  a  glucosid,  i.e., 
it  is  capable  of  being  split  up  into  dextrose  and  a  proteid  radicle, 
the  former  component  representing  about  forty  per  cent,  of  the 
whole.  The  glycosuria  following  its  administration  is  peculiar 
in  that  it  is  probably  not  accompanied  by  an  in- 
creased percentage  of  dextrose  in  the  blood. 
Though  certain  observers  *^  have  found  a  hyperglycsemia  in  this 
condition,  the  majority  have  noted  no  such  increase  in  the  blood- 
sugar,  but  rather  a  diminution ;  and,  indeed,  no  increase  was  noted 


346  THE  BASIS  OF  SYMPTOMS 

even  after  removal  of  the  kidneys.  Pfliiger  explains  these  diverse 
findings  on  the  basis  that  in  the  blood-sugar  determinations  no 
distinction  was  made  between  free  sugar  and  sugar  com- 
bined loosely  with  colloids,  only  the  former  taking 
part  in  the  phenomenon.  This  hypothesis  can  scarcely  be 
accepted,  however,  because  the  sugar  of  the  blood  is 
actually  in  solution.^* 

It  is  possible  that  a  phlorhizin  glycosuria,  being  unaccom- 
panied, as  is  generally  held,  by  a  hyperglycaemia,  is  due  to  t  o  x  i  c 
changes  in  the  renal  cells  which  have  deprived  them  of 
the  power  of  holding  back  sugar.  Another,  far  less  likely,  ex- 
planation is  that  the  phlorhizin  loses  its  sugar  radicle  (ph lor- 
es e)  in  the  kidneys  and  that  this  is  at  once  converted  into 
dextrose  and  eliminated,  while  the  residue  of  the  phlorhizin  mole- 
cule (phloretin)  combines  once  more  with  sugar  and  the 
process  is  repeated.  The  amount  of  dextrose  that  appears  in  the 
urine  after  phlorhizination,  however,  is  so  great  that  it  cannot 
be  accounted  for  by  a  mere  splitting  off  of  the  glucosid;  and, 
furthermore,  it  is  certain  that  the  administration  of  this  substance 
causes  an  actual  removal  of  dextrose  from  the  body. 

In  phlorhizin  poisoning,  the  sugar  excreted 
is  derived,  first  of  all,  from  the  glycogen  of  the 
liver,  which  early  disappears.  It  seems  certain  that  it  is  also 
derived  from  the  proteids  of  the  body,  for  it  is  known 
that  glucose  continues  to  be  excreted  in  phlorhizin  poisoning, 
even  though  the  animal  be  fasting  and  its  liver  presumably  free 
of  glycogen.  The  proteid  decomposition  is  accelerated  owing 
to  the  failure  to  consume  carbohydrates ;  and  even  beta-oxybutyric 
acid  may  be  excreted.  If  phlorhizin  be  given  to  fasting  animals, 
a  fatty  degeneration  of  the  liver  is  produced,  which  can  be  pre- 
vented if  the  animal  be  fed  on  proteids  or  carbohydrates.  At 
times,  the  amount  of  sugar  excreted  after  taking  phlorhizin  is  so 
great  that  it  seems  as  if  it  must  be  formed  in  part  from  the 
fats  of  the  body,^'^  a  possibility  that  will  be  considered  in 
another  place  (p.  351). 

Renal  Diabetes. — The  glycosuria  of  phlorhizin  poisoning, 
therefore,  is  characterized  by  the  fact  that  the  amount  of  sugar 
in  the  blood  is  not  increased ;  and  it  seems  probable  that  in  this 
condition,  as  well  as  in  certain  cases  of  marked  diuresis,  the  result- 
ing glycosuria  is  due  to  an  inability  on  the  part  of  the 


DIABETES  347 

renal  cells  to  hold  back  the  sugar  normally  pres- 
ent in  the  blood.  Little  is  known  about  such  conditions 
in  man,  but  recent  observations  have  tended  to  show  that  glyco- 
suria may  result  from  just  such  a  renal  insufficiency.  To  these 
cases  has  been  given  the  name  of  renal  diabetes.  Liithje^^  has 
shown  that  the  sugar  was  present  in  the  blood  of  his  patient  in 
less  than  the  normal  quantity,  thus  demonstrating  that  the  glyco- 
suria was  due  to  some  abnormal  permeability  on  the  part  of  the 
kidneys  toward  dextrose.  Neubauer,^''^  on  the  other  hand,  has 
observed  hyperglycsemia  without  glycosuria  in  cases  of  nephritis 
with  hypertension.  The  amount  of  sugar  excreted  by 
such  patients  is  independent,  to  a  great  extent,  of 
the  amount  taken  in  the  food;  yet  this  is  not  especially 
characteristic  of  renal  diabetes,  for  the  same  is  true  of  certain 
forms  of  diabetes  mellitus. 

Epinephrin  Glycosuria. — An  increase  in  the  percentage  of 
sugar  in  the  blood  occurs  also  when  epinephrin  in  large  amounts 
is  introduced  into  the  circulation.^®  Epinephrin  is  supposed  to 
^'mobilize"  sugar.  The  amount  of  the  latter  entering  the 
blood  is  directly  proportional  to  the  amount  of  epinephrin  present, 
and  is  dependent,  furthermore,  upon  the  size  of  the  animal's 
glycogen  store ;  for  with  a  diminution  of  the  latter,  larger  amounts 
of  epinephrin  are  required  to  mobilize  the  same  amount  of  sugar. 
As  epinephrin  is  capable  of  causing  a  considerable  increase  in  the 
degree  of  proteid  destruction  in  fasting  animals,^®  it  is  evident 
that  a  glycosuria  (and  a  storing  up  of  glycogen  ^^)  tends  to  occur 
also  in  such  animals.  The  blood  constantly  contains  epinephrin, 
which  acts,  it  may  be,  to  regulate  the  vascular  tonus.  It  is  also 
very  likely  that  the  sugar-content  of  the  blood  is  similarly  under 
the  influence  of  epinephrin  and  in  turn  of  the  sympathetic  ner- 
vous system.  (For  the  most  recent  studies  relative  to  the  func- 
tion of  epinephrin  and  to  the  interpretation  of  the  symptoms  of 
Addison's  disease,  the  reader  is  referred  to  the  preceding  chapter, 
p.  336.— Ed.) 

Transient  Glycosurias. — Glycosurias  lasting  only  a  few  hours 
or  days ^^  have  been  observed  after  various  intoxica- 
tions, infections,  injuries  and  diseases  of  the 
central  nervous  system. 

Of  these  transient  glycosurias,  the  best  studied  is  that  which 
results  from  a  puncture  of  a  certain  limited  area 


348  THE  BASIS  OF  SYMPTOMS 

in  the  floor  of  the  fourth  ventricle  of  animals. 
In  these  cases,  the  appearance  of  sugar  in  the  urine  is  always 
preceded  by  an  increase  in  the  amount  present  in  the  blood,  and 
it  is  favored  by  a  large  store  of  glycogen  in  the  liver.  If  glucose 
be  injected  into  a  mesenteric  vein  in  these  animals,  it  is  not  taken 
up  by  the  liver  as  it  normally  should  be,  but  passes  into  the  general 
circulation  and  is  then  excreted  by  the  kidneys.  If  the  splanchnic 
nerves  be  cut,  or  if  the  liver  be  removed,  a  puncture  of  the  fourth 
ventricle  has  no  effect  upon  the  urine;  while  the  extirpation  of 
the  suprarenals  likewise  prevents  a  piqure  glycosuria. ^^  Fur- 
thermore, after  puncture  of  the  ventricle,  the  amount  of  epinephrin 
in  the  serum  has  been  found  increased,^^  though  this  needs  con- 
firmation for  the  plasma.  All  these  facts  seem  to  indicate  that 
the  glycogen  of  the  liver  is  the  source  of  the  ex- 
cessive amount  of  sugar  in  the  blood  and  that  the 
puncture  causes  the  glycosuria  by  influencing  the  gly- 
cogenic function  of  the  liver  via  the  adrenals, 
epinephrin  and  the  sympathetic  system.  This 
would  point  to  the  action  of  the  same  mechanism  both  in  piqiire 
and  in  epinephrin  glycosurias,  the  former  being  of  central  origin, 
the  latter  peripheral.  Epinephrin,  for  instance,  causes  a  glyco- 
suria after  the  splanchnic  nerves  have  been  cut.^^  Eppinger, 
Falta  and  Rudinger  have  made  the  interesting  observation  that 
the  glycosuria  of  animals  from  which  the  pancreas  has  been  re- 
moved is  increased  by  the  injection  of  epinephrin,^^ 

(Our  knowledge  of  the  position  of  the  hypophysis*®  in 
carbohydrate  metabolism  is  at  best  fragmentary.  According  to 
certain  observers  (Borchardt),  injections  of  the  whole  gland 
extract  in  rabbits  usually  cause  a  glycosuria;  while  Gushing  was 
able  almost  without  exception  to  produce  a  glycosuria — with 
hyperglycsemia — in  rabbits,  by  intravenous  injections 
of  posterior  lobe  extracts  and  even  of  cerebro- 
spinal fluid  (assumed  to  contain  the  secretions  of  the  pos- 
terior lobe).  These  various  results  have  not  been  confirmed  by 
all  observers. 

Gushing  believes  the  following  interpretation  of  the  role  of 
the  hypophysis  in  carbohydrate  metabolism  to  be  permissible: 
"  Normal  posterior  lobe  activity  is  essential  to  effective  carbo- 
hydrate metabolism.  An  intravenous  injection  of  posterior  lobe 
extract  produces  glycogenolysis     .     .     .,   [whereas]   a  diminu- 


DIABETES  S49 

tion  of  posterior  lobe  secretion  occurring  in  certain  conditions 
of  hypopituitarism — whether  experimentally  produced  or  the 
result  of  disease)  leads  to  an  acquired  high  tolerance  of  sugars 

The  glycosuria  frequently  noted  in  cases  of  acromegaly 
and  gigantism,  according  to  this  conception,  would  be  due 
to  the  pressure  of  a  hyperplastic  anterior  lobe  upon  the  posterior 
lobe,  causing  first  stimulation  and  later  cessation  of  the  secretion 
of  the  posterior  lobe. 

The  mechanism  of  hypophysial  glycosuria  is 
not  well  understood.  It  might  be  assumed  to  reside  in  a  pri- 
mary disturbance  of  the  pituitary  body,  or  on  the  other  hand, 
to  act  via  the  nervous  system  or  other  internal  secretions,  e.g., 
epinephrin  and  the  sympathetic  system.  It  is  possible,  however, 
that  the  functional  disorder  of  the  hypophysis  is  only  a  co-ordinate 
part  of  a  more  general  disturbance  of  endosecretory  activity. — 
Ed.) 

Our  recently  acquired  knowledge  of  the  conditions  underlying 
epinephrin  glycosuria  have  thrown  considerable  light  upon  the 
nature  of  piqure  diabetes;  and  it  is  possible  that  we  shall  be  able 
to  correlate  the  different  non-diabetic  glycosurias  by  the  variations 
in  the  blood-sugar  and  in  the  glycogen  content  of  the  liver,  as 
well  as  by  the  results  observed  when  the  splanchnic  nerves  are 
severed. 

Diabetes  Mellitus 

Diabetes  mellitus  is  characterized  by  a  glycosuria  that  is  not 
due  to  any  of  the  above-mentioned  causes,  and  especially  not  to 
the  ingestion  of  large  amounts  of  grape-sugar.  Usually,  the 
dextrose  is  constantly  present  in  the  urine,  though  it  may  be  found 
only  periodically.  In  some  cases  of  diabetes,  Isevulose  and  pentoses 
also  appear  in  the  urine.  The  glycosuria  of  diabetes  mellitus 
always  results  from  an  excessive  amount  of  sugar  in  the  blood, 
ahyperglycsemia;  instead  of  the  normal  percentage  of  about 
O.I,  it  may  rise  even  to  0.7  per  cent.  On  the  other  hand,  the 
contention  of  F.  Miiller  that  the  behavior  of  the  kidneys  in  diabetes 
needs  further  study  is  a  sound  one.^^  For  example,  in  dogs, 
after  pancreas  removal,  there  may  be  a  considerable  hypergly- 
csemia  without  a  glycosuria,  and  a  number  of  similar  observations 
have  recently  been  reported  in  human  diabetes.^*     Possibly  the 


860  THE  BASIS  OF  SYMPTOMS 

total  amount  of  sugar  passing  through  the  renal 
vessels  is  of  more  imp>ortance  in  determining  its  appearance 
in  the  urine  than  is  the  percentage  present.  Indeed,  in  the  light  of 
present  knowledge,  one  may  well  ask  whether  hyperglycaemia 
actually  plays  a  determining  role  in  the  causation  of  glycosuria. 

If  one  accepts  a  hyperglycaemia  as  the  sine  qua  non  of  the 
diabetic  glycosuria,  he  must  assume  the  existence  of  a  renal  im- 
permeability ^®  for  the  many  cases  in  which  there  is  an  increase 
in  the  percentage  of  glucose  in  the  blood  unaccompanied  by  its 
appearance  in  the  urine.  As  a  matter  of  fact,  it  has  been  experi- 
mentally shown  that  the  permeability  of  the  kidneys  for  sugar  may 
be  raised  or  lowered  by  means  of  certain  toxins.^^  In  man, 
however,  it  would  seem  more  likely  that  the  kidneys  are  more  or 
less  unaffected  by  the  percentage  of  sugar  in  the  blood,  rather  than 
that  the  absence  of  a  glycosuria  in  hyperglycaemic  states  is  the 
result  of  a  diminished  renal  permeability.  It  is  possible,  though, 
that  diabetes  does  cause  specific  alterations  in  renal  function,  in 
view  of  the  fact  that  it  is  known  to  injure  the  renal  epithelium. 

Mild  and  Severe  Diabetes ;  Derivation  of  Sugar  from  Proteids 
and  Fats. — In  the  milder  forms  of  diabetes,  sugar  does  not  appear 
in  the  urine  if  no  carbohydrates,  i.e.,  sugars,  starches,  etc.,  are 
taken  in  the  food.  Great  individual  variations  ex- 
ist as  to  the  quantity  of  carbohydrate  material 
that  must  be  taken  in  order  to  produce  glyco- 
suria. On  the  one  hand,  a  patient  may  be  able  to  take  one 
hundred  and  fifty  grams  or  more  of  starch  in  twenty-four  hours, 
without  suffering  from  glycosuria;  while,  on  the  other,  a  glyco- 
suria may  result  when  only  twenty-five  to  thirty  grams  are  taken. 
The  essence  of  a  correct  diabetic  therapy  resides  in  the  effort 
to  determine  the  individual's  tolerance ;  and  this  is  done  by  spar- 
ing, as  far  as  possible,  the  mechanism  of  sugar  metabolism.^^  Not 
all  carbohydrates  show  the  same  tendency  to  cause  glycosuria  in 
these  patients,^'  and  many,  for  example,  will  tolerate  lactose  in 
the  food  even  better  than  starch. 

The  mild  form  of  diabetes  is  distinguishable  from 
alimentary  glycosuria  by  the  fact  that  starch  is  not  tolerated ;  for, 
so  far  as  we  know,  a  mere  excess  of  starch  in  the  diet  of  a  normal 
individual  never  leads  to  the  excretion  of  an  abnormal  quantity 
of  sugar  in  the  urine.  Possibly,  however,  exceptions  do  occur 
to  this  rule,  notably  in  the  case  of  the  infectious  diseases. 


DIABETES  351 

In  the  more  severe  forms  of  diabetes,  sugar  is 
excreted  in  the  urine  even  when  no  carbohydrates  are  taken  by 
mouth,  and  in  some — the  most  severe — cases  the  glycosuria  con- 
tinues even  when  the  patient  is  fasting.  In  these  cases,  the  sugar 
may  come  either  from  the  glycogen  of  the  ingested  meat  and  from 
that  arising  in  the  abnormal  diabetic  metabolism,  or  it  may  come 
from  proteids  or  f  ats.^^  The  origin  from  the  glycogen  has  not  been 
disputed,  but  observers  have  not  always  been  agreed  as  to  the  part 
proteids  and  fats  take  in  the  formation  of  sugar .^^  It  is  now 
generally  accepted  that  sugar  may  arise  from  fats'® 
and  proteids  or  from  both.  Proteid  is  a  more  fertile 
source  because  it  undergoes  a  more  complete  splitting,  even  in 
the  intestines,  than  does  fat. 

Particularly  interesting  is  the  intolerance  of  certain 
diabetics  to  proteid  foods.  Naunyn,  especially,  has 
shown  that  many  diabetic  individuals  become  sugar- free  only  if 
their  proteid  intake  is  kept  within  definite  limits.  Certain  patients 
cannot  tolerate  an  increase  in  their  proteid  quota  as  readily  as 
the  ingestion  of  carbohydrates.'^  This  would  seem  to  indicate 
that  the  metabolic  fault  is  situated  where  the  keto-acids 
are  normally  burned,  or  built  up  into  sugar-like  bodies  after  the 
splitting  off  of  ammonia. 

It  was  formerly  believed  .  that  this  distinction  be- 
tween mild  and  severe  cases  of  diabetes  was  a  sharp 
one,  and  that  it  rested  upon  fundamental  differences  in  the  tis- 
sues. In  the  mild  cases,  the  body  was  unable  to  assimilate  carbo- 
hydrate material  introduced  as  such,  but  was  able  to  consume  the 
carbohydrate  molecules  split  off  from  the  proteids;  whereas,  in 
the  severe  cases,  neither  could  be  utilized.  Yet  we  now  know 
that  no  such  sharp  distinction  can  be  drawn ;  '^  that  the  one  con- 
dition shades  into  the  other;  and  that,  finally,  the  body  may  be 
able  to  consume  a  considerable  proportion  of  the  carbohydrates 
taken  in  the  food,  even  though  the  diabetes  is  so  severe  that  gly- 
cosuria persists  during  fasting.'^  Notwithstanding  these  facts, 
the  above  distinction  has  a  certain  clinical  value; 
and  a  case  of  diabetes  can  hardly  be  considered  a  mild  one  if 
the  body  is  unable  to  assimilate  a  given  amount  of  carbohydrate 
material  in  the  food  without  the  excretion  of  sugar  in  the  urine. 


352  THE  BASIS  OF  SYMPTOMS 

The  Glycogenic  Function  of  the  Liver  in  Diabetes. — The  im- 
mediate cause  of  the  glycosuria  in  human  diabetes  resides,  accord- 
ing to  present  conceptions,  in  a  hyperglycsemia,  which  is 
the  result  in  turn  of  an  inability  on  the  part  of  the 
liver  to  polymerize  the  sugar  it  receives  and  to 
store  it  as  glycogen.  The  lessened  efficiency  of  the  liver, 
in  this  respect,  varies  considerably  in  different  cases,  and  upon 
this  fact  depends  the  variable  tolerance  to  carbohydrates  of  differ- 
ent patients.  The  glycogenic  power  of  the  liver  is 
never  completely  lost;  as  a  rule  it  is  raised  when  in- 
creasing amounts  of  sugar  are  carried  to  the  organ,  i.e.,  ingested; 
though,  infrequently,  in  cases  of  mild  diabetes,  the  excretion  of 
sugar  is  more  or  less  independent  of  the  amount  of  carbohydrates 
in  the  food. 

We  have  already  called  attention  to  the  fact  that  variable 
amounts  of  carbohydrates  must  be  taken  by  different  diabetics  to 
cause  the  appearance  of  sugar  in  the  urine,  and  that  no  single 
factor  has  so  great  an  influence  in  raising  the  assimilative  capacity 
as  sparing  the  mechanism  of  sugar  metabolism. 
Thus,  a  diabetic  who  to-day  can  tolerate  one  hundred  grams  of 
white  bread,  may,  in  the  course  of  a  few  months,  if  kept  within 
his  tolerance  limit,  be  able  to  assimilate  one  hundred  and  twenty 
to  one  hundred  and  forty  grams  with  no  ensuing  glycosuria.  This 
is  an  answer  to  the  skepticism  still  expressed  occasionally  as  to 
the  value  of  a  dietetic  therapy  in  diabetes. 

Certain  diabetics  are  better  equipped  to  take 
care  of  Isevulose,  and  starchy  foods  which  are  converted 
into  laevo-rotatory  sugars,  than  of  dextro-rotatory  carbohydrates. 
We  must  not  generalize  too  widely  in  this  particular,  however, 
for  even  among  diabetics  with  a  relatively  high  tolerance  for  ordi- 
nary starches,  there  is  no  uniformity  in  their  ability  to  handle 
Isevulose ;  and  in  the  severe  cases  with  a  low  tolerance,  particularly 
when  acidosis  is  present,  laevulose  is  no  better  borne  than  dex- 
trose.^^  The  crux  of  this  matter  is  that  every  type  of  carbo- 
hydrate used  in  a  diabetic  for  the  first  time  is 
well  taken  care  of  for  a  short  period,  irrespective  of  the  steric 
grouping  of  its  molecules. 

In  regard  to  the  question  as  to  whether  the  dia- 
betic builds  more  sugar  than  the  normal  indi- 
vidual we  can  answer  in  the  negative  for  the  milder  cases; 


DIABETES  353 

for  every  condition  is  satisfied  by  the  assumption  that  the  blood 
contains  more  than  its  normal  percentage  of  sugar  simply  because 
the  liver  cannot  store  it  as  glycogen.  In  another  place  we  shall 
consider  whether  the  tissues  are  able  to  burn  the  excess  of  sugar 
carried  them  by  such  blood. 

Certain  severe  cases,  on  the  other  hand,  persist- 
ently excrete  more  sugar  than  can  be  accounted 
for  by  the  carbohydrates  in  their  food.  Even  on 
a  strict  proteid  and  fat  diet  such  individuals  lose  large  amounts 
of  sugar.  As  we  have  noted,  this  sugar-excess  is  de- 
rived from  proteids  and  to  a  lesser  degree  from 
fats.  If  one  is  of  the  opinion  that  the  formation  of  sugar 
from  proteids  is  physiological,  he  must  distinguish  sharply  be- 
tween diabetics  who  can  assimilate  proteids  and 
those  who  cannot.  For  there  are,  undoubtedly,  patients 
who  tolerate  enormous  quantities  of  proteids,  yet  who  excrete 
sugar  after  the  ingestion  even  of  small  amounts  of  bread.  One 
can  only  conclude  that  the  behavior  of  the  tissues  to  exogenous 
sugar  is  different  from  that  to  endogenous.  The  distinction  has 
a  practical  bearing  upon  the  origin  of  acidosis  (see  p.  330). 

At  any  rate,  in  these  severe  cases,  the  liver  is  unable  to  store 
glycogen  from  proteid  sugar  any  better  than  that  from  ingested 
carbohydrates,  and  the  result  is  in  both  cases  a  hyperglycsemia  and 
a  glycosuria.  Thus  the  liver  occupies  the  foreground  in  both, 
though  it  is  not  improbable  that  other  tissues,  such  as  the  muscles, 
are  co-ordinately  involved. 

The  Consumption  of  Sugar  in  Diabetes. — We  now  come  to 
the  question  as  to  whether  the  diabetic  body  is  able  to  burn  sugar 
normally.  Investigations  on  the  respiratory  inter- 
change of  gases  have  furnished  evidence  that  the  oxidation 
of  sugar  in  certain  diabetic  patients  is  diminished.^^  We  know 
that  when  carbohydrates  are  completely  burned,  the  volume  of 
carbon  dioxide  given  off  is  equal  to  the  volume  of  oxygen  con- 
sumed; i.e.,  the  respiratory  quotient  is  i.o.  For  the  combustion 
of  proteids  and  fats,  however,  relatively  more  oxygen  is  neces- 
sary ;  and,  in  the  case  of  the  higher  fats,  the  ratio  of  carbon  dioxide 
to  oxygen  is  about  7  to  10  or  0.7.  When  carbohydrates  are  the 
main  source  of  energy  to  the  body,  therefore,  the  ratio  between 
the  carbon  dioxide  given  off  and  the  oxygen  absorbed  approaches 
1.0;  whereas  when  fats  and  proteids  furnish  most  of  the  energy, 
23 


354  THE  BASIS  OF  SYMPTOMS 

this  ratio  falls.  It  has  been  found  that  diabetic  patients  upon  an 
ordinary  mixed  diet  show  a  lower  respiratory  quotient  than  do 
normal  individuals  upon  the  same  diet.  From  this  fact  it  may  be 
inferred  that,  in  spite  of  the  large  amount  of  glucose  circulating 
in  their  blood,  the  utilization  of  carbohydrate  ma- 
terial by  diabetic  patients  is  deficient,  and  that 
most  of  their  energy  is  derived  from  fats  and 
proteids.  Abnormally  low  values,  i.e.,  below  0.74,  are  to 
be  explained  in  part  by  a  co-existing  acidosis  and  in  part  by  a 
conversion  of  proteids  and  fats  into  sugar.  Indeed,  the  de- 
gree of  reduction  of  the  respiratory  coeffi- 
cient may  be  looked  upon  as  an  index  of  the 
severity  of  a  particular  case. 

It  appears,  also,  that  this  change  in  the  respiratory  quotient  is 
more  marked  in  the  severe  than  in  the  mild  forms  of  diabetes; 
in  other  words,  the  former  burn  less  sugar  than  the  latter.  This 
view  is  further  supported  by  the  effect  that  muscular  exer- 
cise and  fever  have  upon  the  excretion  of  sugar.  In  the 
milder  forms  of  the  disease,  muscular  exercise  tends  to  diminish 
the  glycosuria,  apparently  because  the  body  utilizes  the  sugar  cir- 
culating in  the  blood.  In  the  more  severe  cases,  on  the  contrary, 
muscular  exercise  exerts  but  little  effect  upon  the  glycosuria,  for 
the  body  can  utilize  comparatively  little  sugar.  In  dogs  whose 
pancreas  has  been  completely  removed,  muscular  exercise  does  not 
reduce  the  sugar  excretion,  but  after  a  partial  removal,  it  regu- 
larly diminishes  the  glycosuria.  Hence,  the  pancreas,  or  at  least 
a  part  of  it,  is  essential  to  the  combustion  of  sugar. 

Thus  we  see  that  there  is  not  only  an  insuf- 
ficiency of  the  glycogen  reservoirs  in  diabetes, 
which  permits  an  excess  of  sugar  to  enter  the 
circulation,  but  that  there  is,  in  addition,  a 
lessened  ability  on  the  part  of  the  body  to  burn 
the  sugar.  If  the  former  alone  were  true,  the  respiratory 
quotient  would  increase  in  proportion  to  the  amount  of  carbo- 
hydrates ingested,  just  as  in  health,  for  despite  the  sugar  loss 
the  blood  continues  to  carry  it  in  excess. 

The  nature  of  this  lessened  capacity  for  con- 
suming sugar  is  not  well  understood.  Unfortunately,  we 
know  little  concerning  the  manner  in  which  sugar  is  normally 
utilized  in  the  body,  or  concerning  the  intermediary  stages,  such 


DIABETES  355 

as  lactic  acid  or  glycuronic  acid,  through  which  it  may  pass.  There 
seems  to  be  no  general  diminution  in  the  oxidative  ability  of  the 
body,  for  such  substances  as  benzene,  lactic  acid,  fat  and  fre- 
quently even  laevulose,  are  consumed  normally.  Diabetes 
consists  rather  in  a  specific  limitation  of  the 
ability  to  consume  dextrose;  and  it  seems  as  if  the 
diabetic  body  fails  especially  to  initiate  the  combustion  of  this 
sugar.  Nor  is  this  all.  Normally,  carbohydrates  can  be  con- 
verted into  fat  in  the  body,  but  in  diabetes  this  power  is  dimin- 
ished or  lost. 

We  are  acquainted  with  at  least  one  factor  that  is 
necessary  for  a  proper  combustion  of  the  sugar 
in  the  body.  This  is  the  pancreas."*^  If  this  gland  be 
extirpated  from  dogs,  their  ability  to  burn  sugars  is  certainly 
diminished.  The  same  holds  true  for  carnivorous  birds  and  for 
reptiles  and  amphibia.  When  about  twenty  per  cent,  of  the  pan- 
creas is  left  at  an  operation,  an  alimentary  glycosuria  or  a  dia- 
betes of  the  milder  type  may  result ;  whereas,  if  the  whole  gland 
be  excised,  a  diabetes  of  the  severe  type  is  the  consequence. 

There  exists  still  a  considerable  diversity  of  opinion,  even 
among  the  most  competent  investigators,  as  to  the  conditions  essen- 
tial to  the  causation  of  pancreatic  diabetes,  and  as  to  the  signifi- 
cance of  its  clinical  manifestations.*^  A  possible  explanation 
of  certain  conflicting  results  resides  in  the  difficulty  of  completely 
removing  the  pancreas,  even  when  this  is  the  object  sought.  The 
significance  of  the  duodenum  in  this  type  of  diabetes  has  also 
received  considerable  attention.  In  rana  esculenta  extirpation  of 
the  duodenum  causes  an  even  more  severe  diabetes  than  does  pan- 
creas removal;  this  is  not  the  case,  however,  in  warm-blooded 
animals. 

Liithje**  has  shown  that  if,  in  a  fasting  animal,  a  portion 
of  the  gland  be  left,  the  initial  glycosuria  will  completely  disap- 
pear in  the  later  stages  of  starvation,  and  the  percentage  of  sugar 
in  the  blood  will  return  to  normal.  We  must  conclude,  therefore, 
that  in  this  form  of  diabetes  it  is  still  possible  for  an  animal  to 
consume  sugar.  The  consumption  is  greater  when  the  external 
temperature  is  high  than  when  it  is  low.*^ 

The  full  significance  of  the  pancreas  in  the 
mechanism  of  sugar  metabolism  is  still  unsettled.*^ 
The  most  likely  interpretation  hinges  on  the  conception  of  an 


356  THE  BASIS  OF  SYMPTOMS 

internal  secretion.  Cohnheim  believes  it  necessary  to 
assume  the  combined  action  of  such  a  secretion  and  of  muscle 
extract.  Pfluger,  on  the  other  hand,  emphasizes  the  importance 
of  the  nervous  system  in  the  mechanism. 

Glycosuria  may  be  produced  not  only  by  extirpation  of  the 
pancreas,  but  also  by  removal  of  the  salivary  glands  and  of  the 
thyroid.*'^  Furthermore,  the  hypophysis  (see  p.  348)  and 
the  chromaffin  system  play  a  part  in  sugar  metabolism ; 
and  we  have  already  referred  to  the  glycosuria  produced  by  the 
injection  of  epinephrin  (see  p.  347).  Loewi^®  has  made 
the  interesting  observation  that  the  instillation  of  a  drop  of 
epinephrin  into  the  conjunctival  sac  of  animals  whose  pancreas 
has  been  removed  causes  a  mydriasis,  and  that  the  latter  does 
not  occur  in  normal  animals.  This  has  been  noted  also  in  cer- 
tain cases  of  human  diabetes  probably  of  pancreatic  origin,  as 
well  as  occasionally  in  hyperthyroidism.  The  inference  to  be 
drawn  from  the  foregoing  is  that  the  pancreas  inhibits  the  sensi- 
tiveness to  epinephrin  of  certain  organs  of  sympathetic  innerva- 
tion, whereas  the  thyroid  augments  this  sensitiveness.  Eppinger, 
Falta  and  Rudinger*^  have  studied  the  interrelationship 
of  the  pancreas,  the  thyroid  and  the  chromaffin 
system  with  respect  to  proteid  and  carbohydrate  metabolism, 
and  have  shown  a  complicated  interaction  of  these  organs,  in 
part  stimulative,  in  part  inhibitory.  Possibly,  certain  cases  of 
human  diabetes  may  be  explained  on  the  basis  of  such  an  inter- 
action. 

The  liver  has  recently  not  received  the  attention  it  de- 
serves as  a  factor  in  diabetes.  Newer  work  has  again  focused 
our  attention  upon  this  organ,  and  properly  too,  because  of  its 
intimate  relation  to  other  glands,  particularly  the  pancreas. 

Finally,  as  regards  the  pancreas,  we  must  ask  whether  the 
secretions  of  the  cells  of  Langerhans  alone  are  of  impor- 
tance in  sugar  metabolism,  or  whether  the  pancreatic  cells  in 
general  share  this  function.  Observers  are  not  unanimous  on  this 
point. '^  It  would  appear,  however,  from  the  comprehensive  stud- 
ies of  Weichselbaum  ^^  that  a  painstaking  examination  will  show 
striking  pathological  alterations  in  the  islands  of  Langerhans  in 
all  cases  of  human  diabetes. 

The  Etiology  of  Diabetes. — The  tendency  to  acquire  diabetes 
may  be  inherited,  not  alone  from  parents  that  have  had  the 


DIABETES  357 

disease  itself,  but  also  from  those  who  have  had  gout,  obes- 
ity or  nervous  disorders. 

Diabetes  sometimes  follows  severe  cerebral  concus- 
sions and  injuries,  as  well  as  violent  fright  and 
other  psychic  traumata.  Arteriosclerosis  and 
syphilis  are  frequently  associated  with  diabetes,  though  we 
do  not  know  whether  they  cause  it  by  their  action  upon  the 
cerebral  structures  or  not.  Definite  anatomical  lesions  of  the 
brain,  especially  when  situated  in  the  neighborhood  of  the  fourth 
ventricle,  undoubtedly  can  produce  diabetes,  though  this  is  a  very 
rare  event. 

At  times,  diabetes  is  accompanied  by  diseases  of  the 
liver  or  pancreas.  The  condition  of  the  pancreas  in  dia- 
betes is  of  especial  interest  on  account  of  the  glycosuria  produced 
by  an  extirpation  of  this  gland  in  animals. °^  Even  the  older 
investigators  occasionally  noted  changes  in  the  gland  in  cases  of 
diabetes.  If  the  pancreas  is  completely  destroyed  by  disease, 
without  leading  to  death  within  the  first  twenty-four  hours,  dia- 
betes always  develops.  Primary  carcinomata  of  the  pancreas,  how- 
ever, may  completely  destroy  the  gland  without  producing  dia- 
betes, apparently  because  the  carcinoma  itself  retains  some  of 
the  functions  of  the  normal  tissues.  We  have  already  noted 
Naunyn's  analogous  observation,  i.e.,  that  a  carcinoma  of  the  liver 
may  secrete  bile.  It  is  our  opinion,  based  on  Weichselbaum's 
studies,  that  typical  and  severe  cases  of  diabetes  are  due  in  all 
instances  to  lesions  of  the  Langerhans  islets. 

Effects  of  Diabetes  Upon  the  Body. — In  diabetes,  a  certain 
proportion  of  the  energy  taken  in  the  food  is  not  utilized  by  the 
body,  and  it  is  necessary,  therefore,  to  cover  the  loss  by  more 
abundant  nourishment.  Even  in  severe  forms  of  the  disease, 
the  loss  of  carbohydrates  may  be  covered  by  the  administration 
of  large  amounts  of  fats  and  proteids,  providing,  of  course,  that 
the  gastro-intestinal  canal  can  absorb  the  necessary  amount  of 
material.  Fortunately,  this  is  usually  possible  and  only  rarely 
is  absorption  markedly  reduced  in  diabetes. ^^  The  greater  an 
individual's  need  for  energy,  the  more  difficult  will  it  be  to  main- 
tain his  nutrition  when  his  ability  to  utilize  carbohydrates  is 
lessened.  Yet  the  combined  skill  of  physician  and  cook  will  often 
accomplish  wonders  in  this  respect.  If  the  diabetic 
patient     absorbs     sufficient     nourishment,     his 


858  THE  BASIS  OF  SYMPTOMS 

metabolism  does  not,  as  a  rule,  differ  from  that 
of  a  healthy  individual  upon  the  same  diet.  If 
it  is  impossible  to  furnish  sufficient  energy  to 
him,  his  fat  and  body  proteids  are  consumed, 
just  as  are  those  of  a  healthy  individual  during 
partial  starvation.  Some  diabetics  seem  to  consume  the 
proteid  material  in  their  bodies  with  abnormal  rapidity.^*  But 
this  is  probably  due  to  the  fact  that  diabetics,  as  has  been  experi- 
mentally demonstrated,  need  more  proteid  food  to  maintain  their 
nitrogen  equilibrium  than  do  normal  individuals,  and  that  if  this 
added  quota  is  not  forthcoming  they  must  consume  their  own 
proteids,  especially  since  they  cannot  burn  carbohydrates  and  thus 
spare  proteids.  From  what  has  been  said,  it  will  be  seen  that  in 
the  more  severe  forms  of  diabetes,  malnutrition  frequently  de- 
velops; for  the  patient  is  either  unwilling  or  unable  to  take  a 
sufficient  quantity  of  fats  and  proteids  to  cover  his  total  needs, 
and,  in  addition,  his  consumption  of  proteid  material  is  sometimes 
abnormally  rapid. 

The  metabolism  in  diabetic  patients  frequently  shows  other 
peculiarities  as  the  disease  becomes  more  advanced.  Various 
organic  acids,  especially  beta-oxybutyric  and  diacetic  acids, 
are  formed  in  the  body.  Indeed,  they  are  produced  in  such  quanti- 
ties in  no  other  condition  as  in  some  cases  of  diabetes  mellitus. 
We  have  already  stated  that  when  an  excessive  amount  of  acid  is 
present  in  the  body,  it  is  neutralized  by  the  ammonia  which  would 
otherwise  have  been  converted  into  urea  (p.  ^y^y^.  For  this  reason 
the  excretion  of  organic  acids  in  diabetes  is  associated  with  a 
relatively  increased  elimination  of  ammonia  and  a 
relatively  diminished  excretion  of  urea  in  the  urine. 
The  source  of  the  acetone  and  of  the  diacetic  and  beta-oxybutyric 
acids  is  of  great  theoretical  and  practical  interest,  for  the  resulting 
acidosis  is  apparently  the  most  important  cause  of  the  dreaded 
diabetic  coma  (see  p.  332).  Unfortunately,  however,  the  cause 
of  the  acidosis  and  the  source  of  the  acids  is  but  little  understood 
(see  p.  328). 

In  diabetes,  the  nutrition  of  different  parts  of  the  body  suffers 
in  various  ways.  The  crystalline  lens  of  the  eye  may  become 
opaque  (diabetic  cataract),  and  degeneration  of  the  retina 
and  choroid  coat  may  develop.  The  arteries  are  often 
found  to  be  sclerotic. 


DIABETES  359 

Tissues  that  are  permeated  with  sugar  seem  to  offer  an  excellent 
medium  for  the  growth  of  micro-organisms,  and  it  is  well  known 
how  frequently  diabetics  become  infected  and  how  often  these 
infections  terminate  in  gangrene.  The  diabetic  gangrene 
is  due,  in  part,  to  the  presence  of  excessive  amounts  of  sugar  in 
the  tissue  and,  in  part,  to  the  diminished  blood-supply  caused  by 
an  associated  arteriosclerosis.  Patients  with  diabetes  are  fur- 
thermore very  susceptible  to  tuberculosis,  and  here  again 
the  process  shows  a  special  tendency  to  develop  into  gangrene. 
Other  complications,  such  as  furunculosis,  caries  of  the 
teeth,  gingivitis  and  stomatitis,  are  also  frequently  present  in 
diabetic  patients. 

We  know  comparatively  little  concerning  the  relation 
that  lesions  of  the  kidneys  bear  to  diabetes  mel- 
litus.  Albuminuria  is  a  not  infrequent  complication  of  the 
disease^"*  In  some  cases  it  is  due  to  a  true  nephritis,  produced 
by  the  same  cause  which  gave  rise  to  the  diabetes,  such  as  arterio- 
sclerosis, for  example;  in  other  cases  it  is  apparently  quite  an 
accidental  complication.  When  the  albuminuria  develops  late  in 
the  diabetes,  it  may  be  questioned  whether  the  continuous  passage 
of  sugar  through  the  kidneys  has  not  directly  harmed  the  secreting 
cells.  In  this  connection  we  may  recall  the  glycogenic  degeneration 
of  the  kidney  so  often  found  in  diabetes."^  The  immediate  cause 
of  this  degeneration,  and  its  relation  to  albuminuria  are,  however, 
insufficiently  understood.  That  primary  lesions  of  the  kidney 
may  cause  glycosuria  (renal  diabetes)  seems  very  probable  (see 
p.  346). 

The  amount  of  urine  is  often  enormously  increased  in 
diabetes,  and  as  much  as  ten  or  fifteen  litres  may  be  passed  in 
twenty-four  hours.  This  is  undoubtedly  dependent  upon  the 
abnormal  quantity  of  sugar  in  the  blood ;  for  if,  by  proper  methods, 
the  latter  be  diminished,  the  amount  of  urine  also  diminishes. 
Conversely,  the  greatest  diuresis  occurs  in  the  cases  with  the 
largest  amounts  of  sugar  in  the  urine.  The  accumulation  of 
dextrose  in  the  blood,  or  in  certain  tissues,  seems  to  produce  an 
intense  thirst,  and  the  water  that  is  taken  for  this  causes 
the  increase  in  the  amount  of  urine.  Yet  there  exists  no  definite 
relation  between  the  amount  of  urine,  the  excretion  of  sugar  and 
the  feeling  of  thirst ;  and  it  has  been  shown,  for  example,  that  even 


360  THE  BASIS  OF  SYMPTOMS 

though  the  same  quantities  of  sugar  are  being  excreted  daily,  the 
quantity  of  urine  may  be  different  in  different  patients. 

Theory  of  Diabetes. — From  the  foregoing  facts  we  shall  now 
try  to  formulate  a  theory  of  diabetes  mellitus.  The  sugar  is 
excreted  in  the  urine  because  of  a  hypergly- 
c se m i a — a n  excess  of  sugar  in  the  blood.  One 
cause  of  this  excess  in  the  blood  is  that  the 
liver  has  lost  the  property  of  storing  up  the  dex- 
trose that  comes  to  it  either  from  the  food  (mild 
form)  or  from  the  splitting  up  of  proteids  in  the 
body  (severe  form).  To  confirm  the  correctness  of  this 
distinction,  however,  further  evidence  is  needed. 

It  is  impossible  to  say  to  what  extent  the  glycogenic  functions 
of  other  organs,  such  as  the  muscles,  are  impaired  in  diabetes.  It 
seems  certain,  however,  that  in  some  way  the  pancreas  assists 
the  liver  and  muscles  in  their  glycogenic  function,  and  that  human 
diabetes  is  generally  the  result  of  a  disturbance  of  the  islands 
of  Langerhans.  The  loss  of  the  pancreas  function  not  only  seems 
to  interfere  with  the  power  of  the  liver  to  store  glycogen,  but  also 
to  cause  the  liver  to  release  its  glycogen  in  amounts  far  in  excess 
of  those  called  for  by  the  tissues.  For,  after  the  pancreas  has 
been  removed  from  dogs,  even  in  the  fasting  state,  hyperglycsemia 
and  glycosuria  appear  at  once,  and  the  liver  becomes  glycogen- 
free  much  more  rapidly  than  in  starving  dogs  whose  pancreas  is 
intact. 

In  the  milder  cases  of  diabetes,  it  is  possible  that  no  other 
disturbances  of  function  are  present  than  the  above-mentioned  im- 
pairment of  the  glycogenic  functions  in  the  body.  In  the 
more  severe  forms  of  diabetes,  however,  there  is  un- 
doubtedly a  diminution  in  the  ability  of  certain 
cells  of  the  body,  perhaps  of  the  muscle-cells  or 
even  of  all  cells,  to  assimilate  sugar.  The  pan- 
creas seems  to  assist  in  the  assimilation  of  sugar  in  the  body, 
not  only  through  its  influence  on  the  glycogenic  function  of  the 
liver,  but  possibly  also  by  furnishing  an  internal  secretion  that 
activates  the  glycolytic  ferments  in  the  muscles.  This  action  of 
the  pancreas  is  perhaps  similar  to  that  of  the  enterokinase  of  the 
intestines  which  converts  a  protrypsin  into  a  trypsin,  or  to  the 
intermediary  body  that  plays  such  an  important  part  in  haemolysis. 
The  glycc^enic  function  of  the  liver  may  certainly  be  influenced 


DIABETES  361 

through  the  nervous  system,  as  is  proved  by  the  effects 
of  the  experimental  puncture  of  the  fourth  ventricle;  and  it  is 
quite  possible  that  the  nervous  system  serves  in  some  way  to 
connect  the  liver  and  the  muscles.  This  influence  of  the  nervous 
system  upon  the  glycogenic  function  of  the  liver  would  explain 
the  etiological  relation  between  nervous  lesions  and  diabetes,  a 
relationship  that  has  been  insisted  upon  by  so  many  clinicians. 

Finally,  we  know  that  a  glycosuria  may  be  caused 
by  lesions  of  different  organs,  especially  of 
the  liver,  the  pancreas,  the  thyroid,  the  adre- 
nals and  possibly  by  diseases  of  still  other 
organs.  Ultimately,  it  may  be  possible  to  distinguish  different 
forms  of  the  disease  according  to  their  origin;  even  now,  indeed, 
V.  Noorden^'^  has  attempted  such  an  etiological  classifi- 
cation on  the  basis  of  the  interrelationship  of 
the  ductless  glands.  And,  even  though  diabetes  is 
apparently  associated  in  most  cases  with  lesions  of  the  islands 
of  Langerhans,  it  is  not  improbable  that  these  endosecretions 
may  be  influential  in  determining  the  characteristics  of  the  par- 
ticular case. 

LITERATURE 

*  Adler :  Pfliiger's  Arch.,  cxxxix,  93. 

'  F.  M'uller :  Path.  d.  Ernahrung,  235 ;  Blumenthal,  Deutsche  Khnik,  iii,  305. 

"Kiilz:  Festschrift  f.  C.  Ludwig,  Marburg,  1890;  E.  Pfliiger,  Das  Glykogen, 

2nd  edit.,  1905;  Pfliiger  and  Junkersdorf,  Pfluger's  Arch.,  cxxxi,  201. 

*  Langstein :  Asher-Spiro,  Ergebnisse,  i,  I,  63 ;  Embden  and  Almagia,  Hof- 

meister's  Beitrage,  vii,  298. 

*De  Filippi:  Zeitschft.  f.  Biol.,  xlix,  11. 

•v.  Noorden:  Zuckerkrankheit,  5th  edit,  19  (Ht.)  ;  Baer,  in  Naunyn,  Dia- 
betes, 2nd  edit.,  31.  For  the  subject  of  aHment.  galactosuria  see  Bauer, 
Wiener  med.  Wochenschft.,  1906,  2537. 

*  Renter:  Jahr.  d.  Hamburgischen  Staatskrankenanstalten,  vii  (2),  ^^  (Ht.). 

*  Grober :  Arch,  f .  khn.  Med.,  xcv,  137. 
•Strauss:  Berl.  kUn.  Wochenschft.,  1898,  51. 

"Chajes:  Deutsch.  med.  Wochenschft.,  1904,  19;  Hohlweg,  Arch.  f.  khn. 
Med.,  xcvii,  443. 

"  Eppinger,  Falta  and  Rudinger :  Zeitschft.  f.  Klin.  Med.,  Ixvi,  i,  and  Ixvii,  380. 

"Glaessner:  Zentralbl.  f.  Stoffwechsel,  vii,  673,  705;  papers  by  Lusk  et  al., 
Amer.  Jour.  Phys.,  i,  iii,  ix  and  x;  also  the  monograph  by  Lusk,  Phlor- 
hizin  Glykosurie,  Ergeb.  d.  Physiol.,  1912,  xiii,  315  (Ht.). 

"  Pavy :  Jour,  of  Phys.,  xx ;  Pfluger,  Pfliiger's  Arch.,  xcvi,  338. 

"Michaelis  and  Rona:  Biochem.  Zeitschft,  xiv,  476;  v.  Hess  and  McGuigan, 
Jour,  of  Pharm.  and  Exp.  Then,  1914,  vi,  45  (lit.). 

"Rumpf,  Hartogh  and  Schumm:  Arch.  f.  exp.  Path.,  xlv,  11. 

"Miinch.  med.  Wochenschft,  1901,  38;  Bonninger,  Deutsch.  med.  Wochen- 
schft., 1908,  34;  Weiland,  Arch.  f.  klin.  Med.,  cii,  167.  See  also  Frank 
(Harmless  forms  of  diabetes  in  young  individuals),  Therap.  d.  Gegen- 
wart  Nov.,  1914,  439- 

"  Biochem.  Zeitschft.,  xxv,  284. 


S62  THE  BASIS  OF  SYMPTOMS 

"PoUak:  Arch.  f.  exp.  Path.,  Ixi,  157;  Loewi,  in  v.  Noorden's  Handb.,  2nd 
edit.,  810  (Metab.  and  Pract.  Medicine,  London,  1907)  ;  Biedl,  Innere 
Sekretion  (Int.  Secretory  Organs,  New  York,  1913)  ;  Landau,  Zeitschft. 
f.  klin.  Med.,  1914,  Ixxix,  201. 

"Eppinger,  Falta  and  Rudinger:  Zeitschft.  f.  klin.  Med.,  Ixvi,  i;  Underbill 
and  Closson,  Amer.  Jour,  of  Phys.,  xvii,  75. 

*>  Pollak :  1.  c,  166. 

"^  Claude-Bernard :  LeQons  sur  diabetes,  etc. ;  Pfliiger,  Pfliiger's  Arch.,  xcvi, 
303,  860. 

'^  Mayer:  C.  r.  soc.  biol,  1906,  1123. 

**  Waterman  and  Smit :  Pfluger's  Arch.,  cxxiv,  198. 

»*  Pollak:  1.  c. 

"  Zeitschft.  f.  klin.  Med.,  Ixvi,  15  et  seq. 

""For  a  discussion  of  this  subject  see  Gushing:  The  Pituitary  Body  and  its 
Disorders,  1912,  16,  261   (lit). 

"^  See  especially  Naunyn :  Diabetes  Melitus,  in  Nothnagel's  spez.  Path.,  vii,  i, 
1906,  2nd  edit.  (The  Nothnagel  System)  ;  v.  Noorden,  Die  Zucker- 
krankheit,  6th  edit.,  1912,  and  New  Aspects  of  Diabetes,  New  York,  1913 ; 
Lepine,  Le  diabetes  sucre,  1909;  Allen  Glycosuria  and  Diabetes,  Boston, 
1913 ;  Magnus-Levy,  in  Kraus-Brugsch,  Spez.  Path.  u.  Therap.  inn. 
Krankheiten,  1913;  Pavy,  Garbohydrate  Metabolism  and  Diabetes,  1906; 
Gammidge,  Glycosuria  and  Allied  Gonditions,  1913;  Lusk,  Elements  of 
the  Science  of  Nutrition,  2nd  edit,  1909;  Benedict  and  Joslin,  Mletab- 
olism  in  Diabetes  Mellitus,  Garnegie  Institute,  Washington,  1910,  and  A 
Study  of  Metabolism  in  Severe  Diabetes,  1912. 

"•Leyden's  Handb.  d.  Ernahrungstherapie,  2nd  edit,  i,  226. 

*°  HoUinger :  Arch,  f .  klin.  Med.,  xcii,  217. 

'"  See  v.  Noorden,  1.  c. 

*^  Pollak:  Arch.  f.  exp.  Path.,  Ixiv,  415. 

■'  Staubli :  Arch,  f .  klin.  Med.,  xciii,  107. 

•*  Falta  and  Gigon :  Zeitschft.  f.  klin.  Med.,  Ixi,  297. 

**  Pfliiger :  Pfliiger's  Arch.,  cviii,  and  Das  Glykogen  u.  seine  Beziehung  zur 
Zuckerkrankheit,  2nd  edit.,  Bonn,  1905. 

*°  Pfliiger  and  Junkersdorf :  Pfliiger's  Arch.,  cxxxi,  201. 

*'  For  literature  relative  to  the  formation  of  sugar  from  fat  see  Pfliiger : 
Das  Glykogen,  etc.:  Rumpf,  Hartogh  and  Schumm,  Arch.  f.  exp.  Path., 
Iv  and  Ivi;  Falta  and  Gigon,  Zeitschft.  f.  klin.  Med.,  Ixv,  328;  Gigon, 
Arch.  f.  klin.  Med.,  xcvii,  376. 

"  Staubli :  Arch,  f .  klin.  Med.,  xciii,  107 ;  Gigon,  Miinch.  med.  Wochenschft., 
1909,  907 ;  Gigon  and  Massini,  Arch,  f .  klin.  Med.,  xcvi,  531. 

**  Naunyn,  in  Volkmann's  Vortragen,  Nos.  349,  350 ;  Naunyn,  Diabetes  mel- 
itus. 

*»  Fr.  Miiller :  Path.  d.  Ernahrung,  228. 

*°  Bauer :  Wiener  med.  Wochenschft.,  1906,  2537 ;  Petetti,  Berl.  klin.  Wochen- 
schft., 1907,  156;  Brasch,  Zeitschft  f.  Biol.,  1,  113. 

"  Magnus-Levy :  Verhand.  d.  physiolog.  Gesell.  z.  Berlin,  1904,  Nos.  5-8 ; 
Lusk,  Science  of  Nutrition;  Benedict  and  Joslin,  Metabolism  in  Diabetes 
Mellitus,  1910. 

*■  v.  Mering  and  Minkowski :  Arch.  f.  exp.  Path.,  xxvi,  371 ;  Minkowski,  ibid., 
xxxi,  85 ;  Sandmeyer,  Zeitschft.  f.  Biol.,  xxxi,  12. 

*'Liithje:  Miinch.  med.  Wochenschft,  1903,  1537. 

**  See  Pfliiger :  Pfluger's  Arch.,  cviii ;  Pfluger,  Das  Glykogen  u.  seine  Bez. 
z.  Diabetes,  2nd  edit,  1905  (lit). 

"Liithje:  Kongr.  f.  inn.  Med.,  1905,  298;  ibid.,  1907,  264. 

**Gohnheim:  Zeitschft.  f.  physiol.  Ghemie,  xxxix,  xlii,  xliii,  xlvii;  Hall, 
Amer.  Jour,  of  Phys.,  xviii,  283. 

"  Pfliiger :  Das  Glykogen,  etc.,  2nd  edit.,  1905. 

**  Loewi :  Arch,  f .  exp.  Path.,  lix,  83. 

"  Kongr.  f .  inn.  Med.,  1908,  345,  352. 


DIABETES  363 

"Sauerbeck,  in  Asher-Spiro;  Virchow's  Arch.,  clxvii,  Suppl.,  i;  Karaka- 
scheff,  Arch.  f.  klin.  Med.,  Ixxvii,  290;  Marchand,  ibid.,  312;  Herxheimer, 
Verhand.  d.  path.  Gesell.,  1909,  276.  See  also  Bensley,  Amer.  Jour.  Anat., 
191 1,  xii,  297  (intra-vital  staining  technic  and  recognition  of  islet  cells). 

"Wiener  klin.  Wochenschft.,  191 1,  No.  5. 

"  Minkowski :  Ergeb.,  in  Lubarsch-Ostertag.,  1897,  94  (lit.)  ;  Sauerbeck,  ibid., 
1904,  viii,  (2),  538. 

"Salomon:  Deutsch.  Klinik,  xii,  527. 

"v.  Mering,  in  Penzoldt-Stintzing :  Handb.  d.  spez.  Therap.,  3rd  edit.,  ii, 
part  3.  Benedict  and  Joslin,  Publ.  of  the  Carnegie  Inst.,  Washington, 
Nos.  135  and  176. 

"'  See  Naunyn,  v.  Noorden,  1  c. 

*°Fichtner:  Arch.  f.  klin.  Med.,  xlv,  112. 

"  V.  Noorden :  Die  Zuckerkrankheit,  5th  edit,  154. 


CHAPTER  VIII 
THE  METABOLISM  OF  THE  PURIN  BODIES.     GOUT 

The  nitrogen  derived  from  a  certain  class  of  proteids,  the 
nucleo-proteids,  is  not  excreted  in  the  form  of  urea 
and  ammonium  salts  to  the  same  extent  as  is  that  derived  from 
ordinary  proteids.^  The  characteristic  constituents  that  enter 
into  the  composition  of  the  nucleo-proteids  are  the  nucleinic 
acids.  When  these  undergo  cleavage,  they  give  rise  to  the 
purin  or  alloxuric  bases,  among  which  are  adenin, 
guanin,  xanthin  and  hypoxanthin.  A  small  portion  of  these 
bases  appears  in  the  urine  as  such,  but  the  greater  part  is  elim- 
inated in  an  oxidized  form,  as  uric  acid.  The  uric  acid 
and  the  purin  bases  are  often  spoken  of  together  as  the  purin 
bodies. 

The  mechanism  underlying  the  conversion 
of  the  nucleo-proteids  into  the  purin  bodies  is 
one  of  ferment  action. ^  From  the  nucleins  of  the  cells 
anuclease  splits  off  the  purin  bases  adenin  and  guanin.  The 
latter  are  changed  by  a  hydrolytic  ferment  into  xanthin 
and  hypoxanthin.  An  oxydase  converts  hypoxanthin  into 
xanthin,  and  the  latter  in  turn  into  uric  acid.  These  ferments  are 
widely  distributed  in  the  animal  body.  In  man  about  fifty  to  sixty 
per  cent,  of  the  uric  acid  is  destroyed  by  still  another,  urico- 
lytic,  fermen t — u r i c a s e — chiefly  in  the  liver,  muscles  and 
kidneys.  As  this  uricolytic  enzyme  is  absent  from  the  blood,^  a 
certain  portion  of  the  nitrogen  of  the  purin  bases  appears  in  the 
urine  as  urea. 

Most  of  the  uric  acid  that  appears  in  the  urine 
is  derived  in  this  manner  from  nucleo-proteids 
that  are  broken  down  in  the  body,  or  from  purin 
bases  or  related  compounds,  such  as  caffein 
or  theobromin,  that  are  taken  in  the  food.  Not 
all  of  the  uric  acid,  however,  is  derived  from  these  sources,  for 
it  is  now  practically  certain  that  this  acid  may  be  formed 
synthetically  in  the  human  body,  just  as  it  is  in  the 
bodies  of  birds.*  Nor  does  all  of  the  nitrogen  contained  in  the 
nucleinic  acids  appear  in  the  urine  as  uric  acid  or  related  com- 
804 


GOUT  365 

pounds,  for  a  certain  proportion  is  converted  into  urea  in  the 
body.  This  latter  fact  gives  some  basis  to  the  old  conception 
that  uric  acid  represents  an  early  stage  in  the  formation  of  urea. 

The  quantity  of  purin  bases  in  the  urine 
serves  therefore  as  a  rough  index  of  the  bodily  con- 
sumption of  nucleo-proteids  and  purin  bodies, 
derived  either  from  the  cellular  metabolism  or  directly  from  the 
food.  Yet,  as  we  have  seen,  it  cannot  serve  as  an  accurate  and 
absolute  index  of  such  consumption ;  for,  on  the  one  hand,  not  all 
of  the  nitrogen  in  the  nucleinic  acid  appears  in  the  urine  as  purin 
bodies,  and,  on  the  other  hand,  these  bodies  may  be  formed  syn- 
thetically within  the  living  organism. 

Cell  nuclei  are  very  rich  in  nuclei- proteids; 
and  when  the  food  taken  contains  many  nuclei,  as  is  the  case 
with  thymus  gland,  for  example,  the  amount  of  purin  bodies  in  the 
urine  is  greatly  increased.  Conversely,  if  a  person  avoids  those 
substances  which  can  be  readily  converted  into  purin  bodies,  such 
as  the  nucleo-proteids  of  meats  and  seeds,  the  caffein  of  coffee, 
etc.,  the  quantity  of  uric  acid  in  the  urine  is  diminished,  and  that 
which  does  appear  there  represents  the  amount  actually  formed 
within  the  body.  The  amount  of  this  endogenous  uric  acid 
has  been  found  to  be  different  in  different  individuals,  though  it 
is  fairly  constant  for  the  same  individual  at  different  times.*^ 
It  is  apparently  somewhat  influenced  by  the  ingestion  of  large 
quantities  of  non-nitrogenous  food. 

The  elimination  of  endogenous  uric  acid  is  in- 
creased whenever  large  numbers  of  cells  rich  in  nucleo-pro- 
teids are  being  destroyed  in  the  body.  This  was  early  demon- 
strated for  a  particular  kind  of  cells,  the  leucocytes;  and  this 
fact,  among  others,  led  Horbaczewski  to  the  belief  that  the  leuco- 
C)rtes  are  a  specific  source  of  purin  bodies,  a  view  now  proved 
to  be  incorrect.®  Leucocytoses  are,  however,  frequently 
accompanied  by  an  increased  elimination  of  purin  bodies;  and 
when  this  is  so,  we  may  assume  that  an  abnormal  destruction  of 
leucocytes  is  taking  place  in  the  body.  Very  large  amounts  of 
uric  acid  are  excreted  in  the  majority  of  cases  of  leukaemia 
(64  per  cent).  Gottlieb'^  has  demonstrated  in  some  leukaemias 
an  increase  in  the  excretion  of  the  purin  bases ;  while  other  obser- 
vers,® in  a  series  of  cases,  have  found  the  excretion  both  of  uric 
acid  and  of  the  bases  to  be  increased.     The  leuksemic  increase  in 


S66  THE  BASIS  OF  SYMPTOMS 

the  purin  bodies  likewise  speaks  for  an  augmented  destruction 
of  leucocytes. 

The  urine  of  the  new-born  child  also  contains  re- 
markably large  quantities  of  uric  acid.  These  are  found  at  about 
the  same  time  that  uric  acid  infarcts  are  most  liable  to 
occur  in  the  kidneys.  The  explanation  of  this  increased  elimina- 
tion resides  possibly  in  the  marked  destruction  of  leucocytes  which 
occurs  in  the  first  days  of  life  and  which  leads  to  a  saturation 
of  the  tissues  with  the  purin  bodies,  just  as  in  leukaemia;^  while 
the  small  amount  of  urine  excreted  at  this  time  favors  the  precipi- 
tation of  uric  acid. 

Gout. — Gout  ^^  is  characterized  by  the  deposition  of  mono- 
sodium  urate  crystals  in  various  parts  of  the  body,  especially  in 
the  hyalin  and  fibrous  cartilages,  in  the  tendons,  in  the  subcu- 
taneous and  intermuscular  connective  tissues  and  in  the  kidneys. 
These  deposits  take  the  form  of  clusters  of  needle-like  crystals. 
No  symptoms  may  be  caused  by  such  a  deposition  of  urates,  espe- 
cially when  it  takes  place  gradually  and  in  certain  localities,  as 
the  subcutaneous  tissues  and  some  cartilages.  These  urate 
deposits,  known  as  tophi,  often  attain  a  large  size,  and 
they  may  then  break  through  the  skin,  or  again  disappear  with- 
out having  caused  any  unpleasant  sensations.  In  these  cases,  it 
seems  improbable  that  the  uric  acid  should  have  been  formed 
locally  by  the  cells,  for  the  strands  of  connective  tissue  are  pushed 
aside,  and  the  tophi  increase  in  size  by  new  deposits  on  their 
exteriors. 

On  the  other  hand,  the  deposition  of  urates  in  the  tissues  may 
lead  to  a  more  or  less  marked  inflammatory  reaction  in  the 
neighborhood,  and  this  may  be  accompanied  by  the  characteristic 
paroxysm  of  acute  gout.  Suddenly,  or  after  some  pro- 
dromal symptoms,  the  patient  is  awakened  at  night  by  violent 
j>ains  in  one  or  more  joints,  usually  in  the  metatarsophalangeal 
joints  of  the  great  toes.  The  affected  joint  and  the  neighboring 
tissues  become  intensely  inflamed,  and  the  skin  over  them  becomes 
cedematous.  These  very  acute  symptoms  usually  do  not  last 
long,  and  after  a  few  hours  or  days  they  all  disappear  without 
necessarily  leaving  any  alterations  in  the  joint  that  can  be  demon- 
strated even  by  anatomical  methods.  These  typical  acute  gouty 
paroxysms  may  recur  at  varying  intervals;  but  gradually  they 
become  less  and  less  characteristic,  the  patient  becomes  cachectic 


GOUT  867 

and  the  "regular  gout"  is  said  to  have  become  trans- 
formed into  the  asthenic  form. 

The  exact  cause  of  these  typical  paroxysms  is 
uncertain.  According  to  one  view  the  inflammation  is  caused 
by  the  deposition  of  uric  acid  or  some  of  its 
derivatives  in  the  tissues.  That  this  deposition  is  an 
important,  if  not  the  determining,  factor  in  the  gouty  attack  is 
indicated  by  the  following  facts:  Before  the  paroxysm,  the 
amount  of  uric  acid  in  the  blood  is  increased,  whereas  during  the 
attack  and  shortly  thereafter,  the  amount  is  greatly  reduced. 
Again,  it  is  possible  to  produce  typical  paroxysms  in  gouty  indi- 
viduals who  have  lived  on  purin-free  food  for  a  long  time,  by 
feeding  them  large  amounts  of  food  rich  in  the  purin  bodies.^ ^ 
Gouty  attacks  may  occur,  furthermore,  following  a  pneumonia 
when  nucleins  (leucocytes)  in  large  numbers  are  breaking  down.^^ 
Finally,  characteristic  tophi  have  been  produced  in  rabbits 
by  injections  of  uric  acid.^^  Following  the  injection  the  latter 
is  converted  into  the  insoluble  sodium  urate  and  about  the  pre- 
cipitate are  seen  the  inflammatory  phenomena  characteristic  of 
the  gouty  attack,  zns.,  the  infiltration  of  polynuclear  leucocytes,  the 
appearance  of  phagocytes  and  the  growth  of  connective  tissue. 
Indeed,  it  was  demonstrated  many  years  ago  that  the  salts  of  uric 
acid  have  a  far  more  rapid  and  irritating  action  than  does  uric 
acid  itself.  Apparently,  therefore,  it  is  the  deposition  of  the 
crystallized  urates  which  brings  about  the  inflammatory  reaction, 
which  is  not  necessarily  painful,  however. 

Why  this  deposition  occurs  periodically  and  only  in  certain 
tissues  is  not  known.  And  we  are  equally  ignorant  concerning 
the  nature  of  many  associated  gouty  manifesta- 
tions, such  as  the  granular  kidney  and  the  heart 
changes,  the  pulmonary,  nervous  and  ocular  com- 
plications   and    the   general    cachexia. 

It  is  said  that  a  tendency  to  gout  may  be  in- 
herited, and  that  the  disease  may  be  caused  by  excesses  in 
food  and  drink.  We  believe,  however,  that  caution  is  necessary 
in  the  acceptance  of  these  views,  for  they  rest  not  upon  convincing 
statistics,  but  rather  upon  so-called  clinical  experience  and  im- 
pressions. More  accurate  data  on  this  subject  are  therefore  very 
desirable.  That  chronic  lead  poisoning  favors  the 
development  of  gout  can  hardly  be  doubted,**  though  how  it  does 


368  THE  BASIS  OF  SYMPTOMS 

so  is  quite  uncertain.  The  nature  of  the  relationship  between 
gout  and  diabetes  mellitus,  and  between  gout  and 
obesity,  are  Hkewise  unsolved. 

