A contribution to the study of Bright's disease with special reference to the etiological relationship of the bacillus coli

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A CONTRIBUTION TO THE STUDY OF BRIGHT'S DISEASE

WITH SPECIAL REFERENCE TO THE ETIOLOGICAL

RELATIONSHIP OF THE BACILLUS COLL

BY

ALBERT G. NTCHOLLS, M.A., M.D.,

Demonstrator of Pathology, McGill University; Assistant Pathologist to the Royal
Victoria Hospital. Montreal.

(Reprinted from th<- Montreal Medical Journal, March, 1899.)

A CONTRIBUTION TO THE STUDY OF BRIGHT'S DISEASE

WITH SPECIAL REFERENCE TO THE ETIOLOGICAL

RELATIONSHIP OF THE BACILLUS COLL

BY

Albert G. Nicholls, M.A., M.D.,

Demonstrator of Pathology, McGill University ; Assistant Pathologist to the Royal

Victoria Hospital, Montreal.

There is scarcely any subject in the realm of medical pathology which
has been more carefully and persistently studied than Nephritis. Yet
there is no disease, unless it be cirrhosis of the liver, which is more
obscure.

From Bright onward, careful observers like Rokitansky, Ziegler, Wei-
gert, Klebs, Ewald, Grainger-Stewart, and Wagner, have investigated the
subject. Valuable experimental studies have been made by Grawitz and
Israel, Ponfick, Aufrecht, Litten, Roberts, V. Kahlden, Pernice and
Scagliosi, which have materially increased our knowledge. But while
the histological features of the disease are well known, and have been ac-
curately described, and the clinical features of the various stages are in
a general way understood, the ultimate nature of the process is still a
mystery.

With regard to acute nephritis, upon which there have been multi-
tudinous studies of late years, we have probably attained something like
the truth — the whole series of "infections" and mineral or other toxins
being the etiological factors concerned in the vast majority if not in
all the cases. The origin, however, of the chronic forms and their re-
lationship or otherwise to the acute stage, may be said to be largely un-
known.

The clinical symptoms, the character of the urine, give us merely the
roughest sort of information, and every pathologist knows how difficult
it is to predict the actual condition of the kidneys from the clinical ex-

animation in any given case. Indeed the confusion of the whole sub-
ject may be inferred from the numerous attempts at a rational classi-
fication of the various forms of kidney inflammation, which have been
proposed, all of which differ more or less in important particulars.

This, 1 am inclined to think, is the result of too limited a view, and
the failure to realize the different factors in the problem. To have any
degree of comprehension of the disease, clinical studies, histological ex-
aminations, bacteriology, and experimental work, must be laid under
contribution.

Acute inflammation of the kidneys is now said to be the result of
the following conditions: —

1. Intoxication, e.g., from bacterial toxins, alcohol, lead, cantharides,
phosphorus, chlorate of potash, salicylic acid, etc.

2. Complication of : — (a). The acute infections, as. scarlatina, small-
pox, pneumonia, acute rheumatism, erysipelas, endocarditis typhoid,
diphtheria, septieoema, cholera, epidemic cerebro-spinal meningitis,
gastro-intestinal disorders, etc. (h), Chronic diseases and cachexias: —
arterial sclerosis, diabetes, syphilis, pulmonary phthisis, carcinoma, etc.

3. So-called " idiopathic " cases.

In prosecuting the study of such a subject it is well to remember that
the kidney is not the sole field of observation, but that the participation
of the blood, the vessels, and other organs, in the process should be
taken into account. We should too, I think, separate from true "ne-
phritis " or inflammation of the kidney, that whole group of cases clas-
sed under the first divison which are really " degenerations " of the
kidney epithelium, and are not properly inflammations at all.

There is abundant evidence to prove that the toxic substances above
mentioned do bring about degenerations of the nature of cloudy swell-
ing, fatty degeneration, or even necrosis, in the epithelium of the secret-
ing tubules.

Moreover, it has been established by experimental studies, notably
those of Wandervelde (Act. d. poia sur les cell, epithel. n. canalicules
contournces, Brux., 1894). that toxins such as those of cholera.
cholera nostra>. tuberculosis, diphtheria, pneumonia, influenza, and
chemicals, such as chromic acid. lead, phosphorus, mercuric chloride.
when injected into animals exert through the blood-stream a harmful
influence upon the secreting epithelium bringing about changes identical
with those found in the human subject.

Still it must be emphasised that Buch changes do not constitute ne-
phritis, and since inflammation in the organism is so rarely dissociated
from bacterial invasion, it may well be doubted whether when inflam-
mation does supervene, it i- not of the nature of a direct infection.

In the case of true acute nephritis, the trend of the investigation of
the past 1.5 years points strongly to the unity of the process as a result
o. various microbic infections. The varieties of these arc numerous.

Bouchard, (f>es nephritis infectieuses, Rev. de M6d. 1. '81), in niuc
cases of typhoid with nephritis that came to autopsy, found the specific
bacillus in every one and in several other living cases found the germ
so long as the albuminuria persisted. But since this investigation was
six years before the full studies of Gaffky on the bacillus, there may be
some little doubt as to the value of the results.

Letzerich, (Untersuch. u. Beobacht. ueber Nephritis bacillosa inter-
stitialis primaria. Zeitschr. f. klin. Med. Bd. 13, '87, S. 33.) described
;m epidemic of acute intersitial nephritis witn the ordinary clinical
symptoms which was due to a bacillus resembling the B. tuberculosis,
but shorter. Injected into animals it produced nephritis.

Mannaberg (Zeitschr. f. klin. Med. "90), in fourteen cases of acute
Bright's in acute endocarditis, found streptococci in the urine which he
was unable to find in the urine of other cases after a prolonged investi-
gation.

That acute nephritis could be epidemic apart from any relationship
with scarlatina, was shown by Fiessinger (G-a. He'd, de Paris. Oct. 10/01).
Acute nephritis has also been known to follow infected wounds of the
skin, impetiginoid eczema, pemphigus, vaccination, acute tonsillitis and
various lesions of the alimentary tract. Among the bacteria which have
been recently shown to produce acute nephritis, are the B. Typhi, the
diplococcus lanceolatus, meningococcus intracellularis, B. Friedlanderi,
streptococcus pyogenes, staphylococcus albus and aureus, and the B.
Coli.

The condition is to be regarded as an attempt on the part of the
kidneys to eliminate the toxins and micro-organisms of the various dis-
eases. That the kidneys do excrete bacteria even in the absence of gross
lesions of the organs is amply proved. Weichselbaum (Wiener med.
Wbch. No. II, 1885), in a case of ulcerative endocarditis found strepto-
cocci and staphylococci in the urine; the B. Typhi is found in the urine
in quite a large percentage of cases, and numerous other germs have been
found in various diseases.

