I N F E C T I V E H E P A T I C JAUNDICE 58 1

unless the fixation is extremely prolonged or is done immediately the film is made ; if the film is left to dry in the air for a quarter of an hour before fixation, the granules become resistant to ordinary treatment with methyl aIcohol, ethyl alcohol or xylol, though not to ether or chloroform.

The theoretical aspects of the lipoid staining of the granules, the relationship to the oxydase reaction and the previous literature are discussed by Rnyter (1933), Heringa and Ruyter (1935), Bacsich (1935-3G), Bunting (1938) and Ringoen (1938). The chemical constitution of the lipoid has been investigated by Boyd (1935).

REFERENCES. BACSICA, P. . . . . . . BL-NTIXG, C. H. . . . . . BOYD, E. $1. . . . . . HERINGA, G. C., AND RUYTER, ’ J. H. C. LISOX, L. . . . . . . RINGOES, A. R. . . . . .

RUYTER. J. H. C. . . . .

J . Anat. , 1935-36, Ixx. 267. In Handbook of hematology, ed. by H.

Downey, London, 1938, vol. i. p. 165. Surg. Gynec. Obstet., 1935, Ix. 205. Acta, Brev. Neerland., 1935, v. 118.

C: R. Soc. biol., 1934, cxv. 202. In Handbook of hematology, ed. by H.

Downey, London, 1938, vol. i. p. 184. 2. ZeZZforsch., 1933, xix. 106.

616.36-008. 5-091 THE MORBID ANATOMY O F A SPORADIC CASE O F

INFECTIVE HEPATIC JAUNDICE.*

HUGE BARBER and G. R. OSBORN. From the Derbyshire RoyaE In$rmnry.

(PLATE LXXXVII.)

We ha-ve had a very unusual opportunity of studying the morbid anatomy of simple catarrhal jaundice or, as we should prefer to call it, infective hepatic jaundice. A man already indisposed fell down some steps, his indisposition passed on to jaundice, but he died as the result of a head injury. Death took place on the seventh day of the jaundice.

Case history. L. S., aged 38 years, a cotton mill worker, had not been exposed to

chemicals and his previous health had been good. On 15th August 1937 he felt unwell in the morning with nausea and flatulence. He thought he might ‘‘ walk it off,” but on returning from two miles or so he was quite exhausted and was left lying on a couch. About twenty minutes later he was found lying unconscious at the foot of some stone steps, with his nose bleeding. He was taken by ambulance t o the Derbyshire Royal Infirmary and admitted to a surgical ward.

On examination he was a well nourished man; pulse rate G O ; temperature normal. He was restless and not fully conscious, breathing quietly, pale in appearance, with weakness of the left side of the face and bruising of the left eye. The Thwe was slight weakness of the left arm.

* Demonstrated to the Association of Physicians of Great Britain and Ireland, 7th Juno 1938.

582 H . BARBER AND G. R. OSBORN

abdominal reflexes were absent and the plantar response was extensor on both sides. A provisional diagnosis of fractured skull was made, but X-ray examination revealed nothing abnormal.

Next day he appeared to be all right again but on the third day he vomited and the urine was dark in colour. On the fourth day he was obviously jaundiced. On the sixth clay the faxes were normal in colour. On the seventh day he developed hemiplegia and the jaundice became more intense. He was profoundly ill and died on the tenth day after admission, i .e . the seventh day of the jaundice. The temperature was normal until the seventh day, when it was 99'F. It was 100 in the evening of the eighth day and 100.5 on the last day of illness.

Neither liver nor spleen was palpable.

Post -mortem examinat ion.

The emaciated body was rather deeply jaundiced. The essential cause of death was the head injury ; the jaundice appeared to have played little or no part in the fatal issue. The left eye was " black " and near this was s fracture extending to the base ; there was no displacement. There was a large contre-coup hzmorrhage in relation to the right t'emporal lobe and a right intradural hzmorrliage. The clot was partly organised, indicating that some of the hzmorrhage had been present since the head injury 10 days before.

There was no significant lesion in the thorax. Except for slight congestion of the pyloric antrum the stomach appeared

normal. The duodenum was of normal size; it was not congested and contained much tenacious white mucus. This mucus was free from bile but contained a number of droplets of bright metallic mercury. These were collected and when placed together formed about the amount present in a thermometer bulb. It was striking to see how these droplets wcre fixed in the mucus and apparently doing no harm; no mercury could be found beyond the second part of the duodenum. Later it was learned that a nurse had been shaking a thermometer beside his bed four clays before he died. It broke as she shook it and she did not know what happened to the mercury ; it evidently went into his drinking water. The presence of this mercury is of the greatest interest because it shows that there had been absolute stasis of the bile-free mucus for a t least four days before death. Microscopically the duodenum showed few changes. There was some desquamation of the surface cpithelium, ot'herwise its coats were normal ; there was no engorge- ment or inflammatory exudate. The ampulla of Vater'was filled with a loose plug of epithelia1 cells and debris.

