PORTAL HYPERTENSION

Increased resistance to portal blood flow may develop in a variety of circumstances, which can be divided into prehepatic, intrahepatic, and posthepatic causes. The major prehepatic

conditions are obstructive thrombosis and narrowing of the portal vein before it ramifies within the liver. Massive splenomegaly may also shunt excessive blood into the splenic vein. The

major posthepatic causes are severe right-sided heart failure, constrictive pericarditis, and hepatic vein outflow obstruction. The dominant intrahepatic cause is cirrhosis, accounting for

most cases of portal hypertension. Far less frequent are schistosomiasis, massive fatty change, diffuse fibrosing granulomatous disease such as sarcoidosis and miliary

Figure 18-3Schematic of stellate cell activation and liver fibrosis in comparison to the normal liver. Kupffer cell activation leads to secretion of multiple cytokines; cytokines also may be

released by endothelial cells, hepatocytes, and inflammatory cells entering the liver (not shown). These cytokines "activate" stellate cells, whereby they loose their lipid droplets (which are

present in the quiescent state) and acquire a myofibroblastic state. Stellate cell proliferation is stimulated in particular by platelet-derived growth factor (PDGF); tumor necrosis factor

(TNF) is a potent stimulant of the change to a myofibroblastic phenotype. Contraction of the activated stellate cells is stimulated by endothelin-1 (ET-1). Deposition of extracellular matrix

(fibrogenesis) is stimulated especially by transforming growth factor b (TGF-b). Chemotaxis of activated stellate cells to areas of injury, such as where hepatocytes have undergone

apoptosis, is promoted by PDGF and monocyte chemotactic protein-1 (MCP-1). Kupffer cells also are a major source of TNF released into the system circulation. (Schematic based on

concepts presented in Friedman SL: Molecular regulation of hepatic fibrosis: an integrated cellular response to tissue injury. J Biol Chem 275:2247–2250, 2000; and Crawford JM:

Cellular and molecular biology of the liver. Curr Op Gastroenterol 13:175–185, 1997.)

Figure 18-4The major clinical consequences of portal hypertension in the setting of cirrhosis, shown for the male. In women, oligomenorrhea, amenorrhea, and sterility are frequent,

owing to hypogonadism.

Figure 18-5Bilirubin metabolism and elimination. 1, Normal bilirubin production from heme (0.2 to 0.3 gm/day) is derived primarily from the breakdown of senescent circulating

erythrocytes, with a minor contribution from degradation of tissue heme-containing proteins. 2, Extrahepatic bilirubin is bound to serum albumin and delivered to the liver. 3,

Hepatocellular uptake and (4) glucuronidation in the endoplasmic reticulum generate bilirubin monoglucuronides and diglucuronides, which are water soluble and readily excreted into

bile. 5, Gut bacteria deconjugate the bilirubin and degrade it to colorless urobilinogens. The urobilinogens and the residue of intact pigments are excreted in the feces, with some

reabsorption and excretion into urine.

TABLE 18-3-- Causes of Jaundice

Date: 2016-04-22; view: 817