The best statistics on Bright's disease are those of Agnes Bluhm
(Ueber die Aetiologie der Nephritis, D. Arch. f. klin. Med. Bd. 47, '90.)
Of 1 10 cases of acute Bright's disease, 70 per cent, could be traced to
acute infections. Onlv 2.85 per cent, were directly traceable to cold.
<>ne of the cases followed acute ileus.

The acute nephritis of the infections is of various types. At one
time, degenerative processes in the secreting epithelium predominate,
such as extreme cloudy swelling, fatty degeneration, desquamation, and
imperfect nuclear staining. At another, the brunt of the toxin falls
upon the glomeruli bringing about effusion into the Bowanan's Capsules,
congestion of the glomerular capillaries and shedding of the capsular
epithelium; or occasionally small-celled infiltration into and about the
Bowman's capsules. Or at still another, an acute interstitial infiltration of

leucocytes with oedema of the boundary layer (the •• lvmphomatous" ne-
phritis of Wagner). Lastly, all three may be combined. The first form
is most common, but the type seems to depend upon the nature of the
infection. The tendency of scarlatina for instance, to cause a glomerulo-
nephritis or an acute interstitial inflammation is well known.

I Iccasionally the primary infectious diseases are ushered in by an acute
oephritis, which may predominate the clinical pit-tun', as in the so-
called "renal typhus/5 Generally, however, the cases occur late on in
the course of a specific infection, and are to be regarded as complica-
tions due to the effort a1 elimination. They arc probably exaggerations
oi the common conditions of cloudy swelling, between which and true
inflammation, no hard and last line can be drawn. Again, some, of these
cases may be the result of a mixed infection.

Further, all grades of severity exist, from a mild inflammation up to
a true local suppurative condition. The infection may he in some cases
an ' ascending' one from the bladder, hut more commonly a * descend-
ing ' one from the blood-stream. Only on the latter supposition can
we explain the nephritides which occur in skin affections, anginas, and
intestinal disorders.

It should not be forgotten than an acute attack may be grafted upon
a chronic nephritis which was unsuspected, thus simulating a primary
attack. (" Acute recurring nephritis " of Wagner.)

The idiopathic cases are those which occur in previously healthy per-
sons; often the only causes that can be assigned are chilling of the body,
or excessive exercise in the cold. This form is especially apt to occur
in alcoholics. That there is some relation between the skin and the
kidney seems clear.

The etiology of these and the forms occurring in chronic disease will
be discussed later.

When we come to consider the production of chronic nephritis the
task becomes more difficult. It is usual to teach that the acute cases
may become chronic, and that the cirrhotic kidney is an end-stage of the
chronic parenchymatous nephritis, or is due to arterial disease, or again,
to certain poison, as alcohol, gout, and lead. (The "primare Schrumpf-
niere"' of the Vienna School. ) This does not, however, explain all
the cases; cases of contracted kidney occur where there was no history
of any acute attack, and run an insidious course. And again, cirrhotic
kidneys may occur in children, where there could be no question of
arterio-selerosis or chronic intoxications from mineral substances.

Further, the cirrhotic kidney has been known to result from infective
diseases, as pneumonia (diplococcus), and influenza. The etiological
elements in this form then seem to be very various, and the course ap-
parently without any fixed rule.

While it is generally admitted that acute nephritis is in the immense
majority of cases, due to some infective agent, as yet. I believe, no one

has ventured to say that chronic Bright' s disease is due to the direct
aGtion of bacteria.

Hoist, indeed, is inclined to support the view that microbes by their
toxins are able to produce nephritis without being present in ihe kidney
per se, and that the action may appear late or after the primary in-
fection has disappeared, thus producing the chronic disease. But this
view does not seem consistent with the facts. Becent investigations,
almost without exception, go to show that in acute nephritis microbes
are present in the kidney. In the case of pneumonic nephiitis, Massa-
long and Klebs frequently found the diplococcus lanceolatus in the
kidney. Michelle, too, (Morgagni, Aug. 1896), in 19 cases found the
pneumococcus in 18. In sis cases of acute nephritis, and acute nephri-
tis grafted upon chronic in pneumonia, I have found the diplococcus
in every one.

Councilman (Trans. Assoc. Amer. Bhys. Vol. xiii., 1898.), records the
following results : —

42 cases of acute interstitial nephritis were examined bacteriologi-
eally post mortem.

In 24 diphtheritic cases the kidney was sterile in six.
In 11, the B. Coli was found.
In .") the streptococcus pyogenes was found.
In 1 the streptococcus aureus was found.
In 8 the diphtheria bacillus was found.
In 1 the B. Foetidus was found.
In 5 cases of scarlatinal nephritis.
In 3 the streptococcus.
In 2 the B. Coli.
In 1 the staphylococcus.
In 8 of mixed infection of diphtheria with scarlatina or measles.

2 cultures were sterile.

3 the streptococcus.
3 the B. Coli.

In other six cases: —

3 the B. Coli.

2 the staphylococcus aureus.

4 the streptococcus.
1 the pneumococcus.
1 sterile.

He does not resrard the presence of the colon bacillus found under
such conditions as of much etiological value. He obtained the same re-
sults in the kidneys in the same diseases, in which no interstitial nephri-
tis was present.

Thus he concludes that no weight could be laid on the presence of

6

bacteria in the kidneys as a causative factor in the acute interstitial
lesions.

This conclusion does not seem to me to be warranted for it is amply

proved that in these specific diseases germs are to be found in the urine
where no gross Lesion of the kidneys exists, at leasl clinically, and the
production or uo1 of nephritis depends on the correlation of Beveral

factors, outside of the mere presence of bacteria.

With a \iew of gaining further information and ascertaining whether
bacteria were present or uot in the various forms of Bright's disease, I
have availed myself of the pathological material of the Koyal Victoria
Hospital from about 325 autopsies and also the clinical notes of all the
cases of nephritis in the Wards for the past four years.

In approaching this investigation, I have thought that more valuable
information would be attained by examining sections of kidneys which
presented evidence of nephritis microscopically, in addition to those
which were taken from cases which were recognised clinically. For by
this means one gets a wider view of the subject, inasmuch as the study
embraces all grades of the disease from the incipient forms up to the
most advanced stages. Particularly valuable is the study of the early
stages since it is only thus that a true appreciation of the process can be
formed.

Sections were made from 105 kidneys presenting the varous forms of
nephritis. All cases in which there was cystitis or any evidence of an
"ascending" infection, or local tuberculosis, were excluded as unneces-
sarily complicating the subject.

Some of the material of the early years was hardened in Midler's fluid,
so that many kidneys presented evidence of post mortem growth of
bacteria, these were excluded in drawing conclusions. The material,
however, which was hardened in Formol-Muller was satisfactory. All
cases in which there was clearly a terminal infection as shown by plugs
of bacteria in the capillaries were also excluded.