Uric  Acid  in  the  Blood  During  Gout. — During,  and  also  be- 
tween, the  gouty  paroxysms,  uric  acid  crystallizes  out  of  the 
blood  with  abnormal  ease,  even  though  the  diet  has  for  months 
contained  no  purin  bodies,  and  though  the  heart  and  kidneys  are 
free  from  changes.^ ^  It  crystallizes  out  of  normal  blood  in  a 
similar  manner  only  when  a  large  amount  of  nuclein  compounds 
have  been  taken  in  the  food.  In  pathological  conditions  other 
than  gout,  especially  in  leukaemia  and  in  pneumonia  after  the 
crisis,  however,  large  quantities  of  uric  acid  will  at  times  crystal- 
lize out  of  the  blood  just  as  it  does  in  acute  gout.  And  in  chronic 
nephritis  with  uraemia,  uric  acid  may  readily  be  demonstrated  in 
the  blood.  ^®  To  explain  the  practically  constant  uric  acid  con- 
tent of  the  blood  in  gout,  one  must  assume  that  the  power  of 
certain  organs  to  break  up  the  acid  has  been  diminished.^ ''^ 

The  fundamental  question  as  to  the  solubil- 
ity of  uric  acid  in  the  blood  has  recently  been  elabo- 
rated in  its  more  important  aspects  by  Gudzent.^^  As  Emil 
Fischer  first  demonstrated,  uric  acid  occurs  in  two  forms,  the 
one  corresponding  to  the  laktam  formula,  the  other  to  the 
laktim  formula.  Both  series  form  primary  salts  which  differ 
only  in  their  solubility.  Gudzent  was  able  to  demonstrate  that 
the  laktamurate,  while  the  more  soluble,  was  extremely  unstable 
and  was  immediately  converted  into  the  more  stable  laktim  modifi- 
cation. He  has  shown  further  that  radium  is  capable  not  only 
of  retarding  the  change  from  the  soluble  to  the  insoluble  salt, 
but  also  has  the  power  to  convert  the  insoluble  laktim  into  the 
more  soluble  laktam. ^^  Up>on  these  observations  is  based  the 
recently  advocated  and  eminently  successful  radium  therapy 
of  gout. 20 

That  uric  acid  exists  In  the  blood  only  as  the  sodium  salt 
appears  well  established  ;2^  accordingly,  the  view  that  it  is  com- 
bined with  nucleinic  acid  in  the  blood  and  tissues  seems  unten- 
able.22  As  soon  as  one  hundred  c.c.  of  blood  serum  contain  more 
than  18,4  mg.  of  laktamurate  or  8.3  laktimurate,  the  conditions 
are  favorable  for  the  deposition  of  the  uric  acid  salts.^^ 

More  difficult  of  understanding  are  the  causes  of  this  super- 
saturation  of  the  blood  with  uric  acid  and  of  its  deposition  only 


GOUT  369 

in  certain  tissues.  Significant  with  respect  to  the  latter  is  the 
observation  that  cartilage  possesses  an  especial  affinity  for  uric 
acid,  which  crystallizes  out  as  sodium  urate  in  this  tissue.  We 
are  thus  brought  a  step  nearer  to  an  understanding  of  how  tophi 
are  formed. 

Another  question  still  undetermined  is  whether,  with  a  given 
concentration  of  uric  acid  in  the  blood,  deposition  occurs  more 
readily  in  gouty  individuals  than  in  non-gouty.  Leukaemia  is  a 
condition  in  point;  here,  though  unusually  high  uric  acid  values 
are  observed,  gouty  manifestations  are  distinctly  infrequent. 
Nevertheless,  they  are  occasionally  observed  in  typical  form. 2* 

The  Uric  Acid  in  the  Urine  in  Gout. — Previous  to  the  gouty 
paroxysms,  there  is  a  diminished  excretion  of  uric  acid  in  the 
urine;  whereas,  during  and  just  after  the  paroxysm,  more  is  ex- 
creted not  only  than  before,^^  but  also  than  in  the  intervals  between 
the  attacks,  and  this  too  on  a  meat-free  diet.^®  The  excretion 
of  the  purin  bases  is  also  said  to  be  increased  along  with  the 
increase  in  uric  acid,  though  there  is  some  doubt  as  to  this.  The 
endogenous  uric  acid  excretion  exhibits  a  similar  behavior;  after 
the  paroxysm,  indeed,  it  may  fall  below  the  normal  ^'^  and  in  the 
intervals  it  remains  at  the  lower  limit  of  the  normal.^®  If  food 
rich  in  nuclein  compounds,  e.g.,  thymus,  be  taken  during  the 
paroxysm,  the  uric  acid  is  not  excreted  so  well  as  it  is  by  a  normal 
individual.^ 

In  chronic  gout,  and  during  the  intervals  between  the 
paroxysms  of  acute  gout,  no  definite  abnormalities  in  the  excretion 
of  uric  acid  can  be  demonstrated,  although  Soetbeer  believes  that 
after  the  administration  of  meat  the  excretion  of  uric  acid  does 
not  follow  precisely  the  normal  course,  and  that  in  some  cases  it  is 
quantitatively  diminished  or  delayed. 

Brugsch  and  Schittenhelm  ^^  found  that  the  excretion  of 
endogenous  uric  acid  was,  on  the  average,  diminished,  even  though 
the  amount  of  uric  acid  in  the  blood  was  increased  and  the  kidneys 
were  functionating  properly.  The  formation  of  urea  from 
exogenous  purin  bodies  was  delayed  in  gouty  individuals ;  while 
the  total  uric  acid  formation  from  all  sources  was  likewise  re- 
tarded. Hence,  there  exists  a  disturbance  of  uric  acid 
formation,  uric  acid  destruction  and  uric  acid 
elimination.  Bloch^*  has  made  similar  observations  and 
emphasizes  the  importance  of  the  disturbance  in  endogenous  purin 
24 


370 


THE  BASIS  OF  SYMPTOMS 


metabolism.  Umber,^^  q^  the  contrary,  whose  curves  indicate 
a  subnormal  elimination  of  uric  acid  in  the  gouty,  regards  the 
retention  of  uric  acid  as  the  essential  feature.  That  retention 
does  play  an  important  part  seems  to  be  indicated  by  the  success 
generally  reported  from  the  use  ofatophan^^  which  apparently 
exerts  a  specific  eliminative  action  on  the  kidneys. 

One  might  be  inclined,  therefore,  to  attribute  the  increase  of 
uric  acid  in  gouty  blood  to  an  insufficient  excretion 
of  urates  by  the  kidneys,  a  supposition  which  receives 
some  support  from  the  fact  that  other  nitrogenous  waste  products 
may  also  be  retained  in  the  body,  both  in  the  acute  paroxysms 
and  in  chronic  gout.^^  Indeed,  evidence  has  been  accumulated 
which  indicates  that  the  kidneys  are  functionally  de- 
ranged even  early  in  the  course  of  gout.^^  The 
gouty  granular  kidney,  however,  is  a  late  manifestation.  That 
unusual  conditions  are  present  would  appear  from  the  retention 
of  ammonium  and  potassium  salts  during  the  gouty  paroxysm.^* 
The  metabolism  of  proteids,  other  than  that  of  the  nucleo-proteids, 
is  entirely  normal  in  gout.^'^ 

The  Cause  of  the  Local  Deposits  of  Urates. — According  to 
many  of  the  best  observers,^^  the  local  deposits  of  the  urates 
in  gout  are  caused  by  changes  in  the  cells  of  the 
affected  regions.  This  seems  to  be  true  in  the  primary 
attacks  at  least.  As  has  been  mentioned,  however,  there  is  less 
reason  to  believe  that  the  more  chronic  deposits  in  the  subcu- 
taneous tissues,  etc.,  are  caused  by  primary  cellular  changes. 
Ebstein  has  laid  great  weight  upon  a  primary  necrosis  of  the  tissue 
as  the  cause  of  the  precipitation  of  urates,  but  later  researches 
have  not  supported  his  views.  The  solution  of  this  problem  would 
seem  to  reside  in  studies  which  shall  determine  in  what  way,  and 
to  what  degree,  substances  related  to  uric  acid  are  held  in  solution. 


LITERATURE 

*The  more  recent  studies  are  found  in  Brugsch  and  Schittenhelm :  Der 
NukleinstoflFwechsel  u.  seine  Storungen,  Jena,  1910;  Bloch,  Biochem. 
Zentralbl.,  v  (collective  report)  ;  Schittenhelm,  Die  Fermente  d.  Nuklein- 
stoffwechsels  u.  d.  Wirkung,  in  Handb.  d.  biochem.  Arbeitsmethoden 
(Abderhalden),  1910,  ii,  420;  E.  Fischer,  Untersuch.  in  d.  Puringruppe 
(1882-1906),  Berlin,  1906;  Brugsch,  in  Kraus-Brugsch,  Spez.  Path.  u. 
Therapie  inn.  Krankheiten,  1913  (lit.). 

"Schittenhelm:  Zeitschft.  f.  physiol.  Chemie,  xlv,  354,  and  1,  30;  Wiechowski 
and  Wiener,  Hofmeister's  Beitrage,  ix,  247;  Schittenhelm  and  Schmidt; 
Zeitschft.  f.  exp.  Path.,  iv. 


GOUT  371 

•  Brugsch  and  Schittenhelm :  Zeitschft.  f.  exp.  Path.,  iv. 

*  Minkowski:  Die  Gicht,  in  the  Nothnagel   System;  Wiener,  Asher-Spiro, 

Ergeb.,  i,  I,  555.  and  ii,  Z7T>  SchmoU,  Johns  Hopkins  Hospital  Bull.,  xv, 

'Burian  and  Schur:  Pfliiger's  Arch.,  Ixxx,  241,  and  Ixxxvii,  239;  Rockwood, 

Am.  Jour.  Phys.,  xii,  38. 
•Wiener:  1.  c,  585. 

'  Gottlieb  and  Bondzynski,  Arch.  f.  exp.  Path.,  xxxvi,  127. 
*Kiilman:  Zeitschft.  f.  klin.  Med.,  xxviii,  524;  Kolisch  and  Dostel,  Wiener 

klin.  Wochenschft,  1895,  Nos.  2Z  and  24. 
'Niemann:  Jahrb.  d.  Kinderheilk.,  1910,  Ixxi,  586  (lit.). 
*°More  recent  literature  on  gout  (see  also  footnote  i)  :  Ebstein,  Natur.  u. 

Behand.    d.    Gicht,    Wiesbaden,    1906 ;    Minkowski,    1.    c. ;    v.    Noorden, 

Path.  d.  Stoffwechsels,  2nd  edit.,  1908,  ii,  138;  Schittenhelm,  Natur.  u. 

Wesen.  d.  Gicht,  Med.  Klinik,  4th  supplement ;  Schittenhelm  and  Schmidt, 

Die  Gicht  u.  ihre  diatetische  Therapie,  Halle  1910;  Kongr.  f.  inn.  Med., 

Wiesbaden,  1910 ;  F.  H.  McCrudden,  Uric  Acid,  New  York,  1906. 
**  Brugsch :  Zeitschft.  f.  exp.  Path.,  vi,  278. 
"  Ebstein :  Munch,  med.  Wochenschft.,  1907,  No.  34. 
"  Van  Loghems :  Zentralbl.  f.  d.  ges.  Phys.  u.  Path.  d.  Stoflfwechs.,  new  series, 

1907,  244. 
"  Liithje :  Zeitschft.  f.  klin.  Med.,  xxix,  266. 
"  Brugsch  and  Schittenhelm :  Zeitschft.  f .  exp.  Path.,  iv. 
"  Magnus-Levy :  Virch.  Arch.,  clii,  107 ;  Zeitschft.  f .  klin.  Med.,  xxxvi,  372. 
"  Brugsch  and  Schittenhelm :  Zeitschft.  f .  exp.  Path.,  iv. 
"Zentralbl.  f.  d.  ges.  Phys.  u.  Path.  d.  Stoffwechsels,  1910,  v,  289.    Criticism 

by  Bechhold  and  Ziegler,  Biochem.  Zeitschft.,  1910,  xxiv,  146. 
"  Deutsch.  med.  Wochenschft.,  1909,  No.  21 ;  Med.  Klinik,  1910,  No.  42. 
*"  Kongr.  f .  inn.  Med.,  Wiesbaden,  1910. 
** Brugsch:  Zeitschft.  f.  exp.  Path.,  vi;  Schittenhelm,  ibid.,  1909,  vii;  Gudzent, 

Zeitschft.  f.  physiol.  Chem.,  Ixiii,  455, 
""Minkowski:  Das  Wesen  d.  Gicht,  Vienna,  1903. 
**  Gudzent :  1.  c. 

**  Gliickmann :  Leukamie  und  Gicht,  Berlin,  Inaugural  Dissert.,  1910. 
•"His:  Arch.  f.  klin.  Med.,  Ixv,  156;  Magnus-Levy,  Zeitschft.  f.  klin.  Med., 

xxxvi,  380. 

*  Soetbeer :  Miinch.  med.  Wochenschft.,  1907,  No.  28. 
^  Brugsch :  Zeitschft.  f.  exp.  Path.,  ii,  619. 

"  Brugsch :  1.  c. ;  Brugsch  and  Schittenhelm,  Zeitschft.  f.  exp.  Path.,  iv. 

*  Vogt :  Arch,  f .  klin.  Med.,  Ixxi.  21 ;  Soetbeer,  Zeitschft.  f .  physiol.  Chem., 

xl,  25 ;  Bloch  :  Arch,  f .  klin.  Med.,  Ixxxiii,  499. 
**  Brugsch  and  Schittenhelm :  Zeitschft.  f .  exp.  Path.,  iv,  480. 
^  Bloch :  Zeitschft.  f .  physiol.  Chem.,  Ii,  472. 
**  Umber :  Kongr.  f .  inn.  Med.,  1910,  436. 
"  Nicolaier  and  Dorn :  Arch.  f.  klin.  Med.,  xciii,  331 ;  Weintraub,  Kongr.  f. 

inn.   Med.,   1911,  482;   Georgiewski,  Deutsch.  med.  Wochenschft,   1911, 

No.  22. 
"*Vogel:    Zeitschft.    f.   klin.   Med.,   xxiv,    512;    Schmoll,    ibid.,    xxix,    210; 

Magnus-Levy,  ibid.,  xxxvi,  380;  Vogt,  Arch.  f.  klin.  Med.,  Ixxi,  21. 
«Vogt:l.  c. 

"  Soetbeer :  Zeitschft.  f.  physiol.  Chemie,  xl,  55. 
"  Brugsch  and  Schittenhelm :  Zeitschft.  f .  exp.  Path.,  iv,  538. 
"Klemperer,  Horbaczewski,  v,  Noorden. 


CHAPTER  IX 
CONSTITUTIONAL  DISEASES  AND  DIATHESES 

Thus  far,  we  have  considered  metabolic  anomalies  in  so  far 
as  they  have  concerned  variations  in  the  amounts  of  materials 
utilized  by  the  body,  or  alterations  in  the  catabolism  of  the  normal 
constituents  of  the  food  and  tissues.  The  index  of  such  anoma- 
lies is  the  appearance  of  incompletely  metabolized  substances  in 
the  urine — findings  which  open  to  us  the  significant,  extensive  and 
practically  unexplored  domain  of  the  so-called  intermediary 
metabolism. 

It  has  already  been  noted  that  in  the  normal  metabolism  of 
certain  organs,  there  arise  substances  which  influence  the  activity 
of  other  organs.  Thus  the  field  of  intermediary  metabolism  coin- 
cides with  that  of  the  chemical  correlation  of  the 
organs,^  which  seems  to  explain  from  the  physiological  and 
pathological  points  of  view  what  investigators  have  long  since 
sought  to  establish  from  the  morphological,  vi2.,  the  indivisibility 
of  the  organism.  The  nervous  system  has  until  recently  been 
regarded  as  the  essential  mechanism  whereby  the  functions  of 
the  different  bodily  units  are  harmonized;  now,  however,  the 
belief  is  held  that  many  other  organs,  perhaps  all,  mutually  in- 
fluence one  another  in  a  chemical  way  by  means  of  the  so-called 
hormones.  The  sphere  of  the  latter  is  apparently  unlim- 
ited, for  the  activity  even  of  the  nervous  system  may  be  stimulated 
or  depressed  to  a  great  extent  by  chemical  means.  The  subject 
is  so  vast  and  complicated,  however,  that  we  can  touch  upon  only 
a  few  features  which  seem  perhaps  best  established. 

The  gonads,  the  hypophysis,  the  pineal  gland, 
the  thyroid  and  the  suprarenals,  in  some  complex  and 
imexplained  manner,  are  not  only  mutually  interdependent  in  their 
own  development,  but  they  influence  also  the  growth  of  the  bones, 
the  skin,  the  muscles  and  the  general  bodily  and  mental  structure. 
The  bone  changes  occurring  in  pregnancy  and  after 
castration  have  long  been  familiar  to  us;  while  osteoma- 
lacia has  been  ascribed  to  a  disturbed  ovarian  function. 

Disease  of  the  hypophysis  (see  pp.  318,  348, 415)  plays  a  part  in 
the  causation  of  acromegaly,  a  condition  characterized  by 
372 


CONSTITUTIONAL  DISEASES  AND  DIATHESES     373 

a  hyperplasia  of  the  bones  and  soft  tissues  at  certain  points, 
associated  with  inflammatory  manifestations ;  further,  by  marked 
deposits  of  fat  beneath  the  skin,  and  by  a  diminution  of  both 
mental  and  physical,  particularly  sexual,  power.  In  all  probability 
these  disturbances  are  the  result  of  an  increased  functional  activ- 
ity of  the  cells  of  the  anterior  lobe  of  the  hypophysis.  Speaking 
for  this  are  the  benefits  observed  following  removal  of  the  gland 
in  cases  of  acromegaly.^  That  the  hypophysis  and  the 
sexual  glands  are  intimately  related  would  appear  also 
from  the  specific  changes  which  the  hypophysial  cells  undergo  in 
pregnancy.^  The  thyroid  and  the  hypophysis  are  also 
closely  correlated;  the  former  is  often  affected  in  cases  of  acro- 
megaly, and,  furthermore,  myxcedema  and  acromegaly  have  cer- 
tain symptoms  in  common. 

All  of  this  goes  to  show  that  caution  is  indicated  in 
attributing  to  a  particular  organ  the  primary 
changes  leading  to  acromegaly;  indeed,  it  is  espe- 
cially characteristic  of  all  of  these  "nutritional  disorders"  that 
they  exhibit  manifestations  which  might  be  due  to  a  lesion  of 
any  of  a  number  of  organs  coincidently  involved,  thus  rendering 
the  determination  of  the  primary  disturbance  practically  impos- 
sible. 

In  pineal  gland  disease,*  the  characteristic  clinical  picture  is  in 
many  respects  the  antithesis  of  the  acromegalic,  in  that  we  observe 
premature  development  of  the  bones,  skin,  hair  and  sexual  organs, 
and  often  a  mental  precocity.  As  for  the  thymus,  its  entire  ana- 
tomical development,  its  persistence  through  adolescence,  its  re- 
gression as  growth  nears  completion — all  speak  for  its  role  in  the 
building  of  the  body.  The  condition  known  as  persistent 
thymus  has  a  clinical  bearing.  The  so-called  status 
thymico-lymphaticus^  rests  in  part  upon  a  constitu- 
tional, and,  in  part,  upon  a  morbid  basis.  I  am  not  prepared 
to  say,  however,  in  what  way  the  thymus  is  concerned  in  this 
condition;  it  is  possible  that  the  gland  affects  the  sexual  organs 
and  the  nutrition  of  the  bones.  In  the  cases  of  sudden  death 
among  children,  however,  the  role  of  the  thymus  cannot  be  over- 
looked. 

In  the  foregoing  conditions,  the  disturbance  in  function  of  one 
organ  carries  with  it  a  disturbance  of  one  or  several  other  organs. 
What  conclusion  can  we  draw  from  this  as  to  the  effect  of  such 


374  THE  BASIS  OF  SYMPTOMS 

changes  upon  the  organism  as  a  whole  ?  This  opens  up  the  prob- 
lems of  "local  pathology"  as  contrasted  with 
"constitutionalpathology."  Formerly,  emphasis  was 
laid  upon  the  involvement  of  the  entire  body  in  most  diseases;® 
as  evidence  of  this  were  the  constitutional  and  crasial  teachings. 
Later,  under  the  influence  of  pathological  anatomy  and  physiol- 
ogy, interest  turned  to  the  disturbances  in  structure,  or  in  function, 
of  certain  organs  and  organ-systems.  The  physicians  of  our 
generation  have  acquired  their  training  in  this  strongly  localistic 
atmosphere,  in  which  everything  was  explained  on  a  physical  or 
chemical  basis  and  was  interpreted  in  terms  of  weights  and  meas- 
ures. We  regarded  scornfully  the  erases  and  diatheses  of  the 
earlier  teachers,  and  forgot  how  narrow  we  ourselves  were 
becoming. 

Now  the  pendulum  has  swung  back  once  more,  and  we  are 
beginning  to  understand  that  this  "local  pathology"  is  not  com- 
prehensive enough.  Thus  we  meet  with  disturbances  of  function 
for  which  no  organic  substratum  can  be  discovered — or  indeed 
could  be  responsible — and  in  which  a  more  general  and  extensive 
derangement  must  be  assumed ;  while  in  some  conditions,  though  a 
local  change  is  found,  and  is  without  doubt  etiologically  significant, 
such  a  change  is  not  sufficient  to  explain  the  functional  disturb- 
ance in  all  of  its  phases. 

This  does  not  mean,  however,  that  the  older  teachings  must  be 
readopted  in  toto,  but  only  that  certain  fundamental  truths  which 
they  contained  must  be  employed  in  building  a  new  conception  of 
pathology.  Indeed,  we  must  pick  to  pieces  and  analyze  the 
elements  of  the  diatheses,  the  dyscrasias  and  the  constitutional 
anomalies — the  scrofulous,  the  haemorrhagic,  the  gouty  and  the 
arthritic  diatheses — and  determine  what  of  truth  they  contain. 
The  older  conception  of  the  diatheses  has  again  gained  a  foothold 
among  the  pediatricians  in  Germany,  at  least.  We  refer,  in 
particular,  to  the  lymphatic  status  and  the  exudative 
diathesis.*^ 

Let  us  cite  a  few  examples  of  constitutional  diseases  and 
peculiarities.  The  serum-albumins  of  different  spe- 
cies are  for  the  present  chemically  indistinguishable,  yet  each 
is  shown  to  have  individual  characteristics  by  the  phenomena  of 
precipitation.  A  given  serum-albumin  will  not,  as  a  rule,  destroy 
the  erythrocytes  of  animals  of  its  own  species.     In  cases  in  which 


CONSTITUTIONAL  DISEASES  AND  DIATHESES     375 

haemolysis  does  occur,  we  may  assume  that  there  exists  a  con- 
stitutional anomaly  of  the  animal  affected.  Even  though  this 
peculiarity  has  been  demonstrated  only  for  a  single  type  of  proteid 
and  for  a  single  type  of  cell,  it  is  likely  that  there  exists  a  general 
constitutional  fault.  Again,  in  hsemophilic  families, 
the  blood  coagulates  slowly.  There  is  a  deficiency  in  thrombo- 
kinase,^  present  in  all  the  tissues  normally.  This  deficiency  in- 
volves the  blood-corpuscles,  so  far  as  our  present  knowledge  goes, 
yet  it  is  probable  that  all  the  other  cells  are  likewise  poorly  supplied 
with  this  ferment. 

Further,  taking  tuberculosis  as  an  example  of  the  infec- 
tious diseases,  we  have  reasons  to  believe  that  in  this  condition 
the  body  as  a  whole  is  affected.  Tuberculosis  and  syphilis 
were  regarded  as  general  diseases  long  before  their  infectious 
nature  was  determined;  thus  the  term  syphilitic  dia- 
thesis was  once  employed.  Later,  when  our  interests  centred 
in  anatomical  and  bacteriological  studies,  tuberculosis  in  particu- 
lar was  regarded  from  the  localistic  point  of  view.  Still  later 
came  the  proof  that  in  many  infections — in  typhoid  fever,  for 
example — the  causative  organisms  did  not  remain  localized,  but 
entered  the  blood  and  caused  changes  in  the  most  widely  separated 
organs;  and  that  in  cases  of  pulmonary  tuberculosis  the  bacilli 
might  also  invade  the  blood  and  the  organs.®  The  general  nature 
of  the  tuberculous  infection  was  further  confirmed  by  the  dis- 
covery of  V.  Pirquet^^  which  pointed  to  a  cutaneous 
change  in  consequence  of  a  general  infection.  The  most  signifi- 
cant feature  of  the  reaction  is  its  appearance  even  when  the  dis- 
ease focus  is  insignificant  and  causes  no  symptoms.  Could  we 
establish  a  similar  reaction  on  the  part  of  other  tissues,  we  should 
be  fully  justified  in  calling  tuberculosis  a  constitutional  disease. 

In  syphilis  the  principles  involved  are  much  like  those 
in  tuberculosis.  As  pointed  out  by  Martins  the  conception  of 
a  constitutional  syphilis  arose  by  way  of  contrast  with  the  local- 
ized primary  lesion;  yet  the  appearance  in  other  parts  of  the 
body  of  specific  luetic  manifestations  does  not  say  that  the  entire 
organism  is  involved.  Conditions  such  as  tabes  dorsalis,  on  the 
contrary,  which  are  not  immediately  syphilitic,  may  well  be  re- 
garded as  due  to  a  constitutional  alteration  of  the  cells  on  a  luetic 
basis.     The  principles  underlying  the  luetin  and  Wasser- 


376  THE  BASIS  OF  SYMPTOMS 

mann  reactions  are  also  in  keeping  with  the  conception  of 
a  constitutional  disease. 

The  question  arises  as  to  the  features  which  distinguish  such 
a  general  pathological  alteration  from  disease  in  the  current  appli- 
cation of  the  term.  The  mere  fact  that  in  the  former  a  number, 
perhaps  all,  of  the  organs  are  involved  is  too  imstable  a  criterion, 
fluctuating  as  it  does  from  time  to  time  with  the  development  of 
our  knowledge.  We  are  constantly  discovering  indeed  that  dis- 
eases to  all  appearances  local  are  in  reality  affections  of  the  most 
extensive  type.  The  infections  are  a  case  in  point.  In  the  mere 
matter  of  a  widespread  involvement,  therefore,  many,  or  perhaps 
all,  diseases  are  general  in  that  they  usually  produce  changes  in 
more  than  one  organ ;  while  the  subdivision  into  acute  and  chronic 
forms  would  be  as  applicable  to  constitutional  disorders  as  to  the 
infectious  diseases,  for  example. 

But  features  of  another  kind  characterized 
the  constitutional  diseases,  the  dyscrasias  and 
the  diatheses  as  the  terms  were  employed  by  the 
older  writers..  First  of  all,  was  the  fact  that  the  mani- 
festations were  permanent.  Though  the  process 
might  at  times  begin  abruptly,  it  lasted  for  years  and  even  through- 
out life.  Frequently,  furthermore,  there  was  a  congenital 
element.  Haemophilia  is  illustrative  of  these  factors.  As  is 
well  known,  this  condition  is  inherited  in  certain  families,  being 
transmitted  through  the  females,  who  themselves  are  unaffected, 
to  the  males. 

Still  another  characteristic  of  the  constitutional  diseases  is 
their  resemblance  in  a  way  to  malformations  or 
to  anomalies  of  structure^*  rather  than  to  dis- 
eases in  the  present  acceptance  of  the  term.  The 
haemophiliac  is,  as  a  rule,  not  sick  so  long  as  there  is  no  provo- 
cation for  bleeding;  rather  is  he  endowed  with  a  tendency  to 
become  sick.  In  the  same  sense,  I  interpret  the  exudative  dia- 
thesis of  Czerny. 

Some  of  the  conditions  under  discussion,  however,  are  more 
than  a  mere  disease  tendency;  they  are  actually  diseases. 
Thus  the  so-called  uratic  diathesis  is  frequently  associated 
with  manifestations  due  to  renal  sand  and  renal  stones.  It  is 
convenient  to  define  diathesis  as  a  tendency  to  disease,  and  a 
constitutional  disorder  as  a  condition  embracing  a  disease.     At 


CONSTITUTIONAL  DISEASES  AND  DIATHESES     377 

any  rate,  the  attempt  should  be  made  to  distinguish  be- 
tween disposition  and  diathesis,  on  the  one  hand, 
and  actual  disease,  on  the  other. 

Three  possible  factors  are  concerned  in  the  etiol- 
ogy of  the  constitutional  anomalies.  A  portion  of 
them  are  congenital  in  the  sense  that  the  germinal  cells 
have  been  injured.  It  is  not  difficult  to  understand  how  an  injury 
to  these  cells  may  lead  to  widespread  cellular  abnormalities  in 
extra-uterine  life.  The  anomaly  may  then  be  the  direct  outcome 
of  this  early  cell  injury;  or  it  may  be  expressed  in  a  weaker 
anlage  which  later  leads  to  disease  because  the  possessor  is  unable 
to  resist  the  wear  and  tear  of  every-day  life.  This  is  well  illus- 
trated in  the  inherited  psychopathic  tendency  of  certain  indi- 
viduals. 

In  other  cases  the  condition  is  acquired.  The  causa- 
tive factors  in  this  type  are  infections,  intoxications  and 
faulty  living  conditions  in  the  way  of  light,  air,  habitation,  sleep 
and  food.  It  is  well  known  that  these  latter  factors  tend  to 
diminish  the  individual's  resistance,  his  efficiency,  etc.  Under 
their  influence  an  inferior  strain  of  men  is  produced.  The  action 
is  not  merely  quantitative,  i.e.,  leading  to  a  physical  and  mental 
subnormality,  but  also  qualitative,  as  the  unequal  resistance  to 
infections  indicates. 

In  the  older  descriptions  of  the  diatheses  and  constitutional 
anomalies,  no  distinction  was  made  between  those  of  infectious 
origin,  on  the  one  hand,  and  the  toxic  and  congenital  forms  on  the 
other.  To-day  the  infectious  diseases  are  sharply  separated  from 
the  latter.  Yet  it  is  just  in  the  infections  that  our  recently 
acquired  knowledge  of  the  functional  and  morphological  changes 
in  the  different  organs  have  given  us  an  insight  into  the  wide- 
spread nature  of  bacterial  processes.  The  conditions  of  gen- 
eral weakness  so  often  seen  after  the  infection 
has  subsided  have  much  in  common  with  what  we  are 
pleased  to  call  constitutional  disorders.  This  is  particularly  true 
of  such  chronic  infections  as  malaria,  syphilis  and 
tuberculosis,  which  indeed  were  formerly  classified  as 
dyscrasias,  diatheses  and  constitutional  diseases.  We  repeat, 
therefore,  that  in  the  consideration  of  the  infectious  diseases,  we 
encounter  at  one  point  or  another  the  various  elements  which 
go  to  make  up  a  constitutional  disorder — at  one  time  direct  mani- 


378  THE  BASIS  OF  SYMPTOMS 

festations  of  the  infection,  at  others  a  pronounced  depression 
of  the  general  nutrition,  functional  disorders  of  the  organs,  and 
the  tendency  to  peculiar  complications,  as,  for  example,  tabes  and 
paralytic  dementia  in  syphilis. 

As  for  the  chronic  intoxications  and  the  ca- 
chectic states  observed  in  malignant  processes, 
we  are  of  the  opinion  that  they  properly  belong  in  the  category 
of  constitutional  anomalies.  This  indeed  was  the  old  view; 
while  now  the  general  tendency  is  to  assign  them  elsewhere.  That 
chronic  lead  poisoning  is  a  constitutional  disorder  is 
evidenced  by  the  impaired  nutrition,  the  involvement  of  many 
organs  (brain,  nerves,  vessels  and  kidneys)  and  the  tendency  to 
other  diseases,  such  as  gout.  By  cachexia  is  meant  not  a 
mere  undernourishment,  but  rather  a  nutritional  state  which  in 
general  is  below  par.  Still  to  be  solved  in  this  question  is  the 
cause  of  the  characteristic  cachectic  color  of  the  skin,  and  of  the 
oedema  of  the  tissues,  both  of  which  indicate  the  general  nature 
of  the  process. 

The  literature  devoted  to  constitutional  diseases  and  diatheses 
speaks  for  the  great  diversity  of  the  conditions  included  therein. 
This  is  due  in  part  to  the  great  difficulty  in  distinguishing  between 
diseases  which  are  local  and  those  which  are  general,  and  in  part 
also  to  the  tendency  to  place  among  the  constitutional  disorders 
those  conditions  which  have  no  distinct  local  pathology.  Dia- 
betes mellitus  and  diabetes  insipidus  are  illustrative  of 
this.  Depending  upon  the  point  of  view,  the  flooding  of  the 
tissues  with  sugar  may  be  regarded  either  as  secondary  to  some 
local  lesion,  or  as  proof  per  se  of  the  constitutional  nature  of  the 
process. 

Obesity  is  to  be  regarded  as  a  constitutional  disease  only 
in  those  cases  in  which  there  is  actually  a  metabolic  anomaly  pres- 
ent, not  when  the  condition  is  due  to  excesses  in  eating.  Gout 
we  have  seen  results  from  a  disturbance  in  the  metabolism  of 
the  purin  bodies.  Whether  this  is  indicative  of  a  constitutional 
process  depends,  to  a  great  extent,  upon  individual  opinion,  just 
as  in  the  case  of  diabetes,  though  not  unimportant  is  the  question 
as  to  what  cells  are  involved  in  the  disturbance  of  purin  metabolism 
and  how  widespread  is  the  disorder. 

As  proof  of  the  constitutional  nature  of  gout  and  of  diabetes, 
has  been  urged  the  close  relationship  between  the  two,  as  well 


I 


CONSTITUTIONAL  DISEASES  AND  DIATHESES     379 

as  to  obesity.  It  is  true  that  these  three  conditions  frequently 
show  a  family  tendency  and  that  in  individuals  with  any  one  of 
the  three  disorders  there  is  often  a  family  history  of  the  other 
two.  Yet  these  observations  scarcely  afford  a  sufficient  basis 
for  the  assumption  of  a  constitutional  anomaly.  And  in  par- 
ticular is  there  need  for  a  greater  accuracy  in  the  diagnosis  of 
gout,  and  for  a  better  understanding  of  the  relationship  of  obesity 
to  nutrition.  These  are  essentially  physiological  problems,  entail- 
ing a  fuller  knowledge  of  the  metabolism  of  the  purin  bodies  and 
of  sugar.  And  finally,  there  remains  the  problem  of  the  posi- 
tionofdiabetesjobesityandgou  t — ^particularly  the  lat- 
ter— ^in  the  calculous,  uratic  and  arthritic  dia- 
theses. 

A  more  extensive  clinical  knowledge,  in  my  opinion,  is  what 
is  necessary  to  a  better  understanding  of  the  constitutional  dis- 
eases and  diatheses.  There  has  been  too  little  empiricism  in  the 
past  and  too  much  preconception;  too  much  mere  assertion  and 
too  few  observations  as  to  the  fundamental  manifestations  and 
attributes  of  the  diatheses.  This  indefiniteness  is  particularly 
true  of  the  so-called  arthritic  diathesis,  under  which  in 
the  literature  are  included  absolutely  unrelated  conditions. 

The  exudative  diathesis  and  lymphatism  are 
apparently  closely  related,  and  both  are  in  turn  related  to  the 
arthritic  constitution.  Lymphatism  and  the  exudative  diathesis, 
as  they  are  seen  in  the  child,  have  what  most  of  the  other  reputed 
constitutional  anomalies  have  not,  vis.,  a  well-elaborated  disposi- 
tional and  clinical  basis.  The  exudative  diatheses  of 
eosinophilic  nature  (asthmatic  catarrh,  mucous 
colitis)  are  especially  interesting.  Spasmophilia  of 
children,  characterized  as  it  is  by  an  augmented  nervous 
irritability  on  the  one  hand,  and  on  the  other  by  a  relationship  to 
tetany  and  the  later  development  of  nervous  disorders,  urgently 
demands  further  study. 

The  uratic  diathesis  carries  with  it  all  the  inherent 
interpretative  difficulties  that  have  been  noted  in  connection  with 
gout.  On  the  other  hand,  it  is  characterized  by  a  tendency  to 
cause  direct  manifestations.  As  for  rickets  and  chlo- 
rosis, we  may  speak  only  of  general  diseases,  not  of  diatheses, 
otherwise  we  should  lose  sight  of  the  actual  significance  of  a 


380  THE  BASIS  OF  SYMPTOMS 

constitutional  disorder,  and  include  under  the  latter  any  local 
disease  with  involvement  of  other  organs.^  ^ 

LITERATURE 

* Naturforscherversamm.  in   Stuttgart,   1906   (Starling,  Krehl) ;  ibid.,   igii 

(Biedl,   Morawitz)  ;   Biedl,   Innere   Sekretion    (The   Internal    Secretory 

Organs,  New  York,  1913)  ;  Falta,  Die  Blutdriisen,  1913   (translated  by 

Meyers,   IQIS)- 
*Exner  (Hochenegg)  :  Wiener  klin.  Wochenschft.,  1909,  No.  18;  v.  Eisels- 

berg,  ibid.,  287;  Deutsch.  Zeitschft.  f.  Chirurgie,  c,  317;  Gushing,  The 

Pituitary  Body,  etc.,  1912. 
•Erdheim  and  Stumm:  Ziegler's  Beitrage,  xlvi,  i.     See  also  Lewis,  Johns 

Hopkins  Hosp.  Bull.,  1905,  xvi,  157,  and  Jour.  Am.  Med.  Assn.,  1910, 

Iv,  1002. 

*  See  Biedl,  Falta. 

'  See  V.  Neusser :  Der  Status  Thymicolymphaticus,  Ausgewahlte  Kapitel,  iv, 

1911. 
•Martius:  Pathogenese  inn.  Krankh.,  Part  2,  158. 
'  Czerny :  Die  exud.  Diathese,  Jahrb.  f .  Kinderheilk.,  Ixi ;  Pfaundler,  Kongr. 

f.  inn.  Med.,  191 1. 

*  Sahli :  Zeitschft.  f .  klin.  Med.,  Ivi,  264 ;  Morawitz  and  Lessen,  Arch,  f .  klin. 

Med.,  xciv,  no. 

*  Liebermeister,  Jr.:  Kongr.  f.  inn.  Med.,  1907,  180. 
^  Die  Allergic ;  also  Ergeb.  d.  inn.  Med.,  1908,  i,  420. 

"J.  Cohnheim:  Allg.  Path.,  ii,  ist  edit.  (Introduction)  ;  Krehl,  Path.  Physio- 

logie,  6th  edit.    (Introduction). 
"  For  more  recent  literature  see  His,  Pfaundler,  Block,  Mendelssohn :  Kongr. 

f.  inn.  Med.  1911   (lit.)  ;  Mors,  Lubarsch-Ostertag,  1910,  xiv. 


CHAPTER  X 
FEVER 

Fever  is  characterized  by  a  pathological  increase  in  the  tem- 
perature of  the  body.  Whereas  the  rectal  temperature  of  a 
healthy  individual  at  complete  rest  rarely  exceeds  37.5°  C.  (99.3° 
R),  it  may,  in  febrile  states,  reach  41°  or  42°,  and  very  excep- 
tionally, even  44°. 

As  a  rule,  the  diurnal  variations  of  fever  are  of 
the  same  character  as  are  those  which  take  place  in  health,  i.e., 
there  is  an  elevation  toward  evening  and  a  fall  toward  morning. 
Those  who  work  at  night  and  sleep  during  the  day  show  at  times 
the  inverse  type  of  diurnal  variation  both  in  health  and  fever. 
Thus  we  see  that  the  same  causes,  such  as  food,  light,  work,  etc., 
which  influence  the  temperature  curve  of  healthy  persons,  affect 
also  the  variations  in  the  temperature  of  febrile  patients.  Never- 
theless, the  temperature  in  fever  is  much  less  con- 
stant than  in  health,  and  the  considerable  variations  that 
it  undergoes  are  due  partly  to  external  influences  and  partly  to 
causes  which  escape  our  present  methods  of  observation. 

Variations  in  the  Clinical  Picture  of  Fever. — These  depend, 
in  the  first  place,  upon  the  cause  of  the  fever.  Most 
fevers  are  of  bacterial  origin,  and,  as  is  well  known,  bacteria 
may  vary  in  their  virulence,  conditions  of  growth  and  duration 
of  hfe — all  of  which  determine  the  temperature-picture  of  the 
disease  which  they  cause,  as  well  as  its  other  manifestations.  So 
far  as  malarial  fever  is  concerned,  we  know  that  the  paroxysms 
occur  when  the  causative  organisms  are  at  a  particular  stage  of 
development.  The  same  is  true  of  certain  septic  diseases.  All 
in  all,  therefore,  despite  certain  deviations,  we  may  say  that  the 
infectious  diseases  as  a  rule  have  characteristic  fever  curves. 

In  the  second  place,  the  clinical  picture  presented  by  fever 
depends  largely  upon  the  condition  of  the  individ- 
ual affected — upon  his  strength,  nutrition  and  degree  of 
immunity.  During  epidemics,  different  febrile  manifestations 
occur  in  different  individuals.  We  may  say,  in  general,  that 
young  and  strong  patients  react  with  a  higher  fever  to  an  infec- 
tion than  do  old  and  feeble  ones.     Indeed,  the  temperature  may 

381 


382  THE  BASIS  OF  SYMPTOMS 

actually  fall  in  the  latter  class  of  patients.  We  possess  analogous 
experimental  observations ;  ^  thus,  it  is  impossible  to  produce 
fever  by  the  injection  of  certain  non-bacterial  chemicals  into  fast- 
ing animals,  though  the  same  substances  will  regularly  cause  a 
fever  in  well-fed  animals.  Bacterial  infections,  on  the  contrary, 
may  cause  an  elevation  of  temperature  whether  the  animal  be 
starving  or  well  fed. 

The  numerous  other  symptoms  seen  in  fever — some  due  to 
the  fever  itself,  others  to  its  underlying  cause — are  also  subject 
to  considerable  variations.  These  depend  in  part  upon  the  height 
of  the  temperature,  for  this  influences  the  rate  of  the  proteid  and 
other  decompositions,  as  well  as  the  cardiac  and  respiratory  rates. 
Yet  no  exact  ratio  exists  between  the  severity  of  these  phenomena 
and  the  degree  of  temperature,  because  other  factors,  especially 
toxic  influences,  play  so  great  a  role.  This  has  already  been  dis- 
cussed so  far  as  the  pulse-rate  is  concerned  (see  p.  55). 

Indeed,  we  may  say,  in  general,  that  the  symptoms  of 
infection  and  intoxication  predominate  in  the 
clinical  picture  of  fever,  and  that  many  of  the  phe- 
nomena which  were  formally  attributed  to  the  high  temperature 
are  now  ascribed  to  the  action  of  toxins.  Thus  the  psychic 
changes,  the  gastro-intestinal  disturbances  and  the  susceptibility 
of  the  respiratory  tract  to  complicating  inflammations,  are  all  of 
toxic  rather  than  of  thermic  origin.  They  are  rarely  seen  in  the 
"aseptic  fever"  following  simple  fractures;  whereas,  they  are 
most  prominent  in  such  pronounced  intoxications  as  typhoid  fever. 
These  symptoms  also  depend  to  a  certain  extent  upon  individual 
peculiarities — ^heavy  drinkers,  for  example,  being  very  prone  to 
show  serious  nervous  manifestations. 

These  various  considerations  go  to  show  how  difficult  it  is 
to  distinguish  between  the  clinical  picture  of  fever  per  se  and  the 
manifestations  dependent  upon  the  cause  of  the  fever.  Indeed, 
they  often  merge  so  closely  into  one  another  as  to  be  incapable  of 
separation.  A  more  intimate  knowledge  of  the  characteristics 
of  the  etiologic  factors,  particularly  those  of  the  infectious  dis- 
eases, will  probably  tend  to  do  away  with  the  present  tendency  of 
regarding  the  febrile  picture  as  a  well-demarcated  unit  in  the 
disease  process  as  a  whole. 

The  Causes  of  Fever. — The  most  diverse  causes  may  give 
rise  to  fever.^     It  may  be  produced,  first  of  all,  by  the  en- 


FEVER  S83 

trance  of  living  or  dead  bacteria,  or  their  prod- 
ucts, actuallyintotheblood.  Yet  the  mere  presence  of 
micro-organisms  in  the  circulation  does  not  necessarily  raise  the 
temperature  of  the  body,  for  many  bacteria  which  produce  fever  in 
certain  animals  fail  to  do  so  in  others.  Indeed,  an  animal  may  die 
from  an  infection  and  its  heat  production  may  be  markedly  in- 
creased, and  yet,  on  account  of  the  elimination  of  the  extra  heat 
from  the  body,  there  may  be  no  rise  of  temperature.^  This 
would  indicate  that  the  fever  in  bacterial  disease  is  due  to  the  dis- 
turbance of  some  definite  mechanism.  Protozoa  may  also  give 
rise  to  fever,  as  in  the  case  of  malaria  and  of  certain  experimental 
infections.^ 

The  substances  that  cause  the  fever  are  very 
possibly  of  a  proteid  nature,  for  complex  substances  iso- 
lated from  the  bodies  of  bacteria  may  give  rise  to  fever  if  injected 
into  men  or  animals.^  It  is  questionable,  however,  whether  these 
substances  are  themselves  proteids,  or  whether  it  is  merely  difficult 
to  separate  them  from  proteids.  Some  have  attempted  to  show 
that  there  is  a  non-proteid,  fever-producing  substance  common  to 
all  bacteria,^  but  the  evidence  for  this  is  very  inconclusive. 

Though  bacteria  and  bacterial  products  are,  undoubtedly,  the 
most  important  causes  of  fever,  they  are  not  the  only  ones.  Fever 
may  be  produced  by  the  destruction  of  large  num- 
bers of  cells  in  the  body,  even  though  micro-organisms 
play  no  part  in  the  destructive  processes.  As  examples  of  such, 
we  may  recall  the  fever  that  so  frequently  follows  a  simple 
fracture,  or  that  which  may  follow  large  interstitial  hemorrhages.'^ 
The  substance  which  gives  rise  to  these  aseptic  fevers  is 
still  unknown. 

The  fact  that  fever  may  be  produced  by  bodies  not  derived 
from  bacteria  has  led  to  careful  studies  concerning  the  action  of 
numerous  chemical  substances  upon  the  temperature  of  warm- 
blooded animals.  These  studies^  have  demonstrated  that  fever 
may  be  caused  by  the  injection  of  various  forms  of 
proteids,  whether  the  latter  are  assimilated  or  not,  and 
whether  they  be  of  complex  or  comparatively  simple  structure. 
Elevations  of  temperature  also  follow  the  injections  of  many 
organic  compounds  and  salts.  Different  animals,  furthermore, 
differ  in  their  susceptibility  to  the  action  of  these  substances. 

It  has  long  been  known  that  injections   of   certain 


384  THE  BASIS  OF  SYMPTOMS 

salts  may  produce  fever  in  animals.  Finkelstein  has  re- 
cently made  the  interesting  observation  that  the  oral  administra- 
tion to  infants  of  a  one  to  three  per  cent,  solution  of  sodium 
chlorid  likewise  causes  an  elevation  of  temperature.  In  in- 
fants suffering  from  gastro-intestinal  conditions,  smaller  amounts, 
or  weaker  concentrations,  of  such  solutions,  are  necessary  to 
bring  this  about  than  is  the  case  with  healthy  infants.^  In  adults, 
the  parenteral  introduction  of  isotonic  salt  solution  causes  fever. 
But  individual  differences  in  susceptibility  are  especially  marked 
in  the  tendency  to  exhibit  this  so-called  sodium  chlorid 
fever.  (Recent  work  ^^  has  questioned  the  authenticity  of  the 
febrile  reactions  following  salt  injections,  attributing  the  fever 
rather  to  impurities  in  the  water  used  to  dissolve 
the  salt.  Certain  by-effects  of  salvarsan  have  been  laid  to 
the  same  cause.  The  use  of  water  freshly  distilled  obviates  this 
factor. — Ed.  ) 

Is  it  not  possible  that  a  single  chemical  sub- 
stance is  the  cause  of  all  fevers?  Though  this  is 
conceivable,  our  present  information^^  does  not  enable  us  to 
identify  it.  I  am  of  the  opinion,  however,  that  such  an  hypothesis 
is  almost  necessary  in  view  of  the  fact  that  a  single  mechanism 
seems  to  underlie  all  fevers.  Common  to  all  infections  is  a 
marked  cellular  destruction  from  which  this  hypothetical  sub- 
stance might  be  assumed  to  arise.  The  many  studies  devoted  to 
this  problem  have  shown,  among  other  things,  that  the  destruction 
of  red  blood-cells,^^  whether  they  be  those  of  the  particular  animal 
itself,  or  from  animals  of  the  same  or  different  species,  gives  rise 
to  fever-producing  substances  which  pass  into  the  serum  and  do 
not  primarily  cling  to  the  red  cells. 

The  blood-platelets  are  also  of  undoubted  influence 
in  the  causation  of  fever.^^  The  injection  of  intact  platelets 
(obtained  in  citrate  solution)  causes  no  febrile  reaction;  but  as 
soon  as  they  are  disintegrated,  they  give  rise  to  substances  of  a 
pyrogenic  character.  (Vaughan^*  and  others  have  shown  that 
typical  fevers  may  be  produced  by  the  enzymic  destruc- 
tion of  proteids  in  the  body;  and  MandeP^  has  stated 
that  fever  may  be  produced  by  the  administration  of 
purinbases,  such  as  xanthin  or  caffein. — Ed.  ) 

The  Relation  of  the  Nervous  System  to  Fever. — Granting 
that  fever  may  be  produced  by  the  action  of  micro-organisms  and 


I 


FEVER  S85 

of  chemical  substances,  bacterial  or  otherwise,  the  question  arises 
as  to  whether  these  are  the  only  causes  of  fever.  That  the  ner- 
vous system  exerts  an  important  influence  upon  the  heat  regulat- 
ing centre,  is  well  known.  Thus,  a  division  of  the  cer- 
vical cord  in  animals  brings  about  a  marked  disturbance 
of  the  heat-regulatory  apparatus.  Different  animals  behave  dif- 
ferently in  this  respect,  depending  upon  the  level  of  the  injury. 
Rabbits  with  a  severed  dorsal  cord  react  as  do  healthy  animals,^® 
if  the  heat  loss  due  to  vasomotor  paralysis  is  held  within  bounds 
by  an  elevation  of  the  external  temperature  to  about  22°  C.  The 
chemical  heat  regulation  of  such  animals  is  preserved,  for  they 
react  with  fever  to  infections  and  to  the  injection  of  pyrogenic 
substances.  If,  however,  the  division  be  made  above  the  first 
dorsal  segment,  the  animals  lose  both  their  physical  and  chemical 
regulation ;  in  this  case  a  surrounding  temperature  of  about  29°  C. 
is  necessary  to  maintain  their  body  temperature  at  its  normal  level, 
while  their  power  to  react  with  fever  is  entirely  gone. 

The  probabilities  are  that  when  the  cord  is  severed  in  the 
cervical  region,  the  cervical  and  dorsal  sympathetic  fibres  are  cut 
off  from  the  central  nervous  system;  for  a  division  of  the  dorsal 
cord,  plus  a  resection  of  the  stellate  ganglion,  or  a  severance  of 
the  seventh  and  eighth  cervical  roots — whence  the  sympathetic 
originates  to  pass  to  the  stellate  ganglion — produces  the  same 
results.  The  fact  that  injections  of  epinephrin  and 
coca  in  likewise  cause  fever  ^'^  is  in  keeping  with  the  assump- 
tion that  the  sympathetic  system  plays  an  extremely 
important  part  in  the  process;  and  we  shall  encounter  another 
proof  of  this  in  the  behavior  of  the  blood  sugar  in  fever.  Rumpf 
has  shown  that  narcosis  in  cool  external  temperatures  leads 
to  a  considerable  diminution  in  heat  production,  guinea-pigs 
exhibiting  a  fall  of  10°  C,  and  more,  under  these  conditions. 
An  intact  nervous  apparatus  is  essential  also  to  the  production  of 
fever,  the  latter  not  appearing,  as  we  have  seen,  after  section 
of  the  cord  high  up,  or  when  an  animal  is  narcotized. 

In  view  of  the  importance  of  the  nervous  system  in  the  pro- 
duction and  regulation  of  fever,  there  is  no  reason  to  believe  that 
the  heat-regulating  centre  may  not  be  primarily  diseased  or  in- 
fluenced by  impulses  from  other  parts  of  the  cen- 
tral nervous  system.  Many  observations  purporting  to 
be  examples  of  such  a  nervous  fever  will  not  stand  the 
25 


386  THE  BASIS  OF  SYMPTOMS 

scrutiny  of  a  rigid  criticism.  For  example,  in  poliomyelitis, 
polioencephalitis  and  meningitis,  the  elevation  of  temperature  is 
probably  due  to  the  infection;  while  in  other  conditions,  such 
as  large  cerebral  hemorrhages,  it  is  due  in  all  likelihood  to  the 
absorption  of  the  disintegration  products  of  the  red  corpuscles 
or  the  injured  tissue  cells. 

In  other  conditions,  the  nervous  lesion  seems  to  exert  a  more 
direct  influence  upon  the  bodily  temperature.  At  times,  gen- 
eral convulsions,  associated  with  stupor,  lead  to  excessive 
elevations  of  temperature,  though  at  other  times,  when  the  con- 
vulsions are  produced  by  certain  drugs,  there  may  be  an  actual 
reduction  of  temperature.^^  In  the  latter  instances,  the  heat  regu- 
lation is  affected,  and  it  would  seem  that  the  poisons  leading  to  the 
convulsions  also  diminish  the  production  of  heat  in  the  body. 

We  know  that  muscular  movements  will  raise  the 
temperature  of  even  a  healthy  person,  if  the  elimination  of  heat 
is  interfered  with — an  observation  that  has  also  been  experimen- 
tally established  in  animals.^®  If,  however,  the  extra  heat  that  is 
liberated  during  exercise  can  be  eliminated,  no  rise  of  temperature 
results.  As  a  rule,  therefore,  convulsions  do  not  materially  alter 
the  body  temperature.  A  rise  of  temperature  is  especially  apt  to 
be  produced  by  convulsions  when  there  is  reason  to  believe  that 
the  heat-regulating  mechanism  is  paralyzed.  For  example,  fever 
is  rarely  present  in  the  earlier  stages  of  tetanus;  and  the  rise 
of  temperature  toward  the  end  of  the  disease  would  appear  to  be 
caused  by  a  paralysis  of  the  heat-regulating  centre.  The  high  tem- 
perature that  has  been  observed  in  many  cases  of  status  epi- 
leptic u  s  and  in  heat-stroke  is  perhaps  to  be  explained 
in  a  similar  manner.  Possibly,  also,  the  elevations  of  tempera- 
ture in  hysterical  individuals,  which  have  been  de- 
scribed by  some  writers,  are  of  this  character,  though  never  having 
witnessed  a  true  hysterical  fever,  I  personally  feel  somewhat 
skeptical  as  to  its  existence. 

Experimentally,  it  is  possible  to  produce  fever  in  animals  by 
injuring  the  brain.  A  characteristic  example  of  this  is  the  tem- 
perature elevation  which  can  be  caused  in  almost  every  case  i  f 
a  long  needle  be  thrust  into  the  mid-brain  of 
rabbits.^^  The  fever  produced  by  such  a  puncture  begins 
several  hours  after  the  operation,  continues  for  days  and  may 
reach  a  considerable  height.    The  production  of  heat  in  the  body 


FEVER  387 

is  increased,  and  the  loss  of  heat  Hkewise,  but  to  a  lesser  degree. 
The  loss  of  heat  by  evaporation  from  the  skin  is  relatively  greater 
than  it  is  in  the  case  of  infectious  fevers.  Furthermore,  the 
increased  heat  production  is  almost  entirely 
due  to  the  (augmented)  consumption  of  non-ni- 
trogenous material,  a  fact  which  also  serves  to 
differentiate  this  from  ordinary  fever,  in 
which  a  characteristic  hydrolytic  cleavage  of 
proteids  takes  place. ^^  During  the  fever  resulting 
from  a  puncture  of  the  brain,  the  liver  ^^  is  the  warmest  organ 
of  the  body,  and  its  glycogen  store  rapidly  disappears.  Indeed, 
unless  there  is  a  store  of  glycogen  in  the  body,  no  rise  in  tempera- 
ture follows  the  puncture  of  the  brain.  It  is  apparent,  therefore, 
that  the  elevation  of  temperature  caused  by  puncture  of  the  brain 
differs  from  that  due  to  an  infection  in  several  important  par- 
ticulars. 

Experimental  lesions  of  other  portions  of  the 
brain,  i.e.,  other  than  the  typical  mid-brain  puncture,  may 
also  produce  fever,  according  to  certain  observers,^^  though  with 
a  far  less  degree  of  certainty.  The  problems  concerned  here  open 
a  wide  field  for  research. 

It  is  very  questionable  whether  fever  is  ever 
caused  by  reflexes.  The  elevations  of  temperature 
which  may  occur  during  biliary  colic  and  those  which 
may  follow  urethral  operations  (catheter  fever)  are  often 
regarded  as  instances  of  reflex  fevers.  Yet,  in  my  opinion,  it  is 
much  more  probable  that  we  are  here  dealing  with  fevers  caused 
either  by  the  absorption  of  toxic  products  or  by  actual  infections. 

Elevations  of  temperature  have  been  observed  after  inju- 
ries to  the  spinal  cord.  Such  elevations  occur  most  fre- 
quently in  association  with  severe  contusions  of  the  cervical 
region,  produced  by  fractures  of  the  corresponding  vertebrae. 
Temperatures  as  high  as  42°  to  44°  C.  (106.5°  to  111°  F.)  have 
been  observed  in  such  conditions. ^^  It  is  possible  to  produce  the 
same  effect  experimentally  by  crushing  the  uppermost  part  of  the 
cervical  cord  of  large  dogs.  After  injuries  of  this  kind,  the 
temperature  does  not  always  become  elevated,  and  it  may,  indeed, 
fall.  These  varying  results  of  the  experiment  are 
due  to  the  fact  that  if  the  cord  of  a  warm-blooded  animal  be 
severed  high  up,  the  body  temperature  becomes  a  plaything  of 


388  THE  BASIS  OF  SYMPTOMS 

circumstances.  When  the  temperature  of  its  surroundings  is 
high,  the  heat  production  is  increased,  and  when  the  surrounding 
temperature  is  low,  the  heat  production  is  diminished;  in  other 
words,  there  is  no  regulation  of  the  production  of  heat  in  the 
body.  This  is  one  reason  why  animals  easily  become  overheated 
or  cooled  off  after  they  have  sustained  severe  contusions  of  the 
cervical  cord. 

Other  factors  besides  the  surrounding  tem- 
perature also  play  a  part  in  the  elevation  of  the  tempera- 
ture that  takes  place  in  cord  injuries,  though  upon  these  points 
we  are  less  certain.  It  is  possible,  for  example,  that  the 
peripheral  circulation  is  so  altered  that  the  loss  of  heat 
from  the  body  is  diminished.  Furthermore,  the  crushing  of  the 
cord — a  manner  of  injury  which  seems  to  be  an  important  requisite 
for  a  high  temperature — ^may  possibly  produce  an  irrita- 
tion of  the  corresponding  muscles,  and  so  directly 
increase  the  production  of  heat  in  the  body.  This  is  apparently 
the  reason  why  the  elevation  of  temperature  is  more  likely  to  take 
place  in  men  and  large  dogs  than  it  is  in  small  animals.  The 
former  have  a  relatively  small  surface  from  which  to  lose  heat, 
and  a  relatively  large  musculature  in  which  an  increased  heat 
production  can  take  place.  We  see,  therefore,  that  the  rise 
of  temperature  that  may  follow  cord  injuries  is 
due,  partly,  to  a  loss  of  heat  regulation,  and 
partly,  in  all  probability,  to  an  increased  pro- 
duction and  a  diminished  loss  of  heat  from  the 
body.  The  condition,  therefore,  differs  essentially  from  that 
present  in  true  fever  (see  p.  391  et  seq.). 

The  Normal  Regulation  of  the  Body  Temperature. — The  tem- 
perature of  man  is  maintained  at  an  almost  constant  level  under 
the  most  varying  conditions ;  indeed,  it  varies  less  than  that  of  any 
other  animal.  We  shall,  therefore,  first  consider  the  mechanism 
by  which  the  temperature  is  normally  maintained  at  this  uniform 
level.  ^^ 

If  large  quantities  of  heat  are  suddenly  set 
free  in  the  body  from  any  cause,  such  as  muscular  work  or 
the  ingestion  of  large  amounts  of  food,  the  total  loss  of  heat 
from  the  body  is  correspondingly  increased.  The  cutaneous  ves- 
sels dilate  and  the  warmer  skin  loses  heat  more  rapidly  by  radia- 
tion and  conduction.     The  affected  person  perspires  more  freely. 


FEVER  389 

and  the  loss  of  heat  by  evaporation  of  water  from  the  lungs  is 
likewise  increased.  Whether  the  one  or  the  other  of  these  various 
means  for  eliminating  heat  is  utilized  to  a  greater  or  less  extent 
in  the  individual  case  depends  upon  a  variety  of  conditions, 
which  cannot  be  considered  in  this  place. 

If,  on  the  other  hand,  a  warm-blooded  ani- 
mal is  exposed  to  cold,  it  is  able  to  protect  itself  from 
considerable  losses  of  heat,  which  would  otherwise  tend  to  reduce 
its  temperature.  The  skin  vessels  contract  and  the  heat  losses 
through  conduction  and  radiation  are  diminished.  Men  ordinarily 
wear  thicker  clothes  under  these  circumstances  and  so  surround 
their  bodies  with  a  layer  of  comparatively  warm  air.  The  fur 
of  animals  and  the  fat  of  obese  persons  also  diminish  heat  losses. 
By  these  means  it  is  possible  to  maintain  the  normal  bodily  tem- 
perature, even  when  the  individual  is  exposed  to  moderate  de- 
grees of  cold.  If,  however,  this  mechanism  is  insufficient  to  meet 
the  emergency,  then  a  new  factor  is  called  into  play.  The  pro- 
duction of  heat  in  the  body  is  increased,  the  site  of  this  increased 
production  being  the  muscles,  according  to  the  best  authorities. 

When  a  man  is  exposed  to  cold,  therefore,  the  first  regulatory 
mechanism  that  serves  to  maintain  his  body  temperature  at  the 
normal  level  is  of  a  physical  character,  i.e.,  losses  of  heat  are 
prevented.  As  we  have  just  seen,  however,  this  means  of  regu- 
lation may  be  insufficient,  and  the  exposure  to  cold  is  then  fol- 
lowed by  an  increased  production  of  heat  in  the  body.  Frequently, 
the  individual  feels  chilly  and  shivers,  and  thereby  increases  the 
combustion  in  his  body;  but,  even  though  no  gross  muscular 
movements  occur,  the  body  metabolism  may  be  increased,  as  has 
been  proved  by  recent  experiments.  In  either  case,  the  extra 
heat  is  generated  mainly  by  the  combustion  of  non-nitrogenous 
material,^^  just  as  it  is  when  heat  originates  from  muscular 
activity.  This  regulation  of  the  body  temperature  by  variations 
in  the  heat  production  is  termed  a  chemical  regulation 
in  contradistinction  to  that  which  depends  upon  variations  in  the 
heat  losses,  the  so-called  physical  regulation. 

The  point  at  which  the  chemical  mechanism  steps  in  to  main- 
tain the  temperature  of  the  body  depends  in  part  upon  the  degree 
to  which  the  animal  is  able  to  limit  his  loss  of  heat,  and  in  part 
upon  the  amount  of  exercise  and  food  which  have  been  taken. 
The  heat  that  is  immediately  set  free  after  exercise  or  eating  is 


390  THE  BASIS  OF  SYMPTOMS 

ordinarily  quickly  disfKDsed  of  by  an  increased  elimination  of 
heat;  but  if  the  body  is  exposed  to  cold,  this  extra  heat  serves 
to  maintain  the  body  temperature.  It  thus  obviates  the  necessity 
of  calling  the  chemical  regulation  into  play. 

These  are,  in  brief,  the  means  whereby  the  healthy  man 
regulates  his  bodily  temperature  under  varying  external  and 
internal  conditions.  Under  certain  circumstances, 
however,  even  the  normal  mechanism  is  insuffi- 
cient to  keep  the  body  at  a  constant  temperature. 
For  example,  if  heat  be  applied  to  the  surface  of  the  body,  and 
if,  at  the  same  time,  the  compensatory  loss  of  heat  be  interfered 
with,  a  rise  in  temperature  necessarily  follows.  For  this  reason, 
every  man  becomes  warmer  in  a  steam  bath,  or  in  a  warm-water 
bath  of  40°  C.  (104°  F.)  or  over.  Possibly,  however,  some  be- 
come warmer  than  others  under  the  same  conditions. 

An  increased  production  of  heat  within  the 
body  by  excessive  chemical  decompositions  may 
also  cause  a  rise  in  temperature,  an  event  of  more 
frequent  occurrence  than  is  generally  supposed. ^^  Muscular 
exertion,  even  if  not  very  severe,  may  thus  raise  the  tem- 
perature of  the  body.  In  this  respect,  different  individuals  cer- 
tainly react  differently;  the  novice  becomes  overheated  in  doing 
a  certain  piece  of  work  more  easily  than  does  the  adept,  mainly 
because  he  uses  more  energy  to  accomplish  the  same  result.  An- 
other factor  that  is  of  great  importance  here  is  the  ease  with 
which  heat  may  be  eliminated  from  the  body. 
This  explains  many  of  the  apparent  contradictions  met  with  in 
the  literature  concerning  the  effect  of  muscular  exertion  upon  the 
body  temperature.  The  man  that  makes  the  ascent  of  Monte 
Rosa  does  not  become  warmer  from  the  great  exertion,  because 
the  low  temperature  and  the  dryness  of  the  surrounding  air 
greatly  favor  the  loss  of  heat  from  his  skin  and  lungs.  Yet  more 
recent  investigations  have  shown  that  severe  muscular  exertion 
performed  in  high  altitudes  at  low  temperatures  often  causes 
fever. ^  On  the  other  hand,  the  temperatures  of  soldiers  fre- 
quently rise  during  forced  marches,  for  they  are  heavily  dressed 
and  they  must  often  travel  in  a  warm,  moist  climate. 

Heat-Stroke. — If  the  temperature  of  the  body  becomes  con- 
siderably elevated  from  such  outside  causes,  we  speak  of  it  as 
heat-stroke.^®     The   temperature   under   these    conditions    may 


FEVER  391 

reach  43°  C.  (110°  F.)  or  over,  the  pulse  becomes  rapid,  the 
patient  becomes  dizzy  or  dehrious,  and  in  severe  cases,  coma  and 
death  terminate  the  scene.  The  high  temperature  often  persists 
in  these  patients  for  hours,  or  even  days,  after  the  actual  cause 
of  the  stroke  is  over.  This  would  seem  to  point  to  some  in- 
jury to  the  heat-regulatory  mechanism.  Heat- 
stroke patients  are  often  described  as  being  pale,  livid  or  cyanotic, 
conditions  which  indicate  an  improper  peripheral  circulation  and  a 
consequent  imperfect  regulation  of  the  heat  losses  from  the 
surface  of  the  body.  This  poor  peripheral  circulation  is  appar- 
ently due  to  an  injury  to  the  regulating  centres  in  the  brain, 
though  the  nature  of  this  injury  is  not  known. 

The  experience  of  military  surgeons  has  taught  us  that  ex- 
cessive heat  is  most  liable  to  affect  those  who  are  in  some  way 
indisposed,  who  are  foot-sore  or  who  are  convalescent  from 
severe  illness ;  and  it  has  frequently  been  observed  clinically  that 
persons  who  are  ill,  particularly  anaemic  or  tuberculous  patients, 
are  especially  prone  to  show  a  rise  of  temperature  after  exercise, 
or  even  after  meals. 

