FINE STRUCTURE OF THE LIVER IN DUBIN-JOHNSON SYNDROME

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1 THE KURUME MEDICAL JOURNAL Vol.12, No.2, 1965 FINE STRUCTURE OF THE LIVER IN DUBIN-JOHNSON SYNDROME KYUICHI TANIKAWA The Second Department Medice, Kurume University School Medice, Kurume, Japan. (Received for publication August 26, 1965) The creasg use liver biopsy technique recent years, has caused Dub-Johnson syndrome to become a relatively common disease much attention has been paid to characteristic liver cell its relationship to jaundice. This report is devoted to electron microscopic observation liver this disease a special attention given to changes excretory organelles, a discussion concerng mechanism jaundice this disease. MATERIALS AND METHODS Liver biopsy specimens taken from three patients were diagnosed as Dub-Johnsou syndrome by ir histological fdgs dicatg characteristic liver cells. In every cases re was a history recurrent episodes jaundice at an early age. Serum bilirub level at time biopsy was 4.05 mg (direct : 3.09 mg) Case 1, 1.2 mg (direct: 1.0 mg) Case 2, 3.2 mg (direct : 2.2 mg) Case 3, B. S. P retention was creased all cases. For electron microscopy, liver biopsy specimens were fixed a cold 1 per cent osmium tetroxide solution, buffered to PH 7.4 Sodium Veronal acetate. The specimens were n dehydrated graded alcohols embedded Epon 812. Ultra-th sections were cut glass knife on a Porter-Blum microtome, staed uranyl acetate, examed under a HU-11 electron microscope. RESULTS 1) Light microscopic observation (Fig. 1) Liver cells contaed numerous brown, maly centrolobular a. These were also Kupffer cells. Liver cell cords were well preserved no abnormalities were noted except deposition granule. 2) Electron microscopic observation (Figs ) Electron microscope revealed characteristic this disease to be round or oval, electron, sized from 0.5 Đ to 2.5 Đ diameter, 86

2 FINE Fig. Fig electron ferrit-like gras Some mitochondria show endoplasmic, cytoplasm many Most 87 SYNDROME brown, also maly Kupffer seen cells. micrograph. ~ large decreased OF DUBIN JOHNSON Light micrograph. The liver cells conta numerous centrolobular a. These Electron Four STRUCTURE number. to have reticulums characteristic liver larger cell. myel-like agranular The Dub-Johnson matrix syndrome, se structure or (at arrows). The rough surfaced relatively vacuoles contas various sizes.

3 88 KYUICHI Fig. 3. Electron One micrograph. ~ membranes (at arrow). appearance (B), is slightly seen TANIKAWA dilated Golgi Dub-Johnson Many bile loss svndronie its cytaplasm microvilli,. Fe gras larger occasionally matrix. seen surrounded vacuoles liver electron cell by. double lamated Bile canaliculus apparatus. delimited by a sgle surroundg membrane, distributed liver cell. The matrix se contaed fe is granule, have a double surroundg Anor type electron, cytoplasm, mostly around vacuoles diffusely cytoplasm a great many ferrit-like various membrane considered as bile canaliculus sizes. These or a clistae-like structure bile, was also. These bile appearance, frequently were seen vacuoles mostly lamated case 1. Mitochondria apped to be fairly normal appearance, however, myel-like structure or electron were occasionally matrix. The smooth surfaced endoplasmic reticulum was relatively predomant number rough surfaced apped to be reduced number. About one third loss ir microvilli canaliculus, However, bile canaliculi were more or less dilated stunt or a substance was frequently seen lumen rupture termal bar or communication between bile

4 FINE Fig. 4. Electron Bile canalicuelus decreased number STRUCTURE OF DUBIN JOHNSON SYNDROME 89 micrograph. ~ canaliculus fe Disse's is dilated space frequently seen was complete not noted. contaed loss its microvilli electron lumen. The Golgi fe apparatus apped to be it. DISCUSSION The nature characteristic liver cell DubJohnson syndrome has not been elucidated. Most histochemical studies have dicated that y probadly lipusc or lipochrome-like substane, but some reports (1) (2) state seem to resemble melan. Histochemistry s difficult human identify tissue has not been thoroughly nature by this technique established it seems to be : biochemical analysis se after isolation by high power centrifugation liver homogenate would yield more formation on ir nature. Morphological characteristics se have been fully described by Miwa, Kobayashi Ichida, our observations were similar to ir reports. These is a controversy morphological relationship organelles se