The method of staining was as follows: —

Celloidin sections, cut as thin as possible, wen; placed in carbolthionin
for from 12 to 24 hours in the incubator. The formula, of the stain
was: —

Solution of carbolic acid, (1—10) 100 cc.

Thionin, 1 gramme.

Filtered as used.

The sections were then decolorised in weak acetic acid, dehydrated in
aniline oil, washed in xylol and mounted in balsam.

Those sections in which pus cocci, or micro-organisms positive to
Gram, were suspected, were also prepared by the G-ram-Weigert method.
The results were very satisfactory. Carbol-thionin is certainly the best

stain for bacteria in tissues that T have employed. The sections were
examined by l-18th Reicheri oil-immersion lens and No. -4 eye piece.

The classification that I have adopted of the various forms of the
disease, is purely a histological one based mainly upon my own investi-
gations, but is practically that of the German School. The division is
as follows, it being premised that is somewhat arbitrary, the various
forms passing imperceptibly one into the other, the predominant
feature being taken as the guide.

1. Acute Parenchymatous Nephritis, in which there was degeneration
of the epithelium of the secreting tubules as evidenced by cloudy swell-
ing, desquamation of cells, exudate, and 'imperfect staining of the nuclei,
often with casts. It includes hemorrhagic cases.

2. Acute Interstitial, in which there was an acute leucocytic infiltra-
tion about the glomeruli or in the lining cells of the Bowman's capsules
tween the tubules, without grave degenerative changes in the tubular
epithelium,

3. Acute Diffuse, where the first two forms were combined.

-1. Acute Glomerulitis, evidenced by congestion of the glomerular
eapillaries, desquamation of the lining cells of the Bowman's capsules
with effusion and exudation into the capsules.

5. Chronic Parenchymatous, in which there were marked degenera-
tive changes in the secreting cells, but with a tendency to connective
tissue proliferation; haemorrhagic cases included.

6. Chronic Diffuse, where the fibrous hyperplasia had progressed still
further, bringing about atrophy and dilatation of the tubules with some-
times hyaline degeneration of glomeruli with periglomerular fibrosis.

7. Chronic Glomerulitis, a sub-variety in which the glomeruli showed
predominantly, degeneration, atrophy and periglomerular fibrosis.

8. Chronic Interstitial, the terminal stage of the chronic diffuse,
where the secreting cells were extensively atrophied with cystic dilata-
tion of the tubules, sclerosis of the glomeruli and extreme fibrous proli-
feration.

9. Arteriosclerotic and Senile, where the process was most marked
in certain vascular districts.

10. Amyloid Fatty Kidney, a combination of amyloid disease and
parenchymatous degeneration.

1 1. Amyloid Contracted Kidney, amyloid disease in a cirrhotic kidney.

This classification is intended merely to afford a convenient division
for the purpose of the present study.

Tn all, 105 specimens were examined and classified as follows, 28 being

excluded for the reasons mentioned : —

Acute parenchymatous 26 Chronic glomerulitis 1

Acute interstitial :{ Chronic interstitial 10

Acute diffuse 1 Arteriosclerotic and senile 13

Acute glomerulitis 0 Amyloid fatty kidney 2

Chronic parenchymatous 8 Amyloid contracted kidney 0

Chronic diffuse 11

*

The results were very striking.
the lull owing: —

Analysis of the different classes gave

Disease.

Acute Parenchymatous:

Typhoid

Ulcerative Phthisis .
B. Aerogenea Capsul..

Diabetes

Lobar Pneumonia

.Mitral Stenosis

Diphtheria

Pyemia

Eclampsia

Puerperal Septicaemia.
Epid. Cerebro-Spinal
Meningitis

Xo. of
Cases.

Bacteria Found.

Acute Interstitial

Lobar Pneumonia..

Pyemia

Puerperal Septicaemia.

Acute Diffuse :

Cancer with septic peri

tonitis ,

Typhoid

Lobar Pneumonia

B. Typhi 'J, 15. Coli (?) 2

Diplococci and Bacilli -

15. Aerogenea _

Diplococci with halo : \ ery small, 1 . . . .

Lanceolatua t

" with halo, 1

15. Loffleri and Cocci 1

Staphylococci, 1

Long H. with rounded cuds, B. 0>li (?) 1

Staphylococci and B. 1

Diplo. Intracellularis, 1

i Weichselbaum)

Small Diplo. (?) Dijjlo. Lanceolatus;

Cocci and Bacilli

Cult, gave Streptococci

Diplo. in cultures. 1

B. Typhi in areas, of infiltration,

Diplo. Lanceolatus 1

Negative.

Of the 32 acute forms of various kinds, bacteria, generally the specific
germs of the disease, were found in 28. The overwhelming proportion
of positive results leads me strongly to the conclusion that in the vast
majority of cases, if not in all, acute nephritis is due to the presence of
specific microbes. That there were four negative results does not in-
validate the conclusion, for the infection being embolic it is very prob-
able that in such kidneys there are sporadic areas of inflammation sur-
rounded by comparatively healthy tissues. Indeed, this sporadic form is
recognized by several of the recent French observers, and is quite ana-
logous to embolic suppurative nephritis.

It is suggestive that minute diplococci with halos were found in one
case of pancreatic diabetes, and in one of mitral stenosis with passive
congestion of the intestines, while in an eclamptic patient, bacilli were
found strongly resembling the B. Coli. The significance of this will
be seen later.

In the eight examples of chronic parenchymatous nephritis, four
showed minute diplococci with a delicate halo mostly between the lob-
ules in the cortical area. Of these one case, which was associated with
Atrophic Cirrhosis of the liver, showed a few well marked minute diplo-
cocci with a halo. In two, one an alcoholic kidney, bacilli of doubtful
nature were seen. Two others gave negative results.

The chronic glomerulitis case showed a slight acute interstitial in-

flammation as well, and a few rare diplococci were seen. The primary
disease was septic peritonitis.

The amyloid fatty kidneys showed no germs.

Still more interesting and suggestive were the results found in the
chronic diffuse, chronic interstitial, and the arterio-sclerotic type of the
disease.

In the chronic diffuse nephritis, bacteria were found in all 11 ca
In two there were rather large diplococci, which might be the diplococ-
cus lanceolatus as a lobar pneumonia was present. In five, small diplo-
cocci; in four short stumpy bacilli were seen with polar staining closely

imbling the B. Coli. These were situated in the areas of round celled
infiltration, beneath the basement membranes of the tubules, and in
one case within the lining cells of the secreting tubules.

One case, in which the small diplococcus form was seen, was associ-
ated with atrophic cirrhosis of the liver.