In  heat-stroke,  the  conditions  are  very  complicated,  and  the 
rise  of  temperature  is  not  due  to  external  forces 
alone.  Other  factors  are  certainly  present,  for  different  indi- 
viduals show  considerable  differences  in  their  susceptibility  to 
changes  in  their  environment.  Some  lose  heat  more  readily  than 
others,  a  fact  that  is  especially  true  of  thin  individuals  as  com- 
pared with  stout  ones.  Heart  lesions  render  a  patient  very 
susceptible  to  heat-stroke,  for  a  good  peripheral  circulation  is 
a  necessity  when  the  losses  of  the  heat  from  the  body  must 
be  increased,^^  (An  overindulgence  in  alcohol  also 
renders  an  individual  more  susceptible  to  heat-stroke.  Finally, 
those  who  have  once  had  a  sunstroke  may  manifest  for  years 
a  markedly  increased  susceptibility  to  changes  in  the  temperature 
about  them. — Ed.)  All  these  facts  demonstrate  that  changes  in 
the  external  conditions  are  not  the  sole  factors  which  produce 
the  sunstroke.  The  mechanism  for  losing  heat  is  undoubtedly 
less  efficient  in  some  individuals  than  in  others ;  and,  in  so  far  as 
the  heat-stroke  depends  upon  an  insufficiency  of  heat  elimination, 
it  bears  a  certain  resemblance  to  true  fever. 

Heat  Regulation  in  Fever. — The  cause  of  the  high  tempera- 
ture of  fever  must  be  some  disproportion  between  the 


892  THE  BASIS  OF  SYMPTOMS 

production  and  the  loss  of  heat  in  the  body. 
Theoretically,  fever  might  be  caused  either  by  an  excessive  heat 
production  without  a  corresponding  increase  in  the  heat  loss,  or 
by  a  diminution  in  the  heat  loss  without  a  corresponding  diminu- 
tion in  the  heat  production.  We  now  purpose  considering  which 
of  these  conditions  actually  exists  in  fever,  and  whether  or  not 
all  cases  of  fever  are  produced  in  the  same  manner. 

Two  general  methods  have  been  employed  to  determine  the 
amount  of  heat  produced  in  the  body.  In  the  first,  the  amount 
of  heat  lost  has  been  directly  measured  in  a  calorimeter  (direct 
calorimetry);in  the  second,  the  products  of  combustion  have 
been  determined  and  the  heat  produced  calculated  (indirect 
calorimetry).  The  two  methods  have  been  shown  to  yield 
identical  results  in  the  healthy  animal,^^  and  we  have  every  reason 
to  believe  that  the  results  would  also  be  the  same  in  fever,  although 
this  has  not  yet  been  definitely  proved  on  account  of  technical 
difficulties.^^ 

Heat  Production  in  Fever. — I n  the  vast  majority  of 
all  fevers  the  production  ofheat  is  increased. 
This  has  been  proved  for  different  diseases  of  man,^^  such  as 
pneumonia,  typhoid  fever,  pleurisy,  erysipelas,  tuberculin  fever, 
etc.,  as  well  as  for  various  septic  diseases  of  animals,  and  for 
fevers  produced  experimentally  by  injections  of  bacteria  and 
various  chemical  substances.^* 

This  increase  in  heat  production  is  seen  both  at  the  time 
when  the  temperature  is  rising  and  at  the  height 
of  the  fever.  It  is  greatest  of  all  during  the  chill 
which  initiates  so  many  infections,  obviously  on  account  of  the 
violent  muscular  contractions  that  take  place  at  the  time.  During 
the  height  of  the  fever,  it  is  found  to  be  the  most  marked  in 
those  who  breathe  violently,  from  whatever  cause — here  also 
because  of  the  excessive  muscular  exertion.  If  we  eliminate  these 
cases,  in  which  the  heat  production  is  accelerated  by  muscular 
activity,  then  the  increased  production  of  heat  in  fever  usually 
amounts  to  from  ten  to  sixty  per  cent.,  the  average  being  about 
twenty  to  thirty  per  cent. 

In  a  small  number  of  cases  no  apparent  in- 
crease of  heat  production  above  the  normal 
limits  can  be  demonstrated.^^  Such  observations 
have  been  made,  for  the  most  part,  upon  patients  in  whom  there 


FEVER  893 

was  but  little  fever,  or  in  whom  the  fever  was  long-continued. 
In  the  latter  class  of  cases,  it  is  necessary  to  remember  that  the 
organism  tends  to  limit  its  metabolism  in  long- 
continued  illnesses,  so  that  although  the  quantity  of 
oxygen  consumed  by  these  patients  with  fever  may  not  have 
exceeded  the  normal  limits,  it  was  in  reality  above  what  would 
have  been  consumed  had  no  fever  been  present.  In  such  cases, 
comparative  determinations  should  be  made  upon  the  same  indi- 
vidual during  periods  of  fever  and  of  apyrexia;  for  I  do  not 
believe  that  the  possibility  of  fever  without  an  increase  of  heat 
production  has  been  definitively  established. 

In  still  another  class  of  cases,  high  fever  may  be 
associated  with  an  unusually  low  production  of 
heat,  vis.,  when  there  is  a  tendency  to  collapse.  As  we 
shall  see  later,  a  diminution  in  the  heat  production  is  one  of  the 
characteristics  of  collapse,  and  even  when  a  tendency  to  this 
condition  is  present,  the  heat  production  may  be  lessened. 

Thus  we  see  that  in  the  great  majority  of  all  cases  of  fever, 
and  especially  in  fevers  of  short  duration,  the  production  of  heat 
in  the  body  is  increased.  This  increase  is  most  marked  at  the 
beginning  of  acute  infectious  diseases ;  while  in  chronic  wasting 
diseases  the  heat  production  tends  to  become  limited,  and  when 
the  temperature  is  falling  it  may  even  be  less  than  normal. 

As  we  have  said,  the  average  increase  in  the  heat 
production  in  fever  is  about  20  to  30  per  cent. 
Such  an  increase  is  not  extraordinary  when  we  remember  that 
Rubner  was  able  to  increase  the  heat  production  in  dogs  sixty  per 
cent,  solely  by  feeding  them  with  large  quantities  of  proteid  food, 
and  that  in  severe  muscular  exertion  the  heat  production  may 
be  several  times  as  great  as  during  rest.  Normally,  the  body 
can  dispose  of  much  larger  amounts  of  heat  than  are  liberated 
within  it  during  fever,  so  that  the  cause  of  the  high  temperature  in 
fever  cannot  be  an  increased  production  of  heat  alone. 

Indeed,  a  portion  of  the  increase  in  heat  pro- 
duction is  due  to  the  elevation  of  the  body  tem- 
perature itself,  for  we  know  that  oxidative  processes  in 
general  are  accelerated  by  heat.  Pfliiger  has  estimated  that  for 
every  increase  of  1°  C.  in  a  rabbit's  temperature,  its  heat  pro- 
duction increases  about  six  per  cent. ;  and  the  same  has  been 
shown  to  be  true  when  the  temperature  of  man  is  artificially  ele- 


S94  THE  BASIS  OF  SYMPTOMS 

vated.^^  Thus  we  see  that  an  increase  of  heat  production, 
amounting  to  about  twelve  to  eighteen  per  cent,  of  the  normal, 
might  easily  be  regarded  as  an  effect  rather  than  as  a  cause  of 
the  increased  bodily  temperature.  The  excessive  heat  production 
in  fever,  therefore,  may  be  explained  in  part  as  a  result  of  in- 
creased muscular  movements  and  in  part  as  the  result  of  the 
higher  temperature  of  the  body.  The  remaining  increase  in  heat 
production  is  very  slight,  especially  if  it  be  compared  with  that 
which  results  from  violent  exercise  or  from  the  ingestion  of  large 
quantities  of  proteid  food. 

Heat  Losses  in  Fever. — During  the  rise  of  temperature  the 
loss  of  heat  from  the  body  is  almost  always  found  to  be  dimin- 
ished, the  losses  by  radiation  and  conduction  from  the  skin  being 
especially  limited.  The  amount  lost  by  evaporation  of  water  is 
frequently  increased,  however,  for,  even  at  this  period,  the 
metabolic  processes  in  the  body  may  be  accelerated.  Yet  the 
increased  loss  by  evaporation  does  not  neutralize  the  decrease 
in  loss  by  conduction  and  radiation ;  and  often,  furthermore,  the 
loss  of  water  is  also  less  than  normal.  Thus,  at  the  onset  of 
fever,  the  animal  utilizes  all  the  means  at  its  disposal  to  raise  its 
temperature,  the  production  of  heat  being  increased  and  the  losses 
diminished. 

The  loss  of  heat  from  the  surface  of  the  body  is  regulated 
mainly  by  the  contraction  of  the  cutaneous  blood- 
vessels. At  the  onset  of  many  diseases,  these  vessels  con- 
tract excessively,  and,  as  a  consequence,  the  skin  becomes  cold 
and  either  pale  or  cyanotic.  This  cooling  of  the  skin  produces 
in  turn  a  sensation  of  cold  throughout  the  body  and  sets  in  motion 
the  chemical  mechanism  already  referred  to  (p.  389),  which  in- 
creases the  heat  production  within  the  body.  Clonic  muscular 
movements,  giving  rise  to  the  so-called  chill,  are  a  conse- 
quence. During  the  chill  the  temperature  rises  rapidly  to  a  great 
height,  for  the  muscular  movements  greatly  increase  the  heat 
production,  and,  at  the  same  time,  the  heat  losses  are  reduced 
on  account  of  the  contracted  cutaneous  arteries.  That  these 
muscular  contractions  are  due  primarily  to  the  coolness  of  the 
skin  is  proved  by  the  fact  that  if  the  skin  of  these  patients  be 
warmed  the  "  chill "  ceases.  Such  chills  are  particularly  charac- 
teristic of  some  diseases,  and  it  seems  probable  that  the  agents 


FEVER  395 

which  cause  certain  fevers  show  a  special  tendency  to  produce  a 
constriction  of  the  cutaneous  vessels,  and  consequently  a  chill. 

In  the  great  majority  of  cases  the  total  loss 
of  heat  is  increased  at  the  height  of  the  fever. 
This  is  necessarily  true  when  the  heat  production  is  increased, 
and  the  temperature  is  constant,  for  it  is  obvious  that  if  the 
extra  heat  produced  were  not  immediately  given  off  the  tempera- 
ture of  the  body  would  be  raised. 

In  animals,  the  acceleration  in  heat  losses  affects  conduction, 
radiation  and  evaporation,  all  to  about  the  same  degree,  so  that 
the  ratio  between  the  first  two  and  the  third  remains  practically 
the  same  as  in  health,  i.e.,  the  loss  by  evaporation  amounts  to 
about  sixteen  to  seventeen  per  cent,  of  the  total  loss  of  heat.^^ 
In  my  opinion,  however,  we  are  not  permitted  to  infer  from  this 
that  sufficient  evaporation  from  the  body  takes  place  in  fever,  for 
it  has  been  shown  that  if  the  heat  production  be  increased  by 
other  means,  the  losses  by  evaporation  are  relatively  much  more 
increased  than  are  the  losses  by  radiation  and  conduction.^^ 

In  man  it  has  been  found  that  while  the  temperature  is  rising, 
the  elimination  of  water  from  the  skin  approaches  the  lower 
normal  limits,  whereas  at  the  height  of  the  fever  it  is  about  fifteen 
per  cent,  above  normal.^^  During  a  fall  in  temperature,  it  is 
increased  in  proportion  to  the  rapidity  of  the  fall.  The  taking 
of  food  markedly  increases  the  evaporation  from  the  skin,  both  in 
the  healthy  and  in  the  feverish.  The  elimination  of  water  from 
the  lungs  is  increased  proportionately  to  the  greater  volume  of 
air  used. 

In  conclusion,  it  may  be  said  that  at  the  height  of  a 
fever  the  heat  losses  vary  with  the  heat  produc- 
tion, but  always  remain  somewhat  less,  so  that 
an  increase  in  the  temperature  of  the  body  is  the 
result. 

The  conduction  and  radiation  of  heat  from  the  skin  are 
governed  mainly  by  the  amount  of  blood  that  traverses  the 
cutaneous  capillaries,  and,  since  the  latter  are  usually  dilated  at 
the  height  of  the  fever,  the  skin  is  ordinarily  reddened  at  this 
time.  Yet  many  questions  concerning  the  cutaneous  vessels  in 
fever  are  still  unsolved.  They  certainly  respond  excessively  to 
stimulation,  either  mechanical  or  thermic,  and  for  this  reason, 
fever  patients  easily  become  chilled  when  exposed  to  a  draught 


396  THE  BASIS  OF  SYMPTOMS 

of  air,  etc.  Animals  with  fever  also  react  excessively  to  re- 
flexes which  affect  the  cutaneous  vessels  through  the  medulla. 

Many  have  held  that  the  cutaneous  vessels  of  fever  patients 
are  subject  to  frequent  and  rapid  variations  in  their  state  of 
contraction.  This  is  certainly  not  always  so,  however,  for, 
though  recent  and  careful  observations  on  animals  have  shown 
that  during  the  rise  of  temperature  considerable  variations  in  the 
heat  loss  may  take  place,  the  same  is  by  no  means  true  during  the 
height  of  the  fever.  Furthermore,  there  are  no  very  marked 
variations  in  the  skin  temperature  of  man  during  typhoid  fever, 
rheumatic  endocarditis  and  many  other  conditions.*^ 

For  a  better  understanding,  therefore,  of  the  mechanism 
governing  heat  losses  as  a  whole,  we  require,  in  addition  to  our 
knowledge  that  the  loss  by  evaporation  is  small,  quantitative  stud- 
ies bearing  on  the  losses  by  radiation  and  conduction. 

The  heat  loss  during  the  fall  of  temperature 
differs  under  different  conditions.  When  the  fall  of  tempera- 
ture takes  place  by  crisis,  the  loss  of  heat  is  greatly  in- 
creased by  the  sweating  and  by  the  increased  radiation  and  con- 
duction from  the  skin.  When  the  fall  of  temperature  takes 
place  very  gradually,  however,  the  heat  loss  is  often  very 
slight.  In  such  cases  the  fall  is  due  mainly  to  a  diminished 
heat  production,  as  has  been  definitely  proved  for  animals,  and 
as  is  probably  equally  true  for  man.  In  the  majority  of  cases, 
however,  the  fall  of  temperature  seems  to  be  due  to 
a  combination  of  diminished  heat  production 
and  increased  heat  loss.  Sweating,  even  in  febrile 
cases,  does  not  necessarily  produce  a  fall  in  temperature.*^ 

Metabolism  in  Fever. — During  the  rise  of  temperature,  as  well 
as  during  the  height  of  the  fever,  the  oxidative  pro- 
cesses in  the  body  are  usually  increased.*^  They 
run  parallel  to  the  heat  production,  and,  indeed,  may  be  used  to 
measure  heat  production  (indirect  calorimetry),  providing  that 
we  know  what  compounds  are  being  oxidized  and  what  the  end- 
products  are.  Chills  and  rapid  respirations,  i.e.,  muscular  activ- 
ity, greatly  accelerate  the  metabolism,  and  a  high  temperature  will 
do  the  same.  In  some  cases  of  fever,  however,  there  is  no  apparent 
increase  in  the  metabolic  process  (p.  392) .  No  strict  paral- 
lelism exists  between  the  rate  of  decomposition 
and  the  elevation  of  temperature;*^  and  many  in- 


FEVER  397 

fections  run  their  course  with  comparatively  slight  fever  and  yet 
with  relatively  rapid  rates  of  oxidation. 

On  the  contrary,  we  occasionally  meet  with  cases,  which 
despite  their  febrile  character  seem  to  exhibit 
no  increase  in  oxygen  consumption.  Such  a  finding 
nevertheless  does  not  warrant  the  assumption  that  the  oxidative 
processes  are  not  accelerated.  It  is  true  that  brief  observations 
made  during  fevers  which  have  persisted  over  a  long  period  will, 
as  the  days  go  by,  show  a  gradual  diminution  in  nitrogen  elim- 
ination, oxygen  combustion  and  sweat  secretion — or,  in  other 
words,  a  lessened  heat  production  and  heat  loss — but  figures  thus 
obtained  are  not  an  accurate  criterion  of  metabolic  processes 
during  the  fever  as  a  whole.  Short  periods  of  observation  must 
also  take  into  account  how  metabolic  conditions  vary  with  the 
stage  of  the  fever.  The  conception  is  prevalent,  nevertheless,  that 
there  are  occasional  cases  in  which  during  the  febrile  course 
the  oxidative  processes  are  not  increased.^^  I  cannot  convince 
myself,  however,  that  these  will  bear  a  rigid  scrutiny,  for,  as  I 
have  already  said,  we  must  adhere  to  the  maxim  that  in  fever  heat 
production  is  increased. 

Recent  studies  have  given  us  a  fairly  comprehensive  knowl- 
edge of  the  substances  which  are  decomposed  in 
fever.  In  all  but  the  milder  cases  of  infection,  the  febrile 
patient  is  undernourished.  Because  of  his  loss  of 
appetite,  he  generally  takes  insufficient  food  unless  special  meas- 
ures are  resorted  to.^^  Yet  he  needs  more  nourishment  than  the 
normal  individual,  because  of  the  energy  consumed  in  the  in- 
creased heat  production.  For  the  same  reason,  his  decomposition 
processes  exceed  those  of  a  normal  person  on  the  same  dietetic 
regime.  Nor  do  the  kinds  of  substances  which  are  decomposed 
differ  in  any  way  in  the  two  cases.  It  is  true  that  the  febrile 
patient  in  a  fasting  condition  decomposes  more  proteid  than  does 
an  individual  in  a  state  of  inanition,  but  with  no  infection  or 
fever;  yet  so  far  as  the  total  consumption  of  energy  goes,  the 
percentage  of  nitrogen  excreted  runs  parallel  in  the  two.  I  f 
the  patient  with  fever  be  given  an  adequate  diet, 
his  nitrogen  equilibrium  will  be  maintained  and 
his  strength  conserved.'*®  Herein  lies  the  difficulty,  for 
such  patients  are  almost  always  in  a  state  of  inanition  due,  on 
the  one  hand,  to  their  anorexia  and,  on  the  other,  to  their  greater 


398  THE  BASIS  OF  SYMPTOMS 

caloric  need.  The  combination  of  diminished  caloric  intake  and 
increased  caloric  need  explains  the  high  proteid  decomposition 
ordinarily  observed  in  fever. 

The  rapidity  of  proteid  consumption  varies  in 
different  infections  and  with  the  stage  of  the  disease.  Further- 
more, it  is  quite  independent  of  the  height  of  the  fever.^^ 

The  decomposition  of  proteids  to  their  ordinary  end-products 
accounts,  in  part,  for  the  increased  production  of  heat  in  fever, 
but  as  this  source  is  inadequate,  non-nitrogenous  sub- 
stances are  utilized  just  as  is  the  case  in  starvation.  Gly- 
cogen plays  an  insignificant  role,  because  it  is  rapidly  con- 
sumed, and  further  because  it  is  not  stored  up  to  any  great 
extent  in  fever.*®  Fat,  therefore,  must  provide  the  remainder 
of  the  energy  required.*^  In  brief,  metabolism  in  fever 
follows  the  same  laws  as  in  starvation,  as  is  evi- 
denced by  the  fact  that  the  respiratory  quotient  in  the  two  states — 
the  nourishment  being  the  same — is  identical.  The  abnormally 
low  quotient  formerly  frequently  observed  in  febrile  patients  we 
now  know  to  have  been  based  upon  too  short  a  period  of  obser- 
vation.^® 

The  augmented  proteid  combustion  in  fever  is  due,  in  part, 
therefore,  to  the  associated  inanition,  and  in  part  to  the  generally 
increased  production  of  heat.  We  have  already  noted  that  fever 
per  se  accelerates  the  processes  of  combustion,  and  in  this  the 
tissue  proteids  also  naturally  take  part.  So  far  as  man  is  con- 
cerned,^^  it  has  been  shown  that  if  the  temperature  is  artificially 
raised  to  39°  C.  the  proteid  decomposition  is  not  affected ;  whereas, 
if  the  temperature  reaches  40°  C,  an  increase  in  proteid  destruc- 
tion is  said  to  take  place.  In  these  investigations,  however,  the 
total  consumption  of  energy  has  not  been  taken  into  consideration. 

Nor  does  proteid  destruction  take  place  along  different  lines 
from  those  in  simple  inanition.^^  The  formation  of  albumoses 
is  not  of  frequent  enough  occurrence  to  be  looked  upon  as  charac- 
teristic of  fever,  as  was  formerly  supposed.^^  Most  of  the 
end-products  of  proteid  decomposition  that  ap- 
pear in  the  urine  do  not  differ  qualitatively  from  those  present 
in  health.  Thus  the  urea  is  relatively  reduced  and  the  ammonium 
salts  of  organic  acids  increased.  The  increase  in  the  amount 
of  these  organic  acids  in  the  blood  is  the  probable  cause  of  the 
diminution  in  the  amount  of  carbon  dioxide  that  is  present  there. 


FEVER  399 

As  a  rule,  the  creatinin  is  also  increased  in  the  urine.  We  have 
no  positive  information  as  to  the  amount  of  uric  acid  formed 
during  fever. 

That  the  amount  of  heat  set  free  in  fever  by  the  processes  of 
combustion  corresponds  to  that  determined  by  direct  calorimetry, 
is  evidence,  in  my  opinion,  of  the  contention  that  the  excess  of 
heat  which  is  generally  produced  in  fever  arises  solely  from  chemi- 
cal decompositions,  just  as  does  the  total  heat  production  in  the 
normal  individual.  In  other  words,  there  is  no  special  mechanism 
of  heat  production  in  fever.  The  view  ^*  that  heat  is  produced  in 
fever  by  peculiar  processes  of  hydration  can  be  discarded,  for 
the  accumulation  of  water  in  the  tissues  during  long-continued 
fevers  does  not  differ  from  that  in  cachectic  conditions  unasso- 
ciated  with  fever.  Indeed,  in  the  process  of  hydration,  heat  is 
utilized,  not  set  free.^^ 

The  Cause  of  the  High  Temperature  in  Fever. — We  have 
already  said  that  a  rise  in  temperature  must  always  be  due  to  a 
disproportion  between  the  heat  production  and  the  heat  loss  in 
the  body.  Since  the  production  of  heat  in  fever  is 
greater  than  in  health,  it  is  theoretically  possible  that 
this  increased  production  of  heat  may  be  the  sole  cause  of  the 
high  temperature.  Yet  we  know  that  large  amounts  of  heat 
may  be  produced  in  the  normal  individual  by  muscular  exertion, 
and  that  these  do  not  ordinarily  cause  any  marked  rise  in  tem- 
perature. It  might  be  urged,  therefore,  that  in  fever  the  fault 
lies  in  the  mechanism  which  regulates  the  heat 
loss,  or,  in  other  words,  that  the  heat  in  fever  is  produced 
in  such  a  manner  that  it  does  not  furnish  the  normal  stimulus 
to  the  mechanism  that  increases  heat  loss.  This  would  be  an 
acceptable  theory  were  the  mechanism  of  heat  production  in  fever 
different  from  that  in  the  healthy  person;  but  as  this  is  not  the 
case  we  are  in  no  position  to  say  whether  the  mechanism  which 
increases  the  loss  of  heat  from  the  body  is  relatively  inactive  or 
not.  We  would  emphasize  the  fact,  however,  that  there  exist 
no  grounds  for  such  an  assumption. 

The  Site  of  the  Heat  Production  in  Fever, — The  character 
of  the  metabolic  changes  in  fever  gives  us  no  definite  idea  as  to 
the  tissues  especially  affected,  for,  as  we  have  seen,  the  urine 
contains  only  such  decomposition  products  as  appear  when  there 
is  cellular  destruction  of  any  sort  in  the  body.     The  evidence 


400  THE  BASIS  OF  SYMPTOMS 

in  favor  of  an  increased  consumption  of  red  blood- 
corpuscles  is  very  inconclusive.  Neither  the  increased 
amounts  of  potassium  salts  in  the  urine  nor  the  abnormal  pigments 
there  present  can  be  considered  to  prove  a  widespread  destruction 
of  these  elements ;  and  the  blood-picture  itself  is  inconsistent  with 
such  a  conception. 

Observations  on  the  temperature  of  the  blood 
returning  from  various  parts  of  the  body  do,  how- 
ever, give  us  some  data  as  to  the  site  of  the  heat  production. 
Heidenhain  and  Korner  found  that  when  artificial  fever  had  been 
produced  in  dogs  by  the  injection  of  pus,  the  blood  returning 
from  the  legs  was  warmer  than  that  in  the  right  ventricle.^* 
Numerous  other  observers  ^^  have  since  shown  that,  in  artificial 
fever,  the  venous  blood  returning  from  the  kidneys,  and  espe- 
cially from  the  liver,  is  warmer  than  that  from  the  muscles  and 
the  skin.  From  these  observations,  we  may  infer  that  the 
excessive  heat  of  fever  is  produced  mainly  in 
the  large  glands  and  the  muscles;  but  to  what  extent  each 
of  these  participates  in  its  production  is  very  uncertain. 

Since  the  glycogen  of  the  body  is  consumed  during  fever, ^® 
and  since  the  artificial  fever  produced  by  puncture  of  the  brain 
likewise  brings  about  a  consumption  of  glycogen — and  indeed 
occurs  only  when  there  exists  a  store  of  glycogen  in  the  body  ^^ — 
it  seems  highly  probable  that  the  cause  of  the  increased  heat 
production  in  ordinary  fever  is  a  stimulation  of  the  central  ner- 
vous system,  similar  to  that  induced  by  the  puncture.®*^ 

The  Heat-Regulatory  Mechanism  in  Fever. — In  the  healthy 
individual,  a  proper  heat  regulation  cannot  be  maintained  unless 
certain  parts  of  the  mid-brain  are  intact.  If  these  parts  of  the 
brain  be  destroyed,  or  if  the  spinal  cord  be  cut  at  a  high  level, 
then  the  temperature  depends  largely  upon  that  of  the  surround- 
ings, just  as  it  does  in  the  case  of  cold-blooded  animals.  Though 
the  exact  location  of  these  heat-regulating  centres  is 
not  known,  it  would  appear  from  the  studies  of  Isenschmid  and 
myself  that  the  basal  ganglia  are  of  fundamental  impor- 
tance in  this  regard. 

It  would  seem  probable  that  this  nervous  mechanism  which 
regulates  the  temperature  of  the  body  is  diseased  in  fever.  The 
observations  bearing  on  this  question  have  dealt,  for  the  most  part, 
with  the  effect  of  procedures  which  withdraw  heat  from  the  body; 


FEVER  401 

and  experiments  on  men  as  well  as  animals  have  shown  that  if  heat 
be  artificially  withdrawn  from  the  body  by  cold  baths,  etc.,  the 
compensatory  increase  in  the  heat  production  is  less  if  the  animal 
has  a  fever  than  if  it  be  normal.  In  certain  experiments  on  ani- 
mals, indeed,  there  may  be  absolutely  no  increased  production 
of  heat  under  these  circumstances.®^ 

It  follows  that  the  temperature  of  febrile  animals  is  more 
readily  reduced  by  artificial  cooling  than  is  that  of  normal  animals, 
and  that,  other  things  being  equal,  the  patient  with  fever  may  be 
cooled  off  with  comparative  ease.  It  is  also  probable  that  his 
temperature  may  be  more  easily  raised  by  artificial  means.  For 
example,  animals  more  readily  acquire  a  high  temperature  from 
warm  surroundings  if  they  have  been  previously  treated  with 
injections  of  pus.®^  In  apparent  contradiction  to  these  facts  is 
the  observation  that  the  temperature  of  an  animal  with  fever  is 
sometimes  made  higher  by  exposure  to  cold,  possibly  because 
the  cold  increases  the  heat  production  within  the  body. 

It  is  evident,  therefore,  that  in  fever  the  organism  reacts 
qualitatively  to  a  cooling  or  heating  of  the  body  surfaces  like 
a  normal  animal.  Quantitatively,  however,  there  exist  differ- 
ences, in  that  in  pyretic  conditions  the  response  to  external  changes 
is  not  so  prompt  or  so  complete.  Furthermore,  conditions  are 
similar  in  fever  states  with  respect  to  the  heat  which  the  animal 
itself  produces.  Thus  weakly  individuals,  tuberculous  patients 
and  those  running  a  slight  temperature  or  convalescing  from  an 
infection,  often  exhibit  fever  after  muscular  exertion  or  after 
heavy  meals.®^  In  the  case  of  typhoid  fever  and  tuberculosis,  a 
diet  of  high  caloric  worth  ordinarily  causes  no  rise  in  temperature, 
probably  because  the  heat  loss  is  increased  by  evaporation  from 
the  skin.®*  Though  the  latter  is  not  so  great  as  in  health,  it 
serves  nevertheless  as  an  efficient  regulatory  factor. 

We  may  say  then,  at  this  point,  that  though  heat  regu- 
lation is  maintained  in  fever,  the  regulatory 
apparatus  is  less  responsive  than  in  health  to  cer- 
tain demands  made  upon  it. 

It  is  a  matter  of  common  clinical  experience  that  the  tem- 
perature of  patients  with  fever  is  less  resistant 
to  external  influence  than  is  that  of  normal  in- 
dividuals. This  lack  of  resistance  differs  in  amount  in  dif- 
ferent diseases  and  may  even  vary  at  different  periods  of  the 

26 


402  THE  BASIS  OF  SYMPTOMS 

same  disease.  During  typhoid  fever,  for  example,  the  tempera- 
ture can  usually  be  reduced  more  readily  in  the  later  than  in  the 
earlier  weeks  of  the  illness.  One  reason  why  fever  patients  are 
particularly  susceptible  to  the  antipyretic  action  of  the  cold 
bath  is  that  their  cutaneous  vessels  react  abnormally  to  stimuli. 
It  is  when  these  vessels  remain  dilated  for  a  considerable  period 
after  the  cold  bath  that  the  most  marked  falls  in  temperature 
occur.®^  The  antipyretic  drugs  also  reduce  the  tempera- 
tures of  fever  patients  much  more  effectually  than  they  do  those 
of  normal  individuals;^^  and  here  again  these  drugs  are  not 
equally  effective  in  all  cases  nor  in  the  same  case  at  all  stages  of  the 
disease.  Thus  we  see  that  the  temperature  does  not  resist  exter- 
nal influences  during  fever  so  well  as  it  does  during  health,  partly 
because  the  regulatory  mechanism  is  less  effective,  and  partly 
because  the  peripheral  blood-vessels  react  abnormally  to  stimuli. 

Even  during  the  convalescence  from  infec- 
tious diseases,  the  temperature  regulation  is 
often  imperfect.  Patients  who  are  recovering  from  ty- 
phoid fever,  for  example,  easily  acquire  an  elevation  of  tempera- 
ture after  eating  large  amounts  of  food  or  after  excessive  exercise, 
apparently  because  they  cannot  eliminate  the  large  quantity  of  heat 
that  has  been  suddenly  liberated  in  their  bodies.  An  analogous 
condition  is  seen  in  many  captive  animals,  and  it  seems  as  if  their 
temperature  regulation  were  injured  to  a  certain  extent  by  the  life 
of  captivity.  Thus  Finkler  has  observed  a  temperature  of  40°  C. 
(104°  F.)  in  starving  guinea-pigs  after  a  full  meal. 

In  view  of  the  fact  that  the  temperature  is  elevated  in  fever, 
and  that  heat  regulation  is  maintained,  it  may  be  said  that  con- 
ditions are  to  a  certain  extent  correctly  described  by  Lieber- 
meister's  formula,  viz.,  that  the  heat-regulatory 
centre  in  fever  is  "set  at  a  higher  level."  This 
hypothesis  is  at  present  so  widely  accepted  because  of  the  current 
tendency  to  regard  each  natural  process — in  this  case,  fever — as 
essential  to  the  life  of  the  individual. 

This  formula  represents  the  facts  in  so  far  as  it  concerns  heat 
regulation.  But  there  is  more  to  fever  than  a  mere  regulation  of 
heat;  otherwise  in  febrile  states  we  should  expect  to  find  only 
the  evidences  of  this  "higher-pitched"  regulation.  This,  how- 
ever, is  rarely  the  case.  First  and  foremost,  fever  is  generally, 
in  my  opinion  always,  associated  with  an  enormously  increased 


FEVER  40S 

heat  production.  The  adherents  of  Liebermeister's  theory  meet 
this  objection  by  observing  that  the  symptoms  accompanying  the 
new  level  of  regulation  vary  with  the  cause  of  the  fever.  Though 
this  is  to  a  certain  extent  true,  such  associated  symptoms,  e.g.,  an 
increase  in  heat  production,  are  actually  a  part  of  the  febrile 
process.  This  applies  equally  well  to  fever  produced  by  chemical 
means,  in  which  case  an  infection  plays  no  part.  It  is  true  that 
in  bacterial  affairs,  the  micro-organisms  are  capable  of  augment- 
ing the  decomposition  processes,  possibly  without  at  the  same  time 
causing  fever.  This  has  definitely  been  shown  to  be  the  case 
among  cold-blooded  animals  in  which  fever  cannot  be  produced 
because  there  is  no  mechanism  of  heat  regulation.  As  for  warm- 
blooded animals,  the  effects  of  febrile  infections  have  been  little 
studied.  It  is  highly  probable,  however,  that  the  microbic  agency 
itself  may  be  the  cause  of  the  increased  decomposition  processes, 
and  to  this  extent  the  protagonists  of  Liebermeister  are  justified 
in  assuming  that  it  is  difficult,  perhaps  impossible,  to  separate  the 
consequences  of  infection  from  those  of  fever.  But  this  reason- 
ing is  not  applicable  to  the  so-called  aseptic  fever  which  occurs 
after  the  injection  of  albumoses  or  following  blood  extravasations 
into  the  tissues.  Here,  too,  there  is  an  increased  production  of 
heat  and  this  increase  is  not  a  direct  effect  but  associated  with  the 
symptom-complex  of  fever. 

Heat  regulation  is  a  complex  process,  bring- 
ing into  play  factors  which  act  independently 
upon  heat  production  and  heat  loss.  Loss  and  pro- 
duction are  regulated  under  different  conditions  by  different 
physiological  tools;  the  former  by  conduction,  radiation  and 
evaporation,  and  the  latter  by  the  decomposition  of  the  constituents 
of  the  food  or  of  the  tissues.  In  my  opinion,  fever  brings  about 
an  alteration  in  all  the  various  components  of  this  mechanism, 
though  the  extent  to  which  each  is  affected  varies  with  the  case. 
The  faculty  of  regulation  is,  on  the  whole,  preserved.  I  am  of 
the  opinion  that  there  exists  always  a  hyperstimulation  of  those 
places  which  have  to  do  with  heat  production,  or,  in  other  words, 
a  peculiar  linking  of  disturbed  heat  production  and  heat  elimina- 
tion.^^ The  centres  for  the  regulation  of  the  latter  are  variably 
affected,  but  on  the  whole  they  are  inefficient.  In  this  particular 
we  are  agreed  with  Liebermeister,  viz.,  that  the  regulatory  func- 
tion in  its  entirety  is  "higher  pitched."     But  conditions  vary 


404  THE  BASIS  OF  SYMPTOMS 

greatly  in  different  cases.  The  cutaneous  vessels  may  be  con- 
stricted or  dilated.  Sweating  is  always  present  to  some  extent, 
and  oftentimes  greatly  increased — not  infrequently,  indeed,  during 
a  chill.  This  variable  behavior  of  the  centres  depends  upon 
the  nature  r.nd  virulence  of  the  infection,  upon  the  constitution 
of  the  patient  and  upon  the  stage  of  the  disease. 

The  explanation  of  the  different  phases  of  the  febrile  process 
resides,  therefore,  in  the  behavior  of  the  heat-regulating  centres 
in  the  brain,  upon  which  the  hypothetical  fever-producing  sub- 
stances are  assumed  to  act.  We  have  already  discussed  the  facts 
for  and  against  the  conception  of  a  single  substance 
being  responsible  for  all  fevers.  In  view  of 
Friedberger's  epochal  work  on  anaphy latoxin, 
we  are  in  a  better  position  to  answer  this  question.  The  irrita- 
bility of  the  heat-regulating  centre  is  unquestionably  subject  to 
great  variations,  being  particularly  susceptible  to  chemical  actions 
and  infectious  processes.  Friedberger  ^®  has  made  quantitative 
studies  of  the  effects  produced  by  reinjection  in  animals  sensitized 
with  foreign  proteids.  Small  doses  of  the  specific  proteid  caused 
fever;  while  collapse, with  subnormal  temperature, and  even  death, 
followed  the  injection  of  larger  amounts.  Friedberger's  obser- 
vations are  based  ui>on  specific  reactions  which  are  of  genuine 
anaphylactic  nature.  In  this  sense,  fever  may  be  looked 
upon  as  the  most  delicate  response  of  a  sensi- 
tized animal.  The  doses  necessary  to  cause  the  rise  in 
temperature  are  incalculably  small.  Furthermore,  Friedberger 
was  able  by  varying  his  dosage  to  produce  every  known  type  of 
fever  curve.  Though  anaphylatoxin  is  not  a  specific  substance, 
its  mode  of  origin  is  specific;  and  as  such  it  might  be  looked 
upon  as  the  uniform  cause  of  infectious  fevers,  producing  the 
ktter  by  stimulation  of  the  heat-regulating  centre. 

The  Nutrition  in  Fever. — The  nutrition  is  always 
impaired  in  fevers  of  long  duration,  because,  as  we  now  know 
and  as  we  have  already  noted,  the  patients  do  not  take  a  sufficient 
quantity  of  food.  Their  appetites  are  often  very  poor,  though 
this  may  not  be  the  case  in  the  hectic  fever  of  tuberculosis.  For 
these  reasons  most  patients  with  fever  become  emaciated  and 
weak,  and  the  weakness  is  often  greater  than  can  be  accounted 
for  by  the  lack  of  food  alone,  being  dependent,  as  we  have  seen, 


FEVER  405 

upon  the  excessive  consumption  of  both  the  proteid  and  non- 
proteid  materials  of  the  body. 

On  the  other  hand,  in  long-continued  infections, 
a  tendency  to  limit  the  metabolic  processes  is 
often  manifest,  and  in  the  terminal  stages  of  chronic  dis- 
eases the  proteid  decomposition  and  the  total  oxidations  in  the 
body  often  reach  a  surprisingly  low  level.  This  adaptation  en- 
ables many  a  person  to  undergo  a  long-continued  illness  which 
would  otherwise  prove  fatal.  Though  the  excessive  consumption 
of  proteid  material  is  common  to  all  forms  of  fever,  it  seems 
very  probable  that  certain  infections  are  particularly  harmful  in 
this  respect. 

The  cause  of  the  various  forms  of  cellular  degeneration  that 
occur  so  frequently  in  fever  is  not  yet  definitely  determined. 
Some  believe  that  the  high  temperature  may  cause  the  degenera- 
tive changes,®^  whereas  others  hold  that  the  temperature  alone 
will  not  produce  them.'^^  It  is  impossible  at  present  to  reconcile 
these  varying  views. 

The  Water  Retention  in  Fever. — Years  ago  Leyden^^  made 
the  observation  that  patients  with  fever  frequently  lose  but  little 
weight  during  the  course  of  the  acute  process — i.e.,  at  the  time 
when  the  consumption  of  material  in  the  body  is  most  active — but 
that  the  principal  loss  in  their  weight  takes  place  during  convales- 
cence. He  explained  these  results  by  assuming  that  there  is  a 
retention  of  water  in  the  body  during  fever.  From  that  time 
up  to  the  present  this  question  has  awakened  general  interest. 

In  its  discussion  one  might  distinguish  between  an  absolute 
retention  of  water  and  a  mere  relative  retention,  i.e., 
an  increase  in  the  proportion  of  water  in  the  tissues.  So  far  as  an 
absolute  retention  is  concerned,  this  is  not  caused  by  a  high  tem- 
perature or  by  the  infection  itself.  Only  when  the  kidneys  or 
heart  are  diseased  is  there  an  absolute  insufficiency  of  water 
elimination  during  fever.  In  general,  there  is  no  absolute  decrease 
in  the  excretion,  but  on  the  contrary  a  slight  increase,  correspond- 
ing to  the  increased  rate  of  metabolism.  The  diminished  urine 
which  is  so  often  seen  in  the  early  days  of  an  infectious  disease  is 
compensated  for  by  an  increased  evaporation  of  water  from  the 
skin  and  lungs.  The  increased  urine  during  defervescence,  as 
occurs,  for  example,  during  the  late  weeks  of  typhoid  fever,  is  due 
to  the  fact  that  at  this  time  the  sweating  sinks  to  a  minimum.^  ^ 


406  THE  BASIS  OF  SYMPTOMS 

Less  heat  is  eliminated  because  less  is  produced  in  the  late  stages 
of  long-continued  infectious  diseases  (p.  393). 

The  relative  amount  of  water  in  the  tissues 
does  not  change  during  fevers  of  short  dura- 
tion, such  as  pneumonia,  but  in  long-continued 
fevers,  such  as  typhoid  or  tuberculosis,  the 
tissues  become  relatively  rich  in  fluids  and 
poor  in  solids.  The  cause  of  this  seems  to  lie  in  the  ex- 
cessive proteid  destruction,  resembling  in  this  respect  the  cachexia 
of  carcinoma.  A  normal  individual  rapidly  excretes  any  addi- 
tional water  that  may  be  introduced  into  his  body,  up  to  three 
litres  or  more  per  day.  Why  the  patient  with  fever  fails  to  excrete 
the  extra  liquid  in  his  tissues  is  not  known,  though  we  suspect  that 
it  is  because  the  extra  water  is  retained  chiefly  within  the  cells 
themselves  and  does  not  reach  the  blood  or  lymph.  To  what 
extent  this  water  accumulation  may  be  due  to  the  retention  of 
nitrogenous  substances  or  to  an  altered  salt  metabolism,  is  at 
present  undetermined. 

The  Significance  of  Fever. — Whether  or  not  the  elevation  of 
temperature  is  of  advantage  to  the  infected  organism  is  a  subject 
that  has  engaged  the  attention  of  physicians  from  the  most  remote 
times  down  to  the  present.  Three  conflicting  views  have  been 
advocated.  According  to  the  first,  the  elevation  of  tem- 
perature is  in  itself  dangerous  to  the  patient, '^^ 
and  may  even  be  the  cause  of  death;  according  to  the  second, 
the  danger  of  the  infectious  process  depends 
only  to  a  very  slight  extent  upon  the  high  tem- 
perature, and  according  to  the  third,  the  high  tem- 
perature is  advantageous,  for  by  this  means  the  in- 
fected body  is  "  cleansed  by  fire."  '''^  The  treatment  of  fever  must 
depend,  to  a  large  extent,  upon  the  view  that  is  accepted  by  the 
physician. 

Is  the  elevation  of  temperature  in  the  course  of  an  infection 
useful,  harmful  or  of  no  particular  significance?  So  long  as 
the  elevation  remains  within  moderate  limits,  it 
may  certainly  be  regarded  as  relatively  harm- 
less. The  rapid  pulse  and  respirations,  the  loss  of  appetite  and 
the  possible  parenchymatous  degeneration  of  the  organs,  in  so  far 
as  they  are  directly  caused  by  the  temperature,  are  not  in  them- 
selves very  dangerous.    If,  on  the  contrary,  the  elevation  of  tem- 


FEVER  407 

perature  is  very  great,  it  may  undoubtedly  be  harmful,  for 
the  same  dangers  are  threatened  as  in  a  heat-stroke.  Yet  such 
dangerously  high  temperatures  are  comparatively  rare  in  fever; 
and  the  reason  why  a  high  temperature  is  generally  regarded  as  a 
bad  sign  in  an  infectious  disease  is  that  it  indicates  a  severe 
infection.  This  is  well  illustrated  by  the  fact  that  high  tempera- 
tures in  malaria  are  generally  regarded  with  a  certain  amount 
of  indifiference,  whereas  the  same  temperatures  in  rheumatic  fever 
or  pneumonia  would  be  looked  upon  with  alarm. 

Whether  the  elevation  of  temperature  is  directly  bene- 
ficial to  the  infected  organism  or  not,  is  a  question 
that  is  not  so  easily  settled.  In  recent  years  there  has  been  a 
tendency  to  apply  the  Darwinian  theory  to  pathological  processes 
in  general,  and  to  say,  for  example,  that  fever  could  never  have 
survived  throughout  immeasurable  time  were  it  not  inherited 
as  a  useful  weapon  in  the  struggle  for  existence.  Yet  one  may 
question  to  what  extent  the  Darwinian  theory  applies  to  pathologi- 
cal conditions,'^ ^  for  it  seems  equally  reasonable  to  regard  fever 
as  a  blind  reaction  against  an  injury,  possibly  useful  or  possibly 
harmful.  The  question  is  not  one  that  can  be  solved  by  such 
philosophical  considerations,  and  the  final  answer  must  be  based 
upon  established  facts,  derived  either  from  bedside  observations 
or  from  animal  experiments. 

Unfortunately,  clinical  studies  have  done  little  to  solve  this 
problem.  We  have,  it  is  true,  accumulated  extensive  statistics 
on  the  course  of  infectious  diseases,  especially  of  typhoid  fever, 
under  the  expectant  and  antipyretic  forms  of  treatment.  Yet,  even 
though  we  acknowledge  the  advantage  of  the  latter  treatment,  we 
are  helped  but  little  to  a  solution  of  our  problem,  for  cold  water 
not  only  lowers  the  temperature  of  the  body,  but  it  influences  the 
disease  in  many  other  ways;  and  antipyretic  drugs  introduce 
abnormal  chemical  processes  into  the  metabolism,  and  above  all 
act  upon  the  patient's  nervous  system  and  mental  condition. 

It  is  possible  that  at  a  higher  temperature  the  growth  or 
virulence  of  the  micro-organisms  which  cause  the  disease  may  be 
diminished.  At  present,  however,  we  are  unable  to  say  definitely 
to  what  extent  this  actually  occurs  in  disease. 

We  do  possess,  however,  a  number  of  observations  on  the 
effect  of  increasing  an  animal's  temperature  after  it  has  been 
artificially  infected.     Infection  with  diphtheria  bacilli,  chicken 


408  THE  BASIS  OF  SYMPTOMS 

cholera  bacilli  and  pneumobacilli  run  a  milder  course  in  rabbits 
if  the  temperature  be  artificially  elevated  by  puncture  of  the 
brain  ;^®  and  intoxications  with  hydrolytic  ferments  are  also  less 
virulent  at  higher  temperatures  J  ^  The  same  has  been  found  to 
be  true  for  erysipelas  infections  in  rabbits,'^®  and  the  number  of 
such  examples  could  be  still  further  multiplied. 

Perhaps  the  action  or  formation  of  antibodies  is  favored  by 
the  high  temperature.  Kast'^^  found  that  Pfeiffer's  antibody 
against  typhoid  bacilli  was  more  efficient  at  higher  temperatures ; 
though,  on  the  other  hand,  antipyretic  treatment  does  not  seem 
to  influence  the  formation  of  the  immune  body  in  man.®^ 

We  possess,  therefore,  some  noteworthy  experiments 
which  support  the  view  that  the  elevation  of 
temperature  during  an  infection  is  directly 
beneficial  to  the  infected  organism.  It  must  be 
admitted,  however,  that  only  a  beginning  has  been  made,  and 
that  more  observations  are  necessary  before  the  question  can  be 
regarded  as  definitely  settled,  and  before  we  shall  know  whether 
it  is  the  increased  temperature  itself  or  some  associated  changes 
in  metabolism  that  benefit  the  patient. 

The  Temperature  in  Collapse. — ^We  have  had  frequent  occa- 
sion to  mention  that  the  temperature  during  fever  is  subject  to 
great  variations,  and  that  it  tends  to  rise  or  fall  from  relatively 
insignificant  causes.  A  great  fall  of  temperature  during  an 
infection  has  long  been  recognized  as  a  dangerous  symptom, 
mainly  because  it  so  frequently  heralds  the  onset  of  collapse ;  this 
has  been  observed  experimentally.  The  ordinary  fever-producing 
agents  may  cause  a  reduction  in  an  animal's  temperature  if  they 
are  especially  potent,  or  if  the  animals  used  are  very  "  weak  "  or 
"non-resistant."  It  is  difficult  to  say  what  constitutes  this 
"weakness"  or  "lack  of  resistance"  on  the  part  of  infected 
individuals,  though  it  is  possible  that  the  condition  of  the  circu- 
lation plays  an  important  role. 

Not  only  the  resistance  of  the  individual,  but 
the  kind  and  quantity  of  toxins  are  of  impor- 
tance in  the  production  of  collapse.  The  same 
substance  that  will  give  rise  to  fever  in  small  doses  will  lead 
to  collapse  if  given  in  large  doses.  This  is  well  illustrated  in  the 
case  of  Koch's  tuberculin.^^  If  this  substance  be  given  to  ani- 
mals in  very  large  doses,  the  production  of  heat  in  the  body  is 


FEVER  409 

actually  diminished,  and  in  the  fatal  cases  only  fifty-three  per 
cent,  of  the  normal  amount  of  heat  may  be  produced.  At  autopsy, 
the  vessels  in  the  abdomen,  and  especially  those  belonging  to  the 
intestines,  are  found  to  be  dilated.  This  finding  agrees  with  the 
observations  of  Romberg,  Passler  and  Bruhns  (see  page  86), 
who  showed  that  the  circulatory  failure  in  infectious  diseases 
was  principally  caused  by  a  central  vascular  paralysis,  affecting 
especially  the  splanchnic  vessels.  The  dilatation  of  these  vessels 
allows  so  much  blood  to  collect  in  them  that  the  heart  is  no  longer 
properly  filled  from  the  veins,  the  general  blood-pressure  falls, 
and  the  activity  of  the  muscles  becomes  so  reduced  that,  in  spite 
of  the  fact  that  the  heat  losses  are  greatly  diminished,  the  body  is 
no  longer  able  to  maintain  its  normal  temperature.  Thus  we  see 
that  the  fall  of  temperature  in  collapse  occurs  at  a  time  when 
less  heat  than  normal  is  produced  in  the  body. 

A  certain  antagonism  exists,  therefore,  between 
fever  and  collapse.  In  fever,  both  the  heat  production 
and  the  heat  losses  are  increased,  the  former  being  especially  accel- 
erated. In  collapse,  both  of  these  are  diminished,  but  the  heat 
production  is  more  diminished  than  is  the  heat  loss.  On  the 
other  hand,  fever  and  collapse  resemble  each  other  in  certain 
respects,  for  in  both  too  small  an  amount  of  blood  passes  through 
the  cutaneous  vessels.*^  Indeed,  they  tend  to  shade  into  each 
other,  and,  as  we  have  seen,  the  one  or  the  other  may  result  from 
the  same  cause,  depending  upon  the  factors  already  described. 
Of  interest  is  the  fact  that  in  death  from  anaphylactic  shock, 
we  encounter  a  similar  overloading  of  the  splanchnic  vessels 
(see  p.  87). 

Subnormal  Temperature. — Subnormal  temperatures  are  seen 
not  only  during  collapse  from  infectious  diseases, 
but  also  after  extensive  injuries,  severe  hemor- 
rhages, long-continued  narcosis,  perforative 
peritonitis  and  various  other  severe  lesions  within 
the  peritoneal  cavity.  In  many  of  these,  the  same  con- 
ditions are  present  as  in  collapse,  though  it  is  incorrect  to  regard 
all  subnormal  temperatures  as  symptoms  of  collapse.^^ 

Subnormal  temperatures  are  more  common  than  is  generally 
supposed.  They  are  often  seen  during  convalescence 
from  infectious  diseases,  and  are  then  generally  due 
to  a  diminished  production  of  heat  combined  with  an  inefficient 


410  THE  BASIS  OF  SYMPTOMS 

heat  regulation.  A  subnormal  temperature  frequently  accom- 
panies intoxications  with  alcohol  or  related 
drugs.  These  lessen  the  rate  of  oxidation  in  the  body,  and, 
in  addition,  interfere  with  the  mechanism  regulating  the  loss  of 
heat  from  the  skin.**  Consequently,  an  intoxicated  man  is  less 
able  to  withstand  cold  than  is  a  healthy  individual,  and  if  exposed 
to  cold,  the  temperature  of  his  body  is  more  liable  to  fall. 

When  the  temperature  of  the  body  becomes  very  low,  narcosis, 
and  finally  a  general  paralysis,  result.  The  narcosis  will,  in  turn, 
favor  a  further  lowering  of  the  temperature,  for  the  body  can 
no  longer  increase  its  production  of  heat  by  muscular  activity. 
Even  in  ordinary  sleep  the  heat  regulation  is  less  efficient  than 
during  the  waking  hours,  and  this  lack  of  regulation  is  much 
more  marked  during  deep  narcosis.  For  these  reasons,  the  danger 
of  freezing  to  death  is  best  combated  by  continued  muscular  move- 
ments, for  these  not  only  increase  the  production  of  heat,  but  they 
reduce  the  tendency  to  go  to  sleep. 

We  do  not  know  how  low  the  temperature  may  fall  without 
causing  death,  though  it  is  certain  that  both  men  and  animals 
have  recovered  from  very  low  temperatures.*^ 

LITERATURE 

*  Krehl  and  Matthes :  Arch,  f .  exp.  Path.,  xl,  430 ;  Roily,  Arch,  f .  klin.  Med, 

Ixxviii,  248. 

*  Krehl:  Arch.  f.  exp.  Path.,  xxxv,  222  (lit.)  ;  Nebelthau,  ibid.,  Ixiv,  385. 
'  Riethus :  Arch.  f.  exp.  Path.,  xliv,  253. 

*  Cf.  Pfeiffer,  in  Penzoldt-Stintzing,  Handb. ;  Krehl  and  Matthes,  Arch.  f. 

exp.  Path.,  xxxviii,  284. 
'Buchner:   Berl.  klin.  Wochenschft.,  1890,  No.   10;  Miinch.  med.  Wochen- 

schft.,  1891,  No.  49;  Krehl,  Arch.  f.  exp.  Path.,  xxxv,  222. 
'Centanni:   Deutsch.  med.   Wochenschft.,   1894,   Nos.   7  and  8;   cf.  Voges, 

Zeitschft.  f.  Hyg.,  xvii,  474. 
''  See  Freund :  Arch,  f .  klin.  Med.,  cv,  44. 

*  Krehl  and  Matthes :  Arch,  f .  klin.  Med.,  liv,  39  (lit.)  ;  Klemperer,  Natur- 

forscherversamm.,  1903,  ii,  II,  67. 
'  Meyer :  Deutsch.  med.  Wochenschft.,  1909,  No.  5 ;  Bingel,  Arch.  f.  exp. 

Path.,  Ixiv,  I ;   Freund,  ibid.,  Ixv,  225. 
*"  Samuelson :   Monatschft.   f.   Kinderheilk.,  x,  465 ;   Bendix  and  Bergmann, 

ibid.,  387. 
"  Krehl  and  Matthes :  Arch,  f .  klin.  Med.,  liv,  501 ;  Schulthess,  ibid.,  Iviii, 

32s,  and  Ix,  55. 
"  Freund :  Arch,  f .  klin.  Med.,  cv,  44. 
"  Freund :  Arch,  f .  klin.  Med.,  1912,  cvi,  556. 
"  Protein  Split  Products,  1913. 
"  Amer.  Jour.  Phys.,  x,  452 ;  xx,  439. 

"  Freund  and  Strasmann :  Arch,  f .  exp.  Path.,  1912,  Ixix,  12. 
"  Freund :  Arch.  f.  exp.  Path.,  Ixv,  225. 
"  Harnack  and  Schwegmann :  Arch.  f.  exp.  Path.,  xl,  151 ;  Hamack,  ibid^ 

xlv,  45.  447. 


FEVER  411 

"See  Kionka:  Intemat.  Arch.  f.  Pharmakodynamie,  v,  iii   (lit.). 

^  Gottlieb :  Arch,  f .  exp.  Path.,  xx,  167 ;  Schultze,  ibid.,  xliii,  193 ;  Aronsohn, 

Virch.  Arch.,  clxix,  501. 
^  Roily :  Arch,  f .  klin.  Med.,  Ixxviii,  289. 
"  Hirsch  and  Roily :    Arch,  f .  klin.  Med.,  Ixxv,  307. 
"  White :   Jour,  of  Phys.,  xi,  i ;  Aisenstat,  Arch,  f .  Phys.,  1909,  475 ;  Sachs, 

Jour.  Exp.  Med.,  xiv,  408  (lit.). 
""See  Th.  Kocher:  Grenzgebiete,  i,  415  (Ht.). 
^  See  Rubner's   classical  work.   Die   Gesetze  des   Energieverbrauchs   bei   d. 

Ernahrung,  1902;  Benedict,  Am.  Jour.  Phys.,  xi,  145. 
"°v.  Bergmann;  Kongr.  f.  inn.  Med.,  191 1,  490. 

''Hiller:  Zeitschft.  f.  klin.  Med.,  xxiii,  399;  Wolpcrt,  Arch.  f.  Hyg.,  xxvi,  32. 
^  Zuntz :  Hohenklima  u.  Bergwanderungen,  1906,  394. 
^  Zuntz :     Berl.   klin.   Wochenschft.,    1896,   No.   32 ;    Bonnette,   Le   coup    de 

chaleur  dans  les  pays  temperes,  etc.,  1905. 
^  Thurn :  Deutsch.  militararztl.  Zeitschft.,  1895,  289. 
''  Rubner :  Zeitschft.  f.  Biol.,  N.  F.,  xii,  73. 
^-  See  Krehl  and  Matthes :  Arch.  f.  exp.  Path.,  xxxviii,  284. 
^  Roily  and  Hornig :  Arch,  f .  klin.  Med.,  xcv,  74 ;  Roily,  Kongr.  f .  inn.  Med., 

1911,  512 ;  Grafe,  Arch.  f.  klin.  Med.,  ci,  209. 
"Krehl  and  Matthes:  Arch.  f.  exp.  Path.,  xxxviii,  284;  Freund  and  Grafe, 

ibid.,  Ixvii,  55. 
*°  Kraus  and  Chvostek :  Wiener  kHn.  Wochenschft.,  1891,  Nos.  6  and  7 ;  Krehlj 

and  Matthes,  Arch.  f.  exp.  Path.,  xxxviii,  284;  Steyrer,  Zeitschft.  f,  exp. 

Path.,  iv,  720. 
**Linser  and  Schmidt:  Arch.  f.  klin.  Med.,  Ixxix,  514. 
^  Nebelthau :  Zeitschft.  f .  Biol.,  xxxi,  293 ;  Krehl  and  Matthes,  Arch,  f .  exp. 

Path.,  xxxviii,  284. 
"Rubner:  Arch.  f.  Hyg.,  xi,  256;  Wolpert,  ibid.,  xxvi,  32,  68;  Zuntz,  Berl. 

khn.  Wochenschft.,  1896,  No.  32. 
~  Schwenkenbecher  and  Inagaki :  Arch,  f .  exp.  Path.,  liv,  168,  Lang,  Arch. 

f.  Klin.  Med.,  Ixxix,  343. 
*°  Nebelthau :  1.  c. ;  Krehl  and  Matthes,  1.  c. ;  Griinewald,  Arch,  f .  klin.  Med., 

Ixxviii,  333. 
■"StaheHn:  Zeitschft.  f.  klin.  Med.,  Ixvi,  241. 
**  See  footnote  33. 

^  See  Riethus  :  Arch,  f .  exp.  Path.,  xliv,  247. 
■"  Steyrer :   Zeitschft.  f .  exp.  Path.,  iv,  720. 
**  Coleman:  Jour.  Am.  Med.  Assn.,  1909,  1145;  Shaffer  and  Coleman,  Arch. 

Int.  Med.,  iv,  538;  Grafe,  in  studies  presented  to  the  Karlsruher  Natur- 

forscherversamm.,  191 1. 
*°  Loening :   Klin.  Jahrb.,  xviii,  i ;  Grafe,  Arch,  f .  klin.  Med.,  ci,  209. 
*'  Loening :   1.  c. 
**  Hirsch,  Miiller  and  Roily :  Arch,  f .  klin.  Med.,  Ixxv,  307 ;  Roily,  ibid.,  Ixxviii, 

250;  Ott,  ibid.,  Ixxi,  263. 
**  May :  Zeitschft.  f.  Biol.,  xxx,  i ;  Stahelin,  Arch.  f.  Hyg.,  xlix,  77. 
""  See  Grafe :  Arch,  f .  klin.  Med.,  ci,  209 ;  Roily,  ibid.,  ciii,  93. 
"Linser  and  Schmid:   Arch.  f.  klin.  Med.,  Ixxix,  514. 
"'Mohr:  Zeitschft.  f.  klin.  Med.,  Hi,  371. 
"  Morawitz  and  Dietschy :  Arch,  f .  exp.  Path.,  liv,  88 ;   Schultess,  Arch,  f . 

klin.  Med.,  Iviii,  315,  and  Ix,  55;  Krehl  and  Matthes,  ibid.,  liv,  501. 
"  Herz :  Untersuch.  ii.  Warme  and  Fieber,  1893  ;  Kongr.  f .  inn.  Med.,  1896,  86. 
"  F.  Kraus :  Wiener  klin.  Wochenschft.,  1894,  No.  15. 
■^Pfluger's  Arch,  iii,  562. 
'^  Krehl  and  Kratsch :  Arch,  f .  exp.  Path.,  xli,  185 ;  Hirsch  and  Miiller,  Arch. 

f .  klin.  Med.,  Ixxv,  287. 
"  Hirsch  and  Roily  .  Arch,  f .  klin.  Med.,  Ixxv,  305 ;  Roily,  ibid.,  Ixxviii,  250. 
"  Roily :  1.  c. ;  for  an  opposed  view,  see  Senator  and  Richter,  Zeitschft.  f . 

klin.  Med.,  liv,  16. 


412  THE  BASIS  OF  SYMPTOMS 

**  See  Gottlieb,  in  Meyer  and  Gottlieb,  Pharmacology  (Halsey,  Philadelphia, 

.1914.453)- 
"  Liebermeister :  Path.  d.  Fiebers,  341 ;  Colasanti,  Pfliiger's  Arch.,  xiv,  125 ; 

Finkler,  ibid.,  lix,  98 ;  Zuntz,  Du  Bois  Arch.,  1882,  43. 
*"  Dobrzanski  and  Naunyn :  Arch,  f .  exp.  Path.,  i,  181 ;  Finkler,  1.  c. 
"^Penzoldt  and  Birgelen:  Miinch.  med.  Wochenschft.,  1899,  Nos.  15-17;  Ott, 

ibid.,  1901,  No.  50,  and  1902,  No.  38;  Schroder  and  Briihl,  ibid.,  1902, 

Nos.  33-35- 
"  Schwenkenbecher  and  Tuteur :   Arch,  f .  exp.  Path.,  Ivii,  285 ;  Lang,  Arch,  f . 

klin.  Med.,  Ixxx,  353 ;  Lcening,  Klin.  Jahrb.,  1908,  xix,  105. 
"  Finkler :  Kongr.  f.  Inn.  Med.,  1888,  314. 
**  Gottlieb :  Arch.  f.  exp.  Path.,  xxvi,  419,  and  xxviii,  167. 
*^  Cf.  Schmiedeberg :  Grundriss  d.  Pharmakologie,  4th  edit. 
^  See  especially,  Zeitschft.  f.  Immunitatsforsch.,  x,  1 ;  Miinch.  med.  Wochen- 
schft, 1910,  Nos.  50  and  51. 
"Liebermeister:  Path.  d.  Fiebers,  427. 
'"  Naunyn :  Arch,  f .  exp.  Path.,  xviii,  49. 
"  Arch,  f .  klin.  Med.,  v,  366. 

"  Schwenckenbecker  and  Inagaki :  Arch.  f.  exp.  Path.,  liv,  168. 
'"'  Liebermeister :  Path.  d.  Fiebers,  423 ;  Krehl,  Ergeb.  d.  allg.  Path.,  1896,  409. 
"  Pfluger :  Pfliiger's  Arch.,  xiv,  502 ;  Unverricht,  Volkmann's  Vortrage,  N.  F., 

No.  159- 
'°  See  Ziegler :  Miinch.  med.  Wochenschft.,  1896,  No.  43. 
'•  Loewy  and  Richter :  Virch.  Arch.,  cxlv,  49. 
"  Hildebrandt :  Virch.  Arch.,  cxxi,  i. 
^'Filehne:  Jour,  of  Phys.,  xvii  (Proc.  Physiol.  Soc). 
"  Kongr.  f.  inn.  Med.,  1896,  2,7;  Paech,  Diss.  Breslau,  1900;  Roily  and  Meltzer, 

Arch.  f.  klin.  Med.,  xciv,  335;  Liidke,  ibid.,  xcv,  425  (lit). 
""Lemaire:  Arch,  internat.  de  pharmacodyn.,  v,  225;  Schiitze:  Zeitschft.  f. 

Hyg.,  xxxviii,  205. 
•^Matthes:  Arch.  f.  exp.  Path.,  xxxvi,  437;  xxxviii,  299;  Krehl,  ibid.,  xxxv, 

222. 
*^  Maragliano :  Zeitschft.  f.  klin.  Med.,  xiv,  309;  xvii,  291. 
^  Janssen :  Arch,  f .  klin.  Med.,  liii,  247. 
"Rumpf :  Pfliigers  Arch.,  xxxiii,  538. 
"  Janssen ;  1.  c. ;  Cohnheim,  Allg,  Path.,  2nd  edit,  ii,  489« 


CHAPTER  XI 
THE  SECRETION  OF  URINE 

The  major  portion  of  the  solid  waste  products  that  arise 
in  the  body  leaves  it  by  way  of  the  kidneys.  As  we  have  already 
had  occasion  to  describe  many  of  these  substances,  it  is  not  our 
purpose  to  review  in  this  place  the  origin  of  each,  but  rather 
to  deal  with  the  mechanism  of  secretion  itself;  though  it  must 
be  admitted  that  it  is  often  impossible  to  draw  a  sharp  line  between 
the  secreting  mechanism  and  the  products  that  are  eliminated. 

The  composition  of  the  urine  depends  partly  upon  the  con- 
dition of  the  secreting  cells  in  the  kidneys  and  partly  upon 
the  quality  and  quantity  of  blood  which  passes  through  these 
organs.  These  factors  are  more  or  less  interdependent  one  upon 
the  other.  For  example,  if  the  blood-stream  through  the  kidneys 
be  slowed,  not  only  does  less  blood  come  into  contact  with  the 
secreting  cells,  but  the  latter  are  liable  to  suffer  in  structure  and 
function.  On  the  other  hand,  if  the  renal  cells  are  primarily 
injured,  this  frequently  affects  the  circulation  through  the  kid- 
neys. It  is  often  very  difficult,  therefore,  to  tell  which  part  of 
the  renal  apparatus  is  primarily  involved. 

The  Effect  of  an  Increased  Flow  of  Blood  through  the 
Kidneys.! — It  is  a  general  rule  that  the  quantity  of  urine  secreted 
varies  directly  with  the  quantity  of  blood  that  flows 
through  the  kidneys.  It  varies  likewise  with  the  dif- 
ference between  the  pressure  of  the  blood  in  the 
capillaries  and  the  pressure  of  the  urine  within 
the  uriniferous  tubules.  When  the  total  quantity  of 
urine  is  increased,  the  percentage  of  solid  materials  decreases,  and 
vice  versa;  yet  this  percentage  of  solids  nearly  always  remains 
within  certain  limits,  rarely  going  above  twelve  per  cent,  or  below 
three-tenths  per  cent.  The  relation  between  the  total  quantity 
of  solids  excreted  and  the  total  quantity  of  urine  seems  to  be 
subject  to  considerable  variation;  and  the  different  solids  often 
vary  independently  of  one  another. 

