Manifestations of Hepatic Dysfunctions

• The two major consequences of portal hypertension are ascites and varices.
• Hepatic dysfunction results from damage to the liver's parenchymal cells, either from primary liver diseases or from obstruction of bile flow or derangements of hepatic circulation.
• Splenomegaly (enlarged spleen) with possible hypersplenism is a common manifestation of portal hypertension.
• Liver dysfunction may be acute or chronic, with chronic liver disease being far more common.
• Chronic liver disease, including cirrhosis, is the 12th leading cause of death in the United States among young and middle-aged adults.
• At least 40% of deaths due to chronic liver disease are associated with alcohol use.
• The rate of chronic liver disease for men is twice that for women, and chronic liver disease is more common in Asian and African countries than it is in Europe and the United States.
• Compensated cirrhosis, in which the damaged liver is still able to perform normal functions, often goes undetected for extended periods, and as many as 1% of people may have sub clinical or compensated cirrhosis.
• Approximately 80% of patients diagnosed with cirrhosis compensate and remain asymptomatic for the next 10 years.
• Disease processes that lead to hepatocellular dysfunction may be caused by infectious agents such as bacteria and viruses and by anoxia, metabolic disorders, toxins and medications, nutritional deficiencies, and hypersensitivity states.
• The most common cause of parenchymal damage is malnutrition, especially that related to alcoholism.
• Even patients who are overweight or have obesity may suffer from not only malnutrition related to liver disease, but also from sarcopenia, the significant loss of muscle tissue.
• Sarcopenia is associated with increased morbidity and mortality in patients with end-stage liver disease (ESLD).
• The parenchymal cells respond to most noxious agents by replacing glycogen with lipids, producing fatty infiltration with or without cell death or necrosis.
• This is commonly associated with inflammatory cell infiltration and growth of fibrous tissue.
• Cell regeneration can occur if the disease process is not too toxic to the cells.
• The result of chronic parenchymal disease is the shrunken, fibrotic liver seen in cirrhosis.
• Due to the decreased amount of bile in the intestinal tract, the stools become light or clay colored.
• The "benign" cholestatic jaundice of pregnancy, with retention of conjugated bilirubin, is probably secondary to unusual sensitivity to the hormones of pregnancy.
• Gilbert syndrome is a familial disorder characterized by an increased level of unconjugated bilirubin that causes jaundice.
• Phenothiazines, antithyroid medications, sulfonylureas, tricyclic antidepressant agents, nitrofurantoin, androgens and estrogens, and some antibiotics can cause jaundice.
• In general, AST, ALT, and GGT levels rise only moderately, but bilirubin and alkaline phosphatase levels are elevated.
• Other conditions that are probably caused by inborn errors of biliary metabolism include Dubin-Johnson syndrome (chronic idiopathic jaundice, with pigment in the liver) and Rotor syndrome (chronic familial conjugated hyperbilirubinemia, without pigment in the liver).
• Portal hypertension is the increased pressure throughout the portal venous system that results from obstruction of blood flow into and through the damaged liver.
• Portal hypertension is commonly associated with hepatic cirrhosis, but it can also occur with noncirrhotic liver disease.
• Regardless of whether the obstruction is intra- or extrahepatic, and regardless of its cause, bile cannot flow normally into the intestine and becomes backed up into the liver.
• Dyspepsia and intolerance to fatty foods may develop because of impaired fat digestion in the absence of intestinal bile.
• Hereditary Hyperbilirubinemia refers to increased serum bilirubin levels, resulting from any of several inherited disorders, which can also produce jaundice.
• Although serum bilirubin levels are increased, liver histology and liver function test results are normal, and there is no hemolysis.
• Gilbert syndrome affects 3% to 8% of the population, predominantly males.
• Benign recurrent intrahepatic cholestasis is a condition that can cause jaundice.
• Bile is then reabsorbed into the blood and carried throughout the entire body, staining the skin, mucous membranes, and sclerae.
• Bile is excreted in the urine, which becomes deep orange and foamy.
• The consequences of liver disease are numerous and varied.
• The skin may itch intensely, requiring repeated soothing baths.
• Increased serum bilirubin levels and jaundice may result from impairment of hepatic uptake, conjugation of bilirubin, or excretion of bilirubin into the biliary system.
• Patients with this type of jaundice, unless their hyperbilirubinemia is extreme, do not experience symptoms or complications as a result of the jaundice per se.
• Among the most common and significant manifestations of liver disease are Jaundice, portal hypertension, ascites and varices, nutritional deficiencies (resulting from the inability of damaged liver cells to metabolize certain vitamins), and hepatic encephalopathy or coma.
• Fecal and urine urobilinogen levels are increased, but the urine is free of bilirubin.
• In these patients, the bilirubin in the blood is predominantly unconjugated or free.