There were 10 cases of chronic interstitial nephritis. In all were
found the minute diplococci with a halo, mainly in the areas of round-
celled infiltration, some few within the Bowman's capsules, and in one
case within the cells of the tubular epithelium.

Figs. I. and II., Plate 1, show very well the diplococci in the small
celled infiltration. In the 13 arterio-sclerotic and senile forms, three
gave negative results, but the specimens were very poor; nine showed
small diplococci with a halo, chiefly in the areas of round-celled infiltr-
ation, and also in one case in a glomerular capillary, in another, within
a Bowman's capsule, and in a third with the lumen of a secreting
tubule.

In two of the cases besides there were noted bacilli of varying forms.
These were diplo-bacilli of small size, very short bacilli with rounded
ends, a slender form with polar staining and others, large and curved
conforming well to the usual appearance of the B. Coli.

To sum up, in the 45 cases of chronic nephritis of all forms, minute
diplococci, as a rule with a distinct halo, were seen in 29, and bacilli
having the ordinary appearance of B. Coli in 4 more. In only six were
no bacteria seen, but this might easily be due to poor sections or errors
in technique, for it is difficult in a large series of sections to get per-
fectly even results.

These diplococcus forms were very minute and might easily be over-
looked with an ordinary l-12th immersion. Sometimes it could be made
out that they were really very short, fine bacilli with polar staining the
intervening substances being almost colourless. They were generally in
the areas of interstitial round-celled infiltration. Rarely I have seen them
within the Bowman's capsules, and within the secreting cells of the con-
torted tubules ; on one occasion within a lumen. The halo was probably
not a true capsule, but due to the effects of refraction.

10

As Id the nature of these diplococcus forms, ii may be said that they
are identical Ln appearance and size with the diplococci which Adami has
found recently in the Liver, associated with progressive portal cirrhosis,
and which tie has Droved to be a varianl of the colon bacillus. Bis very
important investigations appeared in the Montreal Medk \i. Joi unai, in

July, L898, the British Medical Journal for October, L898, and the
Lancet of Augusi L3th, L898. Be round diplococcus forms in all livers
which stained a brownish hue and were probably dead forms, whil • in
atrophic cirrhosis of the liver they wen increased in number and stained
well. Be lias. 1 think, established the fad thai these forms are really
a modified colon bacillus, and thai the liver in health, is constantly
excreting them, thus constituting a chief barrier of defence againsi bact-
erial infection from the gastro-intestinal traet. In experimental animals
he found that in 15 minutes after intravenous innoculation with a pure
growth of the B. Coli, the endothelium of the capillaries hail enelosed
the germs, and in two hours the bacteria were to he found within the
parenchymatous cells of the liver. The germs which were of the ordin-
ary colon type presented also diplococcus form. The diplococcus
isolated from cirrhotic livers formed very minute colonic- on nutrient
agar and produced relatively little gas, bul in other respects conformed
well to the colon type.

With a view to discover if the colon bacillus is to he found in the
urine of nephritis eases. I have examined the urine in one ease of acute
hemorrhagic nephritis, and in one of chronic interstitial. The method
employed was to sterilise the meatus and glans penis then in allow the
patient to pass several ounces of mine and collect the residue in sterilised
flasks. These wi've then sealed and placed in the incubator for 48
hours. Tn the first case I obtained the colon bacillus, bul it died out
rapidly, and T was not able to study it very closely.

In the second case, the chronic interstitial, various forms were found
as -een in Fig. I.. Plate II. These were stout bacilli, either straigh.1 or
curved with rounded ends, some with polar staining : they all resembled
the ordinary colon forms. Besides these there were small ovate bacteria,
and shorter more delicate bacilli with polar staining. There were also
short chains composed of very short bacilli with rather blunt ends show-
ing polar staining. All were negative to Gram. A broth transfer was
made and after 48 hours all the usual forms of the B. Coli were seen
with the addition of minute diplococci with a halo. These, owing to
the crescent ic form of the stained portions resembled gonococei. Small
diplococci with halos were seen exactly resembling those seen in the
sections, also a similar diplococcus, hut larger.

When transferred to agar for 48 hours, a thick tallowy growth was
produced, and microscopically the germs were shorl oval bacteria, very
.-mall, with the 1-Tith oil immersion exactly like cocci ; also numerous

11

minute diplococcus forms. No bacilli were seen. (Vide Fig. II., Plate
IT.) This was transferred to a Bouillon made from kidney reacting,
1.5 per cent acid to phenolthalein ; this showed minute diplococci with
halos, diplobacilli, a slender bacillus with polar staining and besides
these, the ordinary typical colon. (Fig. 1.. Plate III.)

Cultures from the coccus and diplococcus forms were made on broth,
milk, potato, glucose, agar and litmus agar. Tiny showed that in all
respects the organism reacted like the 1). Coli, with the exception that
indol was not produced. Unlike Dr. Adami's diplococcus, this one pro-
duced a very hea\\ growth on agar.

When grown witii sterilised bile on agar, the cocci and diplococci seen,
were even smaller than those produced on plain agar.

With regard to the pres< ace of B. Coli or other germs in the urine of
chronic nephritis, information is lacking, ami my investigations on this
'point are still going on. being hampered at present for want of enough
clinical material. Still, in the cases I have examined I have found the
colon bacillus, although as is well known, it is also present in other
conditions, notably cystitis, nephrolithiasis and pyelonephritis suppur-
ative. Fernet (Bull, et Mem. do la Soc. des Hop. Paris, Dec. '92), in a
case of acute interstitial nephritis occurring two months after an abor-
lion, found the B. Coli in great numbers in the urine.

- era! observations have been made on normal urine to discover if
it usually contains germs. The best studies are those of Enriquez,
(Kecherches bact. sur L'urine normale, Se"m. MM., No. 57, 1891, p. 468,)
This author collected the urine in the way which I have employed, and
concluded that normal urine was aseptic.

In the urine of 11 healthy people, and five cadavers, the cultures in 10
were sterile, in live staphylococci, and in one, non- pathogenic bacilli
were found. These last cases, however, were taken from tuberculous
wards, and in two there was a history of previous infection. The urine
of seven healthy raid tits was sterile. In the post mortem records I have
studied, as a rule, there is no note of cultures taken from the kidneys
or urine.

In three cases of tuberculosis of the intestine, the B. Coli was found
in the kidney once and in the urine once ; one case sterile. In two
cases of typhoid fever, B. Coli in one ; one sterile.

One case of tubercular pyelonephritis gave 11. Coli.

One case of nephrolithiasis gave B. Coli.

One case of chronic mixed nephritis with amyloid disease gave the
colon bacillus.