Whenever  more  blood  flows  through  the  kidneys,  therefore, 
the  amount  of  urine  is  increased.  The  cause  of  the  increased 
blood-flow  may  lie  either  in  a  higher  arterial  pressure,  unaccom- 

413 


I 


414  THE  BASIS  OF  SYMPTOMS 

panied  by  a  corresponding  contraction  of  the  renal  vessels,  or 
it  may  be  due  to  a  local  dilatation  of  these  vessels,  while  the 
general  blood-pressure  remains  constant.^ 

Many  forms  of  chronic  nephritis  are  accompanied  by 
a  high  blood-pressure  (see  p.  25),  and  this  always  causes  an 
increased  secretion  of  urine,  if  a  sufficient  number  of  functioning 
renal  cells  are  present,  and  if  the  increase  in  the  general  blood- 
pressure  is  not  accompanied  by  a  constriction  of  the  renal  vessels 
of  such  a  degree  as  to  prevent  a  more  rapid  blood-flow  through  the 
kidneys.  As  we  have  said,  the  increased  elimination  of  water  in 
such  cases  reduces  the  percentage  of  solids  in  the  urine.  The 
absolute  excretion  of  the  different  solids,  however,  in  these  forms 
of  nephritis  varies  greatly,^  being  dependent,  apparently,  to  a 
great  extent  upon  the  condition  of  the  epithelial  cells.  On  the 
other  hand,  an  increased  secretion  of  urine  in  chronic  nephritis 
is  less  frequent  than  is  generally  believed,  occurring  according 
to  one  observer*  in  only  one-third  to  one-half  of  the  cases.  The 
increased  blood-pressure  that  follows  the  administration 
of  digitalis  to  patients  with  heart  disease  also  frequently 
causes  an  increased  elimination  of  urine,  because  the  renal  circu- 
lation is  improved. 

Diabetes  Insipidus. — The  second  condition  leading  to  an  in- 
creased flow  of  blood  through  the  kidneys  is  a  local  dila- 
tation of  their  vessels,  the  arterial  pressure  remaining 
constant.  This  can  be  experimentally  proved  by  cutting  the  renal 
nerves. 

Such  a  dilatation  of  the  renal  vessels  is  a  possible  cause  of 
diabetes  insipidus,^  a  disease  which  is  characterized  clinically  by 
the  excretion  of  large  amounts  of  dilute,  sugar-free  urine,  without 
an  associated  increase  in  the  general  arterial  pressure.  The  ex- 
cessive amount  of  urine  frequently  carries  out  with  it  demonstrable 
quantities  of  inosite,  and  at  times  the  total  quantity  of  nitrogen 
is  also  increased.  This  latter  increase  is  caused  in  part  by  the 
large  amounts  of  meat  eaten;  for  many  of  these  patients,  for 
some  unknown  cause,  have  excessive  appetites,  just  as  have 
patients  with  diabetes  mellitus.  In  those  cases  of  diabetes  insipidus 
in  which  an  abnormal  appetite  is  associated  etiologically  with  an 
excessive  thirst — and  into  this  categoiy  falls  the  majority  of 
cases — the  suspicion  is  strong  that  we  have  to  do  with  a  poly- 
dipsia of  psychic  origin.     The   evidence  that  disturb- 


THE  SECRETION  OF  URINE  415 

ances  of  proteid  metabolism  occur  in  diabetes  insipidus  is  not 
convincing,  nor  is  it  likely  that  such  do  occur.^ 

We  really  know  very  little  concerning  the  etiology  of 
diabetes  insipidus.  It  unquestionably  occurs  at  times 
as  a  family  disease.  Syphilis  also  plays  an  etiological 
role.  In  some  cases,  anatomical  lesions  of  the  cere- 
bellum, the  pons  or  the  medulla  have  been  found — 
findings  which  accord  well  with  the  experimental  observation  that 
injuries  to  corresponding  parts  of  the  brain  may  lead  to  polyuria.'^ 
Yet  there  is  some  uncertainty  as  to  the  exact  part  of  the  brain  that 
must  be  affected  in  order  to  produce  this  increased  flow  of  urine, 
and  further  as  to  the  manner  in  which  such  an  injury  brings  about 
the  polyuria.  In  some  cases  the  evidence  at  our  disposal  points  to 
a  disturbance  of  the  vasomotor  system,  leading  to  a  local  dilatation 
of  the  renal  arteries.  Such  an  hypothesis,  however,  would 
scarcely  explain  all  of  the  clinical  manifestations. 

Oftentimes  it  is  impossible  to  say  whether  the  poly- 
dipsia or  the  polyuria  is  primary,  for  the  former 
may  also  be  due  to  certain  cerebral  lesions.  There  is  little  doubt, 
however,  as  we  have  noted  above,  that  some  of  the  cases  diag- 
nosed as  diabetes  insipidus  are  in  reality  instances  of  psychic 
polydipsia.  To  the  latter  belong  those  severe  cases  passing  twenty 
or  more  litres  per  day;  further,  those  in  which  the  individual  is 
addicted  to  the  drinking  of  abnormal  fluids,  such  as  urine;  and 
finally  those  in  which  water  alone  is  capable  of  assuaging  the 
thirst. 

The  characteristic  feature  of  the  disorder,  according  to  Meyer, 
is  in  some  cases  the  inability  of  the  kidneys  to  ex- 
crete a  urine  of  normal  concentration,®  because  of 
which  a  polyuria  is  of  regulatory  significance  in  removing  the 
waste  products  of  metabolism.  In  such  cases  a  disturbance  of  the 
renal  epithelium  must  be  assumed ;  while  in  others,  in  which  the 
kidneys  have  not  lost  the  power  of  delivering  a  concentrated  urine 
and  in  which  the  increased  thirst  is  the  prominent  symptom,  the 
polyuria  would  seem  to  be  due  to  an  abnormal  dilution  of  the 
blood.  It  is  evident,  therefore,  that  what  we  term  diabetes  in- 
sipidus is  not  of  uniform  etiology. 

(Clinical  and  experimental  data  point  strongly  to  the  etio- 
logical importance  of  the  hypophysis  in  dia- 
betes insipidus.     The  frequent  association  of  the  disease 


416  THE  BASIS  OF  SYMPTOMS 

with  lesions  of  the  base  of  the  brain  and  interpeduncular  space — 
especially  with  basal  gummatous  meningitis — is  well-recognized. 
A  more  critical  study  has  shown  that  such  lesions  often  involve, 
or  are  restricted  to,  the  posterior  lobe  of  the  pitui- 
tary body.®  In  keeping  with  these  findings  is  the  presence 
in  the  posterior  lobe  of  a  diuretic  substance  distinct  from  the 
pressor  body  it  contains  (Magnus  and  Schafer).  Lewis  and 
Matthews  ^^  were  able  to  produce  a  transient  polyuria  in  dogs 
in  one-half  of  their  cases  by  operative  procedures.  From  the 
fact  that  the  most  constant  finding  in  those  animals  exhibiting  a 
polyuria  was  a  remnant  of  the  epithelial  covering  of  the  posterior 
lobe,  the  pars  intermedia,  they  have  concluded  that  dia- 
betes insipidus  is  due  to  a  hypyersecretion  of  the  diuretic  sub- 
stance of  the  posterior  lobe,  this  substance  being  the  product  of 
the  epithelial  cells  of  the  pars  intennedia — Ed.  ) 

Under  pathological  conditions,  we  frequently  see  transitory 
increases  or  diminutions  in  the  secretion  of  urine — increases  in 
hysteria,  after  epileptic  convulsions  or  after  ureteral  catheteriza- 
tion, diminutions  in  these  same  conditions  or  after  operations  on, 
or  injuries  of,  the  kidneys.  It  seems  probable  that  many  passing 
variations  in  the  secretion  of  urine  are  caused  by  circulatory 
disturbances  in  the  kidneys  which  are  of  reflex  origin. 

The  Effect  of  a  Diminished  Flow  of  Blood  through  the 
Kidneys. — If  the  quantity  of  blood  that  flows  through  the  kidneys 
be  diminished,  a  small  amount  of  highly  concentrated  urine  is 
secreted;  in  other  words,  the  diminution  in  the  total  solids  does 
not  parallel  that  of  the  water. 

The  cause  of  such  a  diminished  blood-flow 
may  be  either  local  or  general.  Locally,  a  con- 
traction of  the  renal  vessels  will  diminish  the  renal  circulation, 
and  it  may  do  so  even  though  the  general  blood-pressure  be 
increased  from  a  contraction  of  many  other  arteries.  This  local 
constriction  of  the  renal  arteries  is  the  cause  of  the  diminished 
secretion  of  urine  in  asphyxia,  in  strychnin  and  epinephrin  poison- 
ing** and  in  epileptic  and  eclamptic  convulsions. 

In  the  second  place,  a  diminished  renal  circulation  may  occur 
in  the  absence  of  any  local  constriction  of  the  renal  vessels,  either 
because  the  general  arterial  pressure  is  reduced 
or  because  the  pressure  in  the  renal  veins  is 
raised.     The  reduction  of  the  general  arterial  pressure  may 


THE  SECRETION  OF  URINE  417 

result  from  a  widespread  vasomotor  paralysis  or  from  a  weaken- 
ing of  the  left  ventricle.  The  pressure  in  the  renal  veins  may  be 
raised,  either  by  an  occlusion  of  these  veins,  or  of  the  vena  cava 
inferior;  by  an  increase  in  the  general  venous  pressure  from  a 
weakening  of  the  right  ventricle;  or  by  a  diminution  in  the 
aspirating  action  of  the  thorax.  The  most  marked  effect  upon 
the  renal  circulation  will  naturally  be  produced  when  a  lowering 
of  the  general  arterial  pressure  is  combined  with  a  rise  in  the 
venous  pressure.  This  combination  occurs  when  both 
ventricles  are  weakened,  and  this  is  indeed  the  most 
frequent  cause  of  an  insufficient  flow  of  blood  through  the  kid- 
neys. It  is  met  with  in  many  varieties  of  cardiac  dis- 
ease, whether  these  affect  the  endocardium,  the  myocardium 
or  the  pericardium. 

Aside  from  cases  of  cardiac  stasis,  a  diminished  amount  of 
urine  is  observed  most  frequently  in  the  acute  nephrit- 
ides,  a  finding  in  keeping  with  the  fundamental  pathological 
fact  that  the  blood-stream  is  slowed  in  inflamed  tissues.  In 
human  nephritis,  however,  it  has  always  been  a  matter  of  com- 
ment that  the  clinical  manifestations  are  often  out  of  all  propor- 
tion to  the  anatomical  changes  in  the  kidneys.  Schlayer  and 
Takayasu  ^^  have  thrown  considerable  light  upon  this  subject  by 
showing  that  even  the  most  trivial  glomerular  lesion  may  cause 
severe  disturbances  of  urinary  secretion  and  of  the  ability  of 
the  renal  vessels  to  contract  and  dilate. 

This  impairment  of  the  vessel  function  occurs  chiefly  in  the 
so-called  vascular  nephritides,  though  the  tubular  types 
are  not  unaffected  in  this  respect.  In  all  inflammatory  renal 
processes,  therefore,  a  disturbance  of  vascular  integrity  must  be 
taken  into  account,  whether  the  glomeruli  exhibit  a  characteristic 
swelling  of  the  epithelium,  or  seem  to  be  normal.  The  disturb- 
ance may  cause  either  a  lowered  vascular  irritability,  in  which 
case  the  urinary  secretion  is  diminished,  or  an  augmented  irrita- 
bility leading  to  an  increased  secretion.  This  behavior  of  the 
vessels  applies  not  only  to  the  experimental  nephritides,  but  also 
to  acute  and  chronic  cases  in  man. 

In  many  of  these  circulatory  disturbances,  proteids  from  the 
blood  pass  through  into  the  urine ;  yet,  since  this  is  probably  due 
to  changes  in  the  epithelial  cells,  we  shall  defer  its  consideration 
to  another  place. 

27 


418  THE  BASIS  OF  SYMPTOMS 

The  Effect  of  an  Obstruction  to  the  Escape  of  Urine. — The 
obstruction  to  the  escape  of  urine  may  be  situated  within 
the  kidney  itself.  The  uriniferous  tubules  may  be  com- 
pressed by  scar  tissue,  or  their  lumina  may  be  occluded  by  casts 
or  by  precipitates  of  haemoglobin,  bilirubin,  uric  acid,  calcium 
salts,  etc.  It  is  questionable,  however,  if  such  precipitates,  with 
the  exception  of  haemoglobin,  really  offer  much  resistance  to 
the  escape  of  urine;  and  it  is  quite  possible  that  they  lie  in  the 
tubules  merely  because  the  amount  of  water  secreted  is  insufficient 
to  carry  them  away. 

On  the  other  hand,  the  obstruction  to  the  exit  of  urine  may 
be  situated  outside  of  the  kidneys,  in  the  lower  urinary 
passages,  in  which  case  it  may  be  caused  by  calculi,  tumors,  scar 
tissues,  etc.  The  effect  of  such  obstructions  upon  the  total  quan- 
tity of  urine  secreted  depends,  in  the  first  place,  upon  whether 
they  hinder  the  outflow  from  one  or  from  both  kidneys.  If  the 
former  be  the  case,  the  affected  kidney  will  eliminate  less  urine 
than  normal,  but  the  urinary  material  retained  in  the  blood  will 
stimulate  the  other  kidney  and  cause  it  to  do  extra  work  and 
to  hypertrophy.  The  urine,  as  a  whole,  therefore,  will  not  be 
greatly  altered. 

The  effect  of  an  obstruction  upon  the  secretory  activity  of 
the  affected  kidney  depends  largely  upon  the  degree  of 
obstruction.^^  If  this  be  so  complete  that  the  urine  is 
retained  under  a  pressure  amounting  to  sixty  millimetres  of 
mercury  or  more,  the  affected  kidney  ceases  to  secrete.^*  If  the 
obstruction  be  less  complete,  so  that  the  urinary  pressure  above 
the  obstruction  be  less  than  sixty  millimetres,  the  secretion  con- 
tinues, the  rapidity  of  secretion  diminishing  in  proportion  to 
the  increase  in  pressure  of  the  retained  urine.^^  The  details  con- 
cerning the  cessation  of  secretion  are  not  very  well  understood. 
At  first,  the  retained  urine  merely  serves  to  distend  the  urinary 
passages.  As  the  pressure  increases,  however,  a  portion  of  the 
urine  appears  to  be  resorbed  through  the  cells  of  the  urinary 
tubules,  which  then  become  oedematous.  Finally,  the  overfilled 
tubules  and  the  swollen  cells  press  upon  the  veins  and  capillaries, 
thereby  diminishing  their  size  and  lessening  the  rapidity  of  the 
flow  of  blood  through  the  kidneys.  This,  in  turn,  diminishes  the 
secretion  of  urine. 

If  the  obstruction  to  the  flow  of  urine  from  a  kidney 


THE  SECRETION  OF  URINE  419 

be  complete  and  permanent,  the  corresponding  kidney 
atrophies,  and  only  a  moderate  grade  of  hydronephrosis  develops. 
If,  however,  the  obstruction  be  incomplete,  or  if  it 
be  more  or  less  intermittent,  the  structure  and  the  function  of 
the  kidney  are  but  Httle  affected.  Its  pelvis,  however,  gradually 
dilates,  and  an  enormous  hydronephrosis  may  be  produced. 

The  Effect  of  Lesions  of  the  Secreting  Membranes. — We 
have  already  mentioned  the  susceptibility  of  the  renal  epithelium 
to  changes  in  the  quantity  and  quality  of  blood  that  passes  through 
the  kidneys.  Several  membranes  separate  the  blood  in  the  capil- 
laries from  the  lumina  of  the  uriniferous  tubules,  viz.,  the  capil- 
lary walls,  the  basement  membranes  and  the  epithelial  cells.  The 
possibility  exists,  therefore,  that  lesions  of  any  one  of  these  might 
render  the  secretory  apparatus  abnormally  permeable.  Appa- 
rently, however,  lesions  of  the  capillary  walls  are  of  comparatively 
little  importance;  and  it  may  be  said  in  general  that  the 
secretion  depends  rather  upon  the  parenchyma 
cells  than  upon  the  endothelial  lining  of  the 
capillaries.  Indeed,  widespread  amyloid  degeneration  of  the 
renal  capillaries  has  been  observed  without  resultant  changes  in 
the  urine.  It  must  not  be  overlooked,  however,  that  so  far  as  the 
epithelial  constituents  of  these  secreting  membranes  are  concerned, 
different  substances  in  the  urine  are  eliminated  by  different  renal 
structures. 

All  lesions  of  the  epithelial  cells,  degenerative  as  well  as 
inflammatory,  and  especially  those  which  involve  the  glomeruli, 
tend  to  diminish  the  secretion  of  water.  Yet,  in  many  cases  of 
nephritis  this  tendency  is  more  than  neutralized  by  an  associated 
increase  in  the  amount  of  blood  that  flows  through  the  kidneys, 
for,  as  we  have  seen,  this  tends  to  increase  the  excretion  of  urine. 
Th e  quantity  of  urine,  therefore,  that  is  elim- 
inated in  pathological  renal  conditions  de- 
pends mainly  upon  these  two  sets  of  factors: 
first,  the  degree  and  the  extent  of  the  damage 
to  the  secreting  cells,  and  secondly,  the  quan- 
tity and  quality  of  blood  which  comes  into  con- 
tact with  them.  In  widespread  acute  nephritis, 
the  excretion  of  water  is  nearly  always  diminished,  whereas  in 
chronic  diseases  of  the  kidney,  especially  if  these 
be  of  limited  extent,  the  effects  of  the  increased  work  of  the 


420  THE  BASIS  OF  SYMPTOMS 

heart,  the  high  blood-pressure  and  the  well-maintained  renal 
circulation  predominate,  such  patients  frequently  secreting  even 
more  urine  than  does  a  normal  individual.  However,  when  car- 
diac failure  appears,  and  the  general  blood-pressure  falls,  the 
amount  of  urine  secreted  by  these  patients  is  immediately 
diminished. 

In  diseases  of  the  kidney,  a  diminution  in  the  excretion  of 
solids  is  often  one  of  the  earliest  signs.  The  elimination  of  the 
various  solids  varies  greatly  and  for  reasons  but  little  understood. 
The  sodium  chlorid  usually  follows  the  same  law  as  the  water; 
the  phosphates,  sulphates  and  nitrogenous  compounds  usually  vary 
together ;  while  the  uric  acid  pursues  its  own  independent  course. 

Albuminuria. — Although  it  has  been  generally  considered  that 
normal  urine  contains  no  albumin,  recent  work  has  rendered  it 
very  probable  that  traces  of  albumin,  as  well  as  of 
sugar,  are  normally  present.^®  In  order  to  demon- 
strate this  trace  of  albumin,  however,  it  is  necessary  to  make 
use  of  special  methods,  such  as  the  concentration  of  large  quanti- 
ties of  urine.  This  albumin  is  believed  by  Senator  and  Morner 
to  be  derived  from  the  blood  by  a  process  of  filtration  through  the 
glomeruli.  Owing  to  the  presence  of  chondroidin-sulphuric  or 
nucleinic  acids  in  the  urine,  this  albumin  may  be  precipitated  by 
adding  acetic  acid.  One  should  be  cautious,  therefore,  and  not 
conclude  too  hastily  that  the  precipitate  that  so  often  results  from 
the  addition  of  acetic  acid  to  urine  is  necessarily  due  to  mucin 
or  nucleo-albumin,  derived  from  the  cells  of  the  kidneys  or  urinary 
passages.^  ^  The  urine  may,  however,  contain  true  mucin,  which 
is  free  from  phosphorus  and  which  is  derived  from  the  epithelium 
of  the  urinary  passages.  ^^ 

There  are  persons  who  continually,  or  at  inter- 
vals, show  easily  demonstrable  quantities  of 
albumin  in  their  urine  without  feeling  ill  in 
any  way.  We  cannot  assume  that  the  kidneys  of  such  indi- 
viduals are  absolutely  normal,  in  spite  of  the  fact  that  the  ordinary 
symptoms  of  chronic  nephritis  are  absent  and  that  the  affected 
persons  remain,  so  far  as  appearances  are  concerned,  perfectly 
healthy.  It  is  certain  that  chronic  nephritis  frequently  follows 
quite  a  different  course  from  that  ordinarily  described  in  our  text- 
books on  medicine,  and  it  is  possible  that  many  of  these  cases 
represent  exceedingly  mild  forms  of  the  disease. 


THE  SECRETION  OF  URINE  421 

Orthotic  Albuminuria. — ^An  albuminuria  is  of  frequent  occur- 
rence in  childhood  and  during  the  period  of  puberty,  especially 
in  delicate  and  anaemic  individuals.  Adolescence  is  prob- 
ably a  factor  in  some  of  these  cases,  for  the  condition  often  tends 
gradually  to  disappear  after  this  period.  Many  of  these  indi- 
viduals suggest  a  constitutional  fault,  and  not  a  few 
improve  as  their  general  strength  is  built  up.  This  type  of 
albuminuria  may  also  exhibit  a  tendency  to  occur  in 
families.  And  finally,  noxious  influences  of  various  kinds — ■ 
for  example,  the  infectious  diseases — favor  the  onset' 
of  the  condition. 

Orthotic  albuminuria  is  associated  essentially  with  a 
change  from  the  recumbent  to  the  erect  post- 
ure. It  appears  most  readily  in  the  morning  after  arising. 
If  the  individual  remains  upon  his  feet  throughout  the  day,  the 
albuminuria  either  disappears  entirely,  or  is  reduced  to  an  in- 
significant amount.  In  many  cases  the  diurnal  variations  show 
a  definite  cycle,  vis.,  a  maximum  secretion  in  the  morning,  a 
disappearance  of  albumin  at  noon  and  a  secondary  rise  in  the 
afternoon.  Muscular  exertion  and  cold  baths  tend  to 
increase  the  albuminuria,  and  in  some  cases  to  precipitate  it. 
Exercise  is  more  potent  in  this  respect  in  the  morning  hours. 
Excitement  is  another  possible  causative  factor.  Food  tak- 
ing is  probably  of  little  significance;  in  some  cases,  indeed, 
the  albumin  has  been  observed  to  disappear  after  eating.^^ 

It  is  evident,  therefore,  that  the  occurrence  of  an  orthotic 
albuminuria  depends  upon  many  and  diverse  factors.  The  con- 
ception that  the  condition  is  essentially  due  to  circulatory 
disturbances  accords  well  with  the  fact  that  a  postural 
change  is  apparently  the  most  important  precipitating  cause.  The 
observations  of  Loeb^®  speak  for  this  hypothesis.  Jehle^^  has 
emphasized  the  importance  of  a  lumbar  lordosis  as  an 
etiologic  factor  and  has  shown  that  no  albuminuria  appears  even 
in  the  erect  posture  if  the  lordosis  be  corrected.  (Among  other 
views  as  to  the  cause  of  orthotic  albuminuria  may  be  mentioned 
that  of  Teissier  ^^  who  looks  upon  the  condition  as  an  evidence 
of  latent  tuberculosis,  and  that  of  Erlanger  and 
Hooker  23  who  emphasize  as  the  pathogenetic  moment  a 
diminished    pulse    pressure    in    the    glomeruli^ 


422  THE  BASIS  OF  SYMFI'OMS 

which  leads  to  a  retarded  blood  flow  and  possibly  also  to  transi- 
tory injury  of  the  vessel  walls. — Ed.) 

The  proteids  excreted  by  these  patients  have  been  shown 
beyond  question  to  be  the  same  as  those  normally  present  in  the 
blood,  viz.,  albumin  and  globulin.  In  this  respect,  therefore, 
the  albuminuria  in  the  orthotic  type  does  not  differ  from  that 
present  in  nephritis.  In  other  ways,  however,  the  two  conditions 
have  nothing  in  common,  even  though  the  excretion  of  albumin 
in  the  nephritides  may  also  be  influenced  by  the  bodily  position. 
I  have  observed  a  nimiber  of  such  cases  myself  over  a  long  period 
of  years,  and  have  never  seen  one  go  over  into  a  true  nephritis. 
Heubner^*  has  had  the  opportunity  of  examining  at  autopsy  a 
case  of  orthotic  albuminuria  (in  which  death  was  due  to  a  cerebral 
embolism)  and  found  the  kidneys  normal  throughout. 

Orthotic  albuminuria  may  be  cited  as  an  example  of  a  local 
circulatory  disorder  founded  on  the  basis  of  a  "constitutional 
weakness."  The  same  type  is  predisposed  during  puberty  to  other 
local  vascular  disturbances,  for  example,  syncopal  attacks.  In 
many  individuals,  however,  exhibiting  similar  transitory  albu- 
minurias, no  such  constitutional  fault  is  discernible. 

The  Geneteil  Causes  of  Albuminuria. — The  local  disturbance 
in  albuminuria  we  now  know  to  be  due  to  an  abnormal 
permeability  of  the  renal  epithelium  by  reason 
of  which  the  proteids  of  the  blood  are  enabled 
to  pass  into  the  urine.  This  abnormal  permeability 
must  reside  either  in  the  renal  cells  themselves  or  in  the  basement 
membranes,  for  the  walls  of  the  capillaries  will  allow  proteids  to 
pass  through  normally.  The  epithelium  of  the  glomeruli  appears 
to  be  particularly  susceptible  to  agents  that  increase  the  permea- 
bility in  this  manner ;  ^^  whereas  the  cells  of  the  convoluted  tubules 
are  thus  affected  only  when  the  injurious  agent  is  very  powerful. 
It  is  difficult  to  judge,  however,  to  what  extent  the  latter  have 
become  permeable,  for  the  coagulated  proteids  often  seen  in  the 
lumina  of  these  tubules  must  have  come,  in  part  at  least,  from  the 
g'lomeruli  above.  A  priori  there  is  no  evidence  against  the 
assumption  that  the  tubular  epithelium  if  injured  can  secrete 
albumin  just  as  do  other  diseased  parenchymatous  cells. ^®  As  a 
matter  of  fact,  this  has  been  shown  to  occur  in  experimental  toxic 
nephritis.^'^ 

We  do  not  know  the  nature  of  the  changes  which  render  the 


THE  SECRETION  OF  URINE  423 

epithelial  cells  permeable  for  proteids.  In  many  cases  of  albu- 
minuria, no  anatomical  lesions  of  the  kidney  are  demonstrable, 
while,  on  the  other  hand,  granular  and  even  fatty  degeneration  of 
the  cells  may  be  present,  without  any  consequent  albuminuria. 
Some  have  attached  a  certain  significance  to  a  loss  of  flagella  from 
the  cells  of  the  convoluted  tubules,  yet  it  seems  improbable  that 
this  should  be  of  much  importance,  for  these  flagella  may  also 
be  lost  in  conditions  in  which  no  albuminuria  has  been  present. 
The  more  we  attempt  to  correlate  the  grade  of  albuminuria  with 
the  extent  of  the  anatomical  involvement  of  the  kidneys,  the 
more  forcibly  will  we  be  confronted  with  the  meagreness  of  our 
knowledge  of  these  conditions. 

Albuminuria  from  Circulatory  Disturbances  of  the  Kidneys. — 
Circulatory  disturbances  of  the  kidneys  may  lead  to  changes  in 
the  epithelium  and  to  albuminuria  if  the  velocity  of  blood-flow 
through  them  sinks  below  a  certain  limit. ^^  What  this  limit  is, 
is  not  definitely  known,  though  it  seems  to  be  different  in  different 
individuals.  The  retarded  renal  circulation  may  be 
due  to  a  number  of  causes,  such  as  obstruction  of  the 
renal  veins,  increase  in  the  general  venous  pressure,  spasm  of  the 
renal  arteries  from  lead  colic,  tetanus,  etc.,  or  an  increased  pressure 
within  the  urinary  passages,  with  secondary  pressure  upon  the 
renal  capillaries  and  veins.  It  seems  probable  that  the  retarded 
circulation  primarily  injures  the  renal  cells,  either  by  failing  to 
supply  them  with  sufficient  food,  or  by  failing  to  remove  properly 
the  waste  products  derived  from  their  metabolic  activities. 

Toxic  Albuminurias. — It  is  easy  to  conceive  how  poisonous 
substances  circulating  in  the  blood  might  injure  the  epithelial  cells 
of  the  kidney  and  render  them  permeable  to  proteids.  Such  an 
effect  may  be  produced  by  metallic  poisons,  by  the  bal- 
sams, etc.,  as  well  as  by  the  more  complex  bacterial  and 
other  toxins.  The  various  albuminurias  that  occur  dur- 
ing the  infectious  diseases  and  those  occurring  during  pregnancy 
belong,  for  the  most  part,  in  this  category  of  toxic  albuminurias. 
It  is  not  a  great  step  from  these  degenerative  processes  to  the  true 
renal  inflammations.  In  the  former  only  the  parenchyma  cells 
are  affected,  whereas  in  the  latter  the  blood-vessels  and  the  inter- 
stitial tissues  are  more  or  less  diseased.  Many  poisons,  in  small 
doses,  will  produce  degenerations,  and  in  long-continued  or  very 
large  doses,  inflammations;  whereas,  others  seem  to  cause  an 


424  THE  BASIS  OF  SYMPTOMS 

inflammation  from  the  start.     Why  some  should  thus  affect  the 
epithelium  primarily  and  others  the  interstitial  tissue  is  not  known. 

Schlayer  and  Hedinger^^  have  distinguished  two  groups  of 
toxic  nephritides  according  to  the  functional  disturb- 
ance present.  In  the  first — of  which  cantharadin  ne- 
phritis is  an  example — the  renal  vessels  are  primarily 
damaged,  with  the  result  that  the  secretion  of  urine  is  rapidly 
inhibited,  though  anatomical  changes  in  the  kidneys  are  slight  or 
absent.  In  chromium  nephritis,  on  the  contrary,  the 
tubules  are  the  seat  of  the  injury,  the  vessels  at  first  being 
unaffected,  and  polyuria  often  being  present.  Yet  despite  the 
undoubted  affinity  of  certain  poisons  for  particular  tissues,  it  is 
extremely  difficult  by  elective  poisoning  to  interfere  merely  with 
the  function  of  the  different  types  of  cells. 

The  poisons  that  produce  these  toxic  albuminurias  are  usually 
formed  in  the  body  during  acute  infectious  processes ;  and,  even  in 
the  so-called  primary  forms  of  nephritis,  bacteria  have  been  found 
in  some  instances  in  the  urine,  thus  rendering  it  probable  that  the 
nephritis  was  of  infectious  origin.  According  to  the  opinion  of 
experienced  clinicians,  nephritis  may  at  times  develop  after  ex- 
posure to  cold,  as  from  a  severe  wetting  or  from  sleeping 
upon  the  ground,  but  as  yet  no  adequate  explanation  has  been 
offered  of  the  manner  in  which  such  a  nephritis  is  caused. ^^ 

The  Varieties  of  Proteids  in  the  Urine. — Most  of  the  proteids 
that  appear  in  the  urine  during  renal  diseases  come  from  the 
blood-plasma,  though  as  we  have  seen,  a  small  quantity  is  possibly 
derived  from  the  renal  epithelial  cells  themselves.  No  definite 
ratio  exists,  however,  between  the  amounts  of  albumin  and  glo- 
bulin appearing  in  the  urine.^^  Great  importance  was  attached 
to  this  ratio  when  no  distinction  among  the  globulins  was  known. 
As  a  matter  of  fact  the  ratio  between  the  albumin  and  the 
globulins,  and  between  the  two  globulins  (euglobulin 
and  pseudoglobulin)  varies  considerably,  and  inde- 
pendently, it  would  seem,  of  the  extent  or  type  of  the  renal 
lesion,  of  the  state  of  the  circulation  and  of  the  individual's 
general  condition. 

Though  the  albumin  and  globulin  of  the  blood  include  the 
greater  part  of  the  proteids  appearing  in  the  urine  in  the  cases 
of  disease  of  the  secreting  cells  hitherto  studied,  this  does  not  say 
that  these  are  the  only  proteids  that  may  appear  under  these  con- 


THE  SECRETION  OF  URINE  425 

ditions.  It  Is  not  impossible  that  in  certain  processes,  the  infec- 
tious diseases,  for  example,  toxic  albumin  and  globulins  not  identi- 
cal with  those  of  the  blood,  may  arise  and  pass  into  the  urine. 

The  Amount  of  Albumin  Excreted. — The  amount  of  albumin 
in  the  urine  depends  primarily  upon  the  degree  and  extent  of  the 
injury  to  the  secreting  cells,  and  is  largely  independent 
of  the  quantity  of  urine  excreted.  In  addition  it 
seems  to  be  influenced  by  the  same  factors  which  produce  the 
so-called  physiological  albuminurias — posture,  muscular  exertion, 
etc. 

Casts. — The  diseased  renal  epithelium  may  become  permeable 
to  the  red  and  white  corpuscles  of  the  blood,  which  can  then 
pass  into  the  urine.  In  addition  to  these  blood-cells  and  the 
desquamated  renal  cells  themselves,  pathological  urines  often 
contain  casts  of  the  interiors  of  the  uriniferous  tubules.  These 
casts  are  most  frequently  composed  of  a  hyaline  or  granular 
material,  but  they  may  contain  in  addition  various  cells.  The 
material  composing  them  has  been  regarded  by  some  authors 
as  fibrin,  parts  of  it  often  giving  the  Weigert  reaction;  yet  it  is 
questionable  whether  this  hyaline  material  is  true  fibrin  or  not. 
Two  theories  as  to  the  formation  of  casts  have 
been  advanced.  According  to  the  one,  they  result  from  the  coagu- 
lation of  the  constituents  of  the  blood  that  escape  into  the  urinif- 
erous tubules ;  while,  according  to  the  other  and  more  acceptable 
theory,  they  are  derived  more  directly  from  substances  present 
in  the  renal  cells,  and  are  thus  significant  of  the  action  of  a  noxious 
influence  upon  these  cells. ^^  Casts  may  be  looked  upon  as  the 
earliest  evidence  of  an  injury  of  the  renal  epi- 
thelium,^^ and  as  such  they  may  appear  in  the  urine  even 
before  albumin.  In  fact,  the  only  relation  existing  between  the 
appearance  of  casts  and  of  albumin  is  that  each  is  a  sign  of  a 
damaged  epithelium. 

The  Effect  of  Changes  in  the  Composition  of  the  Blood. — 
The  amount  of  water  in  the  body  directly  influences 
the  secretion  of  urine,  and  it  is  well  known,  for  example,  that  he 
who  drinks  much  will  also  urinate  much.  Indeed,  excessive 
drinking  may  be  the  primary  cause  of  certain  cases  classified  as 
diabetes  insipidus,  for  it  is  possible  to  cure  some  of  them  merely  by 
limiting  the  quantity  of  fluids  taken  by  mouth.  And  the  polyuria 
of  certain  cases  of  diabetes  mellitus  is  of  the  same  nature. 


426  THE  BASIS  OF  SYMPTOMS 

On  the  other  hand,  if  the  water  in  the  body  be 
diminished,  either  because  the  patient  drinks  Httle,  or  be- 
cause he  loses  much  water  by  other  channels,  the  quantity  of 
urine  is  correspondingly  diminished.  We  see  such  a  diminution 
after  excessive  sweating,  especially  in  a  dry  climate,  as  well  as 
in  many  diarrhceal  disturbances,  such  as  Asiatic  cholera.  The 
exact  cause  of  the  many  variations  in  the  amount  of  urine,  which 
obviously  serve  to  maintain  a  constant  concentration  of  the  blood, 
is  not  known. 

Many  solidsubstances  also  tend  to  increase  the  urinary 
secretion,  among  which  are  many  of  the  constituents  of  normal 
urine.  These  bodies  appear  in  the  urine,  not  in  proportion  to  their 
concentration  in  the  blood,  but  depending  upon  whether  their 
concentration  in  the  blood  is  greater  or  less  than  normal.  If 
present  in  greater  amount  than  normal,  they  are  rapidly  excreted ; 
if  present  in  an  amount  less  than  normal,  their  excretion  is  greatly 
diminished.  This  depends  upon  the  fact  that  the  secreting  cells 
have  a  different  level  of  permeability  for  each  of  the  substances 
under  consideration.  In  this  way  the  kidney  tends  to  maintain 
the  blood  at  a  constant  composition.  And  for  this  reason,  also, 
the  examination  of  the  urine  often  furnishes  the  physician  with 
valuable  evidence  as  to  the  concentration  of  any  particular  sub- 
stance in  the  blood.  Careful  and  extensive  metabolic  studies  are 
imperative  in  the  particular  case,  however,  because  even  normal 
individuals  living  under  constant  conditions  may  exhibit  consider- 
able and  unexplainable  variations  in  nitrogen  and  sodium  chlorid 
elimination.^* 

When  any  solid  is  being  excreted,  it  tends  to  carry  a  certain 
amount  of  water  along  with  it  into  the  urine.  Advantage  is  taken 
of  this  fact  in  the  use  of  certain  substances  as  diuretics. ^° 
The  bulk  of  the  solid  substances  eliminated  by  the  kidneys  con- 
sists of  waste  products  of  digestion  and  of  cellular  metabolism. 
The  most  important  of  these  have  already  been  considered  (see 
the  chapter  on  Metabolism). 

Special  mention,  however,  must  be  made  of  the  pro- 
t  e  i  d  s .  We  have  said  that  normal  kidneys  hold  back  these  con- 
stituents of  the  blood  plasma  most  carefully.  This  is  not  true, 
however,  of  all  proteids  that  may  happen  to  be  present  in  the  blood. 
Of  the  many  that  have  been  artificially  introduced  into  the  circu- 
lation a  small  number,  such  as  egg  albumin,  casein  and  haemo- 


THE  SECRETION  OF  URINE  427 

globin,  immediately  pass  through  into  the  urine, ^^  Even  when 
uncoagulated  egg  albumin  is  taken  by  mouth  in  large  quantities, 
some  will  often  be  excreted  by  the  kidneys.  Now,  abnormal 
p  rote  ids  are  undoubtedly  formed  in  the  body  during  some 
pathological  processes,  and  especially  during  the  infectious  dis- 
eases, and  it  seems  not  improbable  that  many  of  the  albuminurias 
present  in  these  conditions  are  due,  not  to  a  primary  injury 
to  the  renal  structures,  but  to  the  elimination  of  abnormal  proteids 
that  cannot  be  assimilated  in  the  body.  So,  too,  those  proteids 
sometimes  found  in  the  urine  during  leukaemia,  and  which  are 
precipitated  by  the  addition  of  acetic  acid,  are  also  possibly  ex- 
creted because  they  cannot  be  assimilated.  In  fact,  such  abnormal 
proteids  have  been  demonstrated  in  the  blood  itself. 

Albumoses  and  peptones  will  also  appear  in  the 
urine  if  they  be  injected  into  the  circulation  in  sufficiently  large 
quantities.  They  do  not  appear  normally  during  digestion, 
apparently  because  they  undergo  a  further  cleavage  in  the  intes- 
tines. Possibly  this  splitting  process  does  not  take  place  under 
certain  pathological  conditions  and  this  may  explain  the  albu- 
mosuria s  occasionally  seen  in  connection  with  ulcerations  of 
the  intestinal  wall.^^  In  other  conditions,  as  in  fever,  albumoses 
are  formed  during  a  pathological  destruction  of  the  proteids  of 
the  body,  and  here  again  they  may  appear  in  the  urine. 

Living  bacteria  may  be  excreted  by  the  apparently  intact  kid- 
neys, and  so  reach  the  urine.  They  can  undoubtedly  pass  through 
the  glomeruli  in  this  manner,  for  micro-organisms  have  been  seen 
within  these  structures. 

The  Localization  of  Functional  Disturbances. — For  a  proper 
appreciation  of  pathological  alterations  in  renal  function,  we 
must  have  clearly  in  mind  the  mechanism  of  elimination  under 
normal  conditions.^®  Physiologists  are  for  the  most  part  agreed 
that  the  excretion  of  different  substances  is  car- 
ried out  by  particular  elements  of  the  renal  tis- 
sue. Thus  to  the  glomeruli,  primarily,  is  generally  accredited 
the  elimination  of  water,^^  though  this  function  may  in  turn  be 
affected  by  the  condition  of  the  circulation  in  the  tubules.  Yet 
the  factors  underlying  the  excretion  of  water — to  some  of  which 
we  have  made  reference  in  the  preceding  paragraphs — are  appar- 
ently far  from  simple.  Indeed,  capable  observers  ^°  have  attrib^ 
uted  to  the  tubules  the  task  of  eliminating  the  water.    Further- 


428  THE  BASIS  OF  SYMPTOMS 

more,  the  amount  of  water  excreted  is  assuredly  dependent  upon 
the  sodium  chlorid  elimination.^^ 

An  extensive  literature  has  developed  along  the  line  of  func- 
tional disturbances  in  diseased  kidneys.  In  a  way,  the  more 
recent  studies  are  as  ambiguous  as  the  older  ones.  The  problem 
is  indeed  a  difficult  one,  for,  as  a  rule,  the  nephritides  do  not 
involve  a  particular  structure,  but  are  diffuse,  while  the  tissues 
that  remain  free  not  only  functionate  as  "before,  but  may  become 
compensatorily  active.  These  various  considerations  must  not 
be  lost  sight  of  in  the  interpretation  of  the  different  functional  dis- 
orders. Important  strides  have  been  made,  however,  in  the  clas- 
sification of  the  nephritides  according  to  the 
disturbance  of  function  present. ^^  Thus,  in  some 
cases,  the  elimination  of  urea  may  be  interfered  with, 
while  that  of  sodium  chlorid  is  normal,  and  vice  versa. 
A  disturbed  urea  and  lactose  elimination  is  attributed  by 
many  to  a  functional  disorder  of  the  glomeruli,  while  a  failure 
to  excrete  salt  is  looked  upon  as  evidence  of  an  injured  tubular 
epithelium.  Observers  are  not  lacking,  however,  who  have  dif- 
ferent views  as  to  the  elimination  of  urea  and  sodium  chlorid;  and 
the  old  conception  of  Ludwig,  i.e.,  that  the  excretion  of  water 
and  of  crystalloids  takes  place  by  a  process  of  filtration  in  the 
glomeruli,  has  once  more  been  revived. 

It  may  easily  occur,  therefore,  that  a  diseased  kidney  is  no 
longer  capable  of  maintaining  the  normal  composition  of  the 
blood.  The  acutely  inflamed  organ  is  appreciably  less  efficient 
than  the  normal  one.^^  The  most  diverse  types  of  anatomical 
change  may  be  responsible  for  these  functional  disturbances.  The 
present  lack  of  harmony  between  clinical  and  autopsy  findings  in 
cases  of  nephritides  is  familiar  to  all  of  us.  A  high  degree 
of  functional  insufficiency  may  arise  with 
apparently  insignificant  anatomical  changes, 
a  phenomenon  which  Schlayer  has  also  observed  in  experimental 
nephritis. 

The  Effect  of  Disturbances  of  the  Urinary  Secretion  upon 
the  Body. — Diseases  of  the  kidneys  may  affect  the  body  in  at  least 
two  ways — either  by  allowing  substances  to  pass  out  which 
ought  to  be  retained,  or  by  retaining  substances  which  ought  to  pass 
out.  Of  the  substances  that  escape  abnormally,  albumin  is  the  only 
one  of  importance.     (Sugar  appears  in  the  urine  in  abnormal 


THE  SECRETION  OF  URINE  429 

amount  for  a  different  reason,  viz.,  because  its  concentration  in  the 
diabetic  blood  is  increased.)  The  actual  loss  of  proteids  by  this 
channel  is,  however,  relatively  slight,  amounting  to  only  a  small 
number  of  grams  a  day.  It  seems  quite  improbable  that  this 
small  loss  should  in  itself  produce  much  effect  upon  the  body  as  a 
whole,  though  it  cannot  be  denied  that  it  may  affect  the  composi- 
tion of  the  blood  to  some  extent  (see  p.  140). 

On  the  other  hand,  the  retention  of  substances  in  the  body  that 
should  normally  be  excreted  apparently  leads  to  a  variety  of  dis- 
turbances, among  them  oedema,  arterial  hypertension  and  uraemia. 

Uraemia. — Not  infrequently,  during  the  course  of  renal  dis- 
ease, a  group  of  symptoms  develops  which  seems  to  be  caused  by 
some  sort  of  intoxication.  This  is  called  uraemia,^*  and  it  pre- 
sents the  most  varied  clinical  picture.  The  patient 
may  become  apathetic  or  comatose,  or,  on  the  contrary,  extremely 
irritable.  He  may  have  local  or  general  convulsions,  or  suffer 
from  paralyses  of  various  parts  of  his  body.  Sometimes  he 
becomes  blind,  though  the  eyes  are  objectively  normal.  The 
heart's  action  is  at  first  slow  and  irregular,  but  later  very  rapid ; 
the  respirations  become  deeper  or  assume  the  Cheyne-Stokes  type ; 
finally  there  may  be  vomiting  and  diarrhoea.  These  are  the  most 
important  symptoms  of  this  condition.  They  occur  singly  or  in 
groups,  and  they  may  develop  suddenly  or  slowly.  The  greater 
number  of  them  is  evidently  due  to  cerebral  disturbances,  prob- 
ably to  changes  in  the  nerve  cells  similar  to  those  seen  in  botulism 
and  in  mushroom  poisoning. 

It  has  recently  been  urged  that  these  many  and  varied  symp- 
toms do  not  all  arise  from  a  common  cause,  a  view  with  which  I 
am  inclined  to  agree.  Yet  it  is  difficult  to  decide  this  question, 
for,  as  is  well  known,  the  same  poison  may  act  quite  differently 
upon  different  individuals,  and  upon  different  organs  in  different 
patients,  owing  to  individual  variations  in  susceptibility.  As  we 
shall  see,  furthermore,  there  are  reasons  for  believing  that  a 
number  of  causes  may  be  operative  in  the  production  of  uraemia. 

Beyond  doubt,  the  symptoms  of  uraemia  are  caused  by  some 
sort  of  poisoning,  and  our  first  supposition  would  naturally  be 
that  this  intoxication  is  due  to  the  retention  of 
substances  in  the  body  that  should  normally  be 
excreted  by  the  kidneys.  As  a  matter  of  fact,  patients 
in  uraemia  frequently  excrete  abnormally  small  amounts  of  urine 


430  THE  BASIS  OF  SYMPTOMS 

and  of  urinary  solids,  particularly  those  of  a  nitrogenous  charac- 
ter.*^ Indeed,  the  excretion  of  various  solids  may  be  diminished 
even  though  the  quantity  of  urine  be  increased.  This  latter  fact 
has  been  advanced  as  an  argument  against  the  toxsemic  nature  of 
uraemia.  The  point  is  not  well  taken,  however,  for  if  the  onset 
of  uraemia  manifestations  happens  to  coincide  with  the  resorption 
of  oedematous  fluids — and  hence  with  an  increased  output  of 
urine — we  may  properly  assume  that  poisons  which  have  accumu- 
lated in  the  tissues  are  then  washed  into  the  circulation  and  are 
thus  enabled  to  exert  their  toxic  action. 

The  retention  of  urinary  substances  in  the  body  has,  further- 
more, been  directly  demonstrated  by  examinations  of  the  blood. 
The  number  of  molecules  in  the  plasma  is  increased  during  uraemia, 
for  its  freezing  point  is  lowered.  Since  its  electrical  conductivity 
is  unaltered,  however,  the  increased  concentration  of  the  blood 
cannot  be  due  to  an  excess  of  electrolytes,  such  as  salts,  but  must 
be  laid  to  an  excess  of  organic  molecules  of  some  sort.*^  Chemi- 
cal examinations  have  shown  that  these  are  mostly  organic 
nitrogenous  compounds  that  have  resulted  from 
proteid  decomposition,  and  constituting  the  so-called 
residual  or  non-coagulable  nitrogen. 

Recent  literature  contains  many  studies  indicating  the  im- 
portance of  the  non-coagulable  or  non-protein  nitrogen  element 
in  the  production  of  uraemia  and  in  renal  insufficiency  in  general.*''^ 
The  retention  of  these  bodies  is  greatest  in  cases  of  contracted 
kidney  which  are  on  the  verge  of  uraemia;**  while  in  the  other 
forms  of  nephritis  the  amount  is  considerably  less.  Though 
urea  is  included  in  this  residual  nitrogen,  we  can  readily  eliminate 
it  as  a  factor  in  the  production  of  uraemia,  for,  as  we  shall  at 
once  see,  it  is  non-toxic.  Hence,  for  the  non-coagulable  nitrogen 
to  be  of  significance  in  uraemia,  it  must  contain  poisonous  products 
of  proteid  metabolism.  Soetbeer,*^  in  fact,  has  shown  that  in 
nephrectomized  animals  these  toxic  albuminous  substances  are 
present  most  abundantly  in  the  blood,  and  to  a  less  extent  in  the 
brain  and  other  organs. 

(The  efforts  to  localize  the  disturbance  of  renal  function  by 
the  ability  of  the  kidneys  to  excrete  certain  substances  introduced 
into  the  circulation  (see  p.  427)  have  not  met  with  a  very  great 
success.  This  has  been  due  to  the  fact  already  alluded  to  that 
anatomical  changes  in  the  organs — except  possibly  in  acute  cases 


i 


THE  SECRETION  OF  URINE  431 

— are  ordinarily  not  confined  to  a  single  structure  but  tend  to  be 
more  or  less  diffuse.  For  this  reason,  attention  has  been  focused 
more  recently  upon  the  concentration  in  the  blood  of 
the  non-protein  nitrogen  as  an  index  of  the 
functional  efficiency  of  the  kidneys,  particularly 
in  view  of  the  fact  that  the  quantitative  methods  of  determination 
have  been  greatly  simplified.^"  In  general,  observers  are  agreed 
that  the  degree  of  retention  of  these  bodies  is  of  value  both  in 
a  diagnostic  and  prognostic  way.^^  Attention  has  already  been 
directed  to  those  cases  of  arterial  hypertension  without  apparent 
renal  involvement  in  which  the  estimation  of  the  non-coagulable 
nitrogen  may  speak  unequivocably  for  a  nephritis  (p.  8i). 

It  has  been  asserted  further  that  another  and  simpler  func- 
tional test  parallels  so  closely  the  residual  nitrogen  determination 
as  to  be  available  for  routine  work.  This  is  the  phenol- 
•sulphonphthalein  test  of  Rowntree  and  Geraghty. 
The  considerable  literature  devoted  to  this  point  is  in  general 
confirmatory.  ^2 — Ed.  ) 

A  number  of  facts  speak  against  the  view  that  uraemia  is 
caused  by  the  retention  of  substances  that  are  normally  excreted 
through  the  kidneys  In  the  first  place,  an  absolute  anuria  may 
persist  for  days,  without  producing  uraemic  symptoms,  and,  fur- 
thermore, even  though  death  results  from  suppression  of  urine, 
the  associated  symptoms  do  not  precisely  coincide  with  those  of 
uraemia.  Patients  with  anuria  seem  to  pass  gradually  into  coma 
without  any  irritative  cerebral  symptoms,  and  the  uraemic  hyper- 
tension, bradycardia  and  convulsions  are  generally  absent.  Fur- 
thermore, experimental  ligation  of  both  ureters  is  better  borne 
than  is  extirpation  of  the  kidneys. 

No  well-defined  substance  has  yet  been  found 
that  is  both  retained  in  the  body  during  uraemia 
and  is  capable  of  producing  uraemic  symptoms 
when  injected  into  a  normal  animal.  Many  such  sub- 
stances have  been  described,  yet  not  one  has  stood  the  test  of  time. 
Urea,  for  example,  is  retained  in  the  body  during  uraemia,  yet  it  is 
not  toxic  in  these  amounts,^^  and  a  similar  retention  may  continue 
for  days  without  the  appearance  of  uraemic  symptoms.  Some 
have  regarded  the  potassium  salts  as  toxic  agents,  yet  the  quantity 
of  these  salts  in  the  blood  of  uraemic  dogs  was  not  found  to  be 
increased.     The  evidence  regarding  creatin  and  uric  acid  in  their 


432  THE  BASIS  OF  SYMPTOMS 

relation  to  uraemia  is  likewise  very  inconclusive.  Yet,  despite  the 
apparent  non-relationship  to  uraemia  of  these  various  nitrogenous 
bodies,  as  individuals,  there  is  little  doubt  that  a  retention  of 
nitrogenous  substances  in  the  aggregate  plays  an  important  part  in 
the  condition  (p.  431). 

The  urine  even  in  health,  however,  possesses  certain  toxic 
properties,  the  exact  cause  of  which  is  at  present  unknown,^* 
Its  poisonous  action  is  frequently  increased  in  disease,  and  it  is 
quite  possible  that  in  nephritis  toxic  substances  are 
formed  in  abnormally  large  quantities,  and  that  they  are  not 
eliminated  properly  by  the  kidneys.  Yet  this  is  a  pure  hypothesis 
built  upon  a  very  insecure  foundation,  for  but  little  reliance  can  be 
placed  upon  inferences  as  to  the  toxicity  of  normal  and  patho- 
logical urines,  when  the  inferences  are  derived  from  the  effects  of 
injections  of  the  whole  urine  into  animals.  Until  some  definite 
toxic  substance  can  be  isolated,  this  hypothesis  will  continue  to 
retain  a  more  or  less  questionable  standing. 

Finally,  there  exists  the  possibility  that  uraemia  is  due  not 
to  a  failure  on  the  part  of  the  kidney  to  eliminate  poisonous  sub- 
stances from  the  body,  but  to  a  pathological  altera- 
tion in  some  of  its  metabolic  functions.  Of  these 
functions,  we  know  comparatively  little;  yet  that  the  kidney  does 
possess  such  functions  is  proved  by  the  well-known  fact  that  the 
renal  cells  can  form  hippuric  acid  out  of  benzoic  acid  and  glycocoll. 
Brown-Sequard^^  has  elaborated  the  theory  that  the  kid- 
ney furnishes  an  internal  secretion  to  the  body,  and  he 
has  attempted  to  explain  uraemia  from  this  standpoint.  Various 
effects  are  said  to  follow  the  injection  of  renal  extracts, 
and  it  has  been  found  that  substances  tending  to  raise  the  blood- 
pressure  are  present  in  normal  kidneys,  and  that  they  are  present 
in  especially  large  quantities  in  pathological  kidneys  ^^  (but  see 
P-  339)-  The  theory  of  Ascoli*^^  that  nephrolysins  are  of 
importance  in  the  production  of  uraemia  has  not  been  confirmed. ^^ 
Possibly,  further  work  along  these  suggestive  lines  will  aid  us  in 
our  understanding  of  uraemia. 

In  conclusion,  we  may  say  that  although  a  complete  suppres- 
sion of  urine  is  fatal,  the  symptoms  produced  are  not  absolutely 
identical  with  those  of  uraemia.  The  convulsions,  the  increased 
blood-pressure  and  the  slow  pulse — all  of  which  occur  so  fre- 
quently in  uraemia — are  in  all  probability  caused  not  by  the  reten- 


THE  SECRETION  OF  URINE  433 

tion  of  normal  urinary  products  but  by  some  special  uraemic  toxin. 
This  hypothetical  toxin  acts  especially  upon  the  central  nervous 
system,  and  here  more  particularly  upon  the  cerebral  cortex  and 
the  medullary  centres.  In  either  place  it  may  produce  a  stimu- 
lation or  a  paralysis.^* 

The  Urinary  Passages 

Any  portion  of  the  urinary  passage  from  the  kidney  to  the 
mouth  of  the  urethra  may  be  diseased.  Affections  of 
the  urinary  bladder  and  of  the  renal  pelves  stand 
in  close  etiological  relation  to  one  another.  If,  for  example, 
one  of  the  latter  is  inflamed,  the  infected  urine  that  flows  into 
the  bladder  may  there  cause  changes.  On  the  other  hand,  if  the 
former  be  the  seat  of  an  inflammation,  this  may  easily  spread 
upward  through  the  ureters  to  the  pelves  of  the  kidneys.  Pyelitis 
is  most  frequently  caused  by  just  such  an  ascending  infection, 
and  every  long-continued  cystitis  is  a  menace  to  the  patient,  for  it 
may  produce  an  inflammation  of  the  renal  pelvis  or  of  the  kidney 
itself.  Certain  infections,  especially  tuberculosis,  affect  the  renal 
pelvis  primarily,  in  which  case  the  process  enters  through  the 
kidneys. 

Pathological  conditions  of  the  urinary  bladder  may 
be  caused  by  vesical  calculi,  by  the  irritative  or  infectious  charac- 
ter of  the  urine  that  comes  from  the  kidneys  or  by  inflammations 
in  the  neighborhood  that  extend  into  it  by  contiguity.  More  fre- 
quently, however,  the  infectious  agent  reaches  the  bladder  through 
the  urethra.  It  is  possible  that  in  some  instances  bacteria  enter 
from  the  anterior  urethra,  because  the  sphincters  are  weakened 
or  paralyzed ;  but  as  a  rule  the  micro-organisms  are  directly  intro- 
duced by  a  catheter  or  some  other  instrument.  Such  an  intro- 
duction of  bacteria  into  the  bladder  does  not  necessarily  cause  an 
inflammation,  for  the  normal,  complete  evacuation  of  this  organ 
protects  it  to  a  certain  extent  against  infection.  On  the  other 
hand,  infection  is  greatly  favored  by  stasis  of  the 
urine,  and  for  this  reason  prostatic  hypertrophy,  urethral 
strictures,  vesical  calculi,  tumors,  etc.,  are  frequently  followed 
by  cystitis. 

When  bacteria  develop  in  the  stagnating  contents  of  the  blad- 
der they  may  cause  various  urinary  decompositions. 
Of  these  none  is  more  frequent  than  the  so-called  ammoniacal 
28 


434  THE  BASIS  OF  SYIVIPTOMS 

decomposition,  in  which  a  portion  of  the  urea  is  transformed  into 
ammonium  carbonate,  and  which  may  be  brought  about  by  various 
bacteria.  In  other  forms  of  urinary  decomposition  the  neutral 
sulphur  in  the  urine  is  converted  into  hydrogen  sulphid.  The 
effects  of  such  fermentations  are  both  general  and  local.  The 
ammonium  salts  and  the  hydrogen  sulphid  may  be  absorbed 
through  the  altered  vesical  mucous  membrane  and  produce  their 
general  toxic  effects.  In  addition  to  this,  the  ammonia  directly 
attacks  the  bladder  mucosa. 

Urinary  Calculi. — Urinary  calculi®^  may  be  composed  of 
various  materials,  such  as  uric  acid,  the  urates,  calcium  oxalate, 
cystin,  the  carbonates  and  phosphates  of  the  alkaline  earths,  etc. 
In  addition  to  one  or  more  of  these,  the  calculus  always  contains 
a  framework  of  a  proteid-like  substance,  and  this  is  often  so  inti- 
mately mixed  with  the  salts  present  that  chemical  methods  are 
necessary  to  distinguish  them.  In  some  cases  the  proteid  element 
is  so  pronounced  that  we  speak  of  proteid  stones.®^  Some  stones 
are  of  uniform  structure  throughout,  while  others  show  a  more 
or  less  concentric  arrangement,  owing  to  the  fact  that  layers  of 
one  substance  alternate  with  layers  of  another. 

An  organic  framework  is  present  not  alone  in 
formed  urinary  calculi,  but  in  urinary  crystals  of  every  descrip- 
tion.^^ This  fact  is  of  considerable  theoretical  interest;  and 
whereas  it  was  formerly  supposed  that  the  organic  framework 
was  pathological,  and  was  a  necessary  condition  for  the  formation 
of  calculi,  it  is  now  regarded  as  a  physiological  structure  and 
comparatively  harmless.  The  material  out  of  which  this  frame- 
work is  composed  is  apparently  present  in  every  urine,  and  is 
precipitated  along  with  the  inorganic  salts.  No  special  explana- 
tion, therefore,  of  the  presence  of  this  organic  framework  in 
urinary  calculi  would  seem  to  be  necessary. 

Ebstein,®^  however,  has  expressed  the  opinion  that  the  organic 
framework  of  the  crystals  is  quite  different  from  that  of  the 
renal  calculi.  The  framework  of  the  latter,  in  his  opinion,  is 
formed  only  when,  under  pathological  conditions,  an  abundance 
of  proteid  material  arises  in  the  urinary  passages.  The  albumin 
and  mucin  normally  present  in  the  urine  are  not  adequate  for  this 
purpose.  In  my  opinion,  the  problem  is  satisfactorily  solved  on 
the  basis  that  the  salts,  when  precipitated,  carry  proteid  material 
with  them,  just  as  other  minerals  are  able  to  take  up  proteid 


THE  SECRETION  OF  URINE  435 

substances.  This  calculous  proteid  framework  varies  with  the 
composition  of  the  urine.  It  is  always  secondary,  however,  to 
the  precipitation  of  the  stone-forming  salts. 

The  calculi  most  frequently  found  in  the  bladder  are  com- 
posed of  uric  acid  or  of  the  urates.  Uric  acid  stones  are 
often  formed  in  the  kidneys  themselves  and  apparently  even  dur- 
ing the  earliest  periods  of  life.  As  is  well  known,  uric  acid  de- 
posits are  frequently  present  in  the  uriniferous  tubules  of  the 
fcetus  and  of  the  new-born  infant,  forming  the  so-called  uric 
acid  infarcts.  For  our  present  purposes,  it  is  immaterial  whether 
the  uric  acid  in  these  cases  is  excreted  in  excessive  amounts,  or 
whether  it  is  merely  precipitated  with  unusual  ease ;  for  the  for- 
mation of  calculi  depends  primarily  upon  the  precipitation  of 
salts.  Apparently  these  renal  deposits  in  new-born  infants  are 
normally  washed  out  of  the  kidneys  and  out  of  the  urinary 
passages  without  causing  any  symptoms.  Possibly,  however,  the 
infarcts  stand  in  some  close  causal  relation  to  the  formation 
of  uric  acid  stones  in  childhood. 

Since  the  formation  of  these  calculi  depends  primarily  upon 
the  precipitation  of  the  uric  acid  out  of  the  urine,  two  factors 
are  of  importance  in  this  respect,  first,  the  amount  of  uric 
acid  secreted,  and  secondly,  the  ability  of  the  urine 
to  hold  this  in  solution.  Of  these,  the  latter  is  the 
more  important  and  the  more  variable.  Urine  dissolves  far  more 
uric  acid  than  does  pure  water.®*  Normally,  the  uric  acid  is 
present  in  the  urine  mainly  as  a  mono-sodium  salt.  The  mono- 
sodium  phosphate  of  the  urine,  however,  tends  to  take  the  sodium 
away  from  the  mono-urate,  forming  a  di-sodium  phosphate  and 
leaving  free  uric  acid,  which  is  comparatively  insoluble.  The 
presence  of  free  carbonic  acid  in  the  urine  tends  to  hold  uric 
acid  in  solution.®^  It  is,  furthermore,  quite  possible  that  uric  acid 
is  often  held  in  solution  in  the  urine  as  some  special  combination. 
We  know,  for  example,  that  the  quantity  of  urea  in  the  urine 
affects  the  solubility  of  uric  acid,  and  it  is  probable  that  other 
organic  substances  will  do  the  same.  Uric  acid  calculi  are  often 
associated  with  gout,  the  two  being  grouped  together  under  the 
name  of  the  uric  acid  diathesis.  We  have  already  seen 
that  the  uric  acid  within  the  body  is  probably  held  in  solution  in 
organic  combinations  (c/.  p.  368),  and  the  same  may  be  equally 
true  concerning  the  urine.  We  may  say,  therefore,  that  the  precipi- 


436  THE  BASIS  OF  SYMPTOMS 

tation  of  uric  acid  out  of  the  urine  depends  upon  numerous  factors 
and  that  the  presence  or  absence  of  other  substances  probably  plays 
a  more  important  role  than  does  the  mere  quantity  of  the  acid 
itself.  The  more  important  and  difficult  element  of  the  problem, 
however,  is  the  determination  of  the  mode  of  formation  of  the 
primary  nucleus.  When  the  latter  is  once  present,  the  calculus  will 
arise  in  due  time  by  the  precipitation  of  uric  acid  from  normal 
urine. 

The  mode  of  origin  of  oxalate  calculi  is  not  better 
understood.  The  solution  of  calcium  oxalate  in  the  urine  is 
greatly  favored  by  an  acid  reaction.  If  this  latter  be  reduced 
from  any  cause,  the  mono-sodium  phosphate  tends  to  be  converted 
into  di-sodium  phosphate,  and  the  precipitation  of  calcium  oxalate 
is  favored ;  yet  this  appears  to  be  only  one  factor  in  the  process.®^ 

The  phosphates  of  the  alkaline  earths  are  solu- 
ble in  the  urine  mainly  as  mono-  or  di-phosphatic  salts,  and  they 
tend  to  be  precipitated  when  the  reaction  of  the  urine  becomes 
alkaline  and  normal  phosphates  are  formed.  Ammonium-mag- 
nesium phosphate  is  also  formed  under  these  circumstances. 

These  phosphatic  calculi  are  formed  almost  ex- 
clusively in  the  bladder,  but  they  frequently  precipitate  about 
a  nucleus  composed  of  some  other  material,  such  as  a  uric  acid 
stone  or  some  foreign  body  that  has  been  artificially  introduced 
into  the  bladder.  Their  formation  is  greatly  favored  by 
stagnation  of  urine,  and,  as  a  consequence,  they  occur 
most  frequently  in  association  with  cystitis ;  for  this,  as  we  have 
shown,  is  itself  favored  by  stagnation,  and  is  frequently  accom- 
panied by  an  alkaline  reaction  of  the  urine,  owing  to  the  associated 
ammoniacal  fermentation.  To  stagnation,  also,  is  probably  due 
the  formation  of  calculi  in  individuals  with  cord  lesions. 

In  the  condition  known  as  phosphaturia,  calculus  for- 
mation does  not  take  place,  though  the  phosphates  are  present  in 
the  urine  in  sufficient  amount  to  render  it  cloiidy,  either  when 
passed  or  shortly  afterward.  These  phosphatic  precipitates, 
which  are  made  up  chiefly  of  calcium  and  magnesium  phosphate 
and  carbonate,  appear  when  the  diet  is  rich  in  alkalies  or  when 
there  has  been  a  loss  of  acid  from  the  body,  as  is  seen  for  example 
in  gastric  hyperacidity.  Though  the  causes  of  phosphaturia  are 
generally  unknown,  it  is  a  fact  that  the  condition  is  often  seen 
in    young    individuals    of    a    nervous    constitu- 


THE  SECRETION  OF  URINE  4S7 

t  i  on  .*''^  The  French,  indeed,  speak  of  a  phosphatic  diabetes  and 
see  in  the  condition  a  pronounced  nervous  element.  Why,  in  phos- 
phaturia,  there  occurs  an  increased  elimination  of  calcium  salts 
through  the  urine  at  the  expense  of  the  usual  intestinal  excretion 
is  not  definitely  understood,  Soetbeer  has  suggested  the  presence 
of  a  colitis  as  the  cause  of  this  lessened  intestinal  elimination,  but 
this  has  been  disputed. 

C y s t i n  and  xanthin  calculi  are  extremely  rare.  The 
former  is  a  substance  containing  sulphur,  and  is  derived  from 
proteid  sources.  It  appears  to  result  from  an  inability  on  the 
part  of  the  body  to  complete  the  destruction  of  the  sulphur- 
containing  portion  of  the  proteid  molecule  (p.  336).  Apparently, 
it  never  occurs  in  normal  urine.  Xanthin  is  present  even  in  nor- 
mal urine  in  small  amounts,  but  the  cause  of  its  precipitation  is  not 
understood. 