The gall bladdor and common bile duct were collapsed and contained a little mucus only ; there was no coloured bile. The diameter of the common bile duct was 3 mm. These structures showed the usual post-mortem autolysis of the mucosa but it was clear that they had been practically normal ; there was no inflammatory exudate nor thickening.

The liver weighed 35 oz. The main lesion wa.s in the liver cells them- selves and they were most affected near the central veins of the lobules. They contained fine and coarse granules of bile pigment (fig. 1). Their nuclei showed small numbers of mitotic figures (figs. 2 and 3), on an average less than one per high power field ( x 700). More numerous than the mitotic figures were pairs of hyperchromatic nuclei which had just completed mitotic division. There was thus clear evidence of a lesion affecting the liver cells, i.e. of a hepatitis (McNee, 1919-20). The Iiupffer cells were little affected but the nuclei of the cells around the intralobular bile capillaries were prominent and their cytoplasm was packed with bile pigment. In most

JOUILNAL OB PX~BOLOGY--V~L. XLIS.

k F E C T l V E HEPATIC JAUNDICE

Frc. l.--Numerons hile capillaries are prominently outlined by inspissated bile. Note coarse and fine granule? of hile pigment in the liver cells, absence of fatty chnnger and some pyknotic nuclei. x 825.

FIG. 2.-Nucleus of a h ~ e 1 col1 undergoing FIG. 3.-Nucleils of a liver cell undergoing mitotic dlvision. Metaphnse ; some filaments mitotic division. x 1230. of the spindle con hi> rccogni~ed. J 1230.

INFECTIVE HEPATIC JAUNDICE 583

parts the bile capillaries near the central veins were distended with inspissated bde (fig. 1). I n many places this dark bile formed curious figures, presenting a superficial resemblance to mitoses. No bile was seen in the capillaries nor in the small bile ducts a t the periphery of the lobules. There was no inflammatory exudate about the lobules nor in the portal tracts. The bile ducts in the liver were well preserved, contained some uncoloured mucoid fluid and were not inflamed.

The lymph nodes in the portal fissure were enlarged ; they showed well marked general dilatation of the lymph sinuses and very slight sinus catarrh. There were no follicles with germinal centres. The pancreas showed autolysis but had evidently been normal ; there was no inflammatory exudate. The remainder of the abdomina1 organs showed few significant changes. The jejunum, ileum and appendix were normal. The large bowel contained scybala. No bile was seen in the alimentary tract.

Discussion. The essential lesion in this case appears to be in the liver cells themselves

(figs. 1-3). The region about the central vein of the lobule is most severely affected, the intermediate zone is affected in most cases while the outer zone generally appears normal. There is either a very mild inflammatory exudate or none at all in the fibrous tissue surrounding the vessels and bile ducts a t the periphery of the lobules. The bile capillaries near the centre of the lobules are mostly distended with inspissated bile (fig. 1) ; elsewhere they appear normal and contain no coloured bile. It appears most improbable that the lesions in the liver cells and bile capillaries are secondary to any lesion in the lower parts of the biliary tree. The toxic agent has evidently reached the liver by the blood stream but there is no evidence to show whether by the hepatic artery or portal vein. Why the central zone of the liver lobules is most affected is unknown ; the obvious explanation is that it is because this part of the lobule has the poorest oxygen supply. One result of the lesion in the liver lobules has been a paralysis of bile formation. The effects of this are seen in the lower parts of the biliary tree-collapsed gall bladder and bile ducts, plug of debris in the ampulla of Vater, etc. A most interesting secondary effect is the stasis and character of the duodenal mucus. We do not need to assume any hypothetical primary duodenitis to explain this.

The case most nearly analogous to ours in the literature is that of Gaskell (1933). The patient, a girl of 5 years, died from secondary haemorrhage on the third day of jaundice, which was four days after tonsillectomy. I n the discussion (p. 259) he states : “ The condition found in this case is therefore an acute hepatitis with complete absence of coloured bile from any structure in the liver, thus indicating a complete abeyance of the liver function as regards the removal of bile pigments from the blood stream. The bile duct system throughout the organ is normal and not involved in any inflammatory process.” There are interesting pathological differences between this case and ours, which may depend on the fact that our case died of a simple head injury without anaesthetic, operation or infection. Important clinically is the fact that the liver in our case was small while that in Gaskell’s case was enlarged. This evidently depended on the presence of an inflammatory exudate at the periphery of the lobules in Gaskell’s case, with greater cloudy swelling. The absence of bile pigment from the liver cells in Gaskell’s case was thought to be due to these cells being so damaged (i.e. by the “ hepatitis ”) that they could not pass on to the bile capillaries any of the bile pigment brought to them by the capillary blood vessels. Neither case showed fatty changes in the liver cells.

584 H . BARBER A N D 6. R. OSBORN

Hurst and Simpson (1934) review the subject and record a case dying on the eighth day of jaundice in which there was an inflammatory exudate at the periphery of the lobules, reduced bile formation and normal lower bile passages. Hurst’s interesting observations with the duodenal tube are coniirmed by the state of the duodenum in our case, but, as also with Brugsch’s results (which they quote), great care is needed to distinguirh between cause and effect when interpreting the examination of the duodenal coiitents. They consider at length the evidence for the occurrence of two types of lesion-true catarrhal jaundice and primary hepatic necrosis or as Barber (1937) has termed it “ infective hepatic jaundice.” The Gallipoli cases described by W-illcox (1916, 1919) point to a true catarrhal jaundice and similar cases occur here.