The presence of the colon bacillus so generally in the kidneys, which
I have studied, receives additional importance from the fact that in
this study I have been careful to exclude all cases in which there were
cystitis, suppurative pyelonephritis, and tubercular abscesses — conditions

iii which there is apl to be an 'ascending* infection with the colon bacil-
lus. We must then conclude thai the infection is a 'descending* one by
way of the blood stream. Thai the presence of the colon bacillus is to be
explained as a terminal infection or a post mortem overgrowth, I do not
believe, for it is easy to eliminate rases of this kind as I did very freely,
for the differences are quite distinctive. In ante-mortem terminal in-
fections, the germs are largely in the capillaries, often forming large
plugs, and consist of large fa1 bacilli, Bhorl bacilli, or sometime- diplo-
cocci, Inn always much larger and staining more deeply than the diplo-
coccus forms I describe. Further, there is no evidence of inflammatory
reaction ahout these large bacteria, while in the case of the diplococcus,
they are enclosed by an inflammatory round-celled infiltration. Neither
is ii a post-mortem growth, for in this case, the germs are in the super-
ficial cortical layers, and are always much larger and different in ap-
pearance and staining powers. Such germs can he seen with an ordin-
ary No. ; objective, while the diplococcus re, pure- the L-12th oil im-
mersion at least, or better the l-18th. Then again, the diplococci are
always very few in number, perhaps only five or six in a section.

It is almosl impossible to get perfectly normal kidneys in the post
mortem room, bui 1 have examined a few for diplococci in which
microscopically the tissue showed no abnormality. In LO such sections.
7 showed no germs; three showed rare diplococci similar to those in
the nephritis eases, hut on further examination 1 found that in one case
there had been a hernia operation, and there was an acute local enteritis ;
in the second there had been a gastrotomy performed, and there was
heal peritonitis; and in the third a spina bifida had been removed.
Thus in two there could have been infection from the intestinal tract.

That the process in chronic nenhritis with productive inflammation
is due to an embolic infection, is strongly supported by the histological
features in the sections I have studied. The lesions in the chronic
forms are identical with those in the acute interstitial as to their anato-
mical distribution.

hi the great majority of the acute interstitial and acute mixed
varieties, the areas of round-celled infiltration are to he found around the
glomeruli or around the afferent vessels, and interlobular arterioles ex-
actly as would be expected in an embolic infection. The same holds
good for the chronic cases. In the arteriosclerotic type, that the in-
filt ration and proliferation is mostly confined to vascular districts needs
only to he mentioned. In the early stages of the chronic diffuse nephri-
tis one sees the inflammatory exudation in the same way about the
afferent blood vessels, associated with connective tissue hyperplasia.
The cells of the Bowman's capsules proliferate causing atrophy and
hyaline degeneration of the glomerular tuft, or we get small fibrous
patches about the vessels between the contorted tubules.

13

In both acute and chronic forms the vessels of the affected areas often
show marked congestion. Later on, in the chronic interstitial type
(contracted kindey), the fibrous tissue overgrowth is so generalized that

this relationship to the blood vessels can no Longer he made out. In
my series, the process could he accurately followed out.

What is the starting point then of this colon bacillus invasion? The
most obvious is the intestine. We have ample evidence that intestinal
discorders can cause acute nephritis, it occurs in gastro-enteritis and in
Cholera Asiatica, for instance.

Ebstein, (Deut. Med. Woch., June 15th, 1897), discusses acute nephri-
tis as a complication of chronic gastro-enteritis. In a case hi' records
in a woman of 27, there was a history of diarrhoea for tune months pre-
viously, pain in the epigastrium and anorexia, for six. The nephritis
came on most acutely, and was fatal in a few days from eclampsia,
coma and collapse. At the autopsy acute nephritis was found, a tape-
worm in the intestine, acute follicular ulcerative enteritis and enlarge-
ment of the mesenteric glands. The spleen was normal. Influenza and
all other infections as a cause were excluded and Ebstein concluded that
the condition was due to an intoxication from the intestine.

Dupeu, (Acute Nephritis in Children. — Journ. de Mexl., July 10, !'7),
states that acute nephritis may be a result of ordinary gastro-intestinal
intoxication, particularly when there is dilatation of the stomaih. It
has been observed in children as young as 11 — 1G months fed by the bot-
tle, and in whom vomiting and diarrhoea were prominent symptoms.
In these cases it may last 2 — 4 weeks and present all the usual features
of Bright's Disease.

"With a view to determine the relationship, if any, of various gastro-
intestinal disorders to nephritis. I have examined carefully the clinical
records of the Royal Victoria Hospital for the past four years, having
access to these through the courtesy of Prof. Jas. Stewart. In making
the estimate I have been careful not to accept as an etiological factor the
nausea, vomiting, and diarrhoea, which so often usher in or complicate
an uraemic attack, but I have endeavored to find out if there was any
history of such disorders existing for lengthened periods which might
reasonably be regarded as of etiological moment.

There were 71 cases of nephritis of various forms divided according
to the reports as follows: —

Acute Parenchymatous Nephritis 10

Sub-acute Parenchymatous 15

Chronic Parenchymatous 17

Chronic Interstitial 29

The etiological factors were: —

Chronic Alcoholism 15 times

Dyspepsia, (Gastro-enteritis, nausea,

Vomiting, etc) 15 times

1 t

Infectious Diseases, (Influenza, Acute

Rheumatism, Diphtheria, Typhoid) 11 times

Exposures to wei and cold or to extremes

of temperal are 5 times

Appendicitis Once

Puerperal Eclampsia Twice

Gastralgia I >nce

Acute Gonorrhoea < )nce

* ihronic < \oi 'hcea < >nce

Insidious, (No definite cause) 22 times

Thus it will be seen that of the 71 cases studied, 39 were subsequent
to gastro-enteric disturbances, assuming as one fairly may that such
would be present in the chronic alcoholics. This is a percentage of
■10.84 per cent, of all cases. Excluding the acute cases due to the
various infective Eevers in which the etiology is quite established, the
1 roportion becomes 50 per cent. In 30.98 per cent., the onset was in-
sidious, and do cause could be assigned.

These facts go Ear to show that there is a definite relationship be-
tween nephritis and disorders of the alimentary tract, for when we con-
sider that there were in the records no special investigations made to
establish such relationship, but merely the ordinary routine investi-
gation, the above figures become invested with even greater importance.
Further, there were very few of these gastro-intestinal disorders acute
in character, hut in most there was a history of such symptoms extend-
ing over periods of months or years.

It will be interesting to examine the cases divided according to their
clinical types in relation to previous lesions of the gastro-intestinal
tract.