The  Symptoms  of  Urinary  Calculi. — The  hard,  uneven  stones, 
especially  the  uric  acid  or  calcium  oxalate  calculi,  irritate  the 
mucous  membrane  of  the  urinary  tract  and  cause  inflammations, 
pain  and  hemorrhages.  If  the  calculus  obstruct  a  ureter,  attacks 
of  renal  colic,  with  severe  pain  and  vomiting,  may  follow. 
If  the  occlusion  persists  for  a  long  period  of  time,  hydro- 
nephrosis and  the  other  sequelae  of  urinary  retention  are 
likely  to  develop. 

Vesical  calculi  may  suddenly  stop  the  flow  of  urine  by  drop- 
ping before  the  mouth  of  the  urethra.  This  gives  rise  to  vesi- 
cal tenesmus,  which  is  not,  however,  a  pathognomonic 
symptom  of  calculi,  but  may  be  produced  by  inflammations  of 
the  neck  of  the  bladder,  by  vesical  tumors  or  even  by  a  highly 
concentrated  urine.  The  symptoms  of  vesical  tenesmus  are  very 
similar  to  those  of  tenesmus  of  the  rectum.  The  irritation  of  the 
neck  of  the  bladder  causes  a  frequent  desire  to  urinate,  and  the 
bladder  consequently  contracts  frequently  and  forcibly,  causing 
considerable  pain;  yet,  on  account  of  the  small  amount  of  urine 
present,  but  little  can  be  voided. 

The  Origin  of  Pain  in  the  Urinary  Passages. — A  diseased  kid- 
ney may  cause  pain,  or  at  any  rate,  a  dull  feeling  of  pressure  in 
the  lumbar  region.  This  is  not  infrequently  observed  in  associa- 
tion with  acute  or  chronic  nephritis.  More  severe  pains  are 
usually  due  to  affections  of  the  lower  urinary  passages,  and  they, 
as  a  rule,  are  caused  by  a  spasm  of  the  smooth  muscle 


438 


THE  BASIS  OF  SYMPTOMS 


lining  the  urinary  tract.  These  spasms  are  caused  by 
reflexes  from  the  mucous  membrane,  which  originate  either  from 
the  irritation  produced  by  a  foreign  body,  or  from  inflammatory 
or  ulcerative  processes  in  the  mucous  membrane  itself.  The  mus- 
cular spasm  in  these  cases  is  comparable  to  that  which  gives  rise 
to  biliary  or  intestinal  colic.  Apparently  the  mucous  membrane 
possesses  nerves  of  sensation,  the  direct  irritation  of  which  may 
also  cause  pain. 

LITERATURE 

*  Consult  the  fundamental  studies  from  Ludwig's  laboratory,  in  the  Wiener 

Sitzungsber. ;  Heidenhain,  in  Hermann's  Handb.  d.  Phys.,  v,  I ;  J.  Munk 
and  Senator,  Virch.  Arch.,  cxiv,  i.  Cf.  Spiro  and  Vogt,  in  Asher-Spiro, 
Ergebnisse,  i,  I,  414;  Loewi,  Arch.  f.  exp.  Path.,  xlviii,  410. 

•  See  Gottlieb  and  Magnus :  Arch,  f .  exp.  Path.,  xlv,  223 ;  Starling,  Jour,  of 

Phys.,  xxiv,  317. 

*  Cf.  V.  Noorden:  Path.  d.  Stoffwechsels,  2nd  edit.,  I,  969  (Metabolism  and 

Practical  Medicine,  London,  1907). 

*  Nagel :  Arch,  f .  klin.  Med.,  Ixxxviii,  562. 

'  For  the  more  recent  studies  see  Ebstein,  Arch,  f .  klin.  Med.,  xcv,  i ;  Weber 
and  Gross,  Ergeb.  d.  inn.  Med.,  iii,  i ;  Schwenkenbecher,  Miinch.  med. 
Wochenschft,  1909,  No.  50;  Umber,  in  Kraus-Brugsch,  Spez.  Path.  u. 
Therap.,  1913. 

'  Tallquist :  Zeitschf t.  f .  klin.  Med.,  xHx,  181 ;  Hirschf eld,  Salkowski  Fest- 
schrift, Berlin,  1904. 

^  Claude  Bernard :  Legons  de  phys.,  i ;  Eckhard,  Beitr.  z.  Anat.  u.  Phys.,  iv,  v, 
vi,  and  Zeitschft.  f.  Biol.,  xliv,  407. 

•  E.  Meyer :  Arch,  f .  klin.  Med.,  Ixxxiii,  i ;  v.  Koranyi,  Die  wissenschaf  tl. 

Grundlagen  d.  Kryoskopie,  1904.  See  also  Finkelburg,  Arch.  f.  klin. 
Med.,  xci,  345;  Weil,  ibid.,  xciii,  198;  Fitz,  Arch,  of  Int.  Med.,  1914,  xiv, 
706. 

•  See  for  example,  Simmonds :  Miinch.  med.  Wochenschft.,  1913,  No.  3,  and 

1914,   No.  4;   Goldzieher,   Deutsch.   path.  Gesell.,  xvi,  272;   Berblinger, 

ibid.,  281 ;  Gushing,  The  Pituitary  Body. 
"  Transactions  of  the  Chicago  Path.  Society,  ix,  15. 
"Gottlieb:  Arch.  f.  exp.  Path.,  xliii.  286. 
"Takayasu:   Arch.   f.  khn.  Med.,  xcii,   127;   Schlayer  and  Takayasu,  ibid., 

xcviii,  17,  and  ci,  333;  Schlayer,  ibid.,  cii,  311. 
"See  Cohnheim:  Allg.  Path.,  ii. 
"  Hermann :  Wiener  Sitzber.,  xlv,  II,  317. 

"Cushny:  Jour,  of  Phys.,  xxviii,  431;  Allard,  Arch.  f.  exp.  Path.,  Ivii,  241. 
"  See  Posner :  Virch.  Arch.,  civ,  497 ;  Leube,  Zeitschft.  f .  klin.  Med.,  xiii,  I ; 

Morner,  Skand.  Arch.  f.  Phys.,  vi,  332. 
"  See  Huppert,  in  Neubauer-Vogel,  Harnanalyse,  9th  edit.,  i,  277. 
"  Morner :  1.  c. ;  v.  Noorden,  Arch,  f .  klin.  Med.,  xxxviii,  204. 
"  Edel :  Miinch.  med.  Wochenschft.,  1901,  Nos.  46  and  47. 
"  Arch,  f .  exp.  Path.,  liv,  14 ;  Arch,  f .  klin.  Med.,  Ixxxiii,  452. 
**  Miinch.  med.   Wochenschft.,   1908,   No.   12 ;   Die  lordotische  Albuminuric, 

1909;  Ergeb.  d.  inn.  Med.,  1913,  xii,  808  (lit.). 
*"  Semaine  medicale,  1899,  425,  and  1904,  356 ;  Kongr.  Lyon,  1905. 
•*  Johns  Hopkins  Hosp.  Reports,  xii,  145. 
**Berl.  klin.  Wochenschft.,  1907,  No.  i;  Lehrbuch  d.  Kinderkeilkunde,  191 1, 

II,  508.    See  also  Langstein,  in  Pfaundler  and  Schlossmann,  Handbuch. 


THE  SECRETION  OF  URINE  439 

"See  Schmid:  Arch.  f.  exp.  Path,,  liii,  419;  Gross,  Ziegler's  Beitrage,  li, 

528  (lit). 
*■  Cf.  F.  Miiller,  Ref erat. 

"  Schlayer  and  Hedinger :  Arch,  f .  exp.  Med.,  xc,  i. 
**  See  Hermann:  1.  c. ;  Overbeck,  ibid.,  xlvii,  II,  189;  Litten,  Zeitschft.  f.  klin. 

Med.,  i  and  xxii;  Heidenhain,  1.  c. 
**  Loc.  cit. 
■*  See    Frerichs :    Die    Brightsche    Nierenkrankheit ;    Siegel,    Deutsch.     med. 

Wochenschft.,  1908,  No.  11. 
"See  Cloetta:  Arch.  f.  exp.  Path.,  xlii,  453  (lit.);  Wallerstein,  Dissertation 

Strassburg,  1902 ;  Gross,  Arch,  f .  klin.  Med.,  Ixxxvi,  578. 
•*See  Luthje:    Arch.    f.   klin.   Med.,   Ixxiv,    163;    Wallerstein,   Zeitschft.    f. 

klin.  Med.,  Iviii;  Gross,  Ziegler's  Beitrage,  li,  528  (lit.). 
"*  Liithje :  1.  c. ;  Klieneberger  and  Oxenius,  ibid.,  Ixxx,  25. 
"Brauner:  Zeitschft.  f.  klin.  Med.,  Ixv,  438.     See  also  Baetjer,  Arch.  Int. 

Med.,  1913,  xi,  593  (Renal  Superpermeability). 
•"H.  Meyer,  in  Meyer  and  Gottlieb:  Pharmakologie,  2nd  edit.,  312  (English 

translation  by  Halsey,  1914). 
"  See  Neumeister :  Physiolog.  Chem.,  2nd  edit.,  301, 
"  Schultess :  Arch,  f .  klin.  Med.,  Iviii,  325 ;  ibid.,  Ix,  55. 
"  See  Metzner :  Nagel's  Handb.  d.  Physiologic,  II,  207. 
**  Cf.  the  previously  cited  studies  of  Schlayer. 
*  V.  Monakow :  Arch,  f .  klin.  Med.,  cii,  248. 
**  Gross  :  Ziegler's  Beitrage,  li,  528 ;  Frey,  Pfliiger's  Arch.,  cxxxix,  and  Deutsch. 

med.  Wochenschft.,  191 1,  No.  23. 
**  Schlayer :  1.  c. ;  v.  Monakow,  1.  c. ;  Gross,  1.  c. ;  Pearce,  Arch.  Int.  Med.,  v, 

133  (lit.).    See  also  Rowntree  and  Geraghty,  The  Value  and  Limitations 

of  Functional  Renal  Tests,  Jour.  Am.  Med.  Assn.,  1913,  Ixi,  939. 
^'Soetbeer:   Zeitschft.  f.  phys.  Chem.,  xxxv,  85;  Rowntree  and  Geraghty: 

Arch.  Int.  Med.,  ix,  308. 
**See  Honigmann,   in  Lubarsch-Ostertag,   Ergeb.,   i  and  viii;   Ascoli,  Vor- 

lesungen   ii.   Uramie,    1903;    Bernard,   Les    fonctions   du   rein   dans   les 

nephrites  chronique,  Paris,  1900,  713;  F.  Miiller:  Deutsch.  path.  Gesell., 

1905;  v.  Noorden,  Handbuch,  2nd  edit.,   1041    (Metabolism  and   Pract. 

Med.). 
*^  Cf.    Obermayer  and   Popper:   Zeitschft.   f.  klin.   Med.  Ixxii,  332    (recent 

studies  and  lit.).    See  also  Tileston  and  Comfort,  Arch.  Int.  Med.,  1914, 

xiv,  620  (lit.)  ;  Rowntree  and  Fitz.,  ibid.,  xi,  258. 
•■Bicicel:  Deutsch.  med.  Wochenschft.,  1902,  No.  28;  Engelmann,  Grenzge- 

biete,  xii,  396. 
"  See  for  example  Rowntree  and  Fitz :  1.  c. ;  Tileston  and  Comfort,  1.  c. 
*"  Strauss :  Die  chron.  Nierenentziindungen,   1902 ;   F.  Miiller,   Path.  Gesell- 

schaft,  1905;  Hohburg,  Arch.  f.  klin.  Med.,  civ,  216;  Tileston  and  Com- 
fort, 1.  c. ;  Foster,  ibid.,  1915,  xv,  356. 
*"  Kongr.  f .  inn.  Med.,  1909,  226. 
"Folin  and  Denis:  Jour.  Biol.  Chem.,  xi,  527;  ibid.,  xiv,  33;  Marshall,  ibid., 

1913,  XV,  487  (Blood  Urea). 
"  For  a  recent  discussion  see  Tileston  and  Comfort :  1.  c. 
"For  a  brief  collective  study  see  Elliott:  Jour.  Amer.  Med.  Assn.,  1915,  Ixiv, 

1886  (lit). 
"^  Soetbeer :  Zeitschft.  f.  physiol.  Chem.,  xxxv,  85.    For  an  opposed  view  see 

Voit  Zeitschft.  f.  Biol.,  iv. 
"Bouchard:  Lectures  on  Auto-Intoxication  in  Disease,   1906;  Honigmann, 

1.  c.  (lit)  ;  Abelous  and  Bardier,  Soc.  de  biologic,  1910,  Ixix,  121, 
''See  Biedl:  Innere  Sekretion,  1913  (Internal  Secretory  Organs,  1913.). 
"  Bingel  and  Claus :  Arch,  f .  klin.  Med.,  c,  412. 
"  Ascoli :  Uramie. 


440  THE  BASIS  OF  SYMPTOMS 

"Pearce:  Univ.  of  Penn.  Med.  Bull.,  xvi,  217;  Arch.  Int.  Med.,  1910,  v,  133 
(lit). 

"  Landois :  Die  Uramie. 

"Ultzmann:  Deutsche  Chirurgie,  No.  32;  Ktimmel,  Verhandl.  d.  ersten 
Urologenkong.,  Vienna,  1907,  294;  Rosenbach,  Grenzgebiete,  xxii,  630; 
Kleinschmidt,  Die  Harnsteine,  191 1  (under  Aschoff). 

°  Morawitz  and  Adrian :  Mitt.  a.  d.  Grenzgeb.,  xvii,  579. 

**  Moritz :  Kongr.  f .  inn.  Med.,  1896,  523. 

*°  Ebstein :  Deutsch.  med.  Wochenschf  t.,  1908,  No.  32. 

"  Bunge :  Physiol.  Chem.,  3rd  edit.,  308. 

"  Klemperer :  Zeitschft.  f.  physikal.  Therapie.,  iv,  48. 

■^  Klemperer :  Berl.  klin.  Wochenschft.,  1901,  1289;  Klemperer  and  Tritschler, 
Zeitschft.  f.  klin.  Med.,  xliv,  337. 

"  See  Soetbeer :  Jahrb.  f .  Kinderheilk,  Ivi,  i ;  Soetbeer  and  Krieger,  Arch, 
f.  klin.  Med.,  Ixxii,  553;  Langstein,  Medizin.  Klinik,  1906,  No.  16,  Klem- 
perer, Therap.  d.  Gegenwart,  1908. 


CHAPTER  XII 
THE  NERVOUS  SYSTEM 

The  activities  of  the  nervous  system  give  rise  to  two  classes 
of  phenomena — those  pertaining  to  the  body  and  those  pertaining 
to  the  mind.  We  do  not  purpose  considering  the  latter,  nor  even 
discussing  the  relationship  that  exists  between  the  body  and  the 
mind.  In  the  present  chapter,  we  plan  to  limit  our  discussion, 
in  a  general  way,  to  those  disturbances  of  the  nervous  system 
which  do  not  affect  the  mind,  even  though  this  division  is  an  arti- 
ficial one  and  cannot  be  carried  out  strictly  and  consistently. 

The  nervous  symptoms  that  we  shall  consider  may  be  divided 
into  two  main  groups.  Those  in  the  first  group  are  called  focal 
symptoms,  because  they  are  caused  by  pathological  changes 
involving  certain  limited  portions  of  the  nervous  system.  Those 
in  the  second  group  are  termed  general  symptoms,  be- 
cause the  agent  that  causes  them  affects  the  nervous  system  as  a 
whole.  Of  these  general  symptoms,  some  evidently  proceed  from 
certain  definite  localities ;  while  the  origin  of  many  others  cannot 
be  traced.  The  same  general  injurious  agent  may  act  upon  all 
parts  of  the  nervous  system,  yet  it  affects  certain  portions  more 
than  others,  because  the  former  happen  to  be  more  vulnerable  to 
the  particular  agent  in  question. 

Disturbances  of  the  Circulation. — The  central  nervous  system 
must  receive  a  sufficient  supply  of  blood  in  order  to  functionate 
properly.  Some  of  the  symptoms  that  result  from  circulatory 
disturbances  have  already  been  mentioned  in  the  chapter  on  res- 
piration. We  spoke  there  of  the  extraordinary  sensitive- 
ness of  the  respiratory  centre  to  any  change  in 
the  quantity  or  quality  of  the  blood  that  comes  to  it, 
as  well  as  of  the  effects  of  such  changes  upon  other  medullary 
centres.  The  cerebral  cortex  is  not  affected  until  some  time  after 
the  medulla,  at  which  time  the  consciousness  becomes  clouded 
and  the  horrible  sense  of  suffocation  is  diminished  or  lost.  Al- 
though the  brain  is  ordinarily  extremely  sensitive  to  circulatory 
changes,  it  often  appears  as  if  it  can  accommodate  itself  to  an 
insufficient  blood  supply  in  chronic  circulatory  derangements.  It 
is  extremely  difficult,  however,  to  form  an  accurate  judgment  on 

441 


443 


THE  BASIS  OF  SYMPTOMS 


this  question,  for  we  have  no  method  of  measuring  the  circulatory 
disturbances  in  the  brain;  yet  it  is  often  truly  astonishing  to  see 
wha.t  little  effect  the  most  pronounced  chronic  venous  stasis  or  the 
most  marked  arterial  anaemia  produce  upon  the  cerebral  functions. 

The  temporary  loss  of  consciousness  known  as  fainting 
is  usually  due  to  an  acute  cerebral  anaemia.  It  may  occur  in 
strong  and  healthy  individuals,  but  it  is  much  more  frequent  in 
anaemic  girls  or  in  older  individuals  with  degeneration  of  the 
cerebral  arteries.  During  the  fainting  spell  the  patient  loses 
consciousness,  falls  and  lies  for  a  time,  breathing  quietly,  but 
with  a  pale,  non-cyanosed  face.  Finally,  after  a  while,  he  grad- 
ually recovers.  Although  the  cerebrum  has  ceased  to  act,  the 
medulla  appears  to  perform  its  functions  quite  normally,  just  as 
it  does  during  light  narcosis.  It  seems  improbable,  therefore,  that 
the  disturbance  of  circulation  in  fainting  affects  all  parts  of  the 
brain  equally;  for  if  this  were  so,  we  should  expect  medullary 
symptoms.  We  know  that  localized  anaemias  frequently  occur 
in  other  parts  of  the  body,  and  that  in  arteriosclerosis  such  cir- 
cumscribed circulatory  derangements  are  particularly  frequent; 
and  it  seems  quite  possible  that  the  anaemia  causing  the  syncope 
affects  only  a  part  of  the  brain,  as  might  happen,  for  example, 
if  certain  vessels  became  narrowed  either  by  a  spasm  or  by  a 
relative  thickening  of  their  walls. 

Other  anaemic  manifestations  of  nervous  ori- 
gin are  more  difficult  to  explain.  Some,  such  as  headache, 
ringing  in  the  ears,  spots  before  the  eyes  and  dizziness,  appear 
to  be  irritative  in  character;  while  others,  such  as  the  com- 
mon feeling  of  lassitude,  are  depressive.  These  symptoms 
are  generally  ascribed  to  a  cerebral  anaemia  which  either  dimin- 
ishes the  oxygen  supply  to  the  brain  or  affects  its  nutrition  in 
some  other  way ;  but  these  suppositions  have  not  yet  been  definitely 
proved.  There  are  many  other  possibilities.  Chemical  sub- 
stances, resulting  from  pathological  alterations  of  the  general 
metabolism,  may  poison  the  brain  in  some  manner ;  and  it  is  even 
possible  that  the  symptoms  do  not  originate  in  the  brain  at  all, 
but  in  the  peripheral  sense  organs.  Finally,  Lenhartz  ^  has  shown 
that  the  headache  and  dizziness  of  chlorosis  may  be  associated 
with  an  increase  in  the  subarachnoid  pressure. 

The  Cerebrospinal  Lymphatic  System. — ^The  brain  and  spinal 
cord  are  suspended  in  a  fluid  that  is  constantly  changing  through 


ife 


THE  NERVOUS  SYSTEM  443 

the  processes  of  secretion  and  absorption.  We  need  not  describe 
the  many  advantages  of  this  mechanism ;  how  it  acts  as  a  cushion 
about  the  dehcate  nervous  structures  when  the  body  is  jarred,  nor 
how  the  brain  is  protected  from  rapid  alterations  in  arterial  pres- 
sure by  the  layer  of  lymphatic  fluid  that  encircles  each  of  its 
blood-vessels. 

Most  observers  have  found  the  pressure  of  the  cere- 
brospinal fluid  to  be  normally  rather  low,  although  it 
apparently  varies  considerably  in  different  individuals.^  Its 
height  depends  in  part  upon  the  general  blood-pressure,  but  mainly 
upon  the  relation  that  exists  between  the  secretion  and  the  absorp- 
tion of  the  lymph.  The  characteristic  composition  of  the 
cerebrospinal  fluid — vis.,  a  low  percentage  of  albumin 
and  a  high  percentage  of  potassium  salts — shows  that  it  is  not 
an  ordinary  transudate,  but  a  secretory  product  from  certain  cells, 
probably  those  of  the  choroid  plexuses.^  The  resorption* 
of  this  fluid  takes  place  mainly  in  the  Pacchionian  cor- 
puscles and  to  a  lesser  extent  in  the  lymphatics  of  the  nose  and 
neck.** 

Increased  Cerebral  Pressure. — The  pressure  of  the  cerebro- 
spinal fluid  may  be  pathologically  increased  to  varying  degrees 
and  by  different  causes.®  For  example,  tumors  may  bring  this 
about  merely  because  they  take  up  space  within  the  cranial  cavity, 
though  they  are  especially  liable  to  do  so  when  they  press  upon 
the  veins  of  Galen  and  thus  impede  the  outflow  of  venous  blood. 
Intracranial  hemorrhages  may  also  increase  the 
cerebrospinal  pressure. 

If  the  cranial  cavity  becomes  crowded  irpm  any  cause,  the 
brain  substance  cannot  be  compressed  into  a  smaller  space,  for 
the  nervous  tissue  is  practically  incompressible.'''  A  certain  relief 
is  afforded,  however,  by  the  escape  of  cerebrospinal  fluid  into 
those  portions  of  the  dura  mater  that  are  comparatively  disten- 
sible, such  as  is  the  dura  of  the  cord.  A  new  equilibrium  of 
pressure  is  then  established.  What  the  new  pressure  will  be 
depends  upon  the  size  of  the  compressing  agent,  the  distensi- 
bility  of  the  dura  and,  finally,  upon  the  relation  that  exists  between 
the  secretion  and  absorption  of  cerebrospinal  fluid.  It  is  apparent 
that  when  so  many  factors  enter  into  the  final  result  the  same 
cause  may  produce  quite  different  effects  in  different  individuals. 

From  these  considerations  it  would  appear  that  when  a 


444  THE  BASIS  OF  SYMPTOMS 

hard  body  is  added  to  the  contents  of  the  skull 
the  increase  in  pressure  would  be  roughly  propor- 
tionate to  the  size  of  the  "foreign  body,"  and 
that  the  space  taken  up  by  smaller  bodies  could  be  fairly  well 
compensated  for  by  the  escape  of  lymph  from  the  cranial  cavity.® 
In  some  cases,  however,  especially  in  certain  brain  tumors,®  no 
such  definite  relation  seems  to  exist  between  the  size  of  the  tumor 
and  the  increase  in  the  cerebrospinal  pressure.  The  smallest  tumor 
may  cause  a  tremendous  rise  in  pressure.  Furthermore,  if  some 
of  the  cerebrospinal  fluid  be  drawn  off  in  order  to  relieve  the 
pressure,  it  will  frequently  re-collect  with  great  rapidity.  These 
facts  do  not  accord  with  the  view  that  brain  tumors  increase  the 
cerebral  pressure  solely  by  their  mechanical  action.  It 
would  seem  rather  as  if  the  production  or  the  absorption  of  the 
cerebrospinal  fluid  were  directly  affected.  Possibly  the  condi- 
tions present  are  analogous  to  those  that  exist  in  tumors  of  the 
pleura  or  of  the  peritoneum,  i.e.,  some  sort  of  an  inflam- 
matory process  is  taking  place  in  the  arachnoid.^**  In 
favor  of  this  view  are  the  facts  that  the  cerebrospinal  fluid  of 
these  patients  often  contains  more  albumin  than  normally,^ ^  and 
that  the  accompanying  choked  disk  is  almost  certainly  of  an  in- 
flammatory nature. 

The  increased  cerebral  pressure  that  accompanies  menin- 
gitis is  caused  by  a  disturbance  in  the  balance  between  the 
production  and  absorption  of  cerebrospinal  fluid.  It  seems  prob- 
able, indeed,  that  both  the  production  is  increased  and  the  absorj>- 
tion  diminished  in  this  condition. 

The  chronic  hydrocephalus  of  children  is  char- 
acterized by  a  large  collection  of  cerebrospinal  fluid,  but  its  cause 
is  not  well  understood.  Perhaps  a  mild  inflammatory  process  is 
present  (ependymitis),  though  this  seems  improbable  in  most 
cases,  from  the  fact  that  the  percentage  of  albumin  in  the  fluid 
is  not  increased.  Chlorotic  girls  frequently  show  an  in- 
creased cerebral  pressure,  yet  here  again  the  cause  is  very  uncer- 
tain. The  mild  optic  neuritis  often  seen  in  these  patients  may 
possibly  be  produced  by  the  increased  cerebral  pressure,  though 
it  seems  more  probable  that  it  results  directly  from  the  poor 
nutrition  of  the  optic  nerve.  That  the  headache  accompanying 
cases  of  arterial  hypertension  (nephritis,  arterioscle- 
rosis) is  often  the  result  of  an  increased  cerebral  pressure  is 


THE  NERVOUS  SYSTEM  445 

evidenced  by  the  benefit  seen  in  many  instances  after  a  lum- 
bar puncture. 

When  the  pressure  of  the  cerebrospinal  fluid  is  increased  from 
any  of  these  causes,  certain  symptoms  usually  follow,  among 
which  are  headache,  general  bodily  and  psychic  weakness,  and 
characteristic  alterations  in  the  ocular  fundi — the  so-called 
choked  disks.  These  have  been  termed  the  symptoms 
of  latent  cerebral  pressure,  and  they  are  supposed  to 
be  caused  by  the  tissue  changes  that  follow  the  increased  pressure 
in  the  cranial  cavity.  Possibly  they  depend  less  upon  the  height 
than  upon  the  duration  of  the  increased  pressure.^ ^  It  would 
be  interesting  to  know  what  the  minimum  pressure  is  that  can 
produce  a  choked  disk,  but  the  data  at  our  disposal  do  not  suffice 
to  determine  this.^^  And  it  may  be  that  the  individual  variations 
are  so  considerable  that  no  definite  minimum  can  be  fixed. 

Although  choked  disk  is  one  of  the  most  important  clinical 
signs  of  increased  cerebral  pressure,  the  manner  in  which  it  is 
produced  is  still  very  uncertain. ^^  According  to  the  opinion  of 
most  ophthalmologists,  a  mere  increase  in  the  intracranial  pressure 
does  not  suffice  to  cause  it,  and  other  factors  must  be  present. 
Anatomically,  it  usually  appears  to  be  a  true  inflammation,  in- 
volving both  the  nerve  and  the  neighboring  retina.  The  optic 
papilla  is  swollen,  and  there  is  an  associated  oedema  and  venous 
stasis,  but  we  do  not  know  whether  the  cedema  and  stasis  ordina- 
rily develop  before  the  inflammation  or  not.  That  stasis  alone 
should  cause  the  inflammation  is  contrary  to  all  our  pathological 
experience  with  oedema  in  other  parts  of  the  body.  It  is  quite 
possible  that  some  inflammatory  irritant,  produced  by  the  changes 
within  the  brain,  acts  upon  the  retina.  According  to  this  view, 
two  factors  contribute  to  the  causation  of 
choked  disk:  first,  an  increase  in  the  pressure  of 
the  fluid  within  the  optic  sheath;  and  secondly, 
some  unknown  inflammatory  agent.  This  hy- 
pothesis would  explain  many  peculiar  cases  in  which  a  choked  disk 
is  absent  even  though  the  intracranial  pressure  is  high,  as  happens 
in  some  cases  of  hydrocephalus;  here  it  would  appear  that  the 
inflammatory  factor  is  absent.  On  the  other  hand,  in  intracranial 
conditions  of  slow  development,  such  as  in  certain  abscesses  and 
tumors,  choked  disk  is  often  absent  because  there  is  no  increase 
in  intracranial  tension. 


446  THE  BASIS  OF  SYMPTOMS 

If  the  pressure  of  the  cerebrospinal  fluid  be  still  further 
increased,  a  second  series  of  phenomena  develop,  the  so-called 
direct,  or  manifest,  symptoms  of  cerebral  pres- 
sure. The  essential  cause  of  these  is  a  disturbance  of 
the  cerebral  circulation.  We  have  already  described 
the  peculiar  conditions  that  govern  the  intracranial  pressure  and 
how  space  may  be  made  for  foreign  bodies  by  an  escape  of  lymph. 
When,  in  spite  of  this  compensatory  mechanism,  the  pressure 
attains  a  certain  height,  those  parts  of  the  vascular  system  that 
can  be  compressed  most  easily — i.e.,  the  veins  just  before  their 
entrance  into  the  rigid  sinuses — ^become  narrowed  or  even  closed. 
The  resulting  stasis  of  blood  increases  the  pressure  in  the  cor- 
responding capillaries  and  the  veins  are  then  opened  again,  so  that 
they  alternately  open  and  close,  or,  as  Grashey  says,  they  vibrate. ^"^ 
It  is  not  certain  what  cerebral  manifestations  accompany  this 
phenomenon.  From  experimental  data,  it  would  appear  that  the 
really  characteristic  symptoms  of  cerebral  com- 
pression only  begin  at  about  the  time  when  the 
intracranial  pressure  becomes  sufficient  to 
compress  the  arteries.  It  is  then  that  we  have  the 
characteristic  stupor,  the  vomiting,  the  slowing 
of  the  pulse  and  the  respirations,  and  finally  the 
general  epileptiform  convulsions.  The  primary 
cause  of  these  symptoms  seems  to  be  an  arterial  anaemia  that  occurs 
because  the  subarachnoid  pressure  is  greater  than  the  arterial 
pressure.  It  is  theoretically  possible,  therefore,  that  these  symp- 
toms could  be  produced  either  by  a  rise  in  the  subarachnoid  pres- 
sure or  by  a  fall  in  the  arterial  pressure.  When  the  nervous 
symptoms  of  increased  cerebral  pressure  have  once  become  estab- 
lished, they  may  continue  for  some  time,  even  though  the  intra- 
cranial pressure  lessens,  for  the  reason  that  less  force  is  required 
to  hold  the  vessels  closed  than  to  compress  them  originally. 

The  absolute  amount  of  cerebral  pressure  necessary  to  produce 
these  direct  symptoms  is,  therefore,  rather  indefinite,  and  it  often, 
happens  that  during  the  course  of  indirect  symptoms,  the  direct 
ones  will  appear  and  again  disappear,  apparently  on  account  of 
circulatory  disturbances. 

According  to  Gushing,  a  continuation  of  life  after  com- 
pression of  the  cerebral  arteries  has  once  taken  place,  is  made 
possible  only  by  an  increase  in  arterial  pressure.     The  latter  is 


I 


THE  NERVOUS  SYSTEM  447 

brought  about  by  a  stimulation  of  the  vasomotor  centre  as  a 
result  of  the  anaemia.  To  what  extent  these  experimental  obser- 
vations relative  to  the  interaction  of  the  intracranial  tension  and 
the  cerebral  circulation  are  pertinent  to  conditions  in  man,  is  still 
undetermined.  So  far  as  I  know  no  observations  have  been  made 
which  bear  upon  such  variations  in  blood-pressure  consequent  to 
an  increased  intracranial  pressure.  (A  rise  of  blood-pressure 
after  cerebral  hemorrhages  in  man  has  been  demonstrated,  the 
extent  of  the  rise  being  looked  upon  as  an  index  of  the  amount 
of  compression  exerted  upon  the  medulla. ^^ — Ed.) 

The  recent  tendency,  it  would  seem,  has  been  to  emphasize  the 
circulatory  basis  of  the  manifestations  of  increased  intracranial 
pressure,  thereby  underestimating  the  importance  of  changes  in 
the  brain  substance  itself  as  the  cause.  Symptoms  of  increased 
pressure  may  appear  even  in  the  absence  of  a  cerebral  anaemia, 
indeed  even  when  the  indications  are  that  the  arteries  are  well 
filled.  Too  little  importance  has  been  attached  to 
the  important,  if  not  predominant,  role  played 
by  compression,  distortion  and  displacement  of 
the  cerebral  tissue  itself. 

Cerebral  Concussion. — The  symptoms  of  cerebral  con- 
cussion differ  considerably  from  those  of  compression.  The  pale, 
unconscious  patient  lies  with  relaxed  muscles  and  with  weak 
respirations.  His  pulse  is  soft  and  small,  its  rate  being  either 
increased  or  diminished.  His  pupils  are  often  immobile ;  and 
vomiting  frequently  occurs.  Indeed,  he  might  be  thought  to 
be  suffering  from  a  fainting  spell. 

Cerebral  concussion  is  ordinarily  produced  by  a  violent  blow 
upon  the  head  or  upon  some  other  part  of  the  body,  yet  no 
definite  relation  seems  to  exist  between  the 
force  of  the  blow  and  the  severity  of  the  symp- 
toms, and  even  serious  cerebral  injuries  due  to  violence  may  be 
unaccompanied  by  any  of  the  typical  manifestations.  The  symp- 
toms of  concussion  are  essentially  those  of  cerebral  inactivity, 
reaching  different  grades  in  different  cases.  In  the  milder  form 
of  concussion,  the  cerebral  cortex  alone  is  affected  (unconscious- 
ness), in  the  more  severe  forms  the  medullary  centres  become 
involved  (respiratory  and  circulatory  disturbances),  while,  in  the 
most  severe,  the  vital  functions  are  suspended. 

No  definite  anatomical  changes  in  the  brain. 


?- 


i> 


448  THE  BASIS  OF  SYMPTOMS 

common  to  all  cases  of  concussion,  have  been 
f  o un  d  .^'^  The  symptoms  can  hardly  be  due  to  circulatory  dis- 
turbances, for  they  have  been  produced  on  bloodless  frogs.  It 
seems  quite  probable  that  they  are  caused  by  injuries  to  the 
finer  connections  between  the  nerve-cells  in  the  brain;  and  we 
know  that  very  severe  concussions  may  even  produce  slight  but 
demonstrable  lesions  in  the  central  nervous  system. 

K  o  c  h  e  r  has  called  attention  to  the  fact  that  cerebral  con- 
cussion, so-called,  is  hardly  of  uniform  etiology.  He  has  sug- 
gested as  a  more  suitable  term,  acute  brain  compression 
(Hirnpressung),  the  chief  manifestations  in  the  process 
being,  in  his  opinion,  the  phenomena  of  acute  compression,  and 
the  consequent  lesions  of  the  nervous  tissue.  I  am  likewise  of  the 
opinion  that  we  must  be  reserved  in  our  interpretation  of  cerebral 
concussion,  both  because  of  the  poorly  defined  clinical  picture, 
which  may  closely  resemble  conditions  due  to  definite  anatomical 
lesions,  and  also  because  of  our  inability  to  produce  in  animals 
an  exact  replica  of  the  picture  in  man. 

Cerebral  Hemorrhage  and  Embolism. — Closely  related  to  the 
manifestations  of  increased  intracranial  pressure  are  those  asso- 
ciated with  disturbances  in  the  cerebral  arteries,  and  known  as 
cerebral  insult.  Apoplexy  is  generally  due  to  altera- 
tions in  the  vessel  walls — the  so-called  miliary  aneurisms. 
The  latter,  under  the  influence  of  an  augmented  blood- 
pressure,  or  even  with  a  normal  tension,  rupture  and  per- 
mit of  an  escape  of  blood  into  the  surrounding  tissues.  The 
extent  of  the  hemorrhage  and  its  rapidity  of  formation  depend 
upon  the  size  of  the  vessel  and  of  the  opening  in  its  wall.  The 
severity  of  the  picture  varies  with  the  increase  in  in- 
tracranial pressure  and  with  the  amount  of  the  extravasation. 
There  is  ordinarily  a  loss  of  consciousness  and  a  slowing  of  the 
pulse  and  respirations.  The  early  fall  in  temperature  is  succeeded 
by  a  rise.     Death  often  occurs  without  a  return  of  consciousness. 

These  symptoms  are  the  direct  result  of  the  cerebral  trauma, 
consequent  to  the  extravasation  of  blood ;  added  to  the  extensive 
destruction  of  brain-tissue  is  the  damage  wrought  by  the  increase 
in  intracranial  tension.  In  other  cases,  the  insult  is  gradual  in 
nature,  probably  because  only  a  small  amount  of  blood  escapes 
at  one  time,  in  which  event  the  actual  destruction  of  tissue  is 
slight  and  the  increase  in  tension  is  slow  and  limited.     In  those 


f 


THE  NERVOUS  SYSTEM  449 

cases  in  which  the  insult  is  entirely  absent,  the  hemorrhage  has 
been  small  and  gradual,  and  the  tissue  destruction  and  increase  in 
tension  insignificant,  for  here  the  cerebrospinal  fluid  has  had  time 
to  distribute  itself  elsewhere.  As  the  vessels  of  the  cortex  are 
smaller,  and  exhibit  a  lower  pressure  than  do  those  of  the  base, 
a  rupture  of  the  former  is  attended  with  less  pronounced  insult 
manifestations. 

The  symptoms  consequent  upon  a  sudden  closure  of 
a  cerebral  vessel  are  so  similar  to  those  associated  with 
a  hemorrhage  as  often  to  be  indistinguishable  from  them.  As 
Marchand  has  pointed  out,  the  closure  of  a  cerebral  artery  is 
quickly  followed  by  a  stasis  in  the  neighboring  capillaries  and 
veins.  The  anaemia  of  certain  parts  of  the  brain  thereby  pro- 
duced, accounts  in  all  Hkelihood  for  the  loss  of  consciousness. 
The  next  stage  is  one  of  cerebral  oedema,  to  which  are  due  the 
symptoms  of  increased  pressure.  The  focal  symptoms  accom- 
panying hemorrhage  and  embolism  depend  upon  the  location  of 
the  tissue  injury,  just  as  is  the  case  with  tumors. 

Disturbances  of  Motility. — The  direct  motor  impulses  travel 
from  the  cerebrum  to  the  muscles  through  two  sets  of  fibres. 
Of  these,  the  first  begins  in  the  ganglion  cells  of  the  cortical  motor 
area  and  pass  by  way  of  the  pyramidal  tracts  to  the  anterior 
horn  cells  of  the  spinal  cord,  or  to  the  corresponding  nuclei  of 
the  pons  or  medulla.  The  terminal  fibres  of  these  upper 
neurons  are  believed  by  rhany  merely  to  touch  the  lower 
ganglion  cells,  and  by  others  to  be  continuous  with  them.^^  The 
second  or  lower  set  of  neurons  begins  in  the  large  motor 
cells  of  the  cord  and  medulla,  and  extends  thence  to  the  periph- 
eral muscles.  The  voluntary  nervous  impulse  proceeding  to  the 
muscles  may  be  interfered  with  at  any  point  along  this  long 
course,  with  a  resulting  loss  of  muscular  function.  Disturbances 
of  motility  may  arise,  however,  from  other  causes,  such  as  lesions 
of  the  muscles,  bones  and  joints,  on  the  one  hand,  and  from 
lesions  of  those  parts  of  the  nervous  apparatus  that  assist  in 
co-ordinating  the  movements,  or  that  furnish  the  will  power,  on 
the  other. 

Some  hold  that  the  voluntary  motor  impulses  pass  through 
the  cerebellum.  However  this  may  be,  diseases  of  the 
cerebellum  unquestionably  influence  our  volun- 
tary, movements,^*  independently  of  their  effect  upon  our 
29  " 


450  THE  BASIS  OF  SYMPTOMS 

sense  of  equilibrium.  The  innervation  of  muscles  is  greatly- 
affected  by  the  centripetal  impulses  that  go  from  them  to  the 
brain.  These  centripetal  impulses  pass  through  the  cerebellum, 
so  that  cerebellar  disease  at  times  gives  rise  to  typical  ataxia  even 
in  the  absence  of  any  disturbances  of  cutaneous  sensation.  Since 
the  fibres  from  the  cerebellum  to  the  cerebrum  undergo  decussa- 
tion, and  since  the  impulses  from  the  cerebrum  to  the  muscles 
again  cross  the  median  line,  a  unilateral  lesion  of  the  cerebellum 
will  interfere  with  the  movements  of  the  muscles  on  the  corre- 
sponding side  of  the  body,  and  this  interference  may  be  so  marked 
as  to  cause  a  true  cerebellar  hemiplegia. 

If  a  person  is  unable  to  move  a  certain  group  of  muscles, 
we  speak  of  it  as  a  paralysis.  If  the  strength  of  the 
movement  is  merely  weakened,  we  speak  of  it  as  a  paresis. 
Finally,  if  the  movements  are  uncertain  and  irregular,  so  that 
a  desired  movement  cannot  be  accurately  carried  out,  we  speak 
of  it  as  an  ataxia. 

Paralyses  of  Psychic  Origin . — This  class  com- 
prises many  of  the  motor  disturbances  that  occur  in  insane 
patients,  especially  during  stupor,  as  well  as  many  of  the 
hysterical  paralyses.  It  hardly  lies  within  the  prov- 
ince of  this  book  to  discuss  the  nature  of  these  cases,  although 
the  subject  is  an  extremely  interesting  one.  It  would  be  neces- 
sary to  consider  the  nature  of  the  will,  and  the  relation  that 
sensations,  conceptions  and  memory  bear  to  it,  and  then,  finally, 
to  take  up  the  manner  in  which  these  relations  may  be  disturbed 
in  the  various  pathological  conditions  in  question.^ 

Such  "psychical  paralyses"  are  character- 
ized clinically,  mainly  by  their  distribution. 
We  do  not  will  a  single  muscle  to  contract,  but  we  will  a  certain 
movement  to  take  place,  and  this  movement  ordinarily  involves 
the  use  of  numerous  muscles.  Correspondingly,  the  paralyses 
now  under  consideration  do  not  affect  single  muscles,  but  involve 
whole  extremities  or  the  execution  of  certain  movements.  For 
example,  a  patient  may  be  able  to  move  his  legs  in  every  direction 
without  any  incoordination,  and  yet  be  unable  to  walk.  Or  be 
may  be  able  to  execute  all  ordinary  movements  with  his  hand,  but 
be  unable  to  write. 

Closely  related  to  these  psychic  paralyses  is  the  condition 
known  as  a  p  r  a  x  i  a  ,^^    characterized  by  an  inability  to  per- 


THE  NERVOUS  SYSTEM  451 

form  skilled  movements  with  the  limbs,  though  the  motor  power 
is  intact.  The  dog  becomes  apractic  after  removal  of  the  motor 
area.  As  Liepmann  and  Wilson  have  shown,  the  area  in  man 
concerned  in  these  skilled  movements  is  located  in  the  first  and 
second  convolutions  of  the  left  side.  The  condition  is  generally 
ascribed  to  a  loss  of  motor  "concepts,"  and  is  of  interest  par- 
ticularly because  of  the  insight  it  gives  into  the  nature  of  psychic 
paralyses. 

Paralyses  from  Lesions  of  the  Motor 
Tracts. — The  ganglion  cells  of  the  upper  motor  neurons 
are  situated  in  the  so-called  motor  area  of  the  cerebral  cortex, 
and  the  symptoms  that  result  from  an  injury  to  this  part  of  the 
brain  depend  upon  the  portion  of  the  motor  area  that  is  affected. 
The  axis  cylinders  of  these  cells  may  be  injured  at  any  point 
between  their  origin  and  their  final  termination  about  the  large 
motor  cells  of  the  cord  or  medulla.  The  effect  of  an  injury  to  this 
motor  tract  depends  both  upon  which  nerve-fibres  are  injured 
and  upon  the  severity  of  the  injury.  The  motor  fibres  seem 
to  be  more  susceptible  to  pressure  and  stretching  than  are  the 
sensory.  Injuries  to  this  upper  tract  are  caused  most  commonly 
by  tumors,  inflammations  and  hemorrhages.  The  ganglion  cells 
in  the  cord,  or  their  processes  in  the  nerves,  may  be  affected  by 
metallic  poisons,  such  as  lead,  by  the  action  of  micro-organisms 
or  toxins,  as  in  meningitis,  myehtis  and  neuritis,  or  finally  by 
disturbances  of  the  blood-supply. 

Paralyses  from  Lesions  of  the  Muscles . — Dis- 
eases of  the  muscles  naturally  interfere  with  their  functional  capa- 
bilities ;  as  examples  of  such  we  may  mention  the  muscular  disa- 
bility which  accompanies  the  dystrophies,  trichinosis,  polymyositis 
and  the  parenchymatous  degenerations  that  follow  some  acute 
infectious  diseases. 

Paralyses  from  Vascular  Disturbances. — Dis- 
turbances of  the  blood-supply  to  muscles  may  also  interfere  with 
their  capabilities.  Veterinarians  have  long  known  that  arterial 
disease  in  the  legs  of  horses  seriously  affects  their  powers  of 
locomotion.  The  same  is  true  of  man,  and  the  resulting  in- 
termittent claudication  is  apparently  much  more 
frequent  than  is  generally  supposed. ^^  If  the  arteries  supplying 
an  extremity  become  very  narrow,  the  quantity  of  blood  that 
reaches  this  extremity  may  be  sufficient  to  meet  all  ordinary  needs. 


452  THE  BASIS  OF  SYMPTOMS 

but  at  the  same  time  it  may  be  insufficient  for  any  extraordinary 
demands.  When  the  patient  walks,  therefore,  the  increased  de- 
mands of  the  muscles  for  fresh  blood  cannot  be  supplied,  and, 
after  a  certain  distance,  the  leg  becomes  fatigued  and  painful, 
so  that  the  patient  can  walk  no  farther.  If  he  rests,  however, 
the  power  gradually  returns  and  the  pain  leaves  his  legs,  because 
the  supply  of  blood  is  again  sufficient.  These  characteristic 
symptoms  of  intermittent  claudication  are  usually  associated  with 
definite  anatomical  alterations — usually  an  obliterating 
endarteriti s — in  the  vessels  of  the  affected  extremities.  Not 
infrequently,  these  vascular  changes  eventually  lead  to  gangrene. 
Apparently  a  similar  intermittent  disturbance  of  function  may  be 
caused  by  a  functional,  spasmodic  narrowing  of  the 
arteries  from  nervous  causes.  The  parallelism  be- 
tween intermittent  claudication  and  angina  pectoris  is,  therefore, 
rather  striking,  for  both  are  usually  associated  with  arterio- 
sclerosis, but  both  may  apparently  be  caused  by  a  nervous  spasm 
of  the  corresponding  arteries. 

Myotonia  Congenita . — The  members  of  certain  fami- 
lies, from  youth  on,  are  unable  to  relax  their  muscles  normally 
after  contraction,  because  the  muscle  remains  in  a  sort  of  tetanus. 
This  rigidity  is  most  pronounced  after  a  period  of  rest,  while,  as 
a  rule,  it  lessens  after  each  repetition  of  the  movement.  The 
muscles  themselves  are  usually  quite  strong,  even  more  so  than 
normally.  We  may  infer  that  the  cause  of  the  disability  is  located 
in  the  muscle  itself,  for  its  reaction  to  the  electric  current  is 
abnormal  (Erb's  myotonic  reaction),  and  its  anatomi- 
cal structure  is  also  considerably  altered.^^ 

Asthenic  Bulbar  Paralysis.^* — This  disease,  other- 
wise known  as  myasthenia  gravis  pseudo-paraly- 
tica,  is  characterized  clinically  by  the  ease  with  which  certain 
muscles  become  fatigued  after  comparatively  slight  exertion. 
This  fatigue  occurs  after  voluntary  use  of  the  muscles,  as  well 
as  after  stimulation  by  the  electric  current,  but  the  ease  with 
which  the  fatigue  develops  seems  to  vary  from  time  to  time. 
Certain  muscles,  especially  those  supplied  from  the  medulla,  tend 
especially  to  be  affected.  This  disease  involves  the  motor  appara- 
tus, yet  the  exact  point  affected  is  not  known,  for  anatomical 
investigations  have  thus  far  failed  to  show  any  lesion. 

Disturbances  of  Coordination. — Before   we  proceed  to  the 


THE  NERVOUS  SYSTEM  453 

discussion  of  the  disturbances  of  coordination,^^  it  is  necessary 
to  consider  the  mechanism  whereby  we  normally 
govern  our  movements,  so  that  they  shall  be  executed 
in  a  precise  and  exact  manner.  The  consideration  of  the  normal 
mechanism  of  coordination  presents  certain  difficulties,  however, 
for  we  are  not  certain  that  it  is  the  same  in  every  case.  The 
adult  executes  many  movements  at  will,  whereas  there  are  others 
that  he  learns  only  by  practise.  Of  the  latter,  some,  such  as 
piano-playing,  are  learned  only  by  certain  individuals,  while  others, 
such  as  walking,  speaking  and  writing,  are  learned  by  all  men, 
this  being  facilitated,  doubtlessly,  by  the  fact  that  our  fore- 
fathers have  practised  these  movements  for  generations.  There 
is  a  gradual  transition  from  the  movements  that  must  be  learned 
to  the  purely  voluntary  movements,  and  from  these  voluntary 
movements  again  there  is  a  gradual  transition  to  the  purely  in- 
voluntary movements.  To  this  second  transitional  class  belong 
those  movements  of  a  reflex  or  automatic  type,  such  as  breathing 
and  suckling,  that  are  executed  from  birth  on.  As  an  illustration 
of  the  difficulty  encountered  in  attempting  to  separate  these  dif- 
ferent classes  of  movements,  we  may  cite  the  fact  that,  while 
swimming  must  be  learned  by  man,  many  animals  can  swim  when 
they  first  enter  the  water. 

There  are,  therefore,  all  grades  of  transition  from 
the  pure  reflex  movements  to  the  most  complex 
volitional  acts.  Indeed,  the  transition  occurs  many 
times  in  the  life  of  a  single  individual,  for  movements  that  were 
once  learned  only  with  the  utmost  attention  and  volition  are 
ultimately  executed  almost  unconsciously,  merely  by  willing 
to  do  them.  At  first,  these  complex  acts  are  carried  out  under  the 
conscious  guidance  of  all  our  senses,  particularly  those  of  sight, 
touch,  position,  etc.,  but  by  practice  they  come  to  be  executed 
without  the  individual  constituent  movements  of  the  act  coming 
to  our  consciousness. 

We  know  something  about  the  nervous  mechanism 
that  underlies  these  complex  practised  move- 
ments and  the  more  complicated  reflexes.  These 
movements  may  be  set  in  motion  voluntarily,  or  by  nervous 
impulses  from  the  periphery,  or,  finally,  by  but  little-understood 
internal  chemical  changes.  Since  the  resulting  movements  are 
varied  more  or  less  to  suit  the  occasion,  it  seems  improbable 


454  THE  BASIS  OF  SYMPTOMS 

that  they  should  be  guided  by  a  completely  developed  mechanism 
lying  within  the  central  nervous  system.  It  would  appear  rather 
as  if  they  were  guided  by  impulses  from  the  periph- 
ery, a  supyposition  which  receives  strong  support  from  the  ex- 
periments that  have  been  performed  on  frogs,  dogs  and  monkeys.^ 
If  the  posterior  nerve-roots  in  these  animals  be  cut — i.e.,  if  the 
sensory  impulses  from  the  periphery  be  eliminated — not  only 
the  complicated  reflexes  but  the  more  complex  practised  move- 
ments, such  as  jumping  and  running,  can  no  longer  be  carried  out 
as  the  animal  wills,  with  exactness  and  precision.  Some  muscles 
contract  too  strongly,  others  too  feebly,  and  still  others  at  the 
wrong  time,  so  that  the  resulting  movement,  as  a  whole,  loses  its 
precision,  and  the  picture  is  very  similar  to  that  seen  in  certain 
nervous  diseases  that  occur  in  man,  especially  tabes. 

Since  an  electrical  stimulation  of  the  motor  region  of  the 
cerebral  cortex  gives  rise  to  movements,  not  of  individual  muscles, 
but  of  coordinated  groups  of  muscles,  we  are  led  to  infer  that, 
in  the  cortex,  movements,  and  not  individual  muscles,  are  repre- 
sented.^'^ A  further  grouping  of  muscles  for  the  execution  of 
certain  movements  occurs  in  the  anterior  horn  cells  of  the  spinal 
cord  and  in  the  root-fibres.  It  is  quite  certain,  therefore,  that  a 
certain  degree  of  coordination  is  derived  from 
this  arrangement  of  the  cells  in  the  motor  ner- 
vous system,  though,  as  we  have  seen,  this 
grouping  is  not  sufficient  for  complex  acts. 
For  these  we  depend  more  or  less  upon  periph- 
eral sensory  impulses.  We  may  or  we  may  not  be 
conscious  of  these  impulses,  yet  even  when  we  are  not  conscious 
of  them,  they  may  be  utilized  by  the  lower  centres  in  the  mechan- 
ism of  coordination.  These  two  forms  of  sensation,  conscious 
and  unconscious,  cannot  be  strictly  separated  from  each  other, 
for  our  consciousness  of  them  depends  largely  upon  the  attention 
that  we  direct  to  them.  Clinical  evidence  based  upon  many  cases 
of  syringomyelia  indicates  that  in  man  the  loss  of  sensation  pro- 
ceeding from  the  skin  is  in  itself  insufficient  to  destroy  coordina- 
tion. 

Many  varieties  of  sensation  may  affect  our 
movements.  Of  these,  we  may  name  the  senses  of  sight 
and  of  hearing,  those  of  pressure  upon  the  skin,  muscles,  ten- 
dons and  joints,  and,  finally,  the  senses  of  position  and  of  motion. 


THE  NERVOUS  SYSTEM  455 

Some  of  these  are  of  greater  importance  than  others ;  and  we  have 
seen,  for  example,  that  the  senses  of  sight  and  of  hearing  alone 
are  inadequate  in  the  monkey  and  the  dog  to  maintain  coordina- 
tion during  such  complex  movements  as  jumping  and  running. 

Of  the  sensations  mentioned,  the  most  important  in 
the  coordination  of  voluntary  movements  are 
those  derived  from  the  tendons,  the  joints  and 
the  eyes. ^®  If  the  two  former  are  affected  in  the  first  inter- 
phalangeal  joints,  for  example,  then  even  such  simple  movements 
as  the  flexion  and  extension  of  the  fingers  may  become  ataxic. 
In  addition  to  these  sensations  from  the  joints,  tendons  and  eyes, 
others  from  the  muscles  may  also  play  a  considerable  role  in 
governing  our  movements. 

While  the  grouping  of  muscles  according  to  their  use  in  the 
motor  nervous  apparatus  may,  therefore,  furnish  a  rough  sort 
of  coordination,  this  is  insufficient  for  the  finer  move- 
ments. For  their  execution,  centripetal  impulses 
from  the  periphery  are  necessary  in  order  to  control  the 
time  at  which  the  individual  muscles  shall  begin  their  contractions, 
the  force  with  which  they  shall  contract  and  the  time  during  which 
they  shall  remain  contracted. 

After  this  preliminary  discussion  of  the  theory  of  coordina- 
tion, it  remains  to  inquire  to  what  extent  disturbances  of  sensation 
have  been  actually  found  in  patients  who  suffer  from  ataxia,  i.e., 
from  an  inability  to  carry  out  movements  in  a  precise  and  accurate 
manner.  It  is  quite  certain  that  ataxia  may  occur  without  any 
demonstrable  diminution  in  the  cutaneous  senses  of  pressure,  tem- 
perature or  pain.^**  On  the  other  hand,  it  has  not  been 
shown  that  ataxia  ever  occurs  independently  of 
all  sensory  disturbances,  and  the  earlier  cases  that 
were  believed  to  prove  this  were  not  sufficiently  investigated  as 
to  the  finer  losses  of  sensation  in  the  joints  and  muscles.^^ 
Frenkel,  in  studying  one  hundred  and  fifty  cases  of  tabes,  failed 
to  find  a  single  instance  of  ataxia  unaccompanied  by  sensory 
changes,  at  least  in  the  joints  and  muscles.^^  We  may  say,  there- 
fore, that  the  main  cause  of  tabetic  ataxia  is  a  de- 
ficiency in  the  impulses  proceeding  from  the  joints  and  muscles. 
That  this  deficiency  may  be,  to  a  certain  extent,  compensated 
for  in  other  ways,  is  shown  by  the  reliance  which  ataxic  indi- 
viduals  place   upon   their   visual    impressions.      Possibly    the 


456  THE  BASIS  OF  SYMPTOMS 

absent  reflexes  as  well  as  the  diminution  in  mus- 
cular tonus,  also  play  a  not  inconsiderable  part  in  the 
motor  disturbances  of  tabetics.^^ 

We  now  come  to  a  consideration  of  the  effect  exer- 
cised by  known  disturbances  of  sensation  upon, 
coordination.  In  other  words,  do  such  disturbances 
necessarily  lead  to  ataxia?  Many  young,  apparently  hysterical, 
persons  have  been  observed  who  have  shown  extensive  anaes- 
thesias of  the  skin  and  of  the  deeper  structures,  without,  how- 
ever, exhibiting  any  true  ataxia.^^  When  they  kept  their  eyes 
open,  their  movements  were  perfectly  normal,  which,  as  we  have 
seen,  was  not  the  case  when,  experimentally,  all  sensory  impulses 
from  an  extremity  were  cut  off.  If  these  patients  closed  their 
eyes,  their  voluntary  movements  were  indeed  somewhat  abnormal, 
but  no  true  ataxia  was  present.  To  my  mind,  however,  it  is  neces- 
sary to  be  very  cautious  in  our  interpretation  of  these  observa- 
tions, because  the  sensory  disturbances  were  apparently  of  an 
hysterical  character.  Hysterical  disturbances  of  sen- 
sations unquestionably  have  their  seat  in  the  most  central 
part  of  the  nervous  system — in  the  mind  itself,  so  to  speak — 
and  even  though  these  patients  are  not  conscious  of  their  sensa- 
tions, the  latter  may  certainly  be  utilized  by  the  lower  centres  for 
coordination.  In  no  other  way  can  we  explain  the  fact  that 
an  hysterical  girl,  with  an  absolute  insensibility  of  her  hands, 
is  able  to  execute  the  most  delicate  hand-work.  Indeed,  many 
hysterical  patients  do  not  know  that  they  have  anaesthesias,  mainly 
because  the  latter  do  not  cause  any  motor  disturbances.  It  seems 
probable,  therefore,  that  in  the  cases  cited  above  the  ataxia  was 
absent  because  the  patients  unconsciously  utilized  the  centripetal 
impulses  coming  from  the  extremities. 

Investigations  on  other  forms  of  complete  lack  of  sensation 
are  so  few  that  it  is  impossible  to  render  a  final  verdict  concerning 
the  effect  that  these  produce  upon  coordination.  Striimpell, 
however,  has  recently  published  a  case  in  which  a  complete 
absence  of  sensation  in  the  right  arm  affected  movements  most 
seriously.  So  long  as  the  patient's  eyes  were  kept  open,  the 
ataxia  was  comparatively  slight,  but,  as  soon  as  they  were  closed, 
the  incoordination  became  extreme.^* 

We  have  shown  that  centripetal  sensory  im- 
pulses   are    absolutely    necessary    for    a    proper 


THE  NERVOUS  SYSTEM  457 

coordination  of  any  complex  act.  The  lesion  that 
produces  the  incoordination,  however,  does  not  necessarily  lie 
in  the  peripheral  tracts,  but  may  be  so  situated  in  the  central 
nervous  system  that  it  hinders,  in  some  manner,  the  transmission 
of  impulses  across  this  system,  as  has  been  shown  in  a  number 
of  cases.^^  Ataxias  may,  therefore,  be  due  to  different  causes, 
and  the  resulting  clinical  picture  is  not  always  the  same.  When 
we  speak  of  ataxia  in  general  we  usually  refer  to  the  tabetic  type, 
for  that  is  the  most  common  and  the  best  understood  form.  In 
this  form,  the  ataxia  is  always  accompanied  by  demonstrable 
sensory  changes. 

If,  from  any  cause,  our  movements  become  more  or  less  inco- 
ordinated,  then  we  attempt  to  compensate  for  the  loss  of  peripheral 
control  by  directing  them  through  the  higher  centres,  very  much 
as  does  one  who  is  trying  for  the  first  time  to  execute  a  difficult 
movement.  The  movement,  thus  directed,  is  usually  performed 
more  slowly  and  less  accurately  than  is  one  automatically  regu- 
lated. Indeed,  it  not  infrequently  happens  that  when  a  normal 
individual  attempts  to  execute  some  difficult  feat  particularly  well, 
i.e.,  when  he  watches  each  individual  movement,  the  act  is  done 
particularly  badly.  This  shows  the  superiority  of  the  automatic 
regulation  over  the  volitional.  A  compensation  for  losses  of 
centripetal  control  may  be  developed,  however,  in  another  way. 
When  the  sensory  impulses  from  the  affected  extremity  are  not 
all  shut  off,  the  patient  may  learn  to  utilize  those  that  are  left  to 
a  far  greater  extent  than  they  were  ever  used  previously,  and 
so  to  develop  a  new  automatic  regulation. 

Disturbances  of  sensation  may  affect  the 
functions  of  the  body  in  other  ways  than  by 
causing  ataxia;^®  and  here  again  the  loss  of  certain  sen- 
sations may  be  compensated  for,  to  a  certain  extent,  by  other 
sensations,  and  especially  by  those  that  come  from  the  eyes. 
For  this  reason,  it  frequently  happens  that  such  disturbances 
become  manifest  only  when  the  patient  closes  his  eyes.  When 
the  sense  of  touch  in  the  hands  is  lost,  the  patient  is  unable  to 
grasp  objects  properly  or  to  gain  an  idea  of  the  contour  of  sur- 
faces, unless  the  eyes  follow  the  movements  of  the  hand.  If  the 
senses  of  position  and  of  motion  are  diminished,  all  the  finer 
movements  that  depend  upon  the  position  of  the  body  or  of  the 
hand  in  space  are  not  executed  accurately  except  imder  ocular 


458  THE  BASIS  OF  SYMPTOMS 

control.  The  deaf-mute,  whose  semicircular  canals  are  destroyed, 
becomes  imsteady  as  soon  as  his  eyes  are  closed,  just  as  does  the 
ataxic  tabetic. 

The  ataxias,  depending  upon  their  anatomical  origin,  have 
been  classified  as  peripheral,  spinal  ,  pontine,  cere- 
bellar and  cerebral;  and  each  of  these  types  presents  to 
a  certain  extent  a  characteristic  clinical  complex.  This  is  readily 
understandable  even  for  those  cases  due  to  disturbances  of  centri- 
petal sensory  impulses,  for  the  latter  must  take  paths  which  vary 
with  the  difference  in  location  of  the  lesion  in  the  above-men- 
tioned forms. 

The  disturbances  of  coordination  seen  in 
cerebellar  lesions  deserve  a  final  word.^''^  Certain  of 
these  disturbances  differ  in  nowise  from  those  of  the  tabetic. 
There  is  this  difference,  however,  that  in  cerebellar  affairs  the 
ataxia  becomes  less  pronounced  when  the  patient  lies  in  bed, 
for  the  cerebellum  has  to  do  essentially  with  static  control  and 
with  the  coordination  of  such  movements  as  walking,  standing 
and  running,  which  are  not  immediately  under  voluntary  control, 
but  are  influenced  rather  by  impulses  from  such  sensory  organs 
as  the  semicircular  canals  and  the  eyes.^^  Lewandowsky  ^^  has 
well  expressed  the  function  of  the  cerebellum  in  this  respect  in 
his  statement  "that  the  cerebellum  governs  those  phases  of  our 
movements  not  under  the  influence  of  the  cerebral  threshold  of 
consciousness." 

The  Effect  upon  Motion  of  Variations  in  the  Reflexes. — 
Although  the  reflexes  have  been  carefully  studied,  especially  in 
regard  to  their  diagnostic  significance,  very  little  attention  has 
been  paid  to  the  important  influence  that  they  exert  upon  our 
voluntary  movements,  this  being  due  to  the  effect  that  they 
have  upon  the  state  of  contraction  of  the  muscles. 
In  addition  to  this  they  serve  to  protect  the  joints  from 
forcible  and  sudden  motions.**^ 

It  is  extremely  difficult  to  estimate  the  precise  injury  that 
is  caused  by  an  absence  of  the  tendon  reflexes,  for  such  absence 
is  usually  associated  either  with  paralysis  or  with  definite  sensory 
changes.  The  important  part  played  by  the  latter  in  the  causa- 
tion of  disturbances  of  movement  has  already  been  emphasized — 
a  mechanism  which  may  also  be  regarded  as  a  reflex.  The  stud- 
ies of  Sherrington*^  in  this  field  have  been  extremely  elucidative. 


THE  NERVOUS  SYSTEM  459 

When  the  reflexes  are  much  exaggerated,  the  tension  of  the 
muscles  is  increased  to  such  a  degree  that  the  slightest  irritation 
will  call  forth  a  reflex  spasm.  With  every  motion,  the 
tendons  and  ligaments,  especially  those  opposing  the  movement, 
are  put  more  or  less  upon  the  stretch.  This  initiates  reflex  muscu- 
lar contractions,  which  tend  especially  to  affect  the  antagonists 
of  the  muscles  that  are  innervated.  As  a  result,  all  movements 
become  stiff,  and  in  very  bad  cases  even  impossible.  This  reflex 
innervation  of  antagonistic  muscles  may  cause  such  uncertainty 
of  movement  that  the  resulting  picture  resembles  true  ataxia,  e.g., 
in  multiple  sclerosis. 

Nervous  Disturbances  of  Urination  and  Defecation. — The 
reflex  acts  of  urination  and  defecation  are  so  far  under  the  control 
of  the  will  that,  up  to  a  certain  limit,  we  can  inhibit  or  initiate 
them.  The  nervous  impulses  running  from  the  brain  to  the  lower 
centres  merely  prevent  or  permit  the  reflex  that  is  initiated  by 
peripheral  sensations. 

The  reflex  centres  that  control  defecation 
and  urination  are  not  situated  in  the  cord,  as  has  been 
generally  supposed,  but  lie  in  the  sympathetic  system.^ ^  The 
centripetal  impulses  that  these  centres  receive  from  their  corre- 
sponding organs  are,  in  part,  excited  by  distention  of  the  organ. 
Yet  distention  is  only  one  of  the  factors  that  initiate  the  reflex, 
for  we  urinate  different  amounts  at  different  times,  and  much  less 
when  the  mucous  membrane  of  the  bladder  is  inflamed,  or  when 
the  urine  is  concentrated,  highly  acid  and  irritating. 

In  the  new-born  infant,  urination  and  defecation  are  purely 
reflex  phenomena.  When  the  centripetal  impulses  become  sufii- 
ciently  strong,  the  reflex  mechanism  is  set  in  motion  and  the 
viscus  is  emptied.  Only  through  careful  training  does  the  child 
learn  to  govern  these  reflexes  and  gradually  to  bring  them  within 
the  normal  limits  of  control. 