5 90 KYUICHI TANIKAWA characteristic Dub-Johnson syndrome. Novikf ors reported a close relationship se to lysosome because ir acid phosphatase activity. However, ors have paid more attention to mitochondria because double surroundg membrane or clistae-like structure which found occasionally. Recently, Hunter found to have completely disapped after an fection liver by hepatitis virus, however, y reapped three months later. It is regrettable that an electron microscopic study was not done on this patient, for it may have been possible to determe organelles from which se reapped. Dub reported no obvious crease such liver cell durg course disease. This fdg suggests that should be elimated eir via blood stream or bile order to be dynamic equilibrium. Our observations revealed highly electron substance bile canaliculus Golgi apparatus, suggestg a passible route excretion. In our cases, especially one a high grade hyperbilirubemia, bile were frequently cytoplasm liver cell contag characteristic Dub-Johnson syndrome. Bile easily distguished morphol ically from Dub-Johnson syndrome, sce y maly located around bile canaliculus appear to be mostly lamated vacuoles. Deposition bile cytoplasm implies tracellular cholestasis, such tracellular cholestasis is commonly seen tra- extrahepatic obstructive jaundice degree tracellular cholestasis is known to be well correlated grade hyperbilirubemia. Frequent observation altered bile canaliculi is important etiological consideration. These changes have been mentioned some reports, but ceut too much attention. Though it is not defite wher se canaliculur alterations due to congenital fragility or secondary change, such changes highly suggestive impaired bile excretion. Schoenfield demonstrated a defect hepatic excretion bilirub this disease by a bilirub load test. It has been well established that B. S. P retention is creased this disease, but conjugatg mechanism has been unimpaired. These fdgs by morphological, physiological or biochemical studies suggest that ma defect this disease is excretion mechanism. It seems reasonable to postulate from present observation, that because relative ability excretion due to impaired functions bile canaliculus or excretory organelles, ref lux conjugated bilirub, after stagnation liver cell, to blood stream, is an important factor development jaundice this disease. SUMMARY The liver biepsy specimens taken from three patients Dub-Johnson syndrome were studied under electron microscope. About one third bile canaliculi were found to be more or less dilated stunt or loss microvilli. Bile were frequently cytolasm liver cell contag characteristic Dub-Johnson syndrome. The mechanism jaundice this disease has been discussed light se observations,

6 FINE STRUCTURE OF DUBIN-JOHNCON SYNDROME 91 REFERENCES 1) BYNUM, W. T. : Mavero hepatic icterus (black liver jaundice). Gastroenterology, 33 : 97, ) MASUDA, M., BT AL. : Dub-Johnson syndrome. Saish igaku, 18 : 1087, ) NOVIKOFF, A. B. AND ESSNER, E., : The liver cell. Some new approaches to its study. Am. J. Med.29 : 101, ) ESSNER, E. AND NOVIKOFF, A. B. : Human hepatocellular s lysosomes. J. Ultrastruct. Res. 3: 374, ) ICHIDA, F. AND Funahashi, H. : Electron microscopic observation on liver cells cases Dub-Johnson syndrome. Acta Hepato-spleno-logica, 11 : 332, ) MIWA, S, ET AL. : Dub-Johnson syndrome. Jap. J. Gastroenterol, 55 : 691, ) KOBAVASHI, J. : Electron microscopic fdgs pnchymal liver cells Dub-Johnson syndrome special reference to liver cells morphological study for its jaundice. Jap. J. Gastroenterol. 59 : 209, ) HUNTER, F. M. ET AL. : Hepatitis resultg mobilation hepatic a patient Dub-Johnson syndrome. Gastroenterology, 47 : 631, ) DUBIN, I. N., Chronic idiopathic jaundice : A review fifty cases. Am. J. Med., 24: 268, ) TANIKAWA, K : Electron microscopic observation cholestasis viral hepatitis special attension to mechanism jaundice. proceedg II world congress gastroenterology, Munich 1962, III : ) TANIKAWA, K. : Pathogenesis trahepatic obstructive jaundice. Saish-igaku. 18: ) SASAKI, H. AND ICHIDA, F., : Electron microscopic studies cholestasis. Ann. Rep. Insit. Virus Res. 4 : 172, ) Electron microscopic observation on human liver durg cholestasis. Orli, F., Acta. Hepato-splenol. 9 : 155, ) SCHOENFIELD, L. J. ET AL. Studies chronic idiopathic jaundice (Dub-Johnsonn syndrome). Gastroenterology 44: 101, ) METCE, w., ET AL. : Bilirub glucuronyl transferase activtiy liver disease. J. Lab & Cl. Med. 64 : 89, 1964.