In the 10 cases of acute parenchymatous nephritis, no cause could be
3 ned. in :;. there was a history of :

Acute Tonsillitis (Rheumatic) in 1

Extremes of Temperature, etc.. in 1

Acute Rheumatism, in 1

Acute Infections, in ;j

i .astro-Intestinal Disturbances, in 1

In the 15 sub-acute parenchymatous nephritis, the causes were: —

Acute < ronorrhcea, in 1

Exposure to wei and cold, in 2

Alcoholism (1 case with hernia)

Mild Dyspeptic Symptoms, in 2

1 nsidious I Inset, in 1

Unknown, in 1

Puerperal, in 1

Catarrhal Appendicitis (?), in 1

15

As would be anticipated, the acute infections are the mosi common

causative factors in the acute and sub-acute forms, bu1 in 7 nut of the
25. some gastro-intestinal disturbance existed previously.

The etiological factors in the 1? chronic parenchymatous nephrit's
were : —

Infective Diseases, as Measles, Diphtheria, Mumps,

Scarlatina, etc 2

Chronic Alcoholism 5

Wet and Cold 1

Gastro-intestinal Disturbances, ( Diarrhoea, Dys-
pepsia, etc 5

Unknown 4

In the chronic interstitial types. 29 in all : —

Wet and cold 1

Alcoholism 7

Gastro-intestinal Disturbances, etc 6

Infections, (Influenza, Typhoid, Diphtheria,

Chronic Gonorrhoea, 1 each) -4

Insidious 5

Unknown 6

Clinical evidence then strongly supports the view that Chronic
Bright's Disease, and indeed Acute, may be a result of some long-stand-
ing gastro-intestinal disorder, 50 per cent, of cases giving this history,
thirty per cent, of cases are insidious in onset, all the usual causes being
absent: such might be called " Cryptogenetic forms." Can these be due
to an infection from the intestine ? It is very probable, but the clini-
cian must further elucidate this point by a more careful study of the
history. I certainly have found the diploeoccns form of the colon
bacillus in several diseased kidneys, where no cause could be assigned
for the chronic nephritis, also in the kidneys in one case of cancer of the
pancreas, and in one of passive congestion of the intestines.

That albuminuria occurs as a complication of acute gastro-enteritis,
chronic diarrhoea, dysentery, and the like, is well known. In 21such
cases taken at random from the records, I have found albuminuria in five.
Whether this fact is of much significance or not remains to be proved,
although certain recent observers insist that all albuminuria- arc patho-
logical.

But to afford a point of entrance for tbe B. Coli, a lesion of the in-
testinal tract is not all. There must be an increase in virulence of the
bacillus, and this is the usual condition.

Macaigne, (Arcb.Gen.de Me"d., Dec, 1896,) has published some im-
portant experimental observations. He has found that B. Coli derived
from the healthy intestine is harmless in the abdominal cavity, but it

16

becomes virulent if there is some disorder of the intestinal tract as diar-
rhcea, constipation, strangulation, etc. Ee could produce nephritis in
animals by intravenous innoculation with B. Coli but usually obtained a
suppurative form.

Klechi produced artificially, compression of a loop of intestine in the
dog, and found thai the virulence of the bacillus taken from this part
was greater than that of the germ taken from an uninjured portion.

Sanarelli, (Ann. de I'inst. Pasteur, 1894, pp. 19.3 and 353). found in
guineapigs suffering from typhoid fever, thai the virulence of the colon
bacillus in the intestine was greatly increased.

Anything then which causes a loss of the lining epithelium of the in-
testine with increased virulence of the germ, provides the starting point
for a systemic infection. That this often happens is beyond doubt.
The occurrence of pneumonias due to colon infection is well recognized
in strangulated hernia, and in septic peritonitis due to the same germ,
the bacillus coli has been found in all the organs of the body including
the kidneys.

The usual line of infection is through the mesenteric glands and
liver, which thus constitute the first barrier of defence, either through
the portal blood or by the bile duets or both ; further, it may take place
through the abdominal Lymphatics. Prof. Adami, in his work referred
to. has shown that the liver normally contains the colon bacillus, but ap-
parently in a dead state, and this agrees very well with what we have
found in post mortems, where we very frequently fail to get germs from
the liver. His investigations show thai the cells of the liver take up the
germs and excrete them in the bile thus rendering them inert.

This view, however, is in seeming opposition to that of Roger, (S6m.
He'd., Oct. 10, 1808) who hold the view that the liver is powerless
againsi the colon bacillus, and even assists its growth. His observa-
tions, however, were made on experimental animals, witli virulent cul-
tures so that the case is not the same as that with which we are deal-
ing. Should the condition mentioned exist so that we gei a relatively
virulent germ introduced into the liver, then we get local results on the
liver lending to parenchymatous degeneration, perhaps cirrhosis, and
even to invasion of the systemic circulation. This invasion of the blood
stream would, a priori, he more likely to take place the more severe
the lesion from which the liver was suffering.

To determine whether there is any connection between hepatic dis-
order.-, as for instance, cirrhosis of the liver, and the various forms of
nephritis. I have consulted the posi mortem records of the General
Hospital from 1883 to 1898, to which T have had access through the
courtesy of Or. Wyati Johnston. In addition I have made use of the
Royal Victoria records from 1895 to 1898. In the aggregate there
were 1517 autopsies.

17

Atrophic cirrhosis of the liver, or atrophic cirrhosis with fatty in-
filtration, occurred 24 times. Associated with these : —

Acute Parenchymatous Nephritis was found. . . . Twice

Chronic Parenchymal mis Nephritis Twice

Chronic Diffuse Nephritis Once

Chronic Interstitial Nephritis 15 times

Xo special abnormality to gross appearance -4 times

This was a total percentage of 83.30, or Chronic Nephritis only in 75
per cent. Conversely, the proportion of chronic interstitial nephritis
in all diseases other than cirrhosis of the liver, was 242 cases or 15.64
per cent.

In three cases of hypertrophic cirrhosis, acute parenchymatous
nephritis was present in one ; chronic interstitial in one, and no
change in one. These figures speak for themselves.

Further it has been mentioned by several observers that fibrosis of the
pancreas often goes with cirrhosis of the liver, facts pointing to a com-
mon cause. In the five Royal Victoria Hospital cases, this condition
was present in every case. Of course the same infection that would at-
tack the one would be likely to affect the other, the excreting ducts
opening so close together. I have also frequently observed that there
is a similar relationship between the kidneys and the pancreas in a
large proportion of cases.

But while in the case of the liver and pancreas, the infection could be
through the ducts, in the case of the kidneys, of course, it must be
through the circulatory system. Moreover, it needs only to be men-
tioned that the toxin.- which are supposed to bring about nephritis act
in a similar way upon the liver. This is seen in the case of chronic al-
coholism, and it is far from uncommon to find in the infective diseases
such as tuberculosis and typhoid, at one and the same time, an acute
infiltration in the portal sheaths and in the interstitial substance of the
kidney.

The disease must then be regarded as an attempt on the part of the
kidneys to eliminate the bacteria which reach them. Much information
on this point may be gathered from experimental work.