If  the  impulses  running  from  the  cerebrum  to  the  lower 
centres  be  interrupted  from  any  cause,  voluntary  control  over 
evacuation  is  lost.  For  a  time  after  these  impulses  are  cut  off, 
the  bladder  remains  full  and  continually  overflows  (incon- 
tinence from  retention),  but  gradually  it  comes  to 
empty  itself  reflexly  at  intervals,  just  as  it  does  during  infancy. 
Since  this  reflex  emptying  of  the  bladder  may  occur  even  when 
the  lumbar  cord  is  destroyed,  the  centre  lies  outside  the  cord. 


460 


THE  BASIS  OF  SYMPTOMS 


Other  nervous  lesions  cause  variable  disturbances.  For  ex- 
ample, a  loss  of  centripetal  impulses  from  the  bladder  to  the  reflex 
centre  will  lead  to  a  pure  retention;  while  a  diminution  in  these 
impulses  will  lead  to  difficulty  in  passing  urine,  to  straining  and 
to  delay  in  starting  the  stream.  Lesions  of  the  motor  paths  may 
cause  similar  disturbances,  such  as  slow  urination  and  the  reten- 
tion of  urine  in  consequence  of  a  paresis  of  the  detrusor,  and  con- 
tinual dribbling  as  the  result  of  a  weakness  of  the  sphincter.  Irri- 
.tative  lesions  of  the  tracts  that  connect  the  cerebrum  with  the 
reflex  centre  may  cause  retention  of  urine  from  spasm  of  the 
sphincters.  Finally,  it  must  be  remembered  that  the  external 
sphincter  is  a  voluntary  muscle,  and  that  when  it  is  pvaralyzed 
there  may  result  merely  an  inability  to  hold  the  urine  when  the 
bladder  becomes  filled. 

The  nervous  disturbances  of  defecation  appear  to  be  very 
similar  to  those  of  urination. 

Pathological  Alterations  in  the  Reflexes. — In  a  pure  reflex, 
the  sensory  impulse  acts  immediately  upon  the  motor  apparatus 
without  the  intervention  of  the  will.  The  reflex  mechanism  con- 
sists, therefore,  of  the  sensory  apparatus,  the  motor  apparatus  and 
the  connection  between  the  two.  The  latter  may  be  situated  either 
in  the  brain,  the  spinal  cord  or  the  sympathetic  system. 

The  Deep  Reflexes . — Those  reflexes  which  arise  from 
the  tendons,  periosteum  or  bones,  and  of  which  the  patellar 
reflex  is  the  best-known  example,  traverse  the  spinal  cord  or  the 
subcortical  portions  of  the  brain.  They  are  subject  to  many  and 
diverse  influences,  which  may  act  either  directly  upon  the  sensory 
or  motor  apparatus,  or,  more  indirectly,  may  tend  to  inhibit  or 
to  further  the  transference  of  the  impulse  from  the  sensory  to 
the  motor  side  of  the  reflex  arc.*^ 

Even  normally  there  is  a  great  variation  in  the  intensity  of 
the  reflexes,  not  only  in  different  individuals,  but  in  the  same 
individual  at  different  times,  the  latter  being  especially  true  of 
"  nervous  "  patients.  The  reflexes  tend  to  be  exaggerated  during 
fatigue,  as  well  as  in  marantic  and  cachectic  conditions.  They 
show  considerable  variations  in  the  infectious  diseases.  They 
usually  disappear  just  before  death. 

If  the  reflex  arc  be  broken  at  any  point,  whether 
in  the  sensory,  the  motor  or  central  portion,  the  corresponding 
reflex  is  abolished.     In  the  earliest  stages  of  tabes  dorsalis,  for 


THE  NERVOUS  SYSTEM  461 

example,  the  knee-jerks  may  be  absent  because  that  part  of  the 
cord  through  which  the  sensory  portion  of  the  reflex  must  travel 
has  degenerated.  Even  when  the  reflex  is  absent,  however, 
it  is  possible  that  the  path  is  not  completely  blocked,  but  only 
to  the  extent  that  it  inhibits  the  reflex  taking  place  under  ordi- 
nary conditions.  If  such  be  the  case,  then  a  cerebral  lesion  that 
would  normally  increase  the  reflex  may  cause  the  lost  one  to 
return.     This  has  been  observed  in  a  number  of  cases.** 

A  disease  of  the  reflex  arc,  such  as  a  neuritis,  at 
times  causes  an  exaggeration  of  the  corresponding  reflex.  It  is 
possible  that  in  these  cases  the  inflamed  sensory  nerves  show 
an  increased  irritability  or  conductivity ;  though  it  is  also  possible, 
as  Sternberg  believes,  that  the  exaggeration  is  caused  by  changes 
in  the  reflex  centre. 

The  deep  reflexes  may  be  influenced  by  lesions  that  lie 
outside  of  the  reflex  apparatus  itself.  The  most 
important  of  these  are  the  lesions  which  interrupt  the 
passage  of  impulses  from  the  cerebrum,  or  pos- 
sibly also  from  the  subcortical  centres,  down  to 
the  lower  spinal  reflex  centres.  Injuries  of  this 
character  are  usually  followed  by  an  exaggeration  of  the  deep 
reflexes,  and  it  has  been  assumed  that  this  results  from  a  blocking 
of  the  inhibitory  influence  which  the  brain  is  supposed  to  exert 
upon  the  spinal  centres.*^  Yet  the  correctness  of  this  interpre- 
tation may  justly  be  questioned,  for  numerous  observations  have 
established  the  fact  that  the  patellar  reflexes  may  totally  disappear 
after  a  complete  transverse  section  of  the  spinal  cord.*®  In  some 
such  cases,  however,  the  tendon  reflexes  have  persisted  in  spite 
of  the  transverse  lesion ;  and  experiments  upon  dogs  and  monkeys 
have  yielded  equally  conflicting  results.  In  them,  a  complete 
section  of  the  cord  may  be  followed  either  by  increased  or  by 
diminished  reflexes.  Immediately  after  the  operation  on  these 
animals,  the  reflexes  are  usually  abolished,  but  they  gradually 
return  after  a  certain  length  of  time.  The  primary  injury  itself 
may  possibly  inhibit  them  for  a  time,  thus  causing  their  early 
disappearance ;  but  their  continued  absence  in  clinical  cases  cannot 
be  accounted  for  in  this  manner.  Trendelenburg  and  Munk,  on 
the  basis  of  their  experimental  studies,  have  come  to  the  conclusion 
that  the  brain  exerts  a  stimulating,  rather  than  an  inhibiting 
influence,  upon  the  spinal  centres,  and  that  the  continued  absence 


462  THE  BASIS  OF  SYMPTOMS 

of  the  reflexes  observed  after  section  of  the  cord  high  up  is 
generally  the  result  of  secondary  changes.'*'^ 

The  Superficial  Reflexes. — These  are  of  a  more 
complex  character  than  are  the  deep  reflexes,  and  their  nature 
is  less  understood.'*®  A  relatively  slight  stimulus  applied  to  the 
skin  or  to  a  mucous  membrane  will  often  elicit  a  relatively  strong 
response,  and  the  resulting  movements  are  usually  slower  and 
more  under  the  control  of  the  will  than  are  the  deep  reflexes. 
It  is  quite  possible  that  the  nervous  path  that  some  of  these  skin 
reflexes  follow  traverses  the  cerebrum,  and  that  this  is  the  reason 
why  they  are  so  often  absent  in  the  very  conditions  in  which  the 
tendon  reflexes  are  exaggerated.  Yet  this  is  very  questionable 
and  the  data  at  our  disposal  do  not  permit  us  to  formulate  even 
an  hypothesis  as  to  the  nature  of  the  superficial  reflexes. 

Strychnin  Poisoning  and  Tetanus. — The  violent  muscular 
contractions  that  characterize  these  conditions  are  caused  by  an 
increased  irritability  of  the  cells  in  the  spinal  cord.  In  strychnin 
poisoning,  the  convulsions  are  of  a  purely  reflex  nature,  i.e., 
they  are  excited  by  sensory  impulses  from  the  periphery.  In 
tetanus,  some  are  of  this  character,  while  others  are  due  to  a 
primary  stimulation  of  the  large  motor  cells  in  the  cord.  These 
cells,  undoubtedly,  become  abnormally  irritable  in  tetanus,  and 
some  remarkable  anatomical  changes  in  them  have  been  described. 

The  brilliant  researches  of  Meyer  and  Ransom^®  have  shown 
that  the  tetanus  toxin  travels  from  the  periphery  to  the 
spinal  cord  through  the  axis-cylinders  of  the  nerves,  and  that  it 
cannot  attack  the  cord  directly  from  the  blood  or  lymph.  The 
nerves  must  first  be  entered.  For  example,  if  tetanus  antitoxin 
be  injected  into  certain  nerve-trunks  of  cin  animal,  and  if,  at  the 
same  time,  the  toxin  be  injected  into  the  blood  or  lymph,  the 
regions  corresponding  to  the  nerves  that  have  received  the  anti- 
toxin are  not  affected  during  the  ensuing  tetanus.  When  tetanus 
toxin  is  injected  directly  into  the  spinal  cord,  the  incubation  period 
that  elapses  before  the  appearance  of  symptoms  is  reduced  to 
about  two  and  a  half  hours.  This  demonstrates  that  the  long 
incubation  period  usually  present  in  tetanus  is  due  to  the  time 
consumed  by  the  toxin  in  travelling  from  the  periphery  to  the 
central  structures. 

The  tetanus  toxin  first  affects  the  motor  cells  of  the  cord  in 
such  a  way  as  to  irritate  them  and  to  cause  a  tonic  spasm  of  the 


THE  NERVOUS  SYSTEM  463 

corresponding  muscles,  the  spasm  not  being  of  a  reflex  character. 
The  toxin  then  spreads  to  neighboring  cells,  especially  to  the  motor 
cells  lying  on  the  opposite  side  of  the  cord,  with  resulting  convul- 
sions in  the  same  muscles  as  those  first  affected,  but  on  the  opposite 
side  of  the  body.  Still  later,  when  the  poison  affects  the  sensory 
portion  of  the  reflex  arc,  reflex  convulsions  occur ;  yet  only  those 
reflexes  are  increased  which  pass  through  the  affected  parts  of 
the  cord. 

The  sensory  nerve-fibres  do  not  seem  to  be  affected  by  the 
tetanus  toxin  under  ordinary  conditions ;  yet  Meyer  and  Ransom 
have  shown  that  if  the  toxin  be  injected  directly  into  the  posterior 
nerve-roots,  the  first  symptoms  of  the  poisoning  are  attacks  of 
violent  pain — the  so-called  tetanus   dolorosus. 

Tetanus  in  man  differs  from  that  produced  experimentally 
in  animals  in  that  the  muscles  first  affected  are  usually  those  of 
the  jaw,  causing  the  well-known  trismus ;  whereas,  experimentally, 
the  convulsions  begin  in  the  muscles  that  correspond  to  the  point 
of  inoculation. 

It  is  a  noteworthy  fact  that  tetanus  antitoxin  cannot  be  iso- 
lated from  the  nervous  structures  it  involves ;  nor  does  it  appear 
capable  of  penetrating  these  structures.  This  speaks  against  the 
assumption  that  an  antitoxin  is  produced  in  the  cells  specifically 
attacked  by  the  poison.  If  the  latter  be  prevented  from  reaching 
the  central  nervous  system,  by  cutting  the  nerves  of  the  extremity 
into  which  it  is  injected,  there  occurs  a  marked  formation  of 
antitoxin  and  the  establishment  of  an  immunity. ^^ 

Contractures. — The  bones  about  a  joint  are  not  infrequently 
held  in  a  more  or  less  fixed  position.  This  may  be  due  to  a  num- 
ber of  causes,  such  as  diseases  of  the  joints,  scars  in  the  skin 
or  muscles,  and  changes  in  the  muscles,  either  primary  or  second- 
ary to  nervous  lesions.  Any  of  these  might  be  termed  con- 
tractures, though  it  is  customary  to  restrict  the  use  of  the  term 
to  those  limitations  of  motion  that  follow  disease  of  the  muscles 
or  of  the  nerves.^^ 

If,  for  any  reason,  certain  muscles  remain  shortened  over  a 
long  period  of  time,  this  shortening  tends  to  become  permanent, 
and  the  movements  of  the  joint  are  then  correspondingly  limited. 
This  condition  is  spoken  of  as  a  passive  contracture. 
Of  the  causes  that  may  lead  to  such  a  shortening  of  the  muscles, 
we  may  name  the  maintenance  of  a  certain  posture 


464  THE  BASIS  OF  SYMPTOMS 

foralongtime.  In  this  manner,  a  foot-drop  is  not  infre- 
quently produced  by  the  pressure  of  the  bedclothes  during  a  long 
illness.  When  certain  groups  of  muscles  are  weakened  or 
paralyzed,  either  from  disease  of  the  muscles  themselves  or  from 
disease  of  their  nervous  connections,  the  antagonistic  muscles,  not 
meeting  with  the  normal  resistance  to  their  action,  tend  to  move 
the  joint  into  an  abnormal  position  and  to  hold  it  there.  When- 
ever the  joint  has  been  held  in  a  certain  position  for  a  long  time, 
it  tends  to  be  fixed  in  this  position  both  by  the  development  of 
adhesions  about  the  joint  itself  and  by  anatomical  alterations  in 
the  shortened  muscles.  Passive  contractures  have  been  produced 
experimentally  in  monkeys  by  the  extirpation  of  portions  of  the 
cerebral  cortex,  and  by  subsequently  keeping  the  animals  in  such 
small  cages  that  their  movements  were  very  much  limited.^^ 

In  active  contractures,  the  joints  are  held  in  an 
abnormal  position  by  the  tonic  contraction  of  certain  groups  of 
muscles.  Since  there  is  usually  an  associated  increase  in  the 
tendon  reflexes  in  these  cases,  they  have  been  termed  by  some, 
spastic  contractures.  The  cause  of  the  muscular 
spasm  which  produces  the  contracture  is  not  always  clear,  and 
it  may  not  be  the  same  in  all  cases.  As  we  have  said,  the  re- 
flexes are  usually  exaggerated  in  active  contrac- 
tures, yet  not  necessarily  so,  and  in  some  cases  they  remain 
unaffected. 

When  the  reflexes  are  increased,  the  contractures  might  pos- 
sibly be  caused  by  an  unequal  reflex  stimulation  of 
the  different  groups  of  muscles  about  a  joint. 
To  my  mind,  however,  this  explanation  is  not  an  entirely  satis- 
factory one,  for  it  seems  very  probable  that,  in  many  cases,  at 
least,  the  contractures  and  the  exaggerated  reflexes  are  both  due 
to  a  common  cause. 

Mann^^  has  given  a  very  plausible  explanation  of  post- 
hemiplegic contractures.  He  first  calls  attention  to  the  fact  that 
these  contractures  affect  especially  the  muscles  that  are  least 
paralyzed.  In  the  complicated  innervation  that  directs  every 
voluntary  movement,  there  is  apparently  not  only  a  stimu- 
lation of  the  muscles  that  produce  the  move- 
ment, but  an  inhibition  of  the  antagonistic 
muscles.  A  cerebral  disease,  therefore,  will  not  only  paralyze 
certain  muscles,  but  will,  at  the  same  time,  diminish  the  inhibitory 


THE  NERVOUS  SYSTEM  465 

impulses  sent  to  their  antagonists.  This  lack  of  inhibition  would 
explain  the  contracture  in  the  antagonistic  muscles ;  and  Mann's 
hypothesis  accords  very  well  with  the  experimental  results  of 
H.  E.  Hering.5^ 

At  the  outset,  every  complete  cerebral  paralysis  is  flaccid,  and 
contractures  do  not  occur  until  the  paralyses  of  the  different 
muscle-groups  affected  recede  in  unequal  degree.  Cen- 
tripetal sensory  impulses  likewise  favor  the  ap- 
pearance of  contractures,  whereas  the  absence  of  such 
impulses  tend  to  prevent  them  {e.g.,  in  tabes).  It  is  evident, 
therefore,  that  the  mechanism  of  contracture  production  is  a 
complex  one,  depending  upon  the  reflex,  and  possibly  also  the 
direct,  stimulation  of  muscle-groups  of  antagonistic  action,  and 
upon  the  net  result  of  paralysis  and  inhibition.  That  contractures 
tend  to  be  limited  to  certain  groups  of  muscles  would  seem  to 
be  due  to  an  unequal  stimulation  of  contiguous  cortical  areas. 

In  many  cases,  irritative  processes  seem  to  cause  the  tonic 
muscular  spasm,  though  it  must  be  admitted  that  no  very  sharp 
line  can  be  drawn  between  an  irritation  and  a  diminution  of 
inhibitory  influences.^^  The  valuable  studies  of  Forster^^ 
have  shown  how  complicated  is  the  mechanism  of  spastic  con- 
tractures. A  remarkable  fact,  according  to  him,  is  that  in  the 
spastic  type,  no  less  than  in  the  passive,  the  long-contin- 
ued maintenance  of  a  part  in  one  position  plays 
an  important  role.  If  a  muscle  has  once  become  short- 
ened by  habituation  to  a  certain  position,  it  is  more  difficult 
to  overcome  this  after  the  removal  of  the  cerebral  inhibiting 
influences.  And,  furthermore,  by  making  use  of  the  observation 
that  voluntary  movements  also  tend  to  be  inhibited,  Forster  was 
able  to  influence  even  the  type  of  spastic  contracture. 

A  contracture,  therefore,  is  a  subcortical  reflex  representing 
an  increase  in  the  resistance  offered  by  every  muscle  to  forces 
which  tend  to  lengthen  it.  The  form  of  the  contracture  depends 
upon  the  position  customary  to  the  limbs  and  also  upon  the 
degree  of  restitution  of  voluntary  movements,  which,  in  turn, 
differs  with  the  parts  affected. 

Two  views  have  been  advanced  as  to  the  cause  of  the 
contractures  that  develop  in  joint  disease.     Ac- 
cording   to    the    one,    the    muscle    spasm    is    caused 
reflexly  from  the  joint,  owing  to  a  strong  stimulation 
30 


466  THE  BASIS  OF  SYMPTOMS 

of  the  sensory  nerves  there.  This  view  is  supported  by  the 
fact  that  the  tendon  reflexes  are  often  increased  in  these  con- 
ditions. Personally,  however,  I  am  inclined  to  favor  the  view 
that  the  muscle  spasm  and  peculiar  posture  assumed  by  these 
patients  are  both  the  result  of  a  desire  to  avoid  pain; 
though  it  must  be  admitted  that  this  does  not  explain  the  increased 
tendon  reflexes. 

Hysterical  contractures  are  usually,  but  not  always, 
associated  with  exaggerated  reflexes.  They  would  appear  to  be 
due  in  part  to  this  exaggeration ;  in  part,  perhaps,  to  a  diminution 
of  the  inhibitory  control  normally  exercised  by  the  brain  over 
the  lower  spinal  centres. 

Motor  Irritative  Symptoms. — Tremor  may  be  defined  as  a 
series  of  regular  oscillatory  muscular  movements  about  a  fixed 
axis.  The  rate  of  these  oscillations,  their  amplitude  and  the 
number  of  muscles  affected,  all  vary  in  individual  cases.  In  many 
conditions,  the  tremor  occurs  only  during  volimtary  movements ; 
in  others,  it  is  more  intense  during  rest.  All  forms  of  tremor 
cease  during  sleep.  Unfortunately  we  cannot  discuss  tremor, 
because,  in  our  opinion,  absolutely  nothing  is  known  as  to  its  real 
cause,®"^  and  because  it  is  not  our  purpose  to  enter  into  clinical 
or  diagnostic  details. 

According  to  Bonhoeffer,  the  choreiform  movements  that 
sometimes  develop  after  a  hemiplegia  are  usually  caused  by 
lesions  of  the  superior  cerebellar  peduncles, °^ 
which  would  interrupt  the  centripetal  impulses  that  pass  through 
the  cerebellum  on  their  way  to  the  motor  region  of  the  cerebral 
cortex.  The  muscle  tonus  in  these  conditions  is  usually  dimin- 
ished,^^  a  fact  which  lends  some  support  to  the  hypothesis  that 
the  cerebellar  function  is  affected. 

In  a  variety  of  pathological  conditions,  certain  voluntary 
movements  are  regularly  accompanied  by  other  purposeless, 
so-called  associated  movements.**  As  we  have  already  stated, 
the  innervation  for  a  voluntary  movement  is  extremely  complex, 
impulses  being  sent  to  a  great  number  of  muscles.  The  muscular 
contractions  that  would  result  from  all  these  motor  impulses  are, 
however,  controlled  by  other  impulses  that  come  in  from  the 
periphery.  If  this  peripheral  control  be  lost,  it  is  possible  that 
certain  acts  should  be  accompanied  by  extra,  purposeless  move- 
ments which  would  be  suppressed  in  the  normal  individual.     The 


THE  NERVOUS  SYSTEM  467 

associated  movements  that  may  occur  in  tabes  dorsalis  are,  there- 
fore, related  in  a  way  to  the  ataxia,  for  both  depend  upon  a  loss 
of  centripetal  peripheral  control. 

Convulsions  may  be  of  the  clonic  type,  i.e.,  the  muscles 
are  alternately  contracted  and  relaxed  with  corresponding  move- 
ments of  different  parts  of  the  body;  or  they  may  be  of  the 
tonic  type,  i.e.,  the  contraction  is  continuous  and  the  parts 
affected  simply  become  rigid.  Finally,  the  two  forms  of  con- 
vulsions, tonic  and  clonic,  may  alternate  with  each  other. 

Convulsions  may  be  caused  either  by  stimulation  of  the  motor 
tracts  or  nerve-cells.  For  example,  diseases  of  the  cervical  or 
dorsal  cord  may  cause  convulsive  movements  in  the  legs  owing 
to  an  irritation  of  the  motor  tracts ;  lesions  of  the  internal  capsule 
may  cause  convulsions  in  the  opposite  half  of  the  body;  disease 
of  the  cerebral  cortex  in  the  corresponding  extremity,  etc.  It 
would  appear,  however,  that  the  stimulation  of  the 
cerebral  cortex  is  more  likely  to  produce  convulsions  than 
is  stimulation  of  any  other  part  of  the  motor  apparatus. 

The  paradigm  of  cortical  convulsions  is  the  so-called  Jack- 
Bonian  epilepsy,  which  is  characterized  by  its  limitation,  at  the 
outset,  to  certain  groups  of  muscles,  whence  it  spreads,  as  a  rule, 
to  the  entire  body.  The  convulsions  are  generally  followed  by 
a  more  or  less  transitory  paralysis  of  the  affected  muscles.  The 
order  of  progression  of  the  convulsions  corresponds  to  the 
arrangement  of  the  cortical  centres  governing  the  particular 
groups  of  muscles. 

Many  poisons  produce  convulsions,  some  of  which,  such 
as  the  uraemic  and  diabetic  poisons,  are  formed  within 
the  body  during  pathological  processes.  It  is  impossible  to  say, 
however,  upon  which  part  of  the  central  nervous  system  these 
poisonous  substances  act,  though  in  all  probability  it  is  the  cortex. 

Epilepsy  ^^  is  apparently  due  to  an  excessive  irritability  of 
the  central  nervous  structures.  The  convulsions  themselves  may 
be  precipitated  by  sensory  impulses  from  some  part  of  the  surface 
of  the  body,  but  more  frequently  they  come  on  spontaneously, 
or,  at  least,  without  any  discoverable  cause.  The  attack  is 
often  preceded  by  certain  characteristic  psychic  or  bodily  warn- 
ings (aura).  The  patient  then  becomes  unconscious  and  gen- 
eral convulsions  occur,  which  are  at  first  tonic  and  later  clonic 
in  character.     It  is  possible  to  induce  tonic  as  well  as  clonic 


468 


THE  BASIS  OF  SYMPTOMS 


convulsions  in  animals  by  stimulating  various  parts  of  the  brain, 
such  as  the  medulla,  the  pons  and  the  sensory  and  motor  regions 
of  the  cortex.  Of  these  convulsions,  no  type  presents  so  great  a 
similarity  to  the  attacks  of  epilepsy  as  does  that  which  follows 
stimulation  of  the  cerebral  cortex.  The  latter  may  be  either  fully 
developed  or  rudimentary  in  type,  and  it  often  continues  after  the 
stimulation  has  ceased.  The  similarity  that  exists  between  the 
convulsions  of  epilepsy  and  those  that  follow  stimulation  of  the 
cerebral  cortex  favors  the  view  that  epilepsy  is  of  cortical 
origin.  This  view  is  supported  furthermore  by  certain  clinical 
facts,  such  as  the  frequency  of  rudimentary  epileptic  attacks,  the 
associated  unconsciousness,  the  spread  of  the  convulsions  in 
accordance  with  the  cortical  representation  of  muscles  and  the 
frequent  occurrence  of  sensory  aura. 

Disturbances  of  Sensation. — The  pathology  of  sensation  is  so 
intimately  associated  with  the  mind  itself  that  our  consideration 
of  this  subject  will  necessarily  be  limited,  for,  as  we  have  already 
said,  we  do  not  purpose  discussing  psychic  changes.  It  will  be 
necessary  to  limit  our  discussion  in  still  another  way,  vis.,  by 
omitting  the  special  senses  of  sight  and  hearing,  for  these  subjects 
require  so  much  special  knowledge  that  we  cannot  do  justice  to 
them. 

Disturbances  of  sensation  may  be  either  irritative  or 
paralytic  in  character,  and  the  sensory  mechanism  may  be 
injured  at  any  point  from  its  beginning  in  an  end  organ  at  the 
periphery  to  its  termination  in  the  central  perceptive  part  of  the 
cerebrum.  If  the  peripheral  sense  organ  is  injured,  if  conduction 
of  the  impulse  through  the  nerve  or  cord  be  interrupted,  or  if, 
finally,  the  connections  in  the  brain  be  thrown  out  of  function, 
the  sensation  will  be  either  distorted  in  some  manner,  or  it  will 
not  be  perceived  at  all. 

In  certain  spinal  or  peripheral  diseases,  the  sensations  are, 
indeed,  perceived,  but  they  travel  at  a  slower  rate  than  normal. 
This  occurs  most  frequently  in  tabes  dorsalis  and  affects  oftenest 
the  cutaneous  sensation  of  pain.  We  do  not  know  exactlv  how 
this  delayed  sensation  is  caused. 

When  a  certain  injurious  agent  afifects  at  one  time  a  number 
of  nerve-fibres  of  different  functions,  the  sensory  fibres  usually 
resist  the  injury  better  than  do  the  motor.  Under  such  circum- 
stances, the  motor  fibres  may  be  paralyzed,  while  the  sensory 


THE  NERVOUS  SYSTEM  460 

fibres  are  merely  irritated  and  cause  pain.  This  combination  of 
symptoms  is  seen  especially  from  pressure  upon  the  spinal  cord, 
producing  the  characteristic  picture  of  paraplegia  dolo- 
rosa. 

Our  whole  knowledge  of  the  external  world  comes  to  us 
through  centripetal  nervous  impulses,  all  the  functions  of  our 
bodies  being  more  or  less  affected  by  them.  Thus,  the  sensations 
of  light,  sound  and  temperature  influence  metabolism,  muscular 
activity  and  respiration.  When  one  form  of  sensation  is  lost, 
the  others  become  more  acute  because  more  attention  is  directed 
to  them,  the  best  known  example  of  this  being  the  acute  sense  of 
touch  that  is  developed  in  blind  individuals. 

The  Cutaneous  Sensations. — The  nerves  of  pressure,  pain, 
heat  and  cold,  each  possess  definite  and  characteristic  endings 
in  the  skin.^^  These  delicately  constructed  end-organs  are  with- 
out doubt  injured  in  some  skin  diseases,  although,  so  far  as  I 
know,  no  thorough  study  of  such  injuries  has  yet  been  made. 
Diseases  of  the  nerves  or  of  the  central  apparatus  may  also  affect 
the  cutaneous  sensations,  and  any  one  of  the  latter  may  be  dis- 
turbed without  the  others  being  affected.  Such  "partial 
anaesthesias"  may  result  from  disease  either  of  the  nerves 
or  of  the  central  nervous  system,  but  they  are  especially  frequent 
in  tabes  and  in  syringomyelia.  The  occurrence  of  such 
partial  anaesthesias  is  of  great  practical  and  theoretical  interest, 
for  it  implies  that  special  nerves  exist  for  each  of  the  cutaneous 
sensations.  In  particular,  it  tends  to  prove  that  pain  is 
due  to  the  stimulation  of  special  pain  fibres, 
and  not  to  the  overstimulation  of  other  varie- 
ties of  fibres.  The  physiological  observation  that  cer- 
tain points  in  the  skin  are  sensitive  to  pain  alone  and  others  to 
pressure  alone,  likewise  supports  this  view.  It  must  be  noted, 
however,  that  even  so  experienced  an  investigator  as  Gold- 
scheider^^  denies  the  existence  of  special  nerves  for  pain. 

Lesions  of  the  peripheral  nerves  may  also  affect  the  different 
skin  sensations  to  different  degrees,  and  in  this  manner  give  rise 
to  partial  anaesthesias;  but  the  most  pronounced  instances  of  this 
condition  are  usually  observed  in  diseases  of  the  spinal  cord. 
The  fibres  that  transmit  the  various  forms  of  cutaneous  sensation 
apparently  run  in  different  parts  of  the  cord,  with  the  result  that 
a  limited  lesion  may  block  some  of  them  and  leave  others  intact. 


470 


THE  BASIS  OF  SYMPTOMS 


The  path  pursued  by  the  sensory  fibres  in  the 
central  nervous  system  is  an  extremely  complex  one. 
A  portion  of  the  fibres  that  carry  impulses  to  the  brain  cross 
by  way  of  the  anterior  commissure  to  the  opposite  side  of  the  cord 
shortly  after  they  enter  it.  This  is  the  explanation  of  the 
Brown-Sequard  symptom-complex.  If  one-half  of 
the  spinal  cord  be  destroyed,  the  muscles  on  that  side  below  the 
level  of  the  lesion  will  be  paralyzed,  with  an  associated  loss  of 
the  sense  of  position.  The  cutaneous  sensations  that  are  inter- 
rupted, however,  are  those  that  come  from  the  opposite  side  of  the 
body  below  the  lesion. 

When  the  sensory  tracts  reach  the  brain,  they  connect  with 
various  reflex  and  automatic  centres,  some  finally  terminating  in 
the  cerebral  cortex,  apparently  in  the  neighborhood  of  the  motor 
areas  that  govern  the  movements  of  corresponding  parts  of  the 
body.  For  this  reason,  lesions  of  the  cortical  motor  area  usually 
produce  a  diminution,  though  not  a  complete  loss,  of  sensation  in 
those  parts  of  the  body  that  correspond  to  the  paralysis.  So 
far  as  sight  and  hearing  are  concerned,  we  know  that  a  sensation 
may  be  perceived  without  its  meaning  being  recognized  (soul 
blindness)  ;  thus  a  patient  may  hear  the  ringing  of  a  bell,  but  he 
tmable  to  tell  what  causes  the  sound. 

The  sensory  disturbances  due  to  diseases  of 
the  peripheral  nerves  demand  a  special  word.  The 
observation  that  severance  of  a  cutaneous  nerve  does  not  render 
the  area  supplied  by  that  nerve  entirely  anaesthetic  has  been 
explained  on  the  basis  of  nerve  anastomoses  and  the  overlapping 
of  nerve  supplies.  Head  and  his  co-workers®*  have  elaborated 
another  theory,  zns.,  that  cutaneous  sensation  is  carried  by 
three  distinct  types  of  nerve  fibres,  exclusive  of 
those  for  the  feeling  of  cold,  heat  and  pain.  Those  for  deep 
sensibility  course  with  the  motor  fibres,  entering  the  anterior 
horns,  traversing  the  cord  to  the  posterior  roots  and  thence  enter- 
ing the  spinal  tracts.  Through  the  medium  of  these  fibres  it  is 
assumed  that  we  experience  the  sensations  of  pressure,  pain 
and  movement  of  the  deeper  structures.  Superficial  sensation, 
according  to  Head,  falls  into  two  classes,  which  he  terms  "  e  p  i  - 
critical"  and  **protopathic,"  the  first  conveying  the 
finer  impulses,  the  latter  the  coarser.  The  epicritical  fibres  are 
said  to  correspond  approximately  to  the  anatomical  distribution 


THE  NERVOUS  SYSTEM  471 

of  a  given  nerve,  and  to  regenerate  much  more  slowly  than  do  the 
protopathic  fibres.     This  hypothesis  has  not  been  unchallenged.^'' 

Every  sensation  produces  at  the  same  time  a 
more  or  less  definite  impression  of  the  place 
whence  the  sensation  has  come.  In  the  case  of  the 
eyes  and  skin,  this  localization  is  very  accurate;  in  the  case  of  the 
mucous  membrane  near  the  outside  of  the  body  it  is  somewhat 
less  accurate;  while  in  the  case  of  the  deeper  mucous  membranes 
and  the  organs  within  the  body,  it  is  inaccurate  and  entirely  unre- 
liable. In  certain  nervous  lesions,  especially  in  those  about  the 
optic  thalami,  the  cutaneous  sensations  are  perceived,  but  the 
ability  to  localize  them  is  more  or  less  lost.  Curiously  enough, 
this  sense  of  locality  is  well  preserved  in  cortical  lesions.^^  Ob- 
servers are  not  agreed  as  to  whether  this  sensory  anomaly  is  due 
chiefly  to  a  loss  of  the  sense  of  movement,  or  of  cutaneous 
sensation ;  at  any  rate,  it  is  most  marked  when  both  are  involved. 

The  Orientation  of  Our  Bodies  in  Spaces'^ — We  derive  infor- 
mation as  to  the  position  of  our  bodies  in  space  from  a  number 
of  sources.  Our  eyes  aid  us  by  means  of  the  images  upon  the 
retinae  and  by  their  motion  within  the  orbits;  the  internal 
ear  enables  us  to  estimate  changes  in  the  rate  of  direction  of 
our  movements ;  and  other  more  or  less  valuable  data  are  derived 
from  the  muscles,  tendons,  bones,  joints,  skin, 
etc.  Even  though  we  are  not  conscious  of  these  various  sensa- 
tions, they  all  influence  to  some  extent  the  conception  that  we 
have  as  to  our  position  in  space. 

Certain  of  these  sensations  may  be  lost  without  much  effect 
upon  our  powers  of  orientation,  for  the  reason  that  other 
sensations  compensate  for  the  lost  ones.®®  The 
blind  man  moves  about  a  room  with  great  precision  so  long  as  he 
can  use  his  sense  of  touch;  and  the  deaf-mute  hardly  seems  to 
be  affected  by  the  loss  of  his  internal  ears.  It  is  an  interesting 
fact,  however,  that  deaf-mutes  do  show  a  diminished  power  of 
orientation,  and  that  they  behave  quite  differently  from  normal 
individuals  when  they  are  turned  about  rapidly.®*  The  tabetic 
who  has  lost  certain  of  the  sensory  impulses  coming  from  his 
legs  depends  very  much  upon  his  visual  impressions,  and  if  these 
be  taken  away  from  him  by  closing  his  eyes  he  will  often  imme- 
diately fall  to  the  ground.  We  see,  therefore,  that  various  disor- 
ders of  the  peripheral  sensory  apparatus  will  disturb  the  sense  of 


472 


THE  BASIS  OF  SYMPTOMS 


our  position  in  space.  The  same  effect  may  also  result  from 
lesions  of  the  central  mechanism  in  the  brain — ^above  all,  from 
lesions  of  the  cerebellum. 

DizzinessJ<^ — We  do  not  mean  by  dizziness  a  partial,  transi- 
tory loss  of  consciousness,  but  a  feeling  that  we  are  unable  to 
control  our  equilibrium.  This  feeling  usually  results  from  an 
inability  on  the  part  of  the  central  apparatus  to 
harmonize  the  various  centripetal  impulses  that 
come  to  it.''*  For  example,  if  certain  ocular  muscles  are 
paralyzed,  the  images  of  an  object  looked  at  do  not  fall  upon 
corresponding  points  of  the  two  retinae  as  they  normally  should, 
and  consequently  the  impressions  derived  from  the  two  eyes  will 
not  correspond  to  each  other.  This  causes  a  sensation  of  dizzi- 
ness, which  may  usually  be  relieved  if  the  impressions  derived 
from  the  offending  eye  are  excluded  by  closing  it.  Diseases 
of  the  semicircular  canals,  of  the  sacculus  or 
utriculus,  or  of  their  central  nervous  connec- 
tions in  the  cerebellum,  are  especially  likely  to  cause 
dizziness,  which  is  most  marked  when  the  disease  is  limited  to 
one  side. 

In  aural  vertigo  (Meniere's  disease),  the  dizziness  is  usually 
associated  with  disturbances  of  hearing.^*  The  cochlear  branch 
of  the  auditory  nerve  transmits  sensations  of  soimd ;  whereas  the 
vestibular  branch,  proceeding  from  the  vestibule  and  the  semi- 
circular canals,  carries  impulses  that  are  caused  by  changes  in 
the  rate  or  direction  of  our  movements.  The  symptom  of  dizzi- 
ness in  aural  vertigo  undoubtedly  results  from  disturb- 
ances in  the  impulses  carried  by  the  vestibular 
nerve.  The  associated  anomalies  of  hearing  are  easily  under- 
stood when  we  consider  the  close  proximity  of  the  two  nerves  and 
of  their  end  organs.  In  many  cases,  the  sensation  of  dizziness 
will  disappear  if  the  patient  remain  perfectly  quiet,  while  in 
others  they  are  constantly  present  even  though  the  patient  be  still, 
and  under  such  circumstances  they  are  most  harassing. 

The  dizziness  of  aural  vertigo  is  probably  due  to  an  irritation 
of  the  vestibular  nerve,  or  of  its  connections,  rather  than  to  a 
mere  lack  of  function.  The  patient  becomes  dizzy  because  the 
impressions  received  from  this  source  do  not  coincide  with  those 
received  from  other  parts  of  the  body.  That  the  dizziness  in  these 
cases  is  not  due  to  a  mere  lack  of  sensation  from  the  internal 


THE  NERVOUS  SYSTEM  473 

ear  is  rendered  probable  by  the  fact  that  the  typical  symptoms 
of  aural  vertigo  are  rarely  seen  in  those  deaf-mutes  in  whom 
the  internal  ear  is  entirely  functionless. 

Aural  vertigo,  as  well  as  cerebellar  vertigo,  is  frequently  asso- 
ciated with  other  symptoms,  such  as  vomiting,  uncertainty  in  the 
voluntary  muscular  movements,  especially  in  walking,  and  peculiar 
movements  of  the  eyes.  At  present,  however,  it  is  impossible  to 
explain  these  associated  symptoms  very  satisfactorily. 

The  sensation  of  dizziness  may  also  be  produced  by  many  other 
causes,  such  as  alcoholic  intoxication,  cerebral  pressure,  anaemia 
and  circulatory  disturbances ;  yet  the  exact  mode  of  its  causation 
in  these  conditions  is  not  known. 

Hyperalgesia. — Increased  sensitiveness  to  painful  stimuli  that 
are  applied  to  the  skin  has  been  observed  in  various  diseases  of 
the  cord  and  of  the  more  central  endings  of  the  sensory  tracts. 
The  transition  from  the  normal  to  the  pathological,  however,  is 
here  a  very  gradual  one,  and  individuals  of  a  "  sensitive  "  nature 
are  certainly  more  susceptible  to  pain  than  are  those  of  a  phleg- 
matic type.  The  hypersensitiveness  of  hysterical  patients  is  prob- 
ably of  this  perceptive  character.  Peripheral  abnormalities  rarely 
give  rise  to  hyperalgesia,  although  a  neuritis  will  sometimes  do  so. 
Occasionally,  as  in  cord  lesions,  hyperalgesia  may  result  from  the 
summation  of  many  stimuli,  no  one  of  which  in  itself 
is  sufficient  to  give  rise  to  a  painful  sensation. 

Irritative  Sensory  Symptoms. — These  differ  from  the  pre- 
ceding in  that  the  pain  results  not  from  hypersensitiveness  to 
normal  stimuli,  but  from  a  pathological  irritation  of  the  sensory 
mechanism. 

Itching  IS  usually  caused  by  an  irritation  of  the  sensory 
organs  in  the  skin,  though  sometimes,  as  in  multiple  sclerosis, 
it  may  result  from  lesions  of  the  conducting  apparatus.  It  accom- 
panies most  cutaneous  diseases,  but,  for  some  unknown  reason, 
it  tends  to  be  absent  in  certain  lesions,  such  as  those  produced 
by  syphilis.  Not  infrequently,  itching  is  present  when  no  cutaneous 
changes  can  be  demonstrated,  as,  for  example,  in  jaundice  and 
diabetes.  It  is  possible  that  in  these  cases  the  central  apparatus 
is  directly  irritated.  On  the  other  hand,  paraesthesias,  such  as 
numbness  and  tickling,  rarely  accompany  cutaneous  dis- 
eases, but  are  caused  usually  by  nerve  or  cord  lesions.  They 
have  also  been  observed  in  the  extremity  that  corresponded  to 


474  THE  BASIS  OF  SYMPTOMS 

a  point  of  softening  in  the  sensory  sphere  of  the  cerebral  cortex. 
They  seem,  therefore,  to  be  caused  by  an  irritation  of  the  sensory 
tracts. 

Abnormal  sensations  of  heat  and  cold  are  some- 
times experienced,  but  it  is  often  difficult  to  distinguish  these 
from  the  accompanying  sense  of  pain. 

In  our  opinion,  pain  is  normally  caused  by  the  stimulation 
of  special  pain  fibres  or  sensory  end  organs.  Heavy  pressure, 
for  example,  will  deform  the  skin  and  so  stimulate  the  pain 
points.  Pain  also  results  from  various  inflammations  and  de- 
generations of  the  nerves,  such  as  may  be  caused  by  alcohol, 
arsenic,  malaria,  etc.  The  nerves  may  also  cause  pain  even  when 
no  demonstrable  lesion  is  present,  as  happens  in  the  neuralgias. 

It  is  remarkable  that  pathological  processes  within  the  central 
nervous  system  itself  rarely  produce  much  pain,  so  long  as  the 
peripheral  nerves,  the  posterior  roots  and  the  meninges  remain 
unaffected.  Surgeons  and  physiologists  have  frequently  demon- 
strated that  the  brain  itself  is  practically  insensible;  and  although 
it  cannot  be  denied  that  the  pain  fibres  may  be  stimulated  within 
the  central  nervous  system,*^^  yet  the  general  fact  remains  that 
such  a  stimulation  is  not  easily  brought  about. 

Many  hysterical  pains  are  probably  of  a  central, 
"  psychic  "  nature,  but  these  are  not  related  in  any  way  to  organic 
lesions  of  the  cerebral  cortex. 

The  Influence  of  the  Nervous  System  upon  the  Tissue 
Nutrition. — The  nutrition  of  a  tissue  depends  primarily  upon  the 
activities  of  its  individual  cells.  It  is,  indeed,  necessary  that 
food  material  should  be  supplied  to  it  from  the  blood  in  sufficient 
quantities,  yet  this  food  supply  alone  does  not  stimulate  the 
growth  of  the  cell.  That  stimulus  must  come  from  the  paren- 
chyma itself. 

The  exact  part  that  the  nervous  system  plays  in  this  process 
is  not  at  all  clear.  Beyond  question,  it  exerts  a  very  important 
influence  upon  the  nutrition  of  certain  tissues.  Is  this  influence, 
however,  due  merely  to  the  fact  that  the  cells  do  not  functionate 
properly  without  nervous  impulses,  or  do  the  nerves  contain  some 
specific,  nutritional,  "  trophic  "  fibres  ? 

The  Effect  of  Separating  a  Nerve-Fibre  from  Its  Cell. — The 
nerve-fibres  degenerate  if  they  are  separated  from  their  ganglion 
cells,  or  if  these  cells  are  destroyed.    This  is  explained,  according 


THE  NERVOUS  SYSTEM  475 

to  the  neuron  theory,  on  the  assumption  that  the  nerve-fibre,  a  long 
process  of  the  ganglionic  cell,  dies  when  it  is  separated  from  its 
mother  cell. 

It  is  not  our  intention  to  consider  the  validity  of  the 
neuron  theory  nor  the  recent  arguments  advanced  both  in 
favor  and  against  it.  The  cells  and  their  axis-cylinders  un- 
doubtedly have  an  intimate  histological  relationship.  On  the 
other  hand,  we  can  no  longer  subscribe  to  the  neuron  theory 
in  its  original  form,'^*  for  there  can  be  no  question  of  the  im- 
portant part  played  by  nervous  structures  other  than  the  ganglion 
cells  and  axones,  e.g.,  the  neurofibrillse.  (The  neuron  theory, 
though  in  its  entirety  i>erhaps  not  unassailable,  seems  to  be  the 
most  acceptable  at  our  disposal,  and  is  held  by  the  majority  of 
physiologists.  Especially  indicative  of  the  fact  that  the  nerve- 
cells  are  concerned  not  merely  with  the  nutrition  of  the  conducting 
fibres,  but  themselves  take  part  in  the  transmission  of  impulses, 
are  the  brilliant  researches  of  Harrison "^^  who  was  able  to 
show  in  vitro  that  the  growth  of  the  axis-cylinder  occurs  when  all 
other  nervous  structures  are  eliminated  but  the  nerve-cells  whence 
they  arise. — Ed.  ) 

Some  indeed  assert  that  the  mere  separation  of  the  fibre  from 
the  cell,  or  rather,  the  cessation  of  the  influence  that  the  cell  exerts 
over  the  fibre,  is  not  the  cause  of  the  degeneration,  but  that  the 
latter  is  due  directly  to  the  traumatism  of  the  operation.'''®  It  is 
jxDSsible,  for  example,  experimentally,  to  interrupt  the  transmission 
of  nervous  impulses  through  a  fibre  for  a  very  long  time  without 
having  any  degeneration  take  place;  but  although  the  ordinary 
nervous  impulses  were  interrupted  in  such  a  case,  we  cannot  be 
sure  that  the  nutritional  impulses  were  likewise  affected. 

Even  though  the  nerve-fibre  is  a  part  of  the  ganglion  cell,  the 
two  must  be,  to  a  certain  extent,  independent  of  each  other,  for  the 
fibres  seem  to  be  relatively  much  more  susceptible  to  the  action 
of  certain  toxins.  The  neuritis  that  follows  the  circulation  of 
these  toxins  in  the  blood  apparently  occurs  either  because  the 
fibres  contain  elements  for  which  the  toxins  show  a  special  affinity, 
or  because  the  fibres  are  so  remote  from  their  nutritional  centres, 
the  cells.  The  fact  that  medullated  nerve-fibres  pursue  a  different 
course  of  regeneration  than  do  the  non-medullated,  suggests  that 
the  medullary  sheath  plays  an  important  part  in  this  selective 
action  of  toxins  upon  the  nerve-fibres.     In  many  cases  the  nerves 


476  THE  BASIS  OF  SYMPTOMS 

are  capable  of  exchanging  material  with  their  surroundings,  as  is 
evidenced  especially  by  the  fact  that  the  tetanus  toxin  travels  from 
the  periphery  to  the  cord  through  the  axis  cylinders.  Possibly 
the  toxins  of  other  infectious  diseases  pursue  this  same  course, 
and  if  this  were  so  it  might  explain  the  special  susceptibility  of 
the  nerve-fibres  to  the  toxins  of  infectious  processes. 

In  some  instances,  as  in  lead  poisoning,  different  portions  of 
the  nerve-cell  may  be  affected,  and  consequently,  widely  different 
nervous  symptoms  may  be  produced.  Certain  of  the  systemic 
diseases  of  the  spinal  cord  show  various  transitions  into  one 
another;  and  it  is  easy  to  conceive,  for  example,  that  the  same 
cause  might  produce  in  one  person  a  progressive  muscular  atrophy, 
in  another,  an  amyotrophic  lateral  sclerosis,  and  in  a  third,  a  true 
spastic  paraplegia,  depending  upon  whether  the  pyramidal  tracts 
or  the  motor  cells  of  the  anterior  horns  were  more  especially 
affected. 

When  a  ganglion  cell  is  separated  from  its 
peripheral  neuron,  the  former  also  undergoes  certain 
changes,*^^  which  reach  their  height  in  about  eighteen  days.  After 
this,  a  portion  of  the  injured  cells  may  be  restored  to  their  normal 
condition.  If  the  cell  continues  to  be  functionless,  however, 
for  the  reason  that  the  peripheral  nerve  cannot  regenerate,  then 
it  gradually  undergoes  atrophy.  This  happens,  for  example,  after 
amputations;  and  the  younger  the  individual  the  greater  is  the 
cell  destruction.  These  facts  are  of  considerable  theoretical 
interest,  for  they  show  that  the  normal  existence  of  a 
ganglion  cell  depends  largely  upon  its  ability  to 
exercise  its  function.  Degeneration  occurs  in  the  sen- 
sory cells  because  they  receive  no  impulses  from  the  periphery, 
and  in  the  motor  cells  when  they  no  longer  receive  those  indirect 
stimuli  from  the  muscles  and  other  tissues  whicih  normally  play 
so  great  a  part  in  the  regulation  of  their  activities. 

It  is  apparent,  therefore,  that  our  knowledge  of  the  factors 
concerned  in  degeneration  and  regeneration  of  nervous  elements 
is  by  no  means  complete,  even  though  we  regard  the  neuron  as 
embracing  all  of  the  structures  concerned  in  the  functional  activi- 
ties of  the  nervous  system — a  view,  incidentally,  which  is  un- 
doubtedly too  narrow.  The  interpretative  difficulties  are  only 
increased,  however,  if  we  go  beyond  the  neuron  and  attribute 
special  properties  to  other  structures,  such  as  the  fibrillae,  etc. 


THE  NERVOUS  SYSTEM  477 

Nutritional  Disturbances  in  the  Muscles. — When  the  muscles 
are  separated  from  the  spinal  cells  that  innervate  them,  they 
degenerate.  The  degenerative  changes  consist  mainly  in 
alterations  of  their  chemical  composition''^^  and 
of'theirelectrical  irritability.  Prominent  among  the 
chemical  changes,  according  to  Rumpf,  is  a  marked  diminution 
in  the  potassium,  and  a  considerable  increase  in  the  sodium,  salts. 
In  addition  to  these,  a  simple  reduction  of  their  contractile  sub- 
stance without  degenerative  changes  takes  place.*^®  The  reduc- 
tion of  the  quantity  of  protoplasm  is  caused  by  the  inactivity, 
and  is,  therefore,  an  atrophy  from  disuse.  The  microscopical 
signs  of  degeneration,  such  as  the  granular  and  waxy  degenera- 
tions, are  not  due  to  the  separation  of  the  muscles  from  the  cord, 
but  to  some  associated  action  of  toxic  substances. 

Changes  in  the  Electrical  Irritability  of  Muscles.^^* — After 
a  muscle  has  been  separated  from  its  ganglion  cells  for  a  certain 
time,  it  responds  abnormally  to  the  electric  current.  These 
changes  constitute  the  so-called  reaction  of  degenera- 
tion. It  will  no  longer  contract  when  its  nerve  is  stimulated 
in  any  manner  by  the  electric  current,  nor  will  it  contract 
when  it  is  itself  directly  stimulated  by  an  ordinary  interrupted 
current.  Even  the  healthy  muscle  does  not  contract  if  very  high 
frequency  currents  are  applied  to  it,  so  that  the  loss  of  irritability 
that  the  degenerated  muscle  shows  toward  an  interrupted  current 
is  merely  one  of  degree.  It  is  an  exaggeration  of  the  normal. 
In  this  respect,  the  degenerated  muscle  behaves  like  a  smooth 
muscle,  for  the  latter  also  usually  fails  to  respond  to  an  inter- 
rupted current. 

The  muscle  that  is  separated  from  its  ganglion  cells  will, 
however,  respond  for  a  long  time  to  interruptions  of  the  galvanic 
current;  and  it  will,  indeed,  respond  to  a  much  weaker  current 
than  does  the  normal  muscle.  The  contraction  produced  by  this 
current  is  not  a  prompt  and  short  one,  as  is  the  case  with  the 
normal  muscle,  but  is  very  slow  and  easily  passes  into  tetanus.  A 
slow  contraction  of  this  kind  is  also  seen  in  the  smooth  muscle, 
in  the  fatigued  striated  muscle,  in  the  muscle  subjected  to  cooling 
by  carbon  dioxide®^  and  in  certain  intoxications  and  cachectic 
conditions.  The  contraction  curve  of  the  cooled  muscle — espe- 
cially the  gradual  ascent — may  so  closely  resemble  that  of  the 
reaction  of  partial  degeneration  as  to  be  indistinguishable  at 


478  THE  BASIS  OF  SYMPTOMS 

times,  even  by  capable  observers.  In  certain  fundamental  par- 
ticulars, therefore,  the  fatigued  or  cooled  muscle  reacts  exactly 
as  does  the  degenerated. 

The  degenerated  muscle,  instead  of  responding  more  strongly 
to  a  closure  of  the  current  when  the  cathode  is  placed  upon  it, 
frequently  contracts  more  strongly  to  the  anodal  closure.  It  has 
been  commonly  assumed  that  this  change  is  due  to  some  funda- 
mental alteration  in  its  protoplasm,  whereby  it  is  rendered  more 
irritable  to  the  anodal  closure ;  yet  such  does  not  seem  to  be  the 
case.  The  muscle  conducts  the  current,  and,  when  the  cathode 
is  placed  over  its  centre,  for  example,  the  current  enters  at  the 
end  and  this  receives  an  anodal  stimulation.  In  the  normal 
muscle  the  cathode  causes  a  stronger  contraction,  because  it  is 
placed  over  the  point  of  greatest  irritability,  i.e.,  the  entrance 
of  the  nerve  into  the  muscle.  The  centre  of  the  degenerated  mus- 
cle, however,  early  loses  its  irritability,  and  the  extremities  become 
the  most  irritable  parts.  When,  therefore,  an  electric  pole  is 
placed  over  the  centre  of  a  degenerated  muscle,  and  the  current  is 
closed,  the  end  of  the  muscle  receives  the  main  stimulation.  For 
this  reason  the  maximal  contraction  is  obtained  when  the  anode  is 
placed  on  the  muscle,  for  the  cathodal  stimulus  then  acts  upon 
its  more  irritable  extremity.^^  If  the  degenerated  sartorius  mus- 
cle of  a  frog  be  isolated  and  stimulated,  it  shows  no  diminution 
in  its  irritability  to  the  cathodal,  as  compared  with  the  anodal, 
closure.®^ 

More  recently  the  attempt  has  been  made  to  explain  these 
phenomena  on  a  physico-chemical  basis.®*  According 
to  Nernst,  the  contraction  of  a  healthy  muscle  is  due  to  an 
accumulation  of  electrolytes  at  the  cathode.  R  e  i  s  s ,  using  frog- 
muscle  preparations  freed  from  nervous  connections,  has  found 
that  in  degenerative  conditions  the  normal  cathodal 
accumulation  is  replaced  by  an  anodal,  i.e.,  the 
electrolytes  gather  about  the  anode  instead  of 
the  cathode  when  the  circuit  is  closed.®*^  Though 
it  is  true,  as  pointed  out  above,  that  degenerated  muscle  exhibits 
an  altered  salt  content,^®  and  that  this  alteration  might  account 
for  such  a  reversal  in  the  response  to  cathodal  and  anodal  closure, 
yet  there  exist  a  number  of  objections,  both  interpretative  and 
technical  to  the  Reiss  hypothesis.®'^ 

In  certain  instances,  such  as  in  trichinosis  and  some  muscular 


THE  NERVOUS  SYSTEM  479 

dystrophies,  the  reaction  of  degeneration  has  been  present  without 
demonstrable  lesions  of  the  nerves.  At  the  present  time,  how- 
ever, these  cases  cannot  be  accepted  as  proof  that  the  reaction 
of  degeneration  may  occur  independently  of  nervous  lesions,  for 
it  is  almost  impossible  to  exclude  changes  in  the  finer  nerve  fila- 
ments. Nor  have  the  observations  on  cases  of  this  kind  taken  into 
account  the  pronounced  effect  of  temperature  variations,  such  as 
cooling,  to  which  attention  has  already  been  called.  Against 
Striimpell's  view  that  the  reaction  of  degeneration  is  simply  the 
response  of  a  nerveless  muscle  speaks  the  fact  that  curarized  mus- 
cle does  not  exhibit  this  phenomenon. 

When  a  motor  nerve  is  injured,  but  not  entirely  destroyed, 
electrical  changes  of  a  less  marked  degree  take  place  in  the  muscles 
— the  so-called  partial  reaction  of  degeneration. 

Atrophy  from  Cerebral  Lesions. — When  muscles  are  paralyzed 
from  a  cerebral  lesion,  the  resulting  atrophy  develops  more  grad- 
ually and  is  of  slighter  extent  than  that  which  follows  the  division 
of  a  peripheral  nerve,  and  it  is,  furthermore,  unaccompanied  by 
the  reaction  of  degeneration.  In  such  cerebral  paralyses,  only 
one  form  of  stimulation — the  voluntary — is  shut  off  from  the 
paralyzed  muscle.  The  reflex  and  automatic  stimulations  from 
the  lower  centres  continue  to  act  upon  it.  The  paralyzed  muscles 
frequently  do  contract  from  reflex  stimulation,  and  even  when 
they  do  not  apparently  do  so,  they  still  maintain  their  muscular 
tonus.  The  paralyzed  muscle  that  retains  a  connection  with  its 
ganglion  cells  exhibits  a  more  active  metabolism  than  the  paralyzed 
muscle  that  is  separated  from  these  cells,  a  further  proof  that 
the  former  maintains  a  certain  amount  of  activity. 

In  certain  instances,  especially  in  the  young,  cortical  lesions 
have  been  followed  by  marked  changes  in  the  lower  neurons  and 
by  a  rapid  atrophy  of  the  muscles.^*  The  electrical  reaction  in 
these  cases  is,  usually  qualitatively  normal,  although,  in  a  few,  the 
slow  contraction  of  degeneration  has  been  present.  The  upper 
neurons  apparently  exercise  some  influence  upon  the  peripheral 
neurons,  and  when  this  is  cut  off  in  early  life,  the  latter  may 
degenerate.®* 

Muscular  Atrophy  from  Diseases  of  the  Joints.^*' — The 
atrophies  about  diseased  joints  often  develop  more  rapidly  and 
are  more  severe  than  those  which  are  caused  by  cerebral  lesions. 
As  a  rule,  they  do  not  affect  equally  all  muscles  about  the  joint, 


480  THE  BASIS  OF  SYMPTOMS 

but  tend  especially  to  injure  the  extensors.  The  severity  of  the 
muscular  atrophy  bears  no  definite  relation  to  the  intensity  or 
variety  of  the  joint  lesion.  The  electrical  irritability  of  the 
muscle  is  usually  reduced,  but  no  typical  reaction  of  degeneration 
is  present.  This  form  of  atrophy  differs,  therefore,  from  that 
caused  by  cerebral  lesions  in  its  intensity  and  in  the  rapidity  with 
which  it  develops,  and  from  that  caused  by  nerve-lesions  in  the 
absence  of  a  reaction  of  degeneration. 

Various  attempts  have  been  made  to  explain 
these  muscular  atrophies  about  diseased  joints. 
The  French,  following  Charcot's  lead,  have  generally  con- 
sidered that  the  nervous  impulses  sent  from  the  joint  to  the 
cord  influence  the  motor  cells  there,  and  that  a  disturb- 
ance of  the  impulses  from  these  cells  causes  the 
atrophy.  The  Germans,  following  Striimpell,  have  been 
more  inclined  to  attribute  these  muscular  atrophies  to  an  ex- 
tension of  the  disease  by  contiguity  from  the 
joint  to  the  muscle,  though  it  must  be  admitted  that,  experi- 
mentally, at  least,  no  inflammation  of  the  muscle  is  necessarily 
present,  and  that  the  muscles  atrophy  throughout  their  entire 
length,  and  not  merely  in  the  neighborhood  of  the  joint.  Finally, 
attention  has  been  called  to  the  fact  that  the  most  seriously  affected 
muscles  are  precisely  those  whose  movements  are  most  limited  by 
the  joint  disease,  so  that  the  atrophy  is  probably  caused,  in  part 
at  least,  by  disuse,®^ 

The  Muscular  Dystrophies. — This  disease-group,  which  ex- 
hibits a  distinct  hereditary  and  family  tendency,  is  characterized 
by  a  very  gradual  atrophy  of  certain  muscles.  It  usually  begins 
in  childhood  or  early  youth.  Several  types  have  been  described, 
but  it  seems  very  probable  that  they  are  all  but  different  variations 
of  the  same  disease.  Anatomically,  we  find  many  atrophied 
fibres,  and,  in  addition  to  these,  usually  a  number  of  thickened 
fibres,  which  may,  indeed,  be  so  numerous  that  the  muscle  as  a 
whole  appears  to  be  hypertrophied.  The  adipose  tissue  between 
the  muscle  fibres  is  sometimes  so  increased  in  amount  as  to  pro- 
duce a  large,  weak  muscle,  the  so-called  pseudohyper- 
trophy. In  the  great  majority  of  these  cases,  no  reac- 
tion of  degeneration  is  present,  while  in  the  few  in- 
stances in  which  it  has  been  found,  it  is  extremely  difficult  to 
exclude  some  slight  involvement  of  the  finer  nerve-filaments. 


THE  NERVOUS  SYSTEM  481 

or  the  eflfect  of  cooling.  Even  the  presence  of  changes  in  the 
spinal  cord,  such  as  have  been  described,® ^  do  not  permit  us  to 
assume  that  this  disease  is  of  central  origin;  for,  as  we  have 
seen,  an  atrophy  of  the  ganglion  cells  may  follow  a  primary 
peripheral  condition,  such  as  an  amputation.  In  a  few  cases, 
classified  among  the  dystrophies,  some  complication  may  have 
caused  the  cord  lesion. 

Nutritional  Disturbances  of  Nervous  Origin  in  the  Bones  and 
Joints. — After  an  acute  anterior  poliomyelitis  in  children,  the 
bones  of  the  paralyzed  extremities  frequently  fail  to  develop  to 
their  normal  size;  whereas,  after  the  cerebral  infantile  palsies, 
their  growth  is  rarely  much  affected.  In  the  former  cases,  the 
absence  of  the  varying  pressures  and  movements  to  which  the 
bones  are  normally  subjected,  may  diminish  their  blood- 
supply  and  so  retard  their  development;  but  it  is  possible, 
on  the  other  hand,  that  this  retardation  is  due  to  an  absence  of 
specific,  trophic  influences.  In  adults,  nutritional 
changes  in  the  bones  rarely  result  from  diseases  of  the  peripheral 
motor  neurons  alone. 

In  a  variety  of  other  nervous  diseases,  especially  in 
syringomyelia  and  tabes,  as  well  as  in  certain  periph- 
eral lesions,  very  remarkable  nutritional  disturbances  take  place 
in  the  bones  and  joints.®^  The  anatomical  changes  in  the  joints 
often  resemble  those  of  arthritis  deformans,  but  they  differ  from 
these  in  certain  particulars,  especially  in  the  more  abundant 
effusion,  the  greater  destruction  of  the  joint,  the  rapid  course  and 
the  frequent  absence  of  all  pain.  In  a  certain  proportion  of  these 
cases,  the  lesions  are,  undoubtedly,  due  to  an  absence  of 
the  sense  of  temperature  and  pain.  I  have  myself 
seen  a  man  with  syringomyelia  who,  while  at  work,  frequently 
injured  himself  from  grasping  live  coals,  who  paid  no  attention 
to  his  wounds  on  account  of  the  absence  of  pain,  and  who  event- 
ually developed  the  most  pronounced  deformities  in  his  bones 
and  joints.  Such  observations  are  not  infrequent.  In  loco- 
motor ataxia,  also,  injuries  are  frequently  overlooked  on  account 
of  the  loss  of  sensation  in  the  joints  and  muscles.  In  spite  of 
these  observations,  however,  the  opinion  of  the  authorities  is  now 
gradually  turning  toward  that  of  Charcot,  who  held  that 
the  arthropathies  are  caused,  in  many  instances  at  least,  by  a 
loss  of  trophic  impulses  from  the  cord.  Patients 
81 


482  THE  BASIS  OF  SYMPTOMS 

have  been  observed  in  whom  the  most  severe  joint  destructions 
have  followed  within  a  few  days  after  nervous  lesions,  without 
any  demonstrable  mechanical  injury. 

In  some  nervous  diseases  the  bones  are  abnormally  thin,  and 
they  may  be  fractured  from  very  slight  causes,  or  even,  to  all 
appearances,  spontaneously.  Various  cord  changes  have  been 
found  in  such  patients,^*  and  in  some  cases  a  neuritis  has  been 
present.  Although  a  number  of  other  explanations  has  been 
offered  for  this  abnormally  brittle  character  of  the 
bones,  it  seems  probable  that  a  lack  of  trophic  influences  is 
the  cause  in  many  cases.  In  others,  local  changes,  especially 
syphilitic,  may  be  present  in  the  bone.  Nor  must  the  chemical 
action  of  the  correlated  internal  secretions  be  overlooked. 

The  Influence  of  Nervous  Diseases  upon  the  Skin. — It  is 
well  known  that  those  parts  of  the  skin  which  are  exposed  to 
continued  pressure  tend  in  time  to  become  reddened  and  swollen, 
and  eventually  to  die.  Such  ulcerations,  of  which  bed-sores 
furnish  the  most  familiar  examples,  may  develop  under  a  great 
variety  of  conditions,  depending  mainly  upon  the  nutrition  of 
the  cells  and  the  constancy  of  the  pressure  applied.  They  are  seen 
especially  in  patients  with  nervous,  infectious  or  metabolic  dis- 
eases, who  have  lain  for  a  long  time  in  one  iX)sition.  In  a 
certain  proportion  of  the  nervous  cases — for  these  are  the  ones 
that  especially  interest  us — the  ulceration  is  favored  by  the  cuta- 
neous anaesthesia,  and  by  the  soiling  of  the  skin  with  urine  and 
faeces,  owing  to  a  paralysis  of  the  bladder  and  rectum.  As 
evidence  of  the  importance  of  these  factors,  we  may  instance  the 
brilliant  results  that  follow  the  proper  care  of  this  class  of  patients. 
IWhile  we  must  admit,  therefore,  that  the  anaesthesia  and 
lack  of  cleanliness  are  important  factors  in  the  causation 
of  these  ulcerations,  yet,  in  my  opinion,  they  are  not  the  only 
causes  that  are  present,  for  at  times  the  ulcers  develop  very 
rapidly  even  when  there  is  no  loss  of  sensation  and  no  loss  of 
bladder  or  rectal  control.  In  this  last  class  of  cases,  trophic 
disturbances  certainly  play  an  important  role.  To  what 
extent  such  trophic  disturbances  and  to  what  extent  the  other 
factors  enter  into  the  causation  of  the  ordinary  bed-sores  that 
develop  during  nervous  diseases  can  only  be  determined  by  modern 
observations  during  a  proper  care  of  the  patient. 

Herpes  Zoster. — This  remarkable  eruption  is  associated  with 


THE  NERVOUS  SYSTEM  483 

disturbances  of  the  peripheral  nerves,  usually  an  inflamma- 
tion of  the  sensory  ganglion  itself  or  of  the 
nerve.  (Rosenow,^^  in  a  recent  study,  has  been  able  to  pro- 
duce in  rabbits  and  other  animals  herpes  of  the  skin,  tongue  or 
lips,  and  lesions  in  the  corresponding  spinal  ganglion  by  the  intra- 
venous injection  of  emulsions  of  extirpated  tonsils,  of  mixed  and 
pure  streptococcal  cultures  from  tonsils  or  pyorrhoeal  pockets, 
and  of  streptococci  in  pure  culture  from  the  spinal  fluid.  In  the 
affected  ganglion  were  found,  as  a  rule,  hemorrhages  and  round- 
cell  infiltrations,  and  Gram  positive  diplococci  and  short  chains. — 
Ed.) 

