Fibrosis portal

Hepatobiliary disease occurs due to bile duct obstruction from abnormal bile composition and flow. Hepatomegaly, splenomegaly, and cholecystitis may be present. Hepatic steatosis may also be present due to effects of malnutrition. The progression from cholestasis (impaired bile flow) to portal fibrosis and to focal and multilobar cirrhosis, esophageal varices, and portal hypertension takes several years. Many patients are compensated and asymptomatic but maybe susceptible to acute decompensation in the event of extrinsic hepatic insult from viruses, medications, or other factors.7... 

Sinusoidal damage from cirrhosis is the most common cause of portal hypertension. The sinusoids are porous vessels within the liver that surround radiating rows of hepatocytes, the basic functional cells of the liver (Fig. 19-2). Progressive destruction of hepatocytes and an increase in fibroblasts and connective tissue surrounding the hepatocytes culminate in cirrhosis. Fibrosis and regenerative nodules of scar tissue... 

E. histolytica invades mucosal cells of colonic epithelium, producing the classic flask-shaped ulcer in the submucosa. The trophozoite toxin has a cytocidal effect on cells. If the trophozoite gets into the portal circulation, it will be carried to the liver, where it produces abscess and periportal fibrosis. Liver abscesses are more common in men than women and are rarely seen in children. Amebic ulcerations can affect the perineum and genitalia, and abscesses may occur in the lung and brain. 

Portal hypertension most commonly occurs as a consequence of chronic liver disease. Portal hypertension Is caused by Increased blood flow within the portal venous system and increased resistance to portal flow within the liver. Splanchnic blood flow is increased in patients with cirrhosis due to low arteriolar resistance that is mediated by increased circulating vasodilators and decreased vascular sensitivity to vasoconstrictors. Intrahepatic vascular resistance is increased in cirrhosis due to fixed fibrosis within the spaces of Disse and hepatic veins as well as reversible vasoconstriction of hepatic sinusoids and venules. Among the consequences of portal hypertension are ascites, hepatic encephalopathy, and the development of portosystemic collaterals—especially gastric or esophageal varices. Varices can rupture, leading to massive upper gastrointestinal bleeding. 

A 49-year-old woman developed jaundice after taking pioglitazone 30 mg/day for 6 weeks, and after 3 weeks the alanine transaminase was 131 U/l and aspartate transaminase 79 U/l (106). Tests for viral hepatitis were negative. A liver biopsy showed marked portal edema, patchy chronic inflammation, a cellular infiltrate, and marked bile duct proliferation. There was no fibrosis. The laboratory results worsened after pioglitazone was withdrawn, and 1 month after withdrawal the bilirubin reached a peak of 585 pmol/1. Over the next 8 weeks the symptoms and laboratory tests improved, and after 6 months her condition was the same as when she had started to take pioglitazone. 

A 62-year-old woman with normal hver function tests took troghtazone 400 mg/day in combination with gli-clazide 80 mg/day and pravastatin (125). After 9 months her transaminases were slightly above normal, but the HbAic was 7.0% and treatment was continued. Her hver enzymes were measured monthly and after 19 months rose abruptly. Troghtazone was withdrawn immediately and she received insulin. Her hver enzymes improved rapidly. A biopsy showed hepatic necrosis round the central vein and a mild inflammatory infiltrate and fibrosis in the portal area compatible with protracted acute hepatitis. A lymphocyte stimulation test and a skin test were negative for troghtazone. 

Late adverse effects include hepatic dysfunction, with altered liver function tests and hyperbilirubinemia. After prolonged use of nicotinic acid and nicotinyl alcohol, histological changes, for example parenchymal cell injury, portal fibrosis, cholangitis, cholestasis, biliary casts, and lymphocytic infiltrations around the bile ducts, have occasionally been seen. 

I. Grinko, A. Geerts, and E. Wisse, Experimental biliary fibrosis correlates with increased numbers of fat-storing and Kupffer cells, and portal endotoxemia, J. Hepatol. 23 449-458 (1995). 

Hepatic Fibrosis/Cirrhosis Fibrosis usually results from chronic inflammation which can be the result of continuous exposure to a variety of hepatotoxic chemicals such as organic arscnicals, vinyl chloride, or high doses of vitamin A (Zimmerman, 1999), chronic ethanol ingestion and nonalcoholic fatty liver disease. Fibrosis usually occurs around the portal area, in the space of Disse, and around the central veins. This results in loss of liver architecture and function. The hepatocytes are replaced with fibrous material and thus there is hepatocyte loss. Periportal fibrosis may lead to portal hypertension. 

Fig. 7.16 Inactive, micronodular (drug-related) cirrhosis with fine pathways of connective tissue clinically and histologically definable as liver fibrosis (sonographically no signs of portal hypertension)...

Various infectious, toxic or immunological lesions lead to a presinusoidal block in adults. From a primary endothelial lesion, endophlebitis ensues. Rich in fibres and deficient in cells, it is ultimately responsible for the obliteration and even disappearance of the portal branches. Obliterative portal venopathy (N.C. Nayak et al., 1969) with portal and periportal fibrosis and subsequent perisinusoidal sclerosis is referred to as hepatoportal sclerosis (W P. Mikkelsen et al., 1965). This is a complex disorder involving splenomegaly, hypersplenism and portal hypertension, which has also been described as non-cirrhotic portal fibrosis (XL. Boyer et al., 1967) or idiopathic portal hypertension (K. Okuda et al., 1982). (I2l, 127) Band s syndrome (7) probably fell into this group ... 

Vitamin A intoxication Prolonged and marked vitamin A intoxication leads to a substantial increase in individual Ito cells. This in turn causes constriction of the sinusoids the accompanying fatty degeneration of the hepatic cells supports this obstructive effect. The Ito cells are responsible for perisinusoidal fibrosis. The liver surface is strikingly smooth despite marked portal hypertension (often with considerable oesophageal varices). (119) (s. figs. 14.2, 14.3)... 

However, this reaction is generally accompanied by fibrosis and increased elasticity of the vessel wall. Portal hypertension leads to the dilation and reopening of veins which connect the portal vein system to the superior or inferior vena cava. Hence collateral circulation develops in the region of the oesophagus and gastric fundus as well as in the intestinal tract, retroperito-neum, lungs, spleen and kidneys, and at the anterior abdominal wall. (s. p. 253) (s. tab. 14.10) (s. figs. 7.5 14.11, 14.12 16.9)... 

Shlbayama, Y., Nakata, K. The relation of periportal fibrosis to portal hypertension. J. Hepatol. 1990 11 313-317... 

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