On 28.12.38, for example, one of us (G. R. 0.) made an autopsy on a woman of 47 who died deeply jaundiced eight weeks after the onset of an illness so violent as to be regarded at the time as food poisoning. There was much swelling and cedema about the duodenum, which showed a streptococcal infection. The gall bladder contained mucus and some coloured bile which showed large numbers of streptococci and B. coli. There wa3 an inflammatory exudate a t the periphery of the liver lobules but a general liver necrosis.

Lakin (1938) has reviewed the subject and is prepared to consider the possibility of two varieties of “ catarrhal jaundice.” Cullinan (1936) described a serics of cases of subacute necrosis of the liver in which the infective agent may have been of the same nature as that of infective hepatic jaundice. More recently (1938-39) he has given a full review of the subject, in which he refer.; to our case.

The liver weighed 30 oz.

Conclusions. We believe that the majority of cases of benign jaundice are the result

of a true hepatitis but that the opportunity for examination of such cases post nzortem is quite exceptional. Further, the second post-mortem briefly recorded above supports Hurst’s view that there are two distinct disea.;e.;- mild hepatitis and true catarrhal jaundice. We think the latter is less common clinically and is essentially due to a secondary infection of the bile passages. Probably the majority of these patients recover although a few succumb. We believe that the hepatitis cases (“ infective hepatic jaundice ”), both epidemic and sporadic, are due to some unknown agent which infects the liver and that the disposing cau.;e of true catarrhal jaundice is probably a gastro-intestinal infection.

We are indebted to Professor J. W. McNee for many suggestions in preparing this paper and t o Afr J. J. G. Bates for the photomicrographs.

REFERENCES. BARBER, H. . . . . . . Infective hepatic jaundice, Brit. .Med. J . ,

1937, i. 67. CULLINAN, E. R. . . . . Icliopathic jaundice (often recurrent)

associated with subacute necrosis of the liver. Saint Bartholomew’s Ho.sp. Rep., 1936, Ixix. 55.

9 , . . . . The epidemiology of jaundice. Proc. Roy. Soc. Med., 1938-39, xxxii. 933.

GASKELL, J. F. . . . . . The changes in the liver in a fatal ca-;e of epidemic “ catarrhal ” jaundice. This Journal, 1933, xxxvi. 257.

GASTRIC M UGOSAL SLOUGHS 585

HURST, A. F., AND SIMPSON, Catarrhal jaundice and mild hepatic necrosis : their pathoIogy and diagnosis. Guy’s Hosp. Rep., 1934, lxxxiv. 173.

LAKIN, C. E.. . . . . . Toxic and infective jaundice. Brit. Med. J., 1938, ii. 437.

XCNEE, J. W. . . . . . Spirochaetal jaundice : the morbid anatomy and mechanism of production of the icterus. This Journal, 1919-20, xxiii. 342.

WILLCOX, W. H. . . . . The epidemic jaundice of campaigns. Brit. Med. J. , 1916, i. 297.

3, . . . , On jaundice with special reference to types occurring during the war. Third Lett- somian Lecture.

c. I(.

Lancet, 1919, i. 930.

616.33-072. 2-008. 854

A NOTE ON THE OCCURRENCE OF PIECES O F SLOUGHED GASTRIC MUCOUS MEMBRANE I N ASPIRATED GASTRIC JUICE.

J. C. HAWKSLEY.

From University College Hospital Medical School, London.

(PLATE LXXXVIII.)

A number of methods exist by which it is possible to study the histology of normal and pathological gastric mucous membrane ; upon these methods is based the study of the changes in gastritis in its various forms. Any new method of approach, however slight its contribution to knowledge, is worth considering, and the following note describes an elementary investiga- tion upon material which I believe to have been neglected by other observers.

Mucosal sloughs.

Prior to the performance of gastroscopy, it is the custom to empty any resting juice from the stomach by aspiration with a soft rubber tube. If gastroscopy is carried out before breakfast, this juice will have been collect- ing for a variable period as fasting juice. In approximately 200 consecutive gastroscopies, one or more mucosal sloughs have been found in the aspirated fluid in 21 cases, or about 10 per cent. These sloughs have varied in size from a pin’s head to a strip about 1 cm. in length, but all have been easily recognisable objects in the juice. It might seem probable that these have been removed from the mucous membrane either by the trauma of the tube or by the force of aspiration, but this may be discounted on the following grounds :-

1. The process is gentle, and, with the gullet anzsthetised, does not as a rule give rise to retching.

2. In a vascular mucosa, removal of even a small piece by trauma would produce bleeding and the extravasated blood would be observed in the juice and by subsequent gastroscopy. This has only happened twice in the 21 cases, and in each the blood probably came from a peptic ulcer.

JOURN. OF PATE.-VOL. XLIX. 2 P