The  mere  loss  of  a  sensory  nerve  or  ganglion  does  not  cause 
nutritional  disturbances  in  the  skin  or  mucous  membranes.  This 
has  been  sufficiently  proved  by  the  results  of  extirpation  of  the 
Gasserian  ganglion  for  facial  neuralgia.^®  After  such  extirpa- 
tions, trophic  disturbances  of  the  skin  over  the  face  or  of  the 
mucous  membrane  of  the  nose  or  mouth  do  not  occur.  Even  the 
cornea  and  conjunctiva  remain  intact  if  protected  from  direct 
injury.  The  keratitis  observed  in  animals  after  excision  of  the 
trigeminus  is  due  to  the  dry  condition  of  the  eye.®"^  Since  in 
man  the  eye  may  be  kept  moist  by  proper  precautions,  no  keratitis 
necessarily  results  after  the  nerve  is  severed. 

LITERATURE 

*  Miinch.  med.  Wochenschft.,  1896,  Nos.  8  and  9. 
'  D.  Gerhardt :  Grenzgebiete,  xiii,  501. 

*Weed:  Jour.  Med.  Research,  1914,  xxvi  (N.  S.),  no  (lit). 

*  Weed :  Jour.  Med.  Research,  1914,  xxvi(  N.  S.),  91  (lit.). 

'These  subjects  have  recently  been  reviewed  by  Gushing:  Jour.  Med.  Re- 
search, 1914,  xxvi  (N.  S.),  I,  and  by  Frazier,  Jour.  Am.  Med.  Assn., 
1915,  Ixiv,  1 1 19. 

'  Gushing :  Grenzgebiete,  ix  and  xviii ;  Amer.  Jour.  Med.  Sc,  cxxiv  and  cxxv 
(N.  S.)  ;  Kocher,  in  the  Nothnagel  System;  Leonhardt,  Zeitschft.  f. 
Chirurgie,  Ixxi,  35-  _  _ 

'Grashey:  Allg.  Zeitschft.  f.  Psychiatrie,  xliii,  267. 

*  See  Sauerbruch :  Mitth.  a.  d.  Grenzgeb.,  3rd  suppl.,  1907. 

"  Wernicke :  Gehirnkrankheiten,  iii,  253 ;  Strtimpell,  Spez.  Path.  u.  Therap. ; 

Oppenheim,  Die  Geschwulste  d.  Gehrins,  in  the  Nothnagel  System. 
"  Gowers :  Diseases  of  the  Nervous  System,  ii ;  Elschnig,  v.  Graf e's  Arch,  f . 

Ophthalmologic,  xli,  II,  179. 
"  Lenhartz :  Miinch  med.  Wochenschft.,  1896,  Nos.  8  and  9. 
"  Cf.  Falkenheim  and  Naunyn :  Arch,  f .  exp.  Path.,  xxii,  301. 
"See  Quincke:  Deutsche  Klinik,  vi,  351   (Mod.  (Tlinical  Medicine);  Allard, 

Ergeb.  d.  inn.  Med.,  iii,  100;  Stadelmann,  Grenzgebiete,  ii,  549. 
"See  Schmidt-Rimpler,  in  the  Nothnagel  System;  Abelsdorf,  in  Lewandow- 

sky's  Handbuch,  i,  873;  Elschnig,  1.  c;  Leber,  in  Grafe-Saemisch.  Handb., 

V,  759. 


484  THE  BASIS  OF  SYMPTOMS 

"Grashey:  1.  c. ;  Kocher,  in  the  Nothnagel  System;  Gushing,  Grenzgebiete, 
ix,  ^^:s•,  and  Amer.  Jour.  Med.  Sc,  cxxiv,  375;  Sauerbruch,  Grenzge- 
biete, 3rd  suppl.,  1907,  939. 

"Gushing:  1.  c.  and  Amer.  Jour.  Med.  Sc,  1903,  cxxv,  1017. 

"C/.  Kocher:  1.  c;  Trendelenburg  and  Windscheid,  Neurolog.  Zentralbl., 
1909,  xxviii,  1 194. 

"Bethe:  Allg.  Anat.  u.  Phys.  d.  Nervensystems,  1903;  Nissl,  Die  Neuronen- 
lehre,  1903. 

"Mann:  Monatsschrift  f.  Psych,  u.  Neurol.,  xii,  280;  Bruns,  Berl.  klin. 
Wochenschft.,  1900,  Nos.  25  and  26. 

*  Consuh  Striimpell,  Ziehen,  KraepeUn  and  the  studies  of  Breuer  and  Freud ; 

Binswanger,  Die  Hysterie,  in  the  Nothnagel  System ;  Kohnstamm,  Thera- 

pie  d.  Gegenwart,  191 1. 
"Liepmann:  Das  Kxankheitsbild  d.  Apraxie,  1900;  Die  Storungen  d.  Han- 

delns  bei  Gehirnkranken,  1905 ;  Heilbronner,  in  Lewandowsky's  Handb., 

i,  983  (lit)  ;  Wilson,  Brain,  ig*^. 
""Erb:  Kongr.  f  .inn.  Med.,  1904,  104;  Bing,  Beihefte  z.  Med.  Klinik,  1907, 

No.  S;  Erb,  Miinch.  med.  Wochenschft,  1910,  Nos.  21,  22  and  47  (lit.). 
'^Erb:    Die   Thomsenesche    Krankheit,    1886;    Jensen,    Arch.    f.   klin.    Med., 

Ixxvii,  246. 
'^  See  Strumpell:  Zeitschft.  f.  Nervenheilk.,  viii,  16  (lit.). 
"Frenkel:  Die  Behandl.  d.  tabischen  Ataxic,  1900  (translation  into  English 

by  Freyberger)  ;  Forster,  Die  Physiol,  u.  Path.  d.  Koordination,   1902 ; 

Lewandowsky,  Ataxic,  in  Lewandowsky's  Handb.,  i,  815. 
••Hering:  Arch.  f.  exp.  Path.,  xxxviii,  266,  and  Neurolog.  Zentralbl,  1897, 

No.  23. 
"  Beevor  and  Horsley :  Philosoph.  Trans.,  1900,  clxxxi,  129. 
**  Goldscheider :  Zeitschft.  f.  klin.  Med.,  xv,  82. 

*  Friedreich :  Virch.  Arch.,  Ixviii,  168. 

•"Erb:  Neurol.  Zentralbl.,  1895,  No.  2;  Vierordt,  Berl.  klin.  Wochenschft., 
1886,  No.  21. 

**  Frenkel :  Neurol.  Zentralbl.,  1897,  Nos.  15  and  16. 

**  Frenkel :  Neurol.  Zentralbl.,  1896,  No.  8. 

"  Striimpell :  Arch,  f .  KUn.  Med.,  xxii,  332 ;  Heyne,  ibid.,  xlvii,  75 ;  v.  Ziemssen, 
ibid.,  xlvii,  89. 

**  Striimpell :  Zeitschft.  f.  Nervenheilk,  xxiii,  i. 

*^Liithje:  Zeitschft.  f.  Nervenheilk,  xxii,  280;  Bickel,  Miinch.  med.  Wochen- 
schft., 1903,  No.  5. 

"Exner:  Pfliiger's  Arch.,  xlviii,  592;  Striimpell,  Zeitschft.  f.  Nervenheilk, 
xxiii,  i. 

"See  Ande  Tomas:  La  fonction  cerebelleuse,  191 1;  Babinski,  Revue  de 
medicine  interne,  1909. 

"Edinger:  Neurol.  Zentralbl.,  1910,  706. 

*  Handb.  d.  Neurologic,  i,  362. 

*•  Sternberg :  Die  Sehnenreflexe,  1893,  272. 

"  Integrative  Action  of  the  "Nervous  System,  1906 ;  tJber  d.  Zusammenwirken 
d.  Riickenmarkreflexe,  in  Asher-Spiro,  Ergeb.,  1905,  iv,  IL 

**  L.  R.  Miiller :  Zeitschft.  f .  Nervenheilk,  xxi,  86. 

**  See  Sternberg:  Die  Sehnenreflexe  (ht.)  ;  Lewandowsky,  Handb.  d.  Neu- 
rologic, i,  582;  G.  Hoffmann,  Rubner's  Arch.,  1910,  223. 

^Sternberg:  1.  c,  178;  Jendrassik:  Arch.  f.  klin.  Med.,  Hi,  569. 

"Cf.  Bickel :  Zeitschft.  f.  Nervenheilk.,  xxi,  304. 

*  Sternberg:  1.  c,  142  (lit)  ;  D.  Gerhardt,  Zeitschft.  f.  Nervenheilk.,  vi,  127; 

Bruns,  Arch,  f .  Psych.,  xxv,  759,  and  xxviii,  133 ;  Nonne,  ibid.,  xxxiii, 
393;  Kron,  Zeitschft.  f.  Nervenheilk.,  xxii,  24;  Kausch,  Grenzgeb.,  vii, 
541. 
•Munk:  Sitzungsber.  d.  Preuss.  Akademie,  xHv. 


THE  NERVOUS  SYSTEM  485 

**  Jendrassik :  1.  c;   Ziehen,  Ergebnisse,  etc.,  6i6;   Striimpell,  Zeitschft.    f. 
Nervenheilk.,  xv,  254. 

**  Arch,  f .  exp.  Path.,  xliv,  369 ;  Meyer,  Festschrift  f ,  Jaffe,  297. 

*Loewi  and  Hans  Meyer:  Arch.  f.  exp.  Path.,  Schmedeberg  Festschrift 
(1908),  355. 

"  See  Monakow :  Gehirnpathologie,  in  the  Nothnagel  System ;  Lewandowsky, 
Handbuch,  i,  685. 

"Munk:  Du  Bois'  Arch.,  1896,  564;  Sitzungsber.  d.  Preuss.  Akad.,  xxxi,  823. 

**  Monatschefte  f.  Psych,  u.  Neurol.,  i,  409;  iv,  45,  123. 

"  Pfliiger's  Arch.,  Ixx. 

**  See  Sternberg :  Die  Sehnenreflexe,  etc.,  Leyden  and  Goldscheider,  Krank- 
heiten  d.  Ruckenmarks,  117;  Munk,  1.  c. 

**Die  Kontrakturen  bei  d.  Erkrankungen  d.  Pyramidenbahn,  1906. 

"Mobius:  Diagnostik,  2nd  edit.;  Stephan,  Arch.  f.  Psych.,  xviii,  734,  and 
xix,  18. 

"  Bonhoeff  er :  Monatshef  te  f .  Psych,  u.  Neurol.,  i,  6,  and  x,  383. 

**  Bonhoeffer :  Monatshefte  f .  Psych,  u.  Neurol.,  iii,  239 

*"  Foerster :  Die  Mitbewegungen,  1903. 

*^  See  especially  Binswanger :  Die  Epilepsie,  in  the  Nothnagel  System ;  Fuchs, 
Wiener  klin.  Wochenschft.,  1910,  No.  17. 

**v.  Frey:  Berichte  d.  Kgl.  S.  Gesellschaft  d.  Wissenschaften,  math.-phys. 
Kl.,  March  4,  1895 ;  Abhand.  d.  Sachs.  Ges.  d.  Wissenschaften,  xxiii,  175. 

"  Uber  den  Schmerz,  1894. 

"Head:  Kongr.  f.  inn.  Med.,  1909,  168;  Head,  Rivers  and  Sherren,  Brain, 
190S,  1908. 

"Goldscheider:  Mediz.  Klinik,  1911,  No.  8;  Zeitschft.  f.  inn.  Med.,  Ixxiv,  270. 

*•  See  Ziehen :  Ergebnisse,  etc.,  604. 

"  Cf.  Hartmann :  Die  Orientierung,  1902 ;  v.  Cyon,  Das  Ohrlabyrinth  als 
Organ,  etc.,  1908. 

**  Bickel :  Deutsch.  med.  Wochenschft.,  1901,  No.  12. 

"Kreidl:  Pfliiger's  Arch.,  li,  119. 

"Hitzig:  Der  Schwindel,  in  the  Nothnagel  System  (lit.). 

'  See  Frankl-Hochwart :  Menieres  Symptom-Complex,  in  the  Nothnagel  Sys- 
tem (lit.)  ;  Barany,  in  Lewandowsky's  Handbuch,  i,  919;  J.  R.  Ewald, 
Vortrag  auf.  d.  siidwestdeutsch^n  Neurologenversamm.,  1910. 

"  Ziehen :  Ergebnisse,  etc.,  604. 

''Goldscheider:  Uber  den  Schmerz,  1894,  24  et  seq. ;  Schaffer,  Neurolog. 
Zentralbl.  1909,  224. 

"  See  Nissl :  Die  Neuronenlehre,  1903 ;  Held,  Die  Entwickelung  d.  Nervenge- 
webes,  1909;  Bielschowsky,  in  Lewandowsky's  Handbuch.,  i,  3. 

"Jour,  of  Exp.  Zoology,  iv,  239;  ibid.,  ix,  787.  See  also  Barker,  Jour.  Am. 
Med.  Assn.,  1906,  xlvi,  929,  1006;  Ingebrigsten,  Studies  from  the  Rocke- 
feller Inst.,  1914,  xviii,  350. 

"Bethe:  Allg.  Anat.  u.  Phys.  d.  Nervensystems,  1903. 

"See  Marinesco:  Neurol.  Zentralbl.,  1892,  463,  505,  564  (lit);  Bethe,  1,  c; 
Marinesco,  La  cellule  nerveuse,  1909. 

"Rumpf:  Arch.  f.  klin.  Med.,  Ixxix,  158;  Reiss,  Die  elekt.  Entartungs- 
reaktion,  191 1,  7^- 

*•  Jamin :  Exp.  Untersuchungen  zur  Lehre  v.  d.  Atrophie  gelahmter  Muskein, 
1904  (lit.). 

"Erb:  Elektrotherapie,  2nd  edit.;  Biedermann,  Elektrophysiologie,  1895; 
Reiss,  1.  c. 

"C/.  Achelis  (Schenck)  :  Pfluger's  Arch.,  cvi;  Reinecke  (Verworn),  Zeit- 
schft. f.  allg.  Phys.,  viii,  422;  Schenck,  Marburger  Sitzber.,  1904,  No.  2. 

*■  Wiener :  Arch,  f .  klin.  Med.,  Ix,  264. 

"Krehl:  Unpublished  experiments. 

**  Cf.  Wilke  and  Meyerhof :  Pfluger's  Arch.,  cxxxvi,  i. 


486  THE  BASIS  OF  SYMPTOMS 

"  Reiss :  1.  c 

**Rumpf:l.  c 

"  See  Wiener :  Arch,  f .  klin.  Med.,  Ix,  264. 

"Quincke:  Arch.  f.  klin.  Med.,  xlii,  492;  Steinert,  Zeitschft.  f.  Nervenheilk., 
xxiv,  i. 

"  Goldscheider :  Berl.  klin.  Wochenschft.,  1894,  421 ;  Steinert,  1.  c,  and  Arch. 
f.  klin.  Med.,  Ixxxiv,  445. 

•"Charcot:  Lectures;  Charcot,  Progres  med.,  April  i,  1893;  Strumpell, 
Munch,  med.  Wochenschft.,  1888,  No.  13. 

"  Sulzer :  Anat.  Untersuchungen  viber  Muskelatrophie  artik.  Ursprungs,  Fest- 
schrift f.  Hagenbach-Burckhardt,  1897. 

"See  Bing:  Arch.  f.  klin.  Med.,  Ixxxiii,  199;  Forster,  Charite-Annalen,  xxxii. 

''Charcot's  Lectures;  Weizsacker,  in  Brun's  Beitrage,  iii,  22;  Kredel,  Volk- 
mann's  Vortrage,  No.  309. 

•*  Oppenheim  and  Siemerling :  Arch,  f .  Psych.,  xviii,  98,  487. 

•'Rosenow  and  Oftedal:  Jour.  Am.  Med.  Assn.,  1915,  Ixiv,  1968. 

"  F.  Krause :  Die  Neuralgic  d.  Trigeminus,  1896. 

"E.  V.  Hippel,  Jr.:  Graefe's  Arch^  xxxv,  217  (lit). 


INDEX 


Abderhalden  reaction,  i86,  187 
Abdominal  angina,  259 
Abdominal  muscles,  function  of,  290 
Absorption,   disturbances   of   gastric, 

254 
of  intestinal,  from  alteration 
of     bowel    contents, 
282 
in  absence  of  bile,  265 
in  diseases  of  bowel,  282, 

283 
in  pancreatic  disease,  273, 

274 
Acapnia,  as  a  cause  of  shock,  88 
Accelerator  nerves,  influence  of,  upon 

heart  beat,  55 
Accidental  murmurs,  75 
Acetanilid,  action  of,  on  red  blood- 
corpuscles,  120 
Acetic  acid,  in  urine,  in  metabolic  dis- 
orders, 329 
Acetone  bodies,  formation  of,  328-332 
occurrence  of,  329 

in  diabetes,  330,  358 
toxic  action  of,  332 
Achylia  gastrica,  237 

gastric  motility  in,  250 
Acid  intoxications,  effect  of,  upon  the 
heart,  332 
upon  the  nervous  system,  332 
upon  respiration,  210,  224,  332 
upon  the  temperature,  332 
origin  of,  328 
treatment  of,  333 
Acidosis,  in  chronic  hepatic  disease, 
328 
in    diabetes    mellitus,    330,    332, 

333,  358 
nature  of,  329 
origin  of,  330 

respiratory   disturbances  due  to, 
210,  224,  332 
Acids,   organic,   origin   of,   in   intes- 
tinal contents,  281,  330 
in  the  body,  in  metabolic  dis- 
orders, 327,  328,  329 
in  the  stomach,  in  stagnation, 
246 
significance  of,  in  the  causation  of 

diarrhoeas,  287 
toxic  manifestations  of,  332 
Acromegaly,  relation  of  hypophysis 
to,  372 


Adams-Stokes  symptom-complex,  dis- 
turbances of  cardiac  rhythm  in,  68 
Addison's     disease,     significance     of 

adrenals  in,  336 
Adenie.     See  Pseudoleukaemia. 
Adolescence,  albuminuria  of,  421 
Adrenalin.     See  Epinephrin. 
Agglutination  and  agglutinins,  174 
Aggressins,  i57,   190,  279 
Air,    effect    of    composition    of,    on 
respiration,  215,  218 
of  pressure  variations  of,  on  res- 
piration, 215 
on  the  blood,  143 
Air-passages  (see  also  Respiratory), 
infections  of,  153 
stenoses  of,  pulsus  paradoxus  in, 
70 
respiratory    disturbances    in, 
201-204 
sterility  of  the  lower,  153,  199 
Albumin,  percentage  of,  in  the  blood- 
serum,  137 
Albuminuria,  420-425 

alternation  of,  with  haemoglobi- 

nuria,  118 
causes  of  pathological,  423 

of  physiological,  420,  421 
due  to   circulatory   disturbances, 

423 
to  intoxications,  423 
following  ingestion  of  egg-albu- 
min, 426 
psychic  disturbances,  421 
cold-baths,  421 
in  amyloid  kidney,  419 
in  diabetes,  359 
in  haemoglobinaemia,  121 
in  the  infectious  diseases,  421,  423 
in  nephritis,  423,  424 
injuries  of  renal  epithelium,  rela- 
tion of,  to,  422-424 
occurrence  of,  in  families,  421 
orthotic,  421 
pathogenesis  of,  422 
physiological   (functional),  420 
relation  of,  to  renal  oedema,  140 
results  of,  428 
total  daily  excretion  of,  425 
varieties  of  albumin  in,  422,  424, 
426 
Albumosuria,    in   metabolic   disturb- 
ances, 326,  427 
in  fever,  398 

487 


488 


INDEX 


Alcoholism,  chronic  and  gout,  367 
arterial  changes  in,  86 
as  a  cause  of  cardiac  weakness,  37 
of    increased    blood-pressure 
and  cardiac  hypertrophy,  30 
dilatation  of  heart  in,  30,  31 
effect  of,  upon  accumulation  of 
fat,  313 
upon  the  body  temperature, 
410 
Aleuksemic  leukaemias,   127,    129,   132 
Alexins,  165,  188 

action  of,  118,  166,  167,  173-174 
source  of,  165 
varieties  of,  169 
Alkaptonuria,  334-336 
Allergic.    See   Anaphylaxis. 
Amboceptors,  165,  166,  167,  168,  189 
action  of,  according  to  Ehrlich's 
side-chain  theory,  166 
according  to  Metchnikoff,  189 
effect  of  cold  upon,  118,  160 
relation  of,  to  alexins,  165,  166 
Aminoacids,   in   hepatic   disease,   326 
in  the  blood,  138,  139 
normal  metabolism  of,  335 
of  the  urine :  origin  of,  from  hy- 
drolytic    cleavage    of   pro- 
teids,  325,  326 
normal,  326 
source  of,  335 
Ammonia,  excretion  of,  as  urea,  327, 

333 
in  urinary  stasis,  433 
increased    formation    of,    patho- 
logical, due  to  proteid  de- 
struction, 327,  328 
physiological,  327 
role     of,     in     neutralization     of 
harmful  acids,  z^l,  328,  334 
Amyloid  degeneration  of  the  kidneys, 
behavior  of  heart  in,  26,  32 
oedema  in,  92 
urine  in,  419 
Anaphylactic  shock,  87,  179,  205 
Anaphylaxis,  178-187 

development    of,    during   immu- 
nization, 178 
infection  and,  183,  184 
local  reactions  in,  183,  186 
mode  of  origin  of,  180,  181 
passive,  180 

relation   of,  to  hay   fever,  urti- 
caria, eclampsia  and  echino- 
coccus  disease,  184-186 
to  infection,  183,  184 
serum  disease  as  a  manifestation 

of,  180,  185 
symptoms  of,  179,  181 
transmission  of,  180 


Anaphylatoxin,  181,  183,  184 
in  relation  to  fever,  404 
Anasarca,   cutaneous,   factors  under- 
lying, 89-94 
Ansemia,  102 

acute,  due  to  hemorrhage,  103 

aplastic,  115 

blood-flow  in,  89 

blood,  in  pernicious,  iii-iiS 

in  secondary  mild  and  moder- 
ately severe,  no,  iii 
body  temperature  in,  1 12 
bone-marrow  in,  106,  115 
chronic,  104 

cardiac  insufficiency  in,  41 
due  to  deficient  and  improper 
food,  no 
to  repeated  hemorrhages, 
109 
types  of,  109 
differentiation  of  various   forms 

of,  112,  113,  114 
essential  (Biermer)  type  of,  112- 

114 
gas  interchange  in  lungs,  in,  219 
general  blood  changes  in,  105,  106 
in  miners,  104 

mild  and  moderately  severe  sec- 
ondary, causes  of,  104,  109,  no 
nervous  system  in,  pernicious,  112 
nutritional  disturbances  in,  319 
oedema  in,  94 
pernicious,  in 
primary,  109 
pulse  frequency  in,  55 
severe,  course  of,  114 
Aneurism  of  the  aorta,  hypertrophy 
of  left  ventricle  in,  23 
stenosis  of  upper  air-passages 
caused  by,  200 
Angina,  abdominal,  259 
Angina  pectoris,  79 

etiology  of,  79 
sudden  death,  due  to,  80 
symptoms  of,  79,  80 
vasomotoria,  80 
Ankylostoma  duodenale,  ansemia  due 

to,  104,  113 
Anoci-association,  88 
Antianaphylaxis,  182,  185 
Antibodies,   action  of,  with  antigen, 

content  of,  in  immune  sera,  176 
immunization  with  prepared,  162 
increase  of,  in  the  body,  162 
persistence  of,  in  the  blood,  161, 

162,  171 
source  of,  167,  170 
Antiferments,    in    the    blood-serum, 
138 


INDEX 


489 


Antigens,   characteristics   and  action 

of,  172,  173 
Antiperistalsis,     gastric,     in    pyloric 
stenosis,  255 
oesophageal,  234 
intestinal,  in  ileus,  285,  294 
normal,  in  colon,  285 
Antitoxins,  action  of,  170,  176 
origin  of,  162,  170 
union  of,  with  the  proteids  of  the 
blood,  170 
Anuria,  in  renal  circulatory  disturb- 
ances of  nervous  origin,  416 
in  uraemia,  431 
Aortic  insufficiency,  blood-pressure  in, 

14 

character  of  heart-tones  in,  74,  75 

combined  with  aortic  stenosis,  19 

compensation  in,  33,  35 

effect  of,  upon  lungs  and  respira- 
tion, 13,  35 

murmurs  in,  74,  75 

pain  in,  78 

pulse  in,  35 

pulse-pressure  in,  14,  83 

relative,  12 

significance  of  syphilis  in  etiology 
of,  ID 
Aortic  stenosis,  15 

bradycardia  in,  61 

heart  murmurs  in,  75 

hypertrophy  of  left  ventricle  in, 

15.  23 
precordial  pain  in,  78 
Aortic  tones,  character  of,  in  chronic 
nephritis,  74 
accentuation  of,  71 
Aplastic  anaemia,  115 
Apoplexy,  blood-pressure  in,  447 
cause  of,  448 

symptoms  of  insult  in,  448,  449 
Appetite,  and  hunger,  257,  258 
causes  of  loss  of,  258 
disturbances  of,  in  affections  of 

mouth,  230 
influence  of,  on  secretion  of  gas- 
tric juice,  238,  240 
loss  of,  in  fever,  404 
Apraxia,  450 

Arneth's    classification   of   the   poly- 
nuclear  leucocytes,  121 
Arrhythmia,  cardiac,  62-70 

accompanying  lesions  of  His 

bundle,  42,  45,  6^ 

as  a  result  of  disturbances  of 

conductivity,  42,  45,  67,  69 

associated  with  dyspepsia,  70 

due  to  cardiac  muscle  disease, 

69 
due  to  poisons,  70 


Arrhythmia,    cardiac,    due   to   vagus 
stimulation,  45,  67,  69,  70 
extrasystolic,  63 
in     nervous     conditions     of 

heart,  69 
perpetual,  65 
reflex,  63,  70 
respiratory,  69,  70 
sinus,  70 
Arsenic,  value  of,  combined  with  iron, 

in  chlorosis,  109 
Arseniuretted     hydrogen     poisoning, 
composition  of  bile  in,  261 
haemoglobinaemia  in,  117 
Arterial  paralysis,  85 
heart  beat  in,  55 
symptoms  of,  86 
Arteries,  hypertension  in,  81 

increased  resistance  in,  in  neph- 
ritis, 26,  27,  28 
inflammatory  lesions  of,  27,  87 
influence  of  heart  upon,  80,  88 
narrowing  of,  in  cases  of  local 

dilatation  elsewhere,  2,  80 
rupture  of,  34 
sclerosis  of,  80 
significance  of,  in  the  circulation, 

80 
spasm  of,  2T,  79,  81 
tonus  of,  26-28,  80 
varying  diameter  of,  80,  88 
Arteriosclerosis,  cardiac  hypertrophy 
due  to,  20,  22 
cardiac  insufficiency  due  to,  zTt 

39,  48        . 
contracted  kidney  associated  with^ 

27 
disturbances   of   locomotion   due 

to,  452 
heart  sounds  in,  72 
increased  arterial  pressure  in,  22^ 

22,.  80,  84 
in  diabetes,  359 
pulse-pressure  in,  83 
vasomotor  disturbances  in,  88 
Arthritis  alkaptonurica,  335 
deformans,  481 

and  focal  infections,  153 
Artificial  pneumothorax,  213 
Ascites,  chylous  and  chyliform,  94 

with  anasarca,  91 
Asphyxia,  arterial  spasm  in,  85,  223 
blood  in,  222 
heart-beat  in,  59,  223 
nervous  disturbances  in,  223 
occurrence  and  manifestations  of^ 

103,  222 
urine  in,  416 
Associated  movements,  466 
Asthenic  bulbar  paralysis,  452 


490 


INDEX 


Asthma,  bronchial,  204-206 

behavior  of  lungs  in,  205,  206 
complications  and  exciting  causes 

of,  205 
nature  of  paroxysm  in,  205,  206 
nervous,  205 
relation  of,  to  anaphylactic  shock, 

205,  206 
symptoms  of,  204 
Asthma  cardiac,  causes  of,  ^^ 

lungs  in,  78 
Asthma  dyspepticum,  211 
Ataxia,  450,  455-458 

and  centripetal  influences,  455 
in  cerebellar  disease,  458 
tabetic,  454 
origin  of,  455 
types  of,  458 
Atelectasis,  pulmonary,  213 
*'  Athlete's  heart,"  29 
Atmospheric  pressure,   effect  of,  on 
blood,  143 
on  respiration,  215 
Atony  of  the  stomach,  253,  254 
Atophan,  in  gout,  370 
Atrophy,    muscular,    through    disuse, 
477,  480 
electrical  reactions  in,  477-479 
Atropin  poisoning,  diminution  of  buc- 
cal secretions  in,  230 
effect  of,  on  the  heart-beat, 
54,  61 
Auricular  tone  in  gallop  rhythm,  t^ 
Autoinfection,  193 

enterogenous,  280 
Autolysis,  325 

Bacillus  carriers,  191 
Bactersemia,   159 

Bacteria,  fever-producing,  381,  382 
general  intoxication  due  to,  157 
importance  of  capsule  of,  157 

of  the  number  of,  157 
minimum  lethal  dose  of,  157 
natural  resistance  to,  161,  162 
portals  of  entry  of,  151,  157 
toxins  of,  157 

upon  the  body-surfaces,  151,  193 
virulence  of,  157 

increase  of,  by  symbiosis,  160 
Bacterial  processes,  in  the  biliary  pas- 
sages, 262-264 
in  the  intestines,  277-282 
advantages  of,  277,  278 
effect    of    variations    in 

diet  upon,  278 
in  the  absence  of  bile,  266 
pathogenic  action  of,  279 
in  the  mouth,  229,  230 
in  the  stomach,  245-^48 


Bacterial  processes,  in  stomach,  fol- 
lowing introduction  of 
decomposable  food,  248 
in  gastric  atony  and  dila- 
tation, 246,  254 
in   the   absence   of   free 

acid,  247 
results  of,  248 
in  the  urinary  passages,  433 
Bactericidal   action   of   blood-serum, 

162,  163,  164,  176 
Bacteriohasmolysins,  159 
Bacteriolysis,  products  of,  165 
Bacteriotropins    in    bacteriolytic    im- 
mune sera,  189,  190 
Basedow's   disease.     See    Hyperthy- 
roidism. 
Baths,    cold,    albuminuria   following, 
421 
in  fever,  401 
Beer,  effect  of  excessive  use  of,  on 
alimentary  glycosuria,  344 
on  the  formation  of  fat,  313, 

315 
on  the  heart,  30,  37 
on  the  kidneys,  30 
Belching,  255 

Benzene  therapy  in  leukaemia,  129,  131 
Beta-oxybutyric  acid  in  the  urine  in 
diabetes,  329,  330,  358 
in    metabolic    disorders, 
328-332 
Biermer's    ansemia,    112.      (See    also 
Pernicious  anaemia.) 
blood  regeneration  in,  114, 115 
Bile,  action  of,  on  pancreas,  275 

changes    in,    due    to    action    of 
poisons  on  blood  and  liver,  261 
effect  of  exclusion  of,  from  Intes- 
tines, 265 
in  haemoglobinaemia,  116 
pigment  content  of,  in  conditions 

of  stasis,  260 
resorption    of,    into    circulation, 
266-^68 
Bile,  resorption  of,  effect  of,  upon  the 
body,  270 
upon  the  heart-beat,  60, 
270 
Bile     secretion,     anomalies     of,     in 
amount,  260,  261 
in  composition,  260,  261 
in  intoxications,  261 
disturbances  of,  by  bacterial 
action,  262 
by  calculi,  261 
by  exclusion  from  intes- 
tines, 265,  266 


INDEX 


491 


Bile  secretion,  effects  of  disturbed: 
jaundice,  265,  266 
upon  the  intestines,  265 
Bile,  stasis  of,  and  biliary  calculi,  262, 
264 
anatomical  changes   in  liver 

in,  270,  271 
cerebral   symptoms  in  long- 
continued,  271 
local    from    obstructions    in 
smaller  capillaries,  267 
Biliary  colic.     See  Gall-stones. 
Biliary  salts,  effect  of,  on  pulse,  60, 
270 
on  red  blood-corpuscles, 
117 
Black-water  fever,  117 
Bladder,  causes  of  tenesmus  of,  437 

innervation  for  emptying  of,  459 
Blood,  conditions  essential  to  arterial- 
ization  of,  208 
effect   of   composition    of,    upon 
respiration,    exter- 
nal, 219 
internal,  223,  224 
upon    the    secretion    of 
urine,  426 
in  acid  intoxications,  224 
in  anaemias,  105,  106,  no,  111-116 
in  burns,  119 

in  cardiac  dilatation,  141,  142 
in  changes  in  atmospheric  pres- 
sure, 143-145 
in  chlorosis,  107-iog 
in  circulatory  disorders,  141,  142 
in  congenital  heart  lesions,  50 
in  gout,  368 
in  hydraemia,  139-141 
in  leukaemia,  129^133 
in  nephritis,  140,  141 
in  phosphorus    and    carbon    mo- 
noxide poisoning,  145,  219,  225 
in  pseudoleukaemia,  128,  130,  132- 

regeneration  of,  103,  105,  100,  114 
sites  of  formation  of,  102 
Blood  coagulation,  after  destruction 
of  erythrocytes,  120 
factors    concerned    in,    120, 

126,  135.  136 
in   intoxications   and   burns, 

120 
in  severe  anaemias,  127 
time  of,  136 
Blood-corpuscles,  red,  anomalies  of, 
after  burns,  119 
in  anaemias,  103-106,  107,  no, 
III,  114-116 
in  form,  105,  in 


Blood-corpuscles,  red,  in  haemoglobin, 

105,  107,  III 

in  staining  properties,  105 

in  structure,  105,  119 

changes    in    haemoglobin    of,   by 

conversion    into    met- 

haemoglobin,    116,   117, 

118,  119,  120 

by     destruction    of    the 
stromata,  116,  117,  118, 

119,  121 
significance  of,  120 

effect  of  blood-plasma  upon,  103 
of    oxygen    deficiency    upon, 
142 
in  chlorosis,  107 
nucleated,  105,  107,  in,  113,  116, 

130,  143 
number  of,  in  cardiac  disorders, 

51,  142 

in  low  atmospheric  pressures, 

143 
pathological     increase     of,     per 

volume-unit,  142 
regeneration  of,  105,  115 
resistance  of,  to  haemolysins,  118 
to   hypotonic   salt   solutions, 
115.269 
Blood-corpuscles,      white,      chemical 
characteristics  of  different 
types  of,  122 
eosinophilic,  125,  205 
ferments  of,  122,  188,  189 
granules  of,  121 
in  anaemias,  107,  in,  126 
in  leukaemias,  128-133 
number  of,  123 

diminished  (leucopaenia), 

III,  126 
increased  (leucocytosis), 
123-126 
physiologically,  123 
pathologically,      103, 
III,  124,  128 
percentage  of  different  forms 
of,      in     leucocytoses, 
123,  124,  125 
in  leukaemias,  129 
in  normal  blood,  121 
in  pseudoleukaemias,  128 
phagocytic  properties  of,  187- 

189 
polymorphonuclear,  121,  123, 
124 

Arneth's  subdivision  of, 
121 
source  of,  122 
lymphoid,  122 
myeloid,  122 


49£ 


INDEX 


"  Blood  diseases,"  behavior  of  haemo- 
globin and  red  cells  in,  102 
definition  of,  102 
origin  of,  102 
Blood-flow,    rate   of,    in   relation   to 
systolic  pressure,  48 
significance  of  cardiac  accelera- 
tion on,  59 
through  the  kidneys,  effect  of,  on 
secretion  of  urine,  413, 
416 
on  albuminuria,  423 
(See  also  Circulation  and  Circu- 
latory disturbances.) 
Blood-plasma,  antibacterial  and  anti- 
toxic properties  of,  163-165 
fibrin  content  of,  136 
proteids  of,  137 

solution  of  haemoglobin  in,   116, 
117,  118,  119 
Blood-platelets,     ferments     of,     and 
coagulation,  126 
in   leuksemia   and  pernicious 
anaemia,  127 
Blood-pressure,  arterial,  effect  of,  on 
heart-beat,  55,  59,  63 
on    secretion    of    urine, 
413,  316 
diastolic,  82 

diminished,  results  of,  55,  85,  416 
effect  of  exercise  upon,  83 
increased,  80,  81,  84 

as  a  cause  of  left  ventricular 

hypertrophy,  29 
associated    with    polythemia 
and  splenomegaly,  142,  146 
causes  of,  in  nephritis,  26,  27, 

28,  29 
in  broken  compensation,  40 
in  infections  of  renal  pelves, 

26 
results  of,  34,  59 
in  aortic  insufficiency,  14 
in  arteriosclerosis,  22,  23,  27 
in  compensated    hearts,    dangers 

.   °^'  34      . 

in  dyspnoeic  conditions,  24 
in  nephritis,  25-29 
physiological  variations  of,  83 
regulation  of,  80,  81,  88 
systolic,  82 

venous,  increased,  47,  48 
results  of,  50^-52 
Blood,  quantity  of,  diminished,   iii, 
112,  146 
increased,  145 

without  alterations  in  the 

serum,  145,  146 
with   watery   scrum,   92, 
139 


Blood,  quantity  of,  in  chlorosis,  107 

in  the  body :  its  distribution 
per  unit  of  time  in  circula- 
tion, 345 
in  the  kidneys,  and  influence 
of  same  upon  secretion  of 
urine,  413 
Blood-serum,  action  of,  upon  chemi- 
cal substances,  165,  170 
curative  and  immunizing  ac- 
tion of,  162-165 
enzymic  action  of,  138 
fat  content  of,  137 
ferment  inhibitory  action  of, 

138 
functional  differentiation  of, 

from  plasma,  135 
proteids  of,  137,  138 
in  hydraemia,  139 
in  leukaemia,  131 
residual  nitrogen  of,  138,  430, 

431 
salt  content  of,  137,  139 
water  in,  137,  139^141 
in  chlorosis,  107 
in  pernicious  anaemia,  ili 
in  renal  oedema,  92 
Blood  supply,  to  brain,  441 
to  heart,  40 

to  the  organs,  effect  of  vascu- 
lar tonus  upon,  80 
Blood    toxins,    haemolytic    and    met- 

haemoglobin  forming,  117 
Blood,    total    solids    of,    in    polycy- 
thaemia,  142 
in  pernicious  anaemia,  112 
Blood-vessels,     circulatory     disturb- 
ances in,  3 
in  the  arteries,  80,  81 
in  the  veins,  88 
effect  of  tobacco  upon,  31 
hypertonus    of,    in    arterio- 
sclerosis, 22,  23 
essential,  29,  81 
in  chronic  nephritis,  25- 
29,  84 
injuries    of,    as   a   cause   of 

anaemia,  103 
role    of,    in    movement    of 
blood,  I,  80 
Body,  position  of :  change  from  hori- 
zontal  to   vertical  as   a   cause   of 
albuminuria,  421 
Body  weight,  in  fever,  404 
in  inanition,  309 
in  obesity,  314 
Bone,  diseases  of,  due  to  nutritional 
disturbances,  481 


INDEX 


493 


Bone-marrow    changes    in   anaemias, 
105,  106,  III,  114,  115,  116 
in     leuksemia    and     pseudo- 
leukaemia,  127,  128,  133 
genetic  significance  of,  133 
in  polycythemia,  142 
Bothriocephalus  latus,  as  a  cause  of 

anaemia,  113,  114 
Botulism,  276 

Bradycardia,  causes  of,  59^2 
in  Adams-Stokes  disease,  68 
significance   of,   for   the  circula- 
tion, 62 
Bronchial  stenosis,  causes  of,  203 

effect    of,    upon    respiration, 

203,  204 
in  bronchial  asthma,  204,  206 
Bronchiolitis  exudativa,   relation  of, 

to  asthma,  205 
Bronchitis,    as    a    cause    of    cardiac 
hypertrophy  in  children,  21 
gaseous  interchange  in,  222 
in  passive  hypersemia  of  lungs,  34 
respiratory  movements  in,  204 
Brown  atrophy  of  the  heart,  in  medi- 
astino-pericarditis,  24 
pathological  significance  of, 

43 
Brown-Sequard  paralysis,  character- 
istics of,  470 
Bulbar  paralysis,  asthenic,  muscular 
weakness  in,  452 
salivation  in,  231 
Bundle  of  His,  relation  of  to  heart 

block,  42,  45.  67 
Burns,  blood  changes  due  to,  119 

Cachexia,  blood  in,  126 
in  diabetes,  358 
strumipriva,  322 
Caisson  disease,  218 
Calculi,  biliary,  261 

urinary,  434 
Caloric  needs  of  the  body,  305 
Capillaries,  circulation  in,  2,  3 
Carbohydrates,    metabolism    of,    310, 
311,  3^2 
quantitative  disturbances  of, 
343 
in  diabetes,  349  350 
therapeutic  value  of,  in  acidosis, 
330 
Carbon  dioxide,  amount  of,  in  blood 
in  acid  intoxications,  224 
anaesthetic  action  of,  222 
Carbon  monoxide  poisoning,  blood  in, 
114  219 
respiratory  disturbances  in.  219 


Carcinoma  of  the  stomach,  digestion 
of  proteids  in,  245 
proteolytic  ferments  in,  245 
secretion      of      hydrochloric 
acid  in,  244 
Carcinomatosis,  anaemia  in,  109 

pernicious    form   of   anaemia  in, 

113 
proteid  destruction  in,  319  320 
valvular  disease  in,  9,  10 
Cardiac  im.pulse,  70 
pain,  78 

and  anxiety,  of  local  origin, 

78 
of  psychic  origin,  78 
Cardiac    output    per    beat,    and    the 

pulse-pressure,  82,  83 
Cardjalgia,  259 
Cardiography,  71 
Castration,  relation  of,  to  fat  deposits, 

317 
Casts  in  urine,  in  nephritis,  425 
Cells,  destruction  and  solution  of,  165 
effects  of,  on  increase  of  living 

substance,  311 
effect   of   nervous   system   upon, 

474 
ferments  of,  and  the  splitting  of 

proteid,  325,  326 
gas  metabolism  of,  197,  223-225 

oxygen  need  in,  223,  224 
metabolism  of,  304 

proteid    destruction    in,    327, 

397,  398 
proteid  need  in,  306-308 
sugar  need  in,  343 
resistance  of,  to  bacterial  poisons, 

161,   278 
side-chains  of,  166 
Cerebral  concussion,  447 
embolism,  449 
hemorrhage,  448 
Cerebral  cortex,  circulatory  disturb- 
ances of,  441 
motor   function   of,   and   its 
disturbances,  451 
Cerebral  pressure,  443 

blood-pressure  in,  446 

causes  of,  443-445 

choked  disk  in,  445 

direct  manifestations  of,  446 

due  to  hemorrhage,  443,  447 

in  brain  tumors,  444 

in  chronic  hydrocephalus,  444 

in  meningitis,  444 

indirect    (latent)    symptoms 

of,  445 
pulse  in,  59,  446 
respiratory  movements  in,  446 


494 


INDEX 


Cerebral  symptoms,  In  anaemia,  112, 
441,  442 
in  Cheyne-Stokes  respiration, 

209 
in  diabetes,  332,  333 
in  fever,  386 

in  functional  disturbances  of 
nervous     system,     general 
and  focal,  441 
in  stasis  of  bile,  270,  271 
Cerebral  tumors,  pressure  symptoms 

in,  444,  445,  446 
Cerebrospinal   fluid,   composition  of, 

443.  ^  .         ^ 

secretion  and  resorption  of, 

443 
significance  of,  in  increased 
intracranial  pressure,  443~ 

447 
Cervical  cord,  injuries  of,  eflFect  of, 

on  temperature,  385,  387,  388 
Charcot-Leyden  crystals,  in  the  blood, 
in  leukaemia,  131 
in  the  sputum,  in  asthma,  205 
Chemotaxis,  importance  of,  in  leuco- 

cytosis,  124 
Chemotherapy,  in  infectious  diseases. 

Chewing,  disorders  of,  and  digestion, 

229,  230 
Cheyne-Stokes   respiration,   manifes- 
tations of,  2og 
theories  as  to  cause  of,  209, 
210 
Chloral,  eflfect  of,  on  vasomotor  cen- 
ter, 86 
Chlorosis,  blood  in,  107 
causes  of,  107,  108 
color    of  skin  in,  106 
incidence  of,  106 
intracranial  pressure  in,  444 
parenchymatous  changes  in,   107 
significance  of  hypolastic  aorta  in, 

107 
value  of  iron  in,  108 
water  retention  in,  107,  146 
Choked  disk,  445 
Cholera  Asiatica,  blood  in,  139 
stools  in,  283 

vibrio  of,  distribution  of,  279 
increases    of,    in   bowel, 

iss,  157 

toxic  action  of,  159 
Cholesterin  stones,  262 
Chorea,  disturbances  of  motility  in, 

466 
Chromium  nephritis,  424 
Chylous  and  chyliform  ascites,  94 
Cilia,  protective  function  of,  197,  198 


Circulation,  i 

anomalies  of,  1 

demands  on,  in  health,  3,  4 

in  anaemia,  220 

in  aortic  insufficiency,  12,  35 

in  the  arteries,  2,  80 

in  the  capillaries,  2 

in   compensated   cardiac  lesions, 

33-35 
in  cardiac  weakness,  46-52 
in  tachycardia,  59 
in  the  kidneys,  and  secretion  of 

urine,  413,  416 
in  the  veins,  2,  88 
pulmonary,  i,  2 

in  aortic  insufficiency,   13 
influence  of,  on  respiration, 

220 
relation     of     blood-pressure 

and  rate  of  flow  in,  3 
significance  of,  in  the  func- 
tioning of  the  organs,  i 
significance   of   the   contrac- 
tile and  elastic  attributes  of 
arteries  in,  5,  6,  80,  81 
systemic,  2 
Circulatory    disturbances,    blood    in, 
141,  142 
effect  of,  on  composition  and 
secretion  of  urine,  413, 
416 
en  respiration,  220,  223 
in  the  arteries,  80,  81 
in  asphyxia,  85,  222 
in  the  brain,  manifestation  of, 

441,  442 
in  infectious  diseases,  86,  87 
in  nephritis,  25 
in  pneumothorax,  213 
in  shock,  87,  88 
in  the  veins,  50-52,  88,  90 
Coagulation  of  the  blood.     See  blood 

Coagulation 
Cold,  action  of,  in  paroxysmal  haemo- 
globinuria,    1 18 
on  the  body  temperature,  389 
Colic,  biliary,  264 
gastric,  258 
intestinal,  297 
renal,  437 
Colica  mucosa,  287 
Collapse,    in    dilatation    of    stomach, 

255 
in  fever,  causes  and  symptoms  of, 

4c:^,  409 
in  infectious  diseases,  circulatory 

changes  in,  86,  409 
temperature  in,  408 


INDEX 


495 


Colloids,  increased  hydration  capacity 
of,  as  a  cause  of  oedema,  93 
to  precipitation,  172 
relation  of,  to  agglutination,  175 
Color-index    in    pernicious    anaemia, 

III,  113 
Coma,  acidosis  as  a  cause  of,  332 
carcinomatous  and  enterogenous, 

332 
diabetic,  332,  333,  358 

symptoms  and  treatment  of, 

332,  333  . 
Compensation,  cardiac,  blood-pressure 
in  disturbed,  40 
cause  of  breaks  in,  in  hyper- 
trophied  hearts,  38 
in  non-hypertrophied,  40 
transitory      and     permanent 

breaks  in,  38,  39 
value  of  digitalis  in  loss  of, 
39,  66 
Compensatory  regulations,  in  chronic 
inanition,  309,  310 
in  heart  disease,  2 
in  respiratory  diseases,  221 
Complement.     See  Alexins 

fixation,  mechanism  of,  173 
Concussion,      cerebral      (Commotio 

cerebri),  447 
Congenital  heart  disease,  lesions  of, 
18 
polycythemia  in,  142 
Constipation,  288-291 
bradycardia  in,  60 
in  hyperacidity,  243 
Constitutional  diseases,  as  sequelae  of 
other  diseases,  377 
causes  of,  377 
chronic  course  of,  376 
definition  of,  376 
etiology  of  acquired,  377 
general  bodily  changes  in,  as 
distinguished    from    local, 

374,  375 
metabolism  in,  372 
predisposition  to,  376 
relation  of,  to  chronic  infec- 
tions, 375 
to  chronic  intoxications, 

378 
to  diatheses,  376 
Contagion,  relation  of  virulence  to, 

157 
Contraction  of  the  heart,  mechanism 

underlying,  53,  54 
Contractures,  463-466 
Convalescence,  heart  action  in,  55,  61 
nitrogen  retention  in,  310 
temperature  in,  402,  409 
Convulsions,  causes  of,  467 


Convulsions,  clonic  and  tonic,  467 
epileptic,  467,  468 
fever,  after  cerebral,  386 
in  Adams-Stokes  disease,  68 
in  chronic  biliary  obstruction,  270 
in  hepatic  toxaemias,  271 
in  Jacksonian  epilepsy,  467 
in    strychnin    poisoning    and    te- 
tanus, 462 
in  uraemia,  429 

point  of  origin  of  epileptic,  468 
reflex,  462,  467 
spontaneous,  467 
Coordination,  disturbances  of,  in  cere- 
bellar disease,  458 
in  tabes,  454,  4.55,  457 
theory  of,  452-455 
Coronary  disease,  as  a  cause  of  heart 
weakness,  40,  41 
bradycardia  due  to,  62 
pain  and  anxiety  in,  78,  79 
relation  of,  to  Adams-Stokes 
disease,  68 

to  angina  pectoris,  79 
sudden  death  in,  80 
Coughing  advantages  and  disadvan- 
tages of,  200 
centre  for,  198,  199 
diminished,  199 
mechanism  of,  198 
Creatinin  in  urine  of  febrile  patients, 

399  . 
Cretinism,  relation  of  thyroid  to,  322 
Crises,  gastric,  of  tabes,  259 
Curschmann's    spirals,    in    asthmatic 

sputum,  205 
Cutaneous  reflexes,  462 
Cutaneous  sensations,  disturbances  of, 
455,. 456,  457,  468,  469-471 
irritative  phenomena  in,  473 
Cyanosis,  caused  by  venous  stasis,  50 
congenital,  50 

gas  content  of  blood  in,  224 
Cyanotic  induration  of  kidneys,  heart 

in,  30 
Cystin  calculi,  336 
Cystinuria,  336 

Cystitis,  causes  and  dangers  of,  433 
Cytodiagnosis,  94 

Cytolytic  properties  of  blood  serum, 
165,  166 

Decubitus,  482 

Defecation,  bacterial  inhibiting  action 
of,  280 
complete    cessation    of:    results, 

293,  294,  295 
increased   frequency  of,  285-288 
innervation  for,  460 
painful,  299 


496 


INDEX 


Degeneration,     fatty,     in    pernicious 
anaemia,  112 
glycogenic,  of   the   renal   epithe- 
lium, 359 
of  the  heart  muscle,   functional 

significance  of,  43 
of  the  muscles,  451,  477 
of  the  nerves  (secondary),  474 

in  pernicious  anaemia,  112 
of   the    red    blood-corpuscles,    in 
anaemia,  104,  105,  114 
Delirium    in    long-continued    biliary 

stasis,  271 
Developmental  anomalies  of  heart  and 
large  vessels  in  the  etiology 
of  valvular  lesions,  18 
as  a  cause  of  venous  stasis 
and  cyanosis,  50,  51,  142 
Diabetes  insipidus,  414-416 
causes  of,  415 
hypophysis  and,  415 
influence   of   composition  of 

blood  upon,  425 
nature  and  symptoms  of,  414, 

415 

relation  of ;  to  diabetes  melli- 
tus,  414 

vasomotor  influences  in,  415 
Diabetes  mellitus,  349 

acidosis  in,  328,  329,  330,  358 

amount  of  urine  in,  359,  425 

anomalies  of  sugar  combus- 
tion in,  353 

causes  of  sugar  excretion  in, 
349,  352 

coma  in,  332,  358  _ 

composition  of  urine  in,  349, 

359 
constitutional    character    of, 

378 
etiology  of,  356 
glycosuria  in,  349,  350 
hyperglycemia  in,  349,  352 
limit  of  assimilation  for  car- 
bohydrates, 350,  352 
mild  and  severe  forms  of,  350 
nutritional    disturbances    in, 

357-359 
oxidations  in,  355 
pathology  of,  356 
proteid  destruction  in,  358 
proteid  intolerance  in,  351 
renal,  346 

respiratory  quotient  in,  353 
results  of,  357,  358,  359 
role  of  internal  secretions  in, 
.356 

significance  of  liver  in,  352, 
353,  356 


Diabetes  mellitus,  significance  of  pan- 
creas in,  354,  355,  356,  357 
stomatitis   and  dental  caries 

in,  229,  359 
sugar  consumption  in,  353 
sugar    formation    in :     from 
carbohydrates  and  proteids, 
350,  352 
thirst  in,  359 

utilization  of  dextrose  in,  357 
Diacetic  acid  in  the  urine,  329 
Diaminuria,  336 
Diaphragm,  paralysis  of,  as  a  cause  of 

respiratory  disturbances,  207 
Diarrhoea,    causes   of,    from    without 
the  bowel,  286 
from  within,  by  irritation  of 
abnormal  contents,  287 
effect  of,  on  the  body,  288 
faeces  in,  285,  286 
gastrogenous,  236 
increased  peristalsis  of  colon  in, 

285 
infantile,  280 
in  uraemia,  429 
nervous,  286 

without   subjective    disturbances, 

286 

Diastole,   disturbances   of,  and  their 

effect  upon  cardiac  efficiency,  46 

split  heart  tones  at  beginning  of, 

73 
variations  in  length  of,  5,  46 
Diathesis,     differentiation    of,    from 
constitutional  disease,  376,  378 
eosinophihc,  379 
exudative,  379 
syphilitic,  375,  377 
uratic,  376,  379 
Digestion,  bacterial  processes  in,  245, 
254,  277 
disturbances  of,  due  to  abnormal 
processes  in  bowel,  276 
absence     of     pancreatic 

juice,  273,  274 
anomalies  of  absorption, 

282  _ 
bacterial  activity,  277 
disorders  of  motility,  284 
narrowing       of       bowel 
lumen,  291 
due   to    affections    of    teeth, 

mouth   and   throat,  229 
due  to  disturbances  of  biliary 

secretion,  265 
due    to   oesophageal   disease, 

232 
due  to  gastric  disorders,  236 
gastric  dilatation  in,  251 


INDEX 


497 


Digestion,  disturbances  of,  due  to  gas- 
tric   disorders,    motor 
disturbances  in,  248 
psychic  origin  of,  260 
regurgitation  and  vomit- 
ing in,  255 
secretory  disturbances  in, 
237 
leucocytosis  in,  123 
Digitalis,  action  of,  upon  the  heart, 
39,  42,  66,  67,  68 
upon  the  kidneys,  414 
Dilatation  of  the  heart,  44,  49 

of  the  stomach,  251 
Diphtheria   toxin   and   antitoxin,   43, 

157,  158,  159,  176-178 
Diphtheroid  bacillus  in  Hodgkin's  dis- 
ease, 134 
Disease,  tendency  to,  376,  377 
Diuretics,  action  of,  414,  42i5 
Diverticula  of   the  oesophagus.     See 

CEsophagus 
Dizziness,  472 

in  cerebral  anaemia,  442 
Ductless  glands,  interrelationship  of, 

372,  2,73 
Ductus  Botalli,  potency  of,  18 
Dysentery,  endemic,  etiology  of,  282 

mixed  infection  in,  160 
Dyspepsia,  acida,  241 

effect  of,  on  the  heart,  60,  70 
nervous,  260 
psychic,  260 
Dysphagia,  233-236 
Dyspnoea,  blood-pressure  in,  24 
cardiac,  34,  77 

causes  of,  78 
chronic,    v^rith    hypertension   and 

heart  hypertrophy,  24 
expiratory,  202 
in  bronchial  asthma,  204,  205 
inspiratory,  201 
in  tracheal  stenosis,  201 
subjective  symptoms  of,  225 
Dystrophies,  muscular,  480 

Eclampsia,     puerperal,     anaphylactic 

symptoms  in,  186 
CEdema,  causes  of,  89-94 

collateral,  91 

composition  of  fluids  in,  90, 

94  ,     ,      . 

due  to  mcreased  hydration 
capacity  of  colloids,  93.  141 

experimental,  90,  93,  95 

from  sodium  chlorid  reten- 
tion, 93,  141 

in  anaemia,  malignant  disease 
and  chronic  infections,  94 

in  nervous  diseases,  94 


CEdema,  causes  of,  in  stasis,  localiza- 
tion of,  90 
nature  of,  89 
nephritic,  91,   140 
pulmonary,  95 
Ehrlich's  side  chain  theory,  166 
Embolism,  cerebral,  448 

of  the  coronary  arteries,  40 
Embryocardia,  56 

Emphysema,     pulmonary,     asthmatic 
attacks  in,  205 
cardiac  hypertrophy  in,  21 
causes  of,  208 
condition  of  lungs  in,  208 
gas  interchange  in  lungs  in, 
207,  215,  222 
Endarteritis,   chronic,  as  a  cause  of 
valvular  lesions,  10 
obliterans,  effects  of,  upon  move- 
ments of  legs,  452 
Endocarditis,  acute,  9 
bacteria  in,  9 
chronic,   10 
effect  of,  on  heart  valves,  9,  10,  18 

on  heart  muscle,  27,  38,  41 
fetal,  18 
infectious,  9,  41 
in  focal  infections,  153 
rheumatic,  9 
toxic,  9 

verrucous,  9,  18 
Enteroptosis,  gastric  motility  in,  253 
Enzymes,   gastric,    diminished   secre- 
tion of,  237 
in  blood-serum,  138 
in  carcinoma  of  stomach,  245 
of  the  cells,  325 

proteid  splitting,  in  leucocytes,  189 
uricolytic,  364 
Endotoxins,  159 

Eosinophilia,  general,  local,  12S,  126 
prognostic  importance  of,  125 
Epilepsy,  467 

urine  during  convulsions  in,  416 
Epinephrin,  emergency  functions  of, 
338 
influence  of,  upon  the  blood-pres- 
sure, 28,  339 
upon  the  excretion  of  sugar 
in  the  urine,  345,  347,  348, 

349 
Epithelium,  ciliated,  of  the  air  pas- 
sages, function  of,  197 
normal,     as    a     barrier     against 

micro-organisms,  207 
renal,  permeability  of,  to  proteids 
of  blood,  422 
to  sugar,  346 
Erythrocytes.     See  Blood-corpuscles, 
red 


498 


INDEX 


(Esophagus,  affections  of,  232-36 
Ethereal    sulphates    in    urine,    as    an 
index  of  putrefaction  in  the  intes- 
tines, 281,  293 

motor    disturbances    in, 

248 
psychic  origin  of,  260 
Exanthems,  acute,  immunity  follow- 
ing, 164 
Exchange    of    gases,     compensatory 
mechanisms  for,  in  disturb- 
ances of  external  respira- 
tion, 221 
in  pulmonic  and  pleural  dis- 
eases, 221 
in  anaemia,  219 
in  bronchitis,  222 
Excitement,  effect  of,  on  albuminuria, 
421 
on  intestinal  persistalsis,  286 
on  the  heart  rate,  56 
on  the  size  of  the  heart,  24 
Exertion,  as  a  cause  of  cardiac  accel- 
eration, 55 
cardiac  hypertrophy,  6,  29 
cardiac  insufficiency,  30,  38,  44 
diminution  in  size  of  heart,  fol- 
lowing, 30 
effect  of  excessive,  in  etiology  of 
infections,  159 
on  albuminuria,  421 
Exophthalmic     goitre.     See     Hyper- 
thyroidism 
Expiration,    in    stenosis    of    air-pas- 
sages, 202 
in    volumen    puimonum    auctum, 
207 
Exposure  to  cold,  significance  of,  in 

the  etiology  of  infections,  159 
Extrasystoles     ( Premature    contrac- 
tions), 63 
causes  of,  63 

in  paroxysmal  tachycardia,  58 
interpolated,  63 
ventricular   and   atrioventricular, 

63 
Extremities,  disturbed  movement  of, 
due  to  anomalies  of  sensation,  454- 

457 
Eye,  disturbances  of,  in  anaemia,  442 
in  diabetes,  358 

Facial  paralysis,  effect  of,  on  chewing, 

229 
Fat,  in  the  blood-serum,  137 

in  the  faeces,  in  absence  of  pan- 
creatic juice,  273 
in  pericardial,  pleural  and  peri- 
toneal exudates,  94 
of  food,  metabolism  of,  304,  311 


Fat  necroses,  274 

Fat  storage  in  the  body,  311.    See  also 

Obesity,  314-318 
Fatty  heart,  43 

Faeces,  after  exclusion  of  bile  from 
intestines,  265 
bacterial  content  of,  266,  277 
in  pancreatic  disease,  273 
stagnation  of,  288,  291 
water  content  of,  diminished,  288 
increased,  283 
Fermentation,    ammoniacal,     in    the 
urine,  433 
in  the  intestines,  281 
in  the  mouth,  229 
in  the  stomach,  245-248 
nervous  symptoms  of,  255 
relation  of,  to  atony,  254 
Ferments.     See  Enzymes 
Fever,  381 

acidosis  in,  328,  398 
aseptic,  382,  403 
blood  in,  398 
causes  of,  382 
collapse  in,  408 
diurnal  variations  in,  381 
effect  of  age  and  nutrition  upon, 
381 
of  cooling  and  heating  upon, 

401 
of  food  upon,  394,  402 
of  nervous  system  upon,  384 
of,  on  respiration,  204 
experimental,  382,  383,  386,  387 
glycogen  in,  387,  400 
heat  losses  in,  394 
heat  production  in,  392,  399 
heat  regulation  in,  400-404 
hectic,  132,  404  (in  leukaemia) 
hysterical,  386 
in  leukaemia,  132 
in  pernicious  anaemia,  112 
in  pseudoleukaemia,  132 
individual     disposition     towards, 

384 

in  convulsions,  386 

Liebermeister's    theory    of    heat 
regulation  in,  402 

metabolism  in,  396^399 

nutrition  in,  404 

proteid  destruction  in,  397 

pulse-rate  in,  55 

reflex,  386 

significance  of,  for  the  body,  406 

symptoms  of,  381 

water  retention  in,  405 
Fibrin  content  of  blood,  135,  136 
Fixateur  (Metchnikoff),  166,  189 
Fluid  intake,  importance  of,  in  obesity, 
312-314 


INDEX 


499 


Focal  infections,  152 

relation  of  to  herpes  zoster, 

483 
symptoms  of  nervous  lesions, 
441 
Foods,  effect  of  different  upon  gastric 

emptying,  250 
Foreign  bodies,  in  the  bladder,  and 
the  formation  of  stones,  436 
in  the  respiratory  apparatus, 
removal  of,  197-200 
Fragrnentation  of  the  heart  muscle,  43 
Functional  murmurs,  75 

Gall-stones,  colic  in,  264 
composition  of,  262 
dangers  of,  263 
fever  in  lodgment  of,  387 
formation  of,  261-263 
intestinal  obstruction  from,  291 
jaundice  in,  265,  267 
stenosis  of  common  duct  by,  265 
Ganglion  cells,  relation  of,  to  nutri- 
tion of  nerve  fibres,  474,  476 
Gangrene,  in  diabetes,  359 

in  intermittent  claudication,  452 
in  nervous  disease,  482 
Gases,  exchange  of  between  blood  and 
tissues,  197,  223 
in  disorders  of  external 

respiration,  223 
in  fever,  396 
in  the  lungs,  i,  197 
in  anaemia,  219,  221 
in  bronchitis,  222 
in  cardiac  dilatation,  50 
in  cardiac  dyspnoea,  ^^ 
in  pulmonary  and  pleural  dis- 
eases, 221 
mechanism  for  regulation  of,  in 
disorders  of  external  respira- 
tion, 221 
Gastric  digestion,  236 

bacterial  processes  in,  245  254 
disturbances  of,  absorption  in,  254 
from    anomalies    of    gastric 

movements,  250,  251 
from  anomalies  of  secretion, 

22,7 

from  atony,  253 

from  delayed  emptying,  246 

from  dilatation,  252 
examination  of,  236,  237,  240 

diagnostic  significance  of,  259 
fermentation  in,  246,  247,  252,  254 
leucocytosis  in,  123 
pain  in,  258 
secretion  of  gastric  juice  in,  236, 

240 
stomach  contents  in,  236,  240 


Gastric  diseases.    See  stomach. 
Gastric  juice,  absence  of  free  acid  in, 
244 
acidity  of,  236,  237,  240 
diminished,  243 
increased,  241 
antiseptic  action  of,  245 
diminished  secretion  of,  244 
effect  of,  upon  the  cholera  vibrio, 
279 
upon  the  intestines,  236,  243, 
248 
hypersecretion  of,  239^241 
continuous,  240 
with  hyperacidity,  241,  253 
in  the  fasting  condition,  239 
secretion  of,   factors  underlying, 
238-240 
Gastrogenous  dyspepsias,  22,(i 
Gastro-intestinal  tract,  abnormal  bac- 
terial processes  in,  245,  277 
infections  of  154-156 
Geisbocks  disease,  142,  146 
Gingivitis,  in  scurvy,  229 
Globuhn,  blood  serum  content  of,  137 
Glomeruli,  changes  in,  and  their  rela- 
tion to  the  heart,  26,  28 
to  the  secretion  of  urine, 

417 
sensitiveness  of  epithelium  of,  422 
Glottis,  spasm  of,  201 
Glycogen,  formation  of,  312,  343 
in  diabetes,  351,  360 
in  fever,  387,  398 
Glycosuria,  alimentary,  343 

condition  of  kidneys  in,  346, 

350,  359 
from  beer,  344 
occurrence  of  in  different  dis- 
eases, 345 
relation  of,  to  diabetes,  344 
diabetic,  349 

effect  of  kind  of  sugar  upon,  350 
epinephrin,  338,  347,  349,  356,  361 
experimental,  347 
following  injuries,  357 
hypophysis  in  relation  to,  348 
individual  disposition  to,  344 
in  infections,  345 
phlorhizin,  345 

significance  of  pancreas  in,  355 
transient,  347 
Glycyltryptophan  test  in  gastric  car- 
cinoma, 24s 
Goitre,    effect    of    exophthalmic    on 
heart  rate,  55 
on  respiration,  200 
Gonococci,  as  a  cause  of  valvular  dis- 
ease, 9 


500 


INDEX 


Gout,  364 

action  of  atophan  in,  370 

of  radium  in,  368 
acute  attack  of,  366,  369 
associated  pathology  of,  367 
asthenic  and  regular,  367 
blood  in,  368 
chronic,  369 

constitutional  nature  of,  378 
deposits  in,  367 
theories  of,  367,  368,  369 
tophi  in,  366 
uric  acid  metabolism  in,  364,  368, 

369 
Granular   (contracted)  kidney,  asso- 
ciated    with     arterio- 
sclerosis, 27 
with  gallop  rhythm,  46 
blood-pressure  in,  2S,  84 
cardiac  hypertrophy  in,  22,  25, 

26 
hemorrhages  in,  34 
residual  (non-coagulable)  ni- 
trogen in,  430 
secretion  of  urine  in,  414,  419 
Graves'  disease.     See  Hyperthyroid- 
ism. 