As early as 1874, Franke and Gscheidlen, and in 1879, Watson-
Cheyne, were investigating the fate of bacteria injected into experi-
mental animals. Their investigations together with those of Cohnheim,
proved conclusively that such bacteria were excreted by the urine.

Wyssokowitsch, (Zeitschr. f. Hygiene u. Infectionskr., Bd. 1, '86), after

a long series of experiments with various germs concluded that bacteria

were only excreted by the kidney when there was some local lesion of

the organ, in other words, that a physiological excretion does not exist.

Schweizer, (Virch. Arch. Bd. CX., 1887), on the other hand was of

18

the opinion thai bacteria could pass the kidney epithelium in the ab-
sence of any lesions which it was possible to recognize by the ordinary
methods.

The majority Beem to think that some degeneration of the secreting
parenchyma, be it never so slight, is necessary to permit the passage of
germs into the urine. Such primary lesions would be afforded by the
condition of congestion and cloudy swelling which is such a constant ac-
companiment of the acute infection.

Pernice and Scagliosi, (Beitrag. zu. Aetiologie der Nephritis. Arch. f.
path. Anat., cxxxviii, 3.), injected various pathogenic and non-patho-
genic bacteria beneath the skin such as, anthrax, B. pyocyaneus, staphy-
lococcus, and B. prodigiosus. In the kidney they produced hypersemic
endarteritis, and haemorrhage into Bowman's capsules.

These lesions lead to the passing of the bacteria into the tubules and
hence into the urine. The presence of the germs in the tubules caused
swelling, fatty and hyaline degeneration of the epithelium, later, exuda-
tion and casts. The contorted tubules were chiefly affected, but also
the straight tubules. Later there was desquamation of ells, collapse
of the tubules and hyperplasia of the connective tissue. These authors
got the same results with filtered products of growth.

Through the kindness of Professor Adami, 1 have studied the kidneys
in the case of the rabbits inoculated intravenously with pure growths of
B. Coli, which he employed in his studies on cirrhosis of the liver.
These animals were inoculated in the auricular vein, and then~tilled at.
regular intervals.

Rabbit A., killed 15 minutes after intravenous inoculation with pure
growth of typical B. Coli.

Microscopically, there were relatively few baci ! found which were
confined to the vessels of the cortical region and the neighborhood of
the glomeruli. They appeared as fair-sized bacilli.

Babbit B., Killed 30 minutes after.

The bacteria were found in great numbers in the capsule and as large
embolic masses in the arterise recta? of the pyramidal portion. The
glomerular tufts contained relatively few. Many could be seen in the
perivascular lymph-spaces between the contorted tubules and between
the collecting tubules in the medulla. These had the typical appearance.
Bacteria could be seen in the endothelial cells of the capillaries, within
the secreting cells of the cortical tubules, and in the lumina. When
enclosed in cells they were, as a rule, smaller, often appearing as slender
bacilli with polar staining, and sometimes as a diplococcus form with
a distinct halo. In the cells they stained badly, and seemed to be in a
state of absorption. Fig. II., Plate IV.

Babbit C, killed one hour after.

19

Bacilli were much fewer in number, being mainly confined to the
interlobular and straight vessels, but also being seen as shadows in the
pr.renchymatous cells of the convoluted tubules.

Babbit, D., killed four hours after.

The bacteria were seen largely in the interstitial substances between
the convoluted tubules ; many were within the excreting cells showing
as faint diplococci or short bacilli with polar staining. Some were
also seen beneath the basement membranes of the tubules, and with the
lumina.

The glomerular capillaries contained very few. The diplococcus
form was noted to be much smaller than the usual colon type. Cul-
tures from the urine were sterile.

Babbit E., killed 21 hours after.

Marked parenchymatous degeneration of the secreting cells ; very few
bacteria could be seen, mostly in shadows beneath the basement mem-
brane of the contorted tubules.

These simple facts are in accordance with the observations of Chiari,
^danii and others. After the intravenous inoculation of an animal,
bacteria are found in all organs, principally the liver, kidneys, spleen
and bone-marrow, but after a short time, chiefly in the liver. It is im-
portant to note that the endothelial cells of the capillaries and the secret-
ing cells of the convoluted tubules in the kidney, have the power of in-
gesting bacteria, rendering them for a time, at least, inert. The same
thing has been shown by Adami in the liver, when within 15 minutes
after inoculation, he observed bacteria within the endothelium, and in
two hours within the liver cells themselves. I have seen the same in-
gestion of germs by the secreting cells of the contorted tubules of the
kidney in the case of acute nephritis in lobar pneumonia, and in septi-
caemia. (Fig. 1, Blate IV.) The tendency of the bacillus to assume a
diplococcus form is noteworthy.

Thus the liver and kidney parenchyma are shown to play an import-
ant part in the resistenee of the organism against bacterial invasion.
This resisting power on the part of the parenchyma, however m*y be
diminished in many ways, particularly by chemical and bacterial toxins,
thus permitting the more rapid passage of germs through the organs.

Cavazzani, (Ueber die Absonderung der Bakterien durch die Nieren.
Ctbl. f. allg. Path. u. path. Anat., iv. ii., 1893), found that after the in-
jection into an animal of toxic substances such as cantharides or pyro-
gallic acid, the kidneys permitted the passage of bacteria through their
substance much more quickly than in the case of animals which were
not so treated.

That the kidneys are a most important factor in the elimination of
germs from the body is beyond question ; they may do this when least

20

suspected. Enriquez found streptococci in the urine, of a person whom
lie thought healthy. On more careful examination, however, a minute
abscess was found on our finger : this gave a pure growth of streptococci.

Whether a norma] kidney will allow germs to pass through it is a
moot point. Ortli thinks thai it may do SO, when no gross esion can
be made out.

Neumann and Konjajeff, on the other hand assume that there must
be a local kidney lesion. However, this may be, certainly the kidney

does permit the passage of bacteria when e cannot find a lesion more

severe than cloudy swelling.

It is certain, however, that for a time at least, the kidney cells are
able to attack the bacteria, apparently digesting them, and rendering
them inert. Later, when the vitality of the excreting cells is sufficiently
lowered, living germs are to be found in the urine.

This view is in accord with that of Sherrington, (Journal of Pathology
and Bacteriology, Feb., 1893), who found that the escape of bacteria
tended to occur in the late stages of a communicated disease, and not
immediately upon the introduction of them into the circulation. This
means that only after the tubular epithelium has been depressed by
soluble toxins, do the cells become pervious to the germs, lie. how-
ever, concludes that his experiments do not support the suggestion of
Cohnheim, that the body protects itself against bacterial action by the
excretion of living germs through the kidney and liver.

