THE MERCK MANUAL, Sec. 4, Ch. 38, Clinical Features Of Liver Disease

[Guest guest]

http://www.merck.com/pubs/mmanual/section4/chapter38/38g.htm

This

Other Symptoms And Signs Of Liver Disease

SYSTEMIC ABNORMALITIES

Anorexia, fatigue, and weakness are common features of liver disease caused by hepatocellular dysfunction. Fever may occur, especially in viral or alcoholic hepatitis, but rigors are rare and, in a jaundiced patient, suggest biliary obstruction with cholangitis. Profound anorexia and nausea are especially common in viral and alcoholic hepatitis. Marked deterioration of general health and development of a cirrhotic habitus (ie, wasted extremities, protuberant belly) often signal advanced cirrhosis.

SKIN AND ENDOCRINE CHANGES

Patients with chronic liver disease can develop several cutaneous abnormalities. Spider nevi (vascular spiders), palmar erythema, and Dupuytren's contractures are common, especially in alcoholic cirrhosis. In hemochromatosis, deposition of iron and melanin makes the skin slate gray or bronze. Chronic cholestasis often causes muddy skin pigmentation, excoriations from constant pruritus, and cutaneous lipid deposits (xanthelasmas or xanthomas).

Endocrine derangements are common. Glucose intolerance, hyperinsulinism, insulin resistance, and hyperglucagonemia