Hay  fever,  and  anaphylaxis,  205 
Headache,  in  cerebral  anaemia,  442 
Heart  (see  also  cardiac),  accommoda- 
tive power  of  the 
hypertrophied,     6, 
31,  33.  38 
of    the    normal,   4-6 
adaptability  of,  2 
beat  of,  52 

accelerated,  54 

by  reflex  influences,  56 
irregular,  61,  62-70 
retarded,  59 
blood-supply  of,  40 
brown  atrophy  of,  43 
capabilities  of  the  hypertrophied, 
31.  32,  33,  35-40 
of  the  normal,  2-6 
cavities  of,  in  hypertrophy,  32 
diminution  in  size  of,  after 
overexertion,  30 
congenital  defects  of  septum  of, 

18 
elasticity  and  contractility  of,  4-6 
fatigue  of,  44 
function  of,  i 
influence  of  nervous  system  upon, 

45 
in  pregnancy,  31 
lesions  of,  in  His  bundle,  42,  67 
output  per  beat  of,  4,  5,  6,  82 


Heart,  overdistention  and  overexer- 
tion of,  44 
ratio    of     weight    of,    to     body 

weight,  7,  29 
reserve  strength  of  hypertrophied, 

33 
strengthening  of,  7 
Heart-block,  42,  45,  67 

Adams-Stokes  symptom-com- 
plex and,  68 
Heart  dilatation,  acute  transitory,  in 
paroxysmal  tachycardia,  57 
chronic,  due  to  stasis  of  blood 

in  heart,  49 
compensatory,  12,  17,  49 
Heart,  diseases  of,  anaemia  in,  109 
hydraemia  in,  141 
relation  of,  to  nephritis,  25- 

29 
secretion  of  urine  in,  417 
Heart  failure  cells  in  the  sputum,  34 
Heart  hypertrophy,  6 

ability  of  1  eart  to  hypertrophy,  31 

and  dilatation,  32,  49 

causes  of,  6,  19-31 

causes  of  insufficiency  in,  35-40 

compensatory,  31,  32,  33,  34 

concentric  and  eccentric,  32 

condition  of  heart  muscle  in,  33, 

34.  35-38 
effect  of,  on  the  heart  beat,  76 
on  the  lungs  and  respiration, 
34,  35 
in  smokers,  25 

of    the    left    ventricle    in    aortic 
aneurism,  23 
in  aortic  insufliciency,  14 
in  aortic  stenosis,  15 
in  arteriosclerosis,  22,  37 
in  mitral  insufficiency,  17 
in  renal  disease,  25-29 
of  the  right  ventricle,  in  mitral 
lesions,  15,  17,  19 
in  pulmonary  disease,  20, 

21 
in  pulmonary  stenosis,  18 
in  tuberculosis,  21 
origin  of  bilateral,  24,  25 
Heart  impulse.     See  Cardiac  impulse 
Heart  murmurs,  74-76 
Heart  muscle,  effect  of  degenerations 

of  upon  function,  41,  42,  43 
Heart,  palpitation  of,  76 
Heart  poisons,  accelerating,  54 

causing  irregularities,  70 
effect  of,  on  heart  action,  42, 

43. 
slowing,  60 

Heart  sounds,  71-74 


INDEX 


501 


Heart,  valvular  disease  of,  8 
arteriosclerotic,  lo 
causes  of,  9 
combined,  19 
compensation  in,  33 
congenital,  of  the  right  side, 

18 
due  to  tearing  of  valves  and 

chordae,   10 
extracardial  effects  of,  34 
heart  muscle  in,  32 
left  sided,  12-18 
pathology  of,  9 
right  sided,  19 
syphilitic,  10 
Heart  weakness,  as  a  cause  of  asys- 
tole, 33 
causes  of,  35-38 

of  primary,  40 
effect    of,    on    secretion    of 

urine,  417,  423 
functional,  44 
of  both  ventricles,  46 
of  the  left  ventricle,  20,  37,  47 
of  the  right  ventricle,  37,  48 
primary,  40 
pulse  in,  52,  55 
relation   of,   to   angina   pec- 
toris, 78 
results  of,  46 
symptoms  of,  49-52 
Heart,  work  of,  factors  determining,  2 
in  conservation  of  accommo- 
dation, 2-6 
increased,  of  the  left  ventri- 
cle, 21-24 
of    the    right    ventricle, 
18,19 
in    the    pulmonary    circula- 
tion, I 
in  the  systemic  circulation,  2 
in  varying  demands  on  circu- 
lation, 2-6 
on   exertion,  6,  7,   8,  29,  30 
quantitative"! actors  in,  6 
relation  of,  to   hypertrophy, 
6-8 
to   subjective  symptoms, 
76 
Heat  regulation,  in  fever,  391 

heat  losses  in,  during  rise 
of  temperature,  394 
during  fall,  396 
heat  production  in,  392 

site  of,  399 
mechanism  of,  400 

experimental  factors 
bearing  upon,  385- 
388 


Heart  regulation,  in  health,  regulation 
of,  chemical  and  physi- 
cal, 389 
mechanism  of,  388 
in  obesity,  314,  389 
Heat  stroke,  390 
Hemic  murmurs,  75 
Hemiplegia,  cerebellar,  450 
contractures  in,  463 
muscular  atrophy  in,  479 
Hemisystoles,  66 

Haemoglobin,   changes   in   bile    from 
liberation  of,  261 
conversion  of,  into  methaemoglo- 
bin,  116,  117 
by  entrance  of  poisons  into 
red  cells,  117,  120 
importance  of,  in  respiration,  116, 

120,  219,  220 
in  the  anaemias,  102,  103,  105,  107, 

III 
in  changes  of  atmospheric  pres- 
sure, 143,  144 
in  chlorosis,  107 
in  polycythemia,  142 
solution  of,  in  blood,  103,  116-118, 
168 
Haemoglobinsemia,  116 
Haemoglobinuria,  116 
paroxysmal,  118 
Hsemolysins,  118,  168 
Haemolysis,  by  the  blood  serum,  168, 
169 
in    paroxysmal    haemoglobinuria, 

118 
inhibition  of,  in  the  Wassermann 

reaction,  173 
relation  of,  to  bactericidal  proc- 
esses, 168,  169 
substances  active  in.  168,  169 
Haemophilia,  136,  375,  376 
Hemorrhages,  as  a  cause  of  anaemia, 
103,  109 
of  hydraemia,  140 
of  leucocytosis,  125 
into  the  organs,  in  leukaemia,  132 
in  pseudoleukaemia,  132 
Haepatic  toxaemia,  see  liver 
Hernia,  291 
Herpes  zoster,  482 
Hiccough,  256 

High  altitudes,  blood  in,  143 
metabolism  in,  218 
pulmonary    gas    interchange 
and  respiratory  movements 
in,  215-218 
Hodgkin's    disease,     133.    See    also 

Pseudoleukaemia 
Homogentisic  acid,  in  urine,  334 


502 


INDEX 


Hormones,  action  of,  304,  372 
origin  of,  304 

stimulating  eflfect  of,  on  cells,  i 
Hunger,  257,  258 

gastric  contraction  waves  under- 
lying, 257 
appetite  and,  257 
Hydraemia,  causes  of,  139-141 
relation  of,  to  oedema,  92 
with  retention  of  water,  140,  141 
without  retention  of  water,  140 
Hydrobilirubin,  origin  of,  272 
Hydrocephalus,  chronic,  444 
Hydrochloric  acid  of  the  gastric  juice, 
236,  237,  240 
absence  of,  244 
action  of,  upon  microorganisms, 

154,  245,  246 
diminution  of,  243-246 
increased,  241-243 
in  gastric  carcinoma,  244-245 
Hydrocyanic    acid    poisoning,    as    a 
cause     of     respiratory 
spasm,  210 
effect  of,  on  internal  res- 
piration, 225 
Hydronephrosis,  mechanism  of  pro- 
duction of,  418 
Hydrophobia,   oesophageal  spasm  in, 

233 
Hydrops,     in     acute     and     chronic 
nephritis,  91 
in    cachexias    and    nervous    dis- 
eases, 94 
Hyperalgesia,  473 
Hyperaemia,  active,  in  inflammations, 

91 
venous,  in  cardiac  stasis,  50-52 
Hyperaesthesia,  nature  and  causes  of, 

473 
Hyperglycaemia,  alimentary,  344 

diabetic,  349,  350,  352 
Hyperplasia,   lymphoid  and  myeloid, 

127,  128,  130 
Hyperthyroidism   (Graves's  disease), 
action  of  upon  the  heart,  43 
causes  of,  322,  323 
disturbances  of  the  internal  secre- 
tions in,  323 
glycosuria  in,  345 
pathology  of,  323 
proteid  and  fat  metabolism  in,  321 
pulse-rate  in,  55 

relation  of,  to  changes  in  thyroid 
gland,  322 
to  nervous  system,  323 
rudimentary  forms  of,  323 
symptoms  of,  323 
Hypertonicity  of  the  arteries,  essen- 
tial, 81 


Hypertonicity  of  arteries,  in  arterio- 
sclerosis, 27,  28,  29,  81 
Hypophysis,  in  diabetes  insipidus,  415 
in  obesity  318 

manifestations  of  disturbed  func- 
tion of :  acromegaly,  y]2 
relation  of,  to  glycosuria,  348 
Hysteria,  anaesthesia  in,  456 
contractures  in,  466 
diarrhoea  in,  286 
oesophageal  spasm  in,  233 
fever  in,  386 
heart     action     in:     paroxysmal 

tachycardia,  58 
meteorism  in,  297 
sensory  disturbances  in,  456,  473, 
474 

Icterus.    See  also  Jaundice 
catarrhalis,  2^ 
gravis,  271 
haemolytic,  269 
neonatorum,  269 
Idiosyncrasies  toward  foods,  184,  260 
of  children  to  cow's  milk   (ana- 
phylactic manifestations),  184 
Ileus.    See  Intestinal  obstruction. 
Immune  bodies,  166 
diverse,  166,  169 
isolation  of,  166 
normally  in  blood,  171 
production  of,  in  active  immunity, 
161,  163 
Immune- ferment  reaction  (Abderhal- 

den),  186 
Immune  sera,   162 

antibody  content  of,  176,  177 
haemolytic  action  of,  169 
Immunity,  acquired,  161,  164,  189 

basis  of,  in  infections  with  organ- 
isms not  forming  soluble  toxins, 
176 
epidemiologic  and  experimental, 

.156 
histogenic,  194 
inherited,  161,  164 
Schick's  method  of  determining, 

177 
relation  of,  to  bactericidal  powers 

of  blood,  164 
theories  of,  166,  188 
Immunization,  active,  161,  178 
active-passive,  162,  178 
antitoxic,  176,  177,  191 
duration  of,  162,  177 
passive,  162,  176,  177 
reaction  in,  178 
Inanition,  as  a  cause  of  anaemia,  110 
as  a  cause  of  hydraemia,  140 
as  predisposing  to  infections,  159 


INDEX 


503 


Inanition,  causes  of,  308 
complete,  309 
formation  and  excretion  of  acids 

in,  329 
in  fever,  397,  398,  404 
nitrogen  excretion  in,  318 
partial,  309 
results  of,  309 
types  of,  308 
Incoordination,  452 
Indol,  toxic  effect  of,  282 
Indophenol  reaction,  122 
Infection,  and  immunity,  151 

effect  of  portal  of  entry  upon 

character  and  course  of,  i57 

factors  influencing  character 

of,  156 
general,   of   gastro-intestinal 
origin,  155,  280 

of  pulmonary  origin,  154 
of  vaginal  origin,  156 
manifestations  of,  in  affected 

organism,  156 
protective    barriers    against, 

151-156 
resistance    of    organism    to, 

159,  161,  278 
significance      of       epithelial 
lesions,  in  acute,  151 
Infectious    diseases,    albuminuria   in, 
421 
anaemia  in,  109,  116 
bacillus  carriers  caused  by,  191, 

193 
collapse  in,  86,  87 
fever  course  in,  381 
heart  complications  in,  9,  25,  36, 

39,  41,  43 
haemoglobinaemia  in,  117 
hydraemia  in,  140 
immunity  after,  164 
intoxications  in,  157 
leucpcytosis  in,  125 
metabolism  in  long-standing,  319, 

396 
proteid  destruction  in,  319 
pulse  in,  61,  70 
recovery  in,  194 
saliva  in,  230 
Inflammations,    blood-    and    lymph- 
vessel  changes  in,  91 
collateral  oedema  in,  91 
leucocytosis  in,  125 
purulent  exudates  in,  91 
Inspiratory  disturbances,  from  loss  of 
pulmonary  elasticity,  207 
in  paralysis  of  vocal  cords, 

203 
in  spasm  of  vocal  cords,  200 


Inspiratory   disturbances   in   stenosis 

of  upper  air  passages,  201,  202 
Insufficiency,  of  heart  valves,  aortic, 
12 
in  hypertrophied  hearts,  35,  36,  37, 

38,39 
mitral,  17 
muscular,  11 
primary,  40 
relative.  11 
tricuspid,  18 
Intermediary  bodies.     See  Ambocep- 
tors 
Intermittent  claudication,  79,  451 
Internal   secretions,   interrelationship 

of,  372,  373 
Intestinal  crises  of  tabes,  286 
Intestinal  diseases,  absorption  in,  282 
as  a  cause  of  anaemia,  109,  113 
of  digestive  disturbances, 
282 
due  to  absence  of  bile,  265 

of  pancreatic  secre- 
tion, 273,  274 
to  bacterial  processes  in 

bowel,  277 
to  bacterial  toxins,  281 
to  disorders  of  motility, 

284 
to  protozoa,  282 
to  secretory      disorders, 

283 
to  toxic  substances,  276 
effect  of,  on  heart,  60 
inflammatory,  291 
pain  in,  297 
Intestinal  epithelium,  behavior  of  to- 
ward bacteria  and  their  products, 
154,  277,  278 
Intestinal  gases,  effect  of,  on  intes- 
tinal movements,  287 
in  intestinal  stenosis,  294 
origin  of,  in  health,  296 

in  diseases  of  the  gastro- 
intestinal canal,  296 
Intestinal  movements,  antiperistaltic, 
in  ileus,  294 
associated  with  pain,  295,  297 
cessation  of,  in  complete  sten- 
osis, 294,  295 
decreased,  by  central  nervous 
influences,  289 
by  diminished  irritability 

of  bowel  wall,  289 
by  muscle  spasm,  290 
by  paralysis   of  circum- 
scribed     bowel      seg- 
ments, 291 


504 


INDEX 


Intestinal   movements,   increased,   by 
cooling  of  the  skin,  286 
by    inflammatory    condi- 
tions, 288 
by  irritation  of  abnormal 

contents,  287 
by  nervous  influences,  286 
local  nervous  mechanism  for, 

289 
normal,  of  the  colon,  285 

of     the     jejunum     and 
ileum,  284 
Intestinal  musculature,  paralysis  of, 
289,  291 
spasm  of,  290,  293,  294,  297 
condition    of    abdominal 
wall  in,  290 
Intestinal  obstruction,  causes  of,  291, 
292 
course  of,  295 
mechanism  of,  different  types 

of,  291,  292 
results  of,  293,  294,  295,  296 
Intestinal   parasites,    as    a   cause    of 
anaemia,  113,  114 
of  eosinophilia,  126 
Intestinal    secretions,    anomalies    of, 

283,  284 
Intestines,  spasm  of,   as  a  cause  of 
constipation,  290 
in  obstruction,  293,  294,  297 
Intoxication,      after      operation      in 
echinococcus  disease   (anaphy- 
laxis), 185,  186 
in  diabetes,  358 
in  fever,  382 
in   hepatic  disease   with   chronic 

biHary  stasis,  271 
in  intestinal  afifections,  276 
in  nephritis,  429 
Invagination  (intussusception),  mech- 
anism of,  292 
Iron,  increase  of,  in  the  liver,  due  to 
excessive    destruction    of    ery- 
throcytes, 104,  114,  143 
lack  of,  as  a  cause  of  anaemia,  no 
value  of,  in  chlorosis,  108 
Irritative  phenomena  in  cerebral  anae- 
mia, 442 
Islands   of   Langerhans   in   diabetes, 

356,  360 
Tsolysins,  in  anaemia,  119 
Isoprecipitins,  172 

Itching,  in  diseases  of  sensory  cuta- 
neous end-organs,  473 

Jaundice,  266 

heart  action  in,  60,  270 
haemolytic.  269 
in  anaemia,  114 


Joint  disease,  as  a  cause  of  muscular 
atrophy,  479 
nutritional    disturbances    in, 
481 
Jugular  veins,  murmurs  in,  89 

pulsations    in,    in    auricular 
fibrillation,  52,  65,  66 
in  nodal  rhythm,  52 
in  paroxysmal  tachycar- 
dia, 52,  57 
negative,  51 
positive,  52,  57,  65,  66 

Keith-Flack  node,  52,  53,  54,  58 
Keto-acids,  function  of  in  metabolism, 

311,  320,  357 
Kidneys  (see  also  Renal),  atrophy  of, 
due  to  occlusion  of  urinary  pas- 
sages, 419 
calculi  in,  and  in  renal  pelvis,  434 
function  of,  413 

as  regulators  of  composition 
of  blood,  426 
hypertrophy  of,  418 
relation  of   lesions  of,  to  albu- 
minuria, 422,  423,  424 
to  glycosuria,  343,  344,  346, 

347,  349.  350,  359 
to  haemoglobinaemia,  121 
to  uraemia,  429 
secretion  of,  with  diminished  cir- 
culation, 416 
with  increased  circulation,  413 
Kidneys,    inflammation   of,    albumin- 
uria in,  423 
cardiac  dilatation  in,  31 
cardiac  weakness  in,  31,  37,  39 
composition  of  blood  in,  109 
(anaemia),  139  (hydraemia) 
oedema  in,  91 
functional     disturbances    in, 

424,  428 
increased  blood-pressure  and 
heart  hypertrophy  in,  25-29, 
81,  84 
in  diabetes,  359 
non-coagulable    nitrogen    in, 

430,  431 
phenol  sulphonapthalein  test 

in,  431 
pulse  in,  59 

types  of,  according  to  disturb- 
ance  of   function  present, 
428 
uraemia  in,  429 
urine  in,  414,  417,  423,  424 
Kropfherz,  43,  324 
Kundrat's  lymphosarcoma,  134 
Kyphoscoliosis,  as  a  cause  of  respira- 
tory disturbances,  204 


INDEX 


505 


Labyrinthin  dizziness,  472 

Lactic  acid,  formation  and  excretion 

of,  in  metabolic  disorders,  329 
Lactimurate  and  lactamurate,  368 
Lactosuria,  344 

Laryngeal  stenosis,  effect  of,  on  res- 
piratory movements,  200-203 
Lead  poisoning,  and  gout,  367 
anaemia  in,  109 
arterial  spasm  in,  81,  84 
hypertension  in,  84 
Leucocytes.      See    Blood-corpuscles, 

white 
Leucocytosis,  after  hemorrhages,  125 
diemotaxis  in,  124,  125 
degrees  of,  126 

eosinophilic,  in  asthma,  125,  126 
in  helminthiasis  and  trichin- 
osis, I2S,  126 
inflammatory,  125 
in  children  (pertussis),  124 
in  malignancy,  125 
neutrophilic,  124,  125 
of  the  new-born,  123 
physiological,  123 
ratio  of  different  types  of  white 
cells  in  pathological,  124,   125, 
126 
relation  of  nervous  system  to,  125 
Leucopsenia,  126 
Leukansemia,  130 
Leukaemia,  127 
acute,  131 

stomatitis  in,  230 
aleukaemic,  127,  129 
blood  in,  128-132 
causes  of,  135 
chronic,  129,  131 
combined  with  anaemia,  130 
course  of,  131 

differentiation  of,  from  leucocy- 
tosis, 129 
effect  of  X-rays  upon,  129,  131 

of  benzene  upon,  129,  131 
histological  changes  in,  127,  128, 

129 
increase  of  urinary  purin  bases  in, 

365 

in  children,  131 

lymphoid,  130,  132 

mixed-cell,  132 

myeloid,  129,  130,  132  _ 

oxidase  reaction  in,  122 

pathogenesis  of,  135 

prognosis  of,  131 

submyelemic,  129 

symptoms  of,  132 
Laevulose,    assimilation    of,    by    dia- 
betics, 352 

in  urine,  in  diabetes,  343,  349 


Lasvulosuria,    alimentary,    in   hepatic 

disease,  345 
Lipaemia,  137 
Lipoids,  significance  of,  in  haemolysis, 

114,  169 
Liver,  acute  yellow  atrophy  of,  metab- 
olism in,  325,  326,  329 
Liver,  disturbances  of,  acidosis  in,  328 

alterations  of  bile  in,  260,  261 

aminoacids  in,  326 

anaemia  in,  109,  113  ^ 

excretion  of  ammonia  in,  333 

in  cardiac  stasis,  51 

in  diabetes,  357,  361 

in  jaundice,  269,  270 

metabolic  anomalies  in,  326, 

333 
toxaemia  in,  271 
urine  in,  326,  333 
Liver,  role  of,  glycogenic,  343,  352 

in     combating    poisons     ab- 
sorbed from  intestines,  281 
in    conversion    of    carbohy- 
drates into  fats,  312 
in  diabetes,  352 
in  fever,  387 
in  hsemoglobinsemia,  116 
in  urea  formation,  333 
Local  pathology  as   contrasted  with 

constitutional,  374 
Luetin  reaction  as  an  index  of  the 
constitutional  nature  of  syphilis,  375 
Lungs    (see  also    Pulmonary),   anti- 
septic action  of,  153 
brown  induration  of,  34 
diseases  of,  cardiac  dilatation  in, 

cardiac  hypertrophy  m,  20,  21 
cardiac  insufficiency  in,  37,  47, 

48 
gas  interchange  in  the  lungs 
in,  221,  222 
distention  of,  in  bronchial  asthma, 
205,  206 
in  paroxysmal  tachycardia,  57 
oedema  of,  95 
infections  of,  153,  154 
loss  of  elasticity  of,  207.    See  also 

Emphysaema 
mechanisms  for  protection  of,  197 
Lymph,  bactericidal  properties  of,  163, 
164 
circulation  of,  89 

in    central    nervous    system, 

442,  443 
composition  of,  89,  94 

in  inflammations,  91,  94 
excessive    accumulation    of,    in 

lymph  spaces,  89 
obstruction  to  flow  of,  89,  90,  91 


506 


INDEX 


Lymphatics,  occlusion  of,  91 

pressure  conditions  in,  89,  90 
pressure  difference  between  capil- 
laries and,  89,  90 
Lymph-nodes,    leukaemic   hyperplasia 
of,  127,  128 
genetic  significance  of,  133 
Lymphocytes,  in  normal  blood,  121 
in   pathological   blood,    124,    126, 
130 
Lymphosarcoma,  Kundrat's,  127,  134 

Macrocytase,  188 

Macrocytosis  and  microcytosis,  105 
Macrophages,  188 

Malaria,  blood  in,  109,  116,  118  (par- 
oxysmal haemoglobinuria)- 
fever  in,  381 
Malnutrition     (see    also    Inanition), 
effect  of  previous  state  of  nu- 
trition upon.  309 
effect  of  exercise  upon,  309 
factors  in,  308,  318 
in  various  diseases,  309 
results  of,  309 
Mediastino-pericarditis,  heart  hyper- 
trophy in,  24 
pulsus  paradoxus  in,  70 
Megaloblasts,  106,  107,  iii,  113,  115 
Meniere's  disease,  472 
Meningitis,  cerebral  pressure  in,  444 

serum  therapy  in,  177 
Mercury,  absorption  of,  through  the 
skin,  151 
ptyalism  and  stomatitis  from, 
231 
Metabolism,  ammonia   formation  in, 

course  of,  with  dietetic  sufficiency, 

formation  and  excretion  of  purin 
bases  in,  364 
of  organic  acids  in.  328-333 
of  poisons  in,  and  their  effect 
upon  heart,  42,  43 
in  constitutional  diseases,  372 
in  fever,  396 
influence  of  cellular  activity  upon, 

3" 
of  thyroid  gland  upon,  320 
intermediary,  372 
of     carbohydrates :     quantitative 

disturbances  of,  343 
of  the  fats,  304,  311-318 
of  the  proteids,  318,  325 
proteid  needs  in,  306 
Meteorism,  296 
Microcytase.  188 

Microorganisms,  behavior  of  animal 
body  towards,  151,  159,  161 


Microorganisms,  cultural  media  for, 
and  their  importance,  163 
oxygen  tension  of,  163 
in  affections  of  the  mouth,  229, 
230 
of  the  intestines,  277 
of  the  urinary  passages,  433 
in  the  bile,  262,  263,  264,  268 
in  nephritis  and  albuminuria,  424, 

427 
in  valvular  lesions,  9 
metabolic  products  of:  action  of, 

on  heart,  42,  43 
numbers  of,  in  fatal  infections, 

157 
obstacles    to    entrance  of,     into 

body,  151 
role  of,  in  hydrolytic  cleavage  of 

proteids,  326 
significance  of  the  normal  intes- 
tinal, 277,  278 
of  the  pathological  intestinal, 
279,  280,  281 
virulence  of,  156 
Micturition,  disturbances  of,  459 
Milk,  antitoxin  content  of,  171 

as  a  cultural  medium  for  B.  ty- 
phosus, 159 
hypotensive  action  of,  28 
Mitral  insufficiency,  17 

circulatory  disturbances  due 

to,  17 
combined  with  other  lesions, 

16,  19 
compensation  in,  17 
heart  murmurs  in,  74,  76 
heart  sounds  in,  72,  73 
Mitral  stenosis,  15 

and  insufficiency,  16,  19 
compensation  in,  15 
heart  murmurs  in,  75 
heart  sounds  in,  72,  73 
relation  of,  to  auricular  fibril- 
lation, 66 
Mixed  infections,  160 
Monosodium  urate,  in  gout,  366,  368 
in  the   formation  of  vesical 
calculi,  435 
Morbus  ceruleus,  50 
Motility,  disturbances  of,  atactic,  452- 
458 
choreiform,  466 
due  to  anomalies  of  sensation, 

455 
to    abnormal    irritability 
of  the  cerebral  struct- 
ures, 467 
to  contractures,  463 
to    disturbances    of    re- 
flexes, 460 


INDEX 


507 


Motility,  due  to  incoordination,  452 
to  muscle  disease,  451 
from    intermittent    claudica- 
tion, 451 
from  lesions  of  motor  tracts, 

451 
from  psychic  paralyses,  450 
Mountain  sickness,  diminished  oxygen 

tension  in,  216 
Mouth,  affections  of,  229,  232 

in  diabetes,  229,  359 
Movements  of  the  body,  effect  of,  on 
albuminuria,  421 
on  the  body  temperature, 

386 
on  the  distribution  of  the 

blood,  2 
on  the  excretion  of  sugar 

in  diabetes,  354 
on  the  leucocytes,  123 
Movements,  voluntary,  disorders  of, 
452-454 
disturbances  of  sensation  of, 

454,  455 
effect  of  centripetal  impulses 
upon,  454-458 
of    exaggeration    of    re- 
flexes upon,  459 
of  loss  of  reflexes  upon, 
458 
varieties  of,  453 
Mucous  colitis,  205,  287 
Mucus,  production  of,  in  the  respira- 
tory passages,  198 
in  the  stomach,  248 
Muscarin,  action  of,  on  the  heart,  42, 

60 
Muscles,  as  a  storehouse  for  sugar, 

353- 
disturbances    of,    due    to    faulty 

blood-supply,  451 
innervation  of,  449,  450 

disturbed,  451,  452,  466,  477- 
479,  480  ... 

ocular,    loss    of    orientation    in 

paralyses  of,  472 
tetanus  of,  462 
Muscular   atrophy,    altered   chemical 
composition  of  muscles  in, 

477 
degenerative,  477,  478,  479 
dystrophies  in,  480 
from  disuse,  477,  479 
in  joint  disease,  479 
in  obesity,  314 
reaction  of  degeneration  in, 

477 
partial,  479 


Muscular    contractions,    epileptiform 
and  tetanoid,  in  gastric  dilatation, 

25s 
Muscular  exertion,  as  a  cause  of  heart 
hypertrophy,  29 
of  diminution  in  size  of 

heart,  30 
of      increased      arterial 
pressure,  83 
effect  of,  on  the  blood,  118, . 
123 
on  the  body  temperature, 

386,  390 
on      the      hypertrophied 
heart  muscle,  35,  37 
Muscular  insufficiency  of  heart,  11,  40 
Myasthaenia  gravis,  452 
Myocarditis,  cardiac  pain  in,  78 

heart  beat  in,  56,  61,  62,  63,  64,  68, 

.   69   . 

infectious,  41,  43 

in  hypertrophied  hearts,  35 

in  valvular  disease,  10,  11,  38,  39 

primary,  41 

significance  of  location  of,  41,  42 
Myotonia  congenita  (Thomsen's  dis- 
ease), 452 
myotonic  reaction  in,  452 
Myxoedema,  thyroid  function  in,  322 

Nephritis.     See   Kidneys,    inflamma- 
tion of 
Nerve  cells,  degeneration  of,  476 

independence  of,  475 
Nerves,  degeneration  of,  primary,  due 
to    poisons    and    disturbed 
blood-supply,  451 
secondary,  474 
Nervous  diseases,  anaemia  in,  109 
constipation  in,  289 
diarrhoea  in,  286 
oedema  in,  94 
fever  in,  385,  386 
from  gastric  dilatation,  255 
Nervous  system,  effect  of,  on  regula- 
tion of  vascular  diameter, 
80,  88 
functional  disorders  of,  441 
contractures  in,  463 
general  symptoms  in,  441 
in  acidosis,  332 
focal  symptoms  in,  441 
motor  disturbances  in,  449 
reflex     disturbances    in, 

458,  460 
sensory   disturbances   in, 
468 
influence   of,   on  the  heart- 
beat, 45 


508 


INDEX 


Nervous  system,  influence  of,  on  tem- 
perature      regulation, 
384,  400 
on  tissue  nutrition,  474 
influence    of    diphtheria   and 
tetanus  toxins  upon,  158, 462 
motor  system   affections   of, 

476 
of   the    intestines,    disturbed 

motility  due  to,  289 
pathology   of,   in   pernicious 

anaemia,  112 
relation  of,  to  diabetes,  347, 

357,  361 
sympathetic :       centres      for 
defecation    and    urination, 

459 
Neuralgia  of  the  stomach,  259 
Neurasthenia,  constipation  in,  289 
diarrhoea  in,  286 
heart-beat  in,  56,  58,  61,  69 
Neuritis,  475 
Neuron  theory,  474,  475 
Newborn,  antitoxin  in  blood  of,  171 
jaundice  of,  269 
leucocytosis  of,  123 
renal  infarcts  in,  366,  435 
Nitrogenous  equilibrium,  310,  318  _ 
Nitrogen  excretion  in  the  urine,  in- 
creased,     in      disease, 
318-320,      327       (am- 
monia) 
in  health,  due  to  diet,  327 
influence     of     carbohydrates 

upon,  319,  327 
in  fever,  397,  398 
Noci  impulses  in  relation  to  shock,  87 
Nodal  rhytl  m,  52,  64,  66 
Node  of  Aschoff-Tawara,  52,  53,  67 

of  Keith-Flack,  52,  53.  54,  58 
Non-coagulable  nitrogen,  in  the  blood, 

in  uraemia,  430,  431 
Nose,    diseases    of,    relation    of    to 

asthma,  205 
Nourishment     in    relation    to    albu- 
minuria, 421 
Nursing  infant,  eff"ect  of  food  upon 
intestinal  flora  of,  278 
effect    of    nasal    obstruction 
upon  nutrition  of,  200 
Nutrition,  caloric  needs  of  body  in, 

essential  substances  in  mainten- 
ance of,  304,  305 
metabolism  of  proteids  and  fats 
in,  qualitative,  324 
quantitative,  304,  318 
nitrogen  equilibrium  in,  310 
undernourishment  in,  308 


Nutritional  disturbances,  as  a  result 
of  nervous  lesions,  474-483 
effect  of,  upon  the  blood,  no 
upon  the  heart  muscle,  41 
from    abnormal    proteid    de- 
struction, 318-320 
due  to  toxic  substances, 

.319 

in  hyperthyroidism,  320 
from  destruction  of  fats,  319, 

321 
from  obesity,  313 
in  anaemia,  no 
in  cystinuria,  336 
in  diabetes,  357,  358 
in  fever,  397,  398,  404 
in  the  muscles,  477 
of  the  bones  and  joints,  481 
of  the  nerves,  474-476 
of  the  skin,  482 

Obesity,  314 

associated  with  anaemia,  315,  316, 

cardiac  disturbances  in,  43,  44,  315 
causes  of,  315-318 
constitutional,  316,  378 
diminished  efficiency  due  to,  314, 

315 
hereditary  influences  in,  316 
in  childhood,  316 
ox)'gen  consumption  in,  317 
relation  of,  to  diabetes,  357 
significance  of  hypophysis  in,  318 
Occlusion  of  the  bowel,  causes  of,  291 

course  of,  295  (strangulation) 
Ochronosis,    relation  of,   to  alkapto- 
nuria, 335 
Oligemia,  146 
Oligocythemia  in  chlorosis,  107 

in  nephritis,  109 
Ophthalmoplegia  as  a  cause  of  dizzi- 
ness, 472 
Opsonins,  189 

in  therapy  (Wright),  190 
Optic  neuritis,  in  cerebral  pressure. 

See  Choked  Disk 
Orientation  of  the  body  in  space,  471 
loss  of,  dizziness  in,  472 

due    to    labyrinthin    disease, 

472 
due  to  ocular  palsies,  472 
mechanism  of,  471 
Orthotic  albuminuria,  421 

theories  as  to  cause  of,  421 
Oxalate  calculi,  436 
Oxidative  processes  in  fever,  396 
Oxyacids,  origin  of,  in  intermediary 
metabolism,  328,  335 


INDEX 


500 


Oxydase  reaction,  in  cells  of  bone- 
marrow  origin,  122 
Oxygen   tension,    intraalveolar,    res- 
piratory movements  in 
diminished,    215,    216, 
218 
oxygen  supply  to  tissues 
in,  215-218 
of  the  tissues,  in  relation  to 
bacterial  growth,  163 

Pain,  causes  of,  474 

delayed  perception  of,  468 
in  angina  pectoris,  79 
in  diseases  of  the  mouth,  229,  230 
in  oesophageal  disease,  233,  235 
in  gall-stones,  263,  264 
in  gastric  disturbances,  243,  259 
in  intestinal  diseases,  298,  299 
in  the  precordium,  78 
in  respiratory  disturbances,  226 
in  urinary  calculi,  437 
on  urination,  437 
origin  of,  474 
psychic,  474 
Palpitation  of  the  heart,  76 
Pancreatic  diabetes,  355~357.  360,  361 

acidosis  in,  330,  358 
Pancreatic  juice,  effect  of  absence  of, 
upon  gastric  and  intestinal 
digestion,  273,  274 
effect  of  penetration  of,  into 

abdominal  cavity,  275 
secretion  of,  273 
Paralyses,  449-452 

Brown- Sequard,  470 
cerebral,  contractures  in,  464 
in  uraemia,  429 
psychic,  450 

sensory,  456  (in  ataxia),  468 
Paraplegia  dolorosa,  469 
Pararhythmias,  cardiac,  63,  65 

due  to  extrasystoles,  63 
Parathyroid    glands,    effects    of    re- 
moval of,  324 
Pareses,  motor  disturbances  in,  450 
of  the  gastric  musculature,  effects 
of,  251,  254 
Paraesthesias,  due  to  gastric  disorders, 
259 
due  to  disease  of  the  peripheral 
and  spinal  sensory  paths,  473 
Paroxysmal  tachycardia,  56 

methods  for  ending  paroxysm 

in,  58 
pathogenesis  of,  58 
Pericardial  adhesions,  as  a  cause  of 
heart  hypertrophy,  24 
as  a  cause  of  pulsus  para- 
doxus, 70 


Periosteal  reflexes,  460 
Peristaltic  hormone,  285 
Peristaltic  rust,  284 
Peritonitis,  bradycardia  in,  60 

constipation  in,  289 

exudates  in,  94 

tympany  in,  297 

vascular  changes  in  fatal  cases  of, 
86 
Pernicious  anaemia,  iii 

indication  for  splenectomy  in, 

IIS 
Perpetual  arrhythmia,  39,  52,  65 
Pertussis,  nature  of  paroxysms  in,  20l 
Phagocytosis,  theory  of,  187 
Phagolysis,  165,  188 
Phlorhizin  glycosuria,  acidosis  in,  329 

causes  of,  345,  346 

in  starvation,  346 
Phosphatic  calculi,  436 
Phosphaturia,  calcium  elimination  in, 

436  . ,     .  '  . 

Phosphorus    poisoning,    acidosis    in, 

328,  329 
bile  in,  261 

blood  in,  145  (polycythemia) 
hydrolytic  cleavage   of   pro- 

teids  in,  325,  326 
internal  respiration  in,  225 
jaundice  in,  268 
metabolism  in,  325,  326 
urine  in,  325,  326,  345 
Pigmentation,  cutaneous,  in  jaundice, 
267,  270 
of   the   bone-marrow,    liver   and 
spleen   in    pernicious    anaemia, 
114 
Pineal  gland  disease,  373 
Pirquet    test,    as    indication    of    the 
constitutional    nature    of    tubercu- 
losis, 375 
Plethora,  behavior  of  heart  in,  30,  31 
genuine,  145 

with  hyperglobulism  and  hy- 
pertension, 146 
serous  in  hydraemia,  141 
Pleuritis,  exudative,  effect  of,  on  gas 
interchange    in    lungs, 
221 
on  respiration,  211 
on  vena  cava,  211 
obliterative,  as  a  cause  of  heart 
hypertrophy,  21 
Pneumococci,  in  endocarditis,  9 
Pneumonia,  bradycardia  following,  61 
hypertrophy  of  right  ventricle  in, 

21 
interchange  of  gases  in  the  lungs 

in,  222 
respiration  in,  211 


510 


INDEX 


Pneumothorax,  artificial,  Sl'^ 

behavior  of  healthy  lung  and  me- 
diastinum in,  212 
circulatory  disturbances  in,  213 
interchange  of  gases  in  lungs  in, 

221 
pressure  relations  in  closed  and 
open,  212 
Poikilocytosis,  in  anaemia,  105 
in  chlorosis,  107 
in  pernicious  anaemia,  ill 
in  secondary  anaemia,  iii 
Poisons,  action  of,  upon  the  bile,  261 
upon  the  blood,  104,  109,  113, 

117,  120 
upon  the  heart,  25,  42,  54,  60, 

70,  79  (nicotin) 
upon  the  intestinal  processes, 

276 
upon  metabolism,  319,  320 
upon  the  nervous  system,  451, 

467  ^ 

upon  respiration,  when  mixed 
with  inspired  air,  218 
as  a  cause  of  albuminuria,  423 
of  anaemia,  109,  113 
of  jaundice,  268 
eflfect  of,  on  proteid  decomposi- 
tion, 319,  320 
on  respiration,  218,  224,  225 
in  leucopenia,  126 
in  methemoglobinaemia,  120 
in  polycythaemia,  145 
resistance  of  parasites  to  (chemo- 
therapy), 191 
Poisons,  iS7~iS9 

bacterial,  action  of,  upon  the 
heart  muscle,  43 
protective  forces  of  the 
body  against,  169 
Polyarthritis  rheumatica,  heart  com- 
plications of,  9,  39,  41 
Polychromatophilia,  105,  ill 
Polycythaemia,  142 

Polydipsia  of  psychic  origin,  414,  415 
Polyuria,  following  catheterization  of 
ureters,  416 
from   drinking  of  excessive 

fluids,  425 
in  diabetes  insipidus,  414 
in  diabetes  mellitus,  359 
in  epileptic  attacks,  416 
in  nephritis,  414 
in  paralysis  of  renal  nerves, 

414 
Portals  of  entry,  in  infections,  151 
Posture,  effect  of,  on  albuminuria,  421 
Potassium  chlorate,  action  of,  on  red 
blood-corpuscles,  120 


Potassium  salts,  in  their  relation  to 

uraemia,  431 
Precipitins,  171 

importance    of,    in    medico-legal 
conditions,   173 
Pregnancy,  blood  in,  123 
heart  in,  31,  38,  62 
urine  in,  423  (albuminuria) 
Premature  contractions  of  the  heart, 

63 
Propionic  acid  in  the  urine  in  metabo- 
lic disorders,  329 
Proteids,    bacterial,    as    a    cause    of 

fever,  383 
Proteids,  pathological  destruction  of : 
causes  of,  318-320 
course  and  products  of, 

325-327 
dangers  of,  320 
hydration     products    of, 

325-327 
in  anaemias,  223,  319 
in  carcinoma,  319,  320 
in  diabetes,  358 
in  fever,    319,    382,    397, 
.  398 

in  intermediary  metabo- 
lism, 324,  32s 
ammonia    formation 
in,  327 
significance   of   liver  in, 
333    (excretion  of 
ammonia) 
of  thyroid  substance 
in,  321 
Proteid  needs  of  the  body,  306 
Proteids,  of  the  blood  serum,  137 
amount  of,  137 
occurrence     of,     in    the 

urine,  422,  424 
proteid  ratio  in,  137 
of  the  food,  chemotactic  action 
of,  on  leucocytes,  124 
qualitative  metabolism  of, 

324. 
quantitative    metabolism 

of,  304,  311,  318 
of  the  urine,  source  of,  424 

total  daily  excretion  of, 

425 
types  and  chemistry  of, 
422,  424,  425,  426,  427 
produced  by  bacterial  processes  in 

the  intestines,  281 
significance  of,  in  heat  production, 

383,  394 
Protozoa,    intestinal,    as    causes    of 
anaemia,  109 
of  dysentery,  282 
of  fever,  383 


INDEX 


511 


Pseudocroup,  200 

Pseudoleukaemia  (see  also  Hodgkin's 
disease),  127,  133 
blood  changes  in,  128,  130,  132 
definition  of,  broad,  133 

strict,  127 
differentiation  of,  from  tubercu- 
lous and  sarcomatous  processes, 
127,  134 
fever  and  hemorrhages  in,  132 
lymph   glandular  hyperplasia  in, 

127,  128,  133,  135 
pathogenesis  of,  132,  135 
relation  of,  to  leukaemia,  127,  128, 

129,  132,  133,  13S 
types  of,  133 
Ptomains,  toxic  symptoms  due  to  in- 
troduction of,  into  intestines,  276 
Ptyalism,  231 

Puberty,  albuminuria  in,  421 
sinus  arrhythmia  in,  70 
Puerperium,  bradycardia  of,  62 
Pulmonary  circulation,  i 

condition  of,  in  compensated 

heart  lesions,  34 
disorders  of  and  their  effect 
on   right  heart,   19-21, 

39 
in  cardiac  asthma,  78 
in    valvular   disease,    13, 
16,  17 
Pulmonary  diseases.    See  Lungs 
Pulmonary  insufficiency,  18 
Pulmonary      rigidity,       in      cardiac 

asthma,  "JJ 
Pulmonary  stenosis,  18 
Pulmonary    tuberculosis,    gas    inter- 
change in  lungs  in,  222 
heart  hypertrophy  in,  21 
in  diabetes,  359 
transmission    of,    by    moist 
droplets,  154 
Pulmonic  second  sound,  accentuation 
of,  71,  ^2 
character  of,  in  aortic  insuffi- 
ciency, 13 
in  mitral  insufficiency,  Vj 
in  mitral  stenosis,  16 
in    pulmonary    tubercu- 
losis, 21 
reduplication  of,  "jz 
Pulse,  arterial,  acceleration  of,  54-59 
behavior     of     in     cardiac 
asthma,  78 
in  Cheyne-Stokes 

breathing,  209 
bigeminy  of,  64,  66,  67,  69 
effect  of  cerebral  influences 
upon,  55,  59,  60 


Pulse,  arterial,  effect  of  reflex  in- 
fluences upon,  56, 60,  70 
in  aortic  insufficiency,  35 
in  paroxysmal  tachycardia, 
.  56 
inequahty  of,  66,  70  (pulsus 

paradoxus) 
irregularity  of,  62-69 

causes  of,  69 
origin  of  (heart-beat),  53, 

67 
retardation   of    (bradycar« 
cardia),  59^2 
in  Adams-Stokes  syn- 
drome, 68 
variations  in,  in  health,  52, 
54 
respiratory,  69,  70 
Pulse-pressure,  82 

in  aortic  insufficiency,  14 
relation  of  to  cardiac  output  per 
beat,  82 
Pulse,  venous,  origin  of,  51 
negative,  51 
positive,  52 

in   auricular    fibrillation,, 

52,  65,  66 
in  nodal  rhythm,  52 
in  paroxysmal  tachycar- 
dia, 57 
in  tricuspid  insufficiency, 
52 
Pulsus,  alternans,  66 

bigeminus,  64,  66,  drj,  69 
celer,  in  aortic  insufficiency,  35 
irregularis  perpetuus,  65 
paradoxus,  70 
pseudoalternans,  59 
Puncture  of  the  brain,  as  a  cause  of 
fever,  386,  400 
of  glycosuria,  347 
Pupils   in   Cheyne-Stokes   breathing, 

209 
Purin  bodies,  364 

as  a  cause  of  fever,  384 
Pyaemic  processes  due  to  mixed  infec- 
tions, 160 
Pyloric  reflex,  249 

stenosis,  250,  252,  254,  255 
Pyogenic  organisms,  action  of,  intro- 
duced subcutaneously  and 
intravenously,  157 
as  a  cause  of  valvular  disease;, 

9 
Pyrosis,  256 

Reynaud's  disease,  vascular  reflexes 

in,  88 
Reaction  of  degeneration,  477-479 
partial,  479 


512 


DTOEX 


Receptors,  167  (side-chains),  170,  192 
Rectum,  disturbed  emptying  of,  due 

to  nervous  causes,  459,  460 
Reflexes,  absence  of,  458 

disturbances  of  deep  and  super- 
ficial, 460-462 
effect  of,  on  defecation  and  urina- 
tion, 459 
on  the  heart-beat,  56,  60,  70 
on  respiration,  211 
on  the  secretion  of  saliva,  232 
on  vessel  tonus,  80 
on  voluntary  movements,  453, 
458 
increased,  459 

in  strychnin  poisoning  and  teta- 
nus, 462 
origin  of,  460 
Regeneration  of  red  blood-corpuscles, 

105,  115 
Relapsing  fever  in  Hodgkin's  disease, 

132 
Renal  diabetes,  346 
Renal  function,  disturbed,  localization 
of,  427,  430 
phenolsulphonephthalein 
test  in,  431 
Renal  vessels,  effect  of  diameter  of, 
on  the  secretion  of  urine,  413,  416, 

423,  424         .  .    ,         , 

Rennin,  secretion  of,  as  an  mdex  of 

pepsin  secretion,  238 
Residual  nitrogen,  in  the  blood,  138 

in  uraemia,  430,  431 
Resistance,  against  infection,  artificial, 
161,   162,  175   (typhoid 
vaccination),  178 
natural,  161,  177  (Schick 
test) 
bacterial,  increased,  191 
Respiration,  accelerated,  204,  214 
automatic  regulation  of,  202 
Cheney-Stokes    phenomenon    in, 

209 
deep,  203,  210,  214 
effect    of    atmospheric    pressure 
upon,  215,  218 
of   changes    in   the   alveolar 

membranes  upon,  215 
of  composition  of  air  upon, 

215 
of  the  blood  upon,   120, 
219,  220 
of   stenoses   of  the   air-pas- 
sages upon,  200-204 
of  temperature  upon,  214 
of  the  pulmonary  circulation 
in,  220 


Respiration,  effect  of  uniform  distri- 
bution of  inspired  air  in  the 
alveoli  upon,  208,  215 
external,  197 
importance  of  olfactory  nerves  in, 

198,  218 
phases  of,  202,  203 
protective  mechanisms   for,   197- 

200 
regulation  of  the  normal,  204,  209 
slow,  202,  203,  209 
superficial,  204 

undisturbed,  conditions  essential 
to,  197 
Respiration,  internal,  223 
Respiratory  apparatus,  methods  of  re- 
moving foreign  material  from,  197- 
200 
Respiratory  centre,  alterations  in  the 
activity   of.      See   Cheyne- 
Stokes  breathing,  209 
disturbances  of,  as  a  cause  of 

cardiac  dyspnoea,  "jj 
sensitiveness  of,  to  changes  in 
gas  content  of  blood,  201, 
222,  441 
Respiratory  disturbances,  effect  of  on 
gaseous  interchange  in 
tissues,  223 
on   total   interchange  of 
gases,  221,  222 
from    altered    irritability    of 

the  centre,  209 
from  diminution  of  the  res- 
piratory surfaces,  211,  213, 
214 
from  insufficient  distention  of 

thorax  and  lungs,  206-208 
from  paralysis  of  respiratory- 
muscles,  206 
from  poisons  in  inspired  air, 

218 
from  stenoses  in  air-passages, 
200 
altered  respiratory  move- 
ments in,  201,  202 
from  variations  in  composi- 
tion of  air,  215-218 
in  anaemia,  219 
in  asphyxia,  222 
in  bronchitis,  204 
in  emphysema,  207 
in  heart  diseases,  13,  34,  50, 

in  intoxications,  210 
in  obesity,  315 

in  paroxysmal  tachycardia,  57 
in  uraemia,  210,  429 
in  volumen  pulmonum  auc- 
tum,  207 


EsTDEX 


513 


Respiratory  disturbances,  mechanism 
for  compensation  of,  221 
subjective  manifestations  of, 
22s 
Respiratory  muscles,  diseases  of,  and 

their  effect  upon  respiration,  206 
Rheumatism,  as  a  cause  of  heart  dis- 
ease, 9,  39,  41 
of  muscular  atrophy,  479 
Rhythm  of  the  heart,  normal,  52-54 

pathological,  62-70 
Rhythmic  segmentation,  284 
Rontgen  rays,  in  leukaemia,  129,  131 
Rupture  of  arteries  due  to  increased 
blood-pressure,  34 
of  the  oesophagus,  236 

Saline  cathartics,  mode  of  action  of, 

284 
Saliva,    anomalies    in   secretion    and 

composition  of,  230^232 
Salivary  glands,  reflex  stimulation  of, 

232 
Salvarsan,  theory  underlying  produc- 
tion of,  191 
Sarcolactic  acid  in  the  urine,  328 
Scarlatinal   nephritis,  cardiac  hyper- 
trophy in,  25 
oedema  in,  92 
Schick  test,  177 

Scurvy,  mouth  symptoms  of,  229 
Secondary  infections,  160 
Secretion,    disturbances    of,    gastric, 
237-245,  252 
intestinal,  283 
pancreatic,  273 
salivary,  230-232 
Semicircular  canals,  disease  of,  as  a 

cause  of  dizziness,  472 
Sensitization  of  red  blood-corpuscles 

and  bacteria,  173 
Sensory  disturbances,  cutaneous,  469, 

473 
delayed  perception  of,  468 
from  the  heart,  78 
from  the  intestines,  297 
from  the  lungs,  225 
in  diseases  of  the  peripheral 
nerves,  468,  469,  470 
of  the  spinal  cord,  468, 
469,  470 . 
irritative   manifestations   of, 

468,  473 
localization  in,  471 
of  the  stomach,  243,  257 
painful,  474 
paralytic    manifestations    in, 

468 
Yoluntary  movements  in,  455- 

457 


Septic  diseases,   heart   complications 
of,  9 
hypinosis  in,  136 
in  mixed  infections,  160,  161 
Septum  defects,  cardiac,  18 
Serodiagnosis  in  gonorrhoea,  echino- 
coccus  disease  and  other  condi- 
tions, 174 
in  syphilis,  173,  174 
in  typhoid  fever,  174,  175 
Serum  disease,  178,  180,  185 

prevention   of,    177    (Schick 
test),  185 
Serum  of  the  blood  (see  also  Blood 
Serum),    agglutination   in, 

aminoacids  in,  139 
antitoxins  of,  169 
bacteriotropins  of,  189,  190 
cytolytic  properties  of,   162- 

168,  169 
diminution  of  proteids  in,  139, 

140 
fat  in,  137 
ferments  and  anti  ferments  in, 

138 
immunological  characteristics 

of,  162-165 
inactivation  and  reactivation 

of,  166 
precipitins  in,  171 
proteids  in,  137 
watering  of,  139-141 
Shock,  anaphylactic,  87,  179 
surgical,  87 

acapnia  in,  88 
anoci-association  in,  87,  88 
venous  pressure  in,  88 
Side-chain  theory,  166 
Sinus  arrhythmias,  70 
tachycardias,  58  ^ 
Skee    runners,    cardiac    hypertrophy 

in,  8 
Skin,  blood-vessels  of,  in  fever,  394, 

395,  396 
in  normal  regulation  of  body 

terfiperature,  388,  389 
in    stasis    dilatation    of    the 
heart,  50 
nutritional  disturbances  of,  482 
reflexes  of,  462 

water  excretion  of,  in  fever,  395, 
396,  404,  405 
Sneezing,  198 
Sodium  chlorid,  as  a  cause  of  fever, 

384 
retention  of,  as  a  cause  of 
oedema,  93 
Spasm,  of  the  arterial  muscles,  79 
(angina  pectoris),  81,  84,  452 


514 


INDEX 


Spasm  of  the  oesophagus,  233  (cardio- 
spasm) 
of  the  intestinal  musculature,  290 
tonic,    in    occlusion    of    the 
bowel,  294,  297 
of  the  pylorus,  as  a  cause  of  gas- 
tric dilatation,  252,  253 
Spasmophilia  in  children,  379 
Spinal  cord,  diseases  of,  in  anaemia, 
112 
injuries  of,  and  temperature 
regulation,  385,  387,  400 
Spleen,  hyperplasia  of,  in  leukaemia 
and   pseudoleukaemia,    127, 
128,  130,  133 
in  polycythaemia,  142 
Splenectomy    in   pernicious    anaemia, 

IIS 
m  haemolytic  uterus,  269 
Sputum  in  asthma,  205 
Staphylococci,     in     the     etiology    of 

endocarditis,  9 
Stasis,  cardiac,  secretion  of  urine  in, 

417 

oedema  from,  90,  95,  96  (pul- 
monary oedema) 

in  aortic  insufficiency,  13 

in  decompensated  hearts,  34, 
47,  48,  49.  50,  SI 

in    paroxysmal    tachycardia, 

57 
venous,  manifestations  of,  50, 
142  (polycythemia) 
Stenocardia.    See  Angina  Pectoris 
Stenosis,  of  the  bowel,  291-296 
of  the  cardiac  orifices,  10,  15,  18 
of  the  oesophagus,  233 
of  the  pylorus,  252,  254 
of  the  respiratory  passages,  200, 
204 
Sternberg's  peculiar  form  of  tubercu- 
losis, 134 
Stomach  (see  also  Gastric)  affections 
of,  absence  of  free  acid  in 
chronic,  244 
as  a  cause  of  secondary  anae- 
mia, 109 
as  a  cause  of  cardiac  arrhyth- 
mia, 70 
as  a  cause  of  pernicious  anae- 
mia, 113 
bradycardia  in,  60 
paroxysmal  tachycardia  and, 
57 
Stomach,  atony  of,  253 
Stomach,  dilatation  of,  248,  251,  252, 
254 
acute,  253 
atonic,  253 


Stomach,  dilatation  of,  bacterial  de- 
composition in,  248,  254 
disturbed  resorption  in,  254 
due  to  anomalies  of  position 

and  form,  252 
fulness  and  pressure  in,  258 
in  hyperacidity  and  hyperse- 
cretion, 243 
in  pyloric  stenosis,  252 
nervous  symptoms  of,  255 
without  pyloric  stenosis,  253 
Stomach,  emptying  of,  delayed,  251, 
252,  254 
effect  of,  on  gastric  flora,  254 
of   character   of   g^astric 
contents  upon,  250 
hurried,  250 
pyloric  reflex  in,  249 
through  the  cardia,  255 
Stomach,  movements  of,  248 

hunger  contraction  waves  in, 
257 
Stomach,  secretions  of.    See  Gastric 

Juice 
Stomatitis,  229 

in  acute  leukaemias,  230 
Strangulation  of  the  intestines,  295 
Streptococci,  in  focal  infections,  153 
in  mixed  infections,  160,  161 
on  the  heart  valves,  9 
mutation  of,  153 
Struma,  cardiac  disturbances  due  to, 
55..  56,  323.  324  (exophthalmic 
goitre) 
respiratory  disturbances  due  to, 
200 
Strychnin   poisoning,   arterial   spasm 
in,  81,  84  ^ 
convulsions  in,  462 
urine  in,  416 
Substance    sensibilisatrice    (Bordet), 

166 
Subjective  disturbances,  cardiac,  76, 
17,  78 
dyspeptic,  257^-260 
intestinal,  297-299 
respiratory,  225 
urinary,  437 
Sugar  content,  of  the  blood,  343 

after  phlorhizination,  345 

346 
in  diabetes,  349 
in  renal  diabetes,  346 
in  transitory  glycosurias, 
348 
of    the    urine,    in    hypergly- 
caemia,  344,  348,  349 
Surgical  shock.     See  Shock 
Swallowing,  232 


INDEX 


515 


Sweat,  secretion  of,  in  fever,  395,  396, 
404,  405 
in  obesity,  313,  314 
Sypathetic  system,  role  of,  in  causa- 
tion of  fever,  385 
Syncope,  442 

action  of,  on  the  heart,  74 
Syphilis,  etiological  role  of,  in  anae- 
mias, 109,  113 
in  aortic  insufficiency,  10 
in  hasmoglobinuria,  118 
serodiagnosis  of,  174 

Tachycardia,  54~59 
paroxysmal,  56 
causes  of,  58 
symptoms  of,  56 
sinus,  58 
Teeth,  diseases  of,  in  diabetes,  229, 

359 
effect  of,  upon  digestion,  229 
relation   of,   to   focal   infec- 
tions, 153 
Temperature  of  the  body   (see  also 
Fever),    centres    for    the 
regulation  of,  400,  403 
diurnal  variations  in,  381 
effect  of  exercise  upon,  390 
elevations  of,  in  fever,  381  _ 
in    injury    of    the    mid- 
brain, 386 
in  collapse,  408 
in  heat-stroke,  390 
Liebermeister's     theory     of 
higher  pitched  level  of,  402 
lowering  of,  by  toxic  mate- 
rials, 410 
pulse-rate  and,  55 
regulation  of,  in  fever,  391, 
400 
in  health,  388 
subnormal,  409 
Tendon  reflexes  (see  also  Reflexes), 
conditions  underlying,  460 
effect  of,  on  motility,  458 
exaggerated,  contractures  in, 

464 
in  disturbances  of  the  reflex 

arc,  460 
in  dissociation  of  brain  and 
reflex  centres,  461 
Tenesmus,  rectal,  299 

vesical,  437 
Tetanus,  action  of  spores  of,  in  mixed 
infections,  160 
antitoxin  content  of  blood  in,  170, 

causes  of  insusceptibility  to,  170 
convulsions  in,  462 


Tetanus,  haemolytic  action  of  bacillus 
of,  159 
spread  of  toxin  in,  158,  462 
treatment  of,  158 
Tetany,  relation  of,  to  gastric  dilata- 
tion, 255 
Throat,  affections  of,  229,  232 
Thrombokinase,    in    coagulation    of 

blood,  136,  375 
Thymus,  importance  of,  in  bodily  de- 
velopment, 373 
in  sudden  death,  373 
Thyroid  gland    (see  also  Hyperthy- 
roidism),    effect     of, 
upon  the  heart,  55,  56, 
323,  324 
upon  metabolism,  320 
function  of,  321,  322 
results  of  extirpation  of,  322 
Tobacco,  as  a  cause  of  angina  pec- 
toris, 79 
of  arrhythmia,  70 
of  intermittent  claudication, 

79 
of  palpitation,  tj 
Toluylendiamin,  action  of,  on  secre- 
tion of  bile,  261 
Tongue,  diseases  of  and  disturbances 
of  chewing,  229 
paralysis  of,  as   a  cause  of 
dysphagia,  229,  233 
Tonsils,  importance  of,  as  portals  of 
entry  for  microorganisms, 
152 
in  focal  infections,  152,  153 
Tonus  of  the  arteries, 

effect  of,  on  blood-pressure. 
Tophi, 

Toxic  albuminurias,  423 
Toxic  symptoms.     See  Intoxication 
Toxins,  bacterial,  157-159 

action  of  blood  serum  upon, 
169 
of  gastric  juice  upon,  245 
as  a  cause  of  albuminuria,  423 
of  cardiac  disease,  9,  43 
of  haemoglobinaemia,  117 
of    intestinal    disorders, 
276 
minimum  lethal  dose  of,  157 
Tracheal  stenoses,  effect  of,  on  res- 
piratory movements,  201 
Transfusion  in  anaemia,  dangers  of, 

119 
Transudate  formation,  due  to  venous 

stasis,  51,  90 
Trauma,  as  an  etiological  factor  in 

infections,  159 
Tremor,  466 


516 


INDEX 


Tricuspid  lesions,  i8 

venous  pulse  in,  51 
Trigeminal    nerve,    relation    of,    to 
trophic   disturbances    in   eyes   and 
face,  483 
Trypanosomes,         destruction         of 

(chemotherapy),   191 
Tubercle  bacillus,  passage  of,  through 

intestinal  wall,  155 
Tuberculosis,  as  a  cause  of  anaemia, 
109 
of  cardiac  hypertrophy,  21 
of  valvular  lesions,  9 
general  bodily  changes  in,  375 
proteid  destruction  in,  319 
serodiagnosis  of,  174 
Tuberculosis   glandular,   resemblance 

of,  to  pseudoleuksemia,  127,  134 
Tumors,  malignant,  as  a  cause  of  anae- 
mia, 109,  113 
of  increased  proteid  de- 
struction, 319 
Tympanites,  296 
Typhoid  fever,  blood  in,  126 

bradycardia  following,  61 
dissemination  of,  by  bacillus 

carriers,  191,  279 
immunity  after,  164 
local    allergic     in     (chante- 

messe),   186 
prophylactic    vaccination    in, 

17s 
serodiagnosis  of,  174 
vaccine    and   serum   therapy 
of,  178 
Tyrosin,  relation  of  to  alkaptonuria, 
335 

Ulcer,  gastric,  complications  of,  243, 

253 
etiology  of  chronic,  242 
hyperacidity  in,  241 
infection  in  the  etiology  of, 
242 
intestinal,  effect  of,  on  peristalsis, 
288 
Urea,  elimination  of,  in  fever,  398 

significance      in      functional 
tests,  428 
formation  of,  333 
in  uraemia,  431 
Uraemia,  429^433 

heart  action  in,  60,  70,  429 
hypertension  in,  28 
in    chronic    infections    of    renal 
pelves,  26 
Ureteral  stenosis,  secretion  of  urine 

in,  418,  419 
Urethral  fever,  387 


Uric  acid,  excretion  of,  in  the  urine, 

364 
in  gout,  369 
in  leukaemia,  365 
in  the  new-born,  366 
in  the  blood,  in  gout,  368 
in  calculi,  435 
origin  of,  364,  365 
Uric  acid  infarcts  of  the  new-born, 

366,435 
Urinary  bladder,  relation  of,  to  renal 

pelves,  433 
Urinary  calculi,  434 
Urinary  fermentation,  ammoniacal  in 
urinary  stagnation  in  the  bladder, 
433 
Urinary  passages,   formation  of  cal- 
culi in,  434 
inflammations  of,  433 
occlusion  of,  418 
painful  sensations  in,  437 
Urine,  characteristics  of,  in  acidosis, 
327,  329 
in  burns,  119 
in  diabetes  insipidus,  414 
in  diabetes  mellitus,  330,  332, 

359 
in  dyspnoea,  223 
in  fever,  39i8,  495 
in  haemoglobinaemia,  1 18,  121 
in  hepatic  disease,  334 
in  hyperglycaemia,  344 
in  infections  of  the  urinary 

passages,  433,  434 
in  intestinal  obstruction,  293 
in  jaundice,  267 
in  pernicious  anaemia,  114 
in  phosphorus  poisoning,  345 
in  renal  oedema,  92 
in  urinary  retention,  433,  434 
Urine,  secretion  of,  diminished,  416, 
417 
disturbed,  sequelae  of,  428 
functional    disturbances   and 
their   localization   in   rela- 
tion to,  427 
increased,  413-416 
influence    of    circulation    in 
kidneys  upon,  413,  416 
of    composition    of    the 

blood  upon,  425 
of     diuretic     substances 
upon,  426 
in   disturbances   of   innerva- 
tion, 459 
of  elimination  of  formed 
elements     (casts), 

42s 
of     urmary     solids, 
420,  426 


INDEX 


617 


Urine,  secretion  of,  in  disturbances  of 
elimination  of  water,  419, 
426,  427 
in   lesions    of   the   secreting 

membranes,  419 
in  obstruction  in  the  kidneys 
by  blocking  of  the  tubules, 
418 
outside  the  kidneys  (uni- 
lateral), 418 
mechanism  of,  413,  427 
Urobilin   and   urobilinogen   in   urine 
and    faeces,    diagnostic 
significance  of,  272 
formation  and  circulation 
of,  272 

Vaccines,  immunization  with,  175,  178 
Vagina,  infections  in,  156 
Vagotonus,  in  old  age,  52 
in  the  puerperium,  62 
Vagus,  relation  of,  to  arrhythmia,  69, 

7°   t-     • 

to  asphyxia,  59,  223 

to  bradycardia,  59^1,  62 
to  heart  block,  45,  67 
to  paroxysmal  tachycardia,  58 
to  respiration,  202,  204 

Vascular  crises,  81,  84 

Vascular  disease,  as  a  cause  of  dis- 
turbances of  motility,  451 

Vascular  spasm,  in  angina  pectoris,  79 
in   intermittent   claudication, 

79,  451 
Vasomotor  paralysis,  as  a  cause  01 
tachycardia,  55 
in  the  infectious  diseases,  8i6 
Veins,  circulatory  disturbances  of,  due 
to     anomalous     heart 
action,  50,  88 
to  disorders  of  the  lungs, 

116 
to    pressure    upon    the 
great  veins,  116 


Veins,  increased  blood-pressure  in,  47, 
88,  90 
lymph     transudation     from,     in 

venous  stasis,  90 
murmurs  in,  89 

pulsations  in,  in  cardiac  stasis,  51 
Venous  hum,  89 
Vesical  tenesmus,  437 
Vocal  cords,  paralysis  of,  203 

spasm  of,  200,  201 
Volumen  pulmonum  auctum,  effect  of, 

on  respiration,  200,  207 
Volvulus,  292 
Vomiting,  255 

Wandering  cells,  role  of,  in  the  proc- 
ess of  immunity,  187,  193 
Wassermann  reaction,  in  syphilis,  174 
as  an  indication  of  the  constitu- 
tional nature  of  syphilis,  375 
Water,  absorption  of,  through  the  in- 
testines, 283,  288 
effect  of,  on  the  storage  of  fat, 

312 
elimination  of,  in  fever,  388,  395, 

405 
through  the  kidneys,  413,  414, 
416,  419,  424,  425,  426,  427 
retention  of,  in  nephritis,  92,  140, 
141 
Water  content  of  the  serum,  137 

in  chlorosis,  107 
Whooping  cough,  201 
Wright's     method     of     vaccination 
against  typhoid  fever,  175 

Xanthin,  in  the  urine,  364 
in  urinary  calculi,  437 
X-rays  in  leukaemia,  129,  131 

Zymogens.    See  Enzymes 


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