In the light of the present study we get an entirely new conception of
the process at work in the case of Brightfs Disease. All cases, acute and
chronic, are brought into the category of 'infections.' The nature of
the infecting germ varies; in the acute forms it is usually the specific
germ causing the primary disease although in some cases it is the colon
bacillus. In the chronic cases, in the gnat majority, it is the colon
which is the infective agent, hut there is some e\*idence to favor the
view that a U'\v germs like the bacillus Pfeifferi and the diplococcus
lanceolatus are capable of producing fibrosis. Two processes are at
work, parenchymatous degeneration and productive inflammation.
Parenchymatous degeneration alone is not to be regarded as a true
nephritis, but is the result of chemical and bacterial toxins, bringing
about injury to the secreting epithelium. Whether inflammatory in-
filtration occurs in addition or not depends on several factors.

1st, the number and size of the infecting germs.

2nd, the degree of virulence.

3rd, their specific qualities.

If the germs are few in number and of small size, they may pass
through the glomerular capillaries, and merely produce degeneration and
necrosis without further change. If they be sufficiently numerous to

21

block the vessels or get into the capillary endothelium, then we get
local inflammatory reaction with acute leucocytic infiltration.

A germ of low virulence brings about a low grade of infiltration, but
if of high virulence, and in sufficient numbers, extreme degeneration
is brought about, and interstitial abscess formation. The inherent
quality of the germ is of importance. Thus sonic germs nearly always
bring about suppurative inflammation, while others are more apt to
bring about a reparative fibrous hyperplasia. This has been shown
recently by Yon Wunscheim, in a study of pyelonephritis. When the
infection was due to streptococci or staphylocri, suppuration resulted,
but when it was due to the B. Coli, he saw distinct evidences of con-
nective tissue production. However, these differences probably have
something to do with the virulence and abundance of the bacteria con-
cerned.

In the chronic cases where fibrous hyperplasia is beginning to make
its appearance, just as in the leucocytic infiltration of the acute cases,
we see the fibrous change beginning about the afferent and interlobular
vessels associated with vascular dilatation, followed later by compression
and degeneration of the glomeruli, atrophy of the tubules, and the for-
mation of casts. Interstitial proliferation then is the key-note of the
process. This proliferation is the more readily brought about since there
is present a germ which tends to nroduce fibrous hyperplasia ; present
too, in very small numbers in an infective process probably extending
over years. And further, the progressive nature of the lesion is due
to continuous action of a germ which has been shown to be present in
all stages. I consequently cannot believe as Hoist does, that a toxin can
go on acting so as to bring about a fibrous hyperplasia, long after the
original infection has disappeared. That an infective agent, like the B.
Coli, for instance, can be shown to be the corpus delicti, in all the stages
of Bright's, explains the anatomical distribution of the lesions, the
pathological process, and the etiological momenta, in a way that none of
the usual theories have been able to do. We must, I think, assume that
before the germs can act there must be a lowering of the vitality of the
epithelium through toxins or otherwise.

To explain the nephritis that occurs in a chronic disease in the case
of the constitutional diseases, diabetes, tuberculosis, etc., we have mostly
a degenerative process from toxic influences, or a mixed infection. In
carcinoma we must look for secondary infection or an intestinal lesion.
The idiopathic or 'cryptogenetic cases, are most likely to be of the
nature of infections from the alimentary tract, a mere congestion of
this tract being sufficient.

To sum up, my conclusions are as follows: —

1. The different forms of Bright's Disease are to be regarded as

22

various stages m the .-nine general process, there being a unity prevailing

the whole pathological picture.

II. All forms of nephritis are due in the immense majority of cases
to infective agents ; the acute, to the usual specific germs of the primary
disease, and the chronic, as a general rule, to the bacillus coli. though
other germs may, sometimes, be concerned.

III. Acute interstitial inflammation and subsequent connective tissue
hyperplasia are the key-note of the process; this is, however, preceded
by parenchymatous degeneration.

IV. The point of invasion by the B. Coli is the gastro-intestinal tract;
for other germs it may be various.

V. The liver and mesenteric glands are the first barriers of defence;
and the endothelial cells of the capillaries and secreting tubules of the
kidney have the power of ingesting bacteria, this being an attempt at in-
hibition and elimination.

PLATK I. Fig. I.

Eeichert oil-immersion TVth. Without eyepiece.
Kidney. Area of round-celled infiltration showing minute diplocoec
at A. and B.

Patient, a male, aged 27 ; clinically a chronic nephritis of one year's
standing ; thei-e was a history of repeated exposure to wet and cold.
The kidneys were of the large white variety passing into the con-
tracted stage ; microscopically a chronic diffuse nephritis.

PLATK I. Fig. II.
Reichert ^th.

Kidney. Area of round-celled infiltration showing a diplococcus at C
Patient, a female, aged 21 ; clinically a chronic nephritis of 8 months
standing ; onset insidious.

Kidneys were extremely contracted ; microscopically extreme inter-
stitial nephritis.

PLATK II. Fig. I.
Reichert, TLt 1 i .

Original growth of B. Coli from the urine of a patient with advanced
chronic interstitial nephritis.

Shows colon bacilli of the ordinary type, bacilli with polar staining,
cocci and diplococci ; also chains of minute bacilli with polar staining.
Taken from a flask in which the urine had been allowed to stand for
3 days at 37°(\

PLATE II. Fig. II.
Reichert ^th.

The same organism as last transferred to 1.5 per cent, acid agar for
48 hours.
Now single coeci and diplococci.

PLATE I, FIG. I.

C

PLATE I. FIG. II.

PLATE II. FIG. I.

PLATE II. FIG. II.

PLATE III. FIG. I.

»'

' ^JP

':

u

PLATE III- FIG. II.

I \

PLATE IV. FIG. I.

PLATE IV. FIG. II.

23

PLATE III. Fig. I.
Reichort ^th.

Same as last on kidney bouillon 1.5 per cent. acid. Ordinary colon
forms and minute diplococci.

Note. — The diplococci in the sections and in the slides from the
cultures when viewed by transmitted electric light were seen to bo
really minute short bacilli with polar staining.

PLATE III. Fig. II.
Eeichert y^tb.

Acute parenchymatous nephritis in acute lobar pneumonia.
Figure shows part of a glomerulus with numerous diplococci of
pneumonia in a capillary.

PLATE IV. Fig, I.

Eeichert Tl¥th.

Acute parenchymatous nephritis in acute lobar pneumonia.
Diplococci of pneumonia in the lumen of a contorted tubule. Under
the microscope, however, the diplococci could be seen as shadows
within the secreting cells.

PLATE 1Y. Fig. II.
Eeichert ygth.

Kidney showing secreting tubules from an experimental rabbit half
an hour after inoculation with pure growth of B. Coli.
The bacilli are seen as diplococcus like forms within the secreting
cell shown at A.

\<>te. — For the above photographs I am greatly indebted to Dr. David
Patrick who has admirably succeeded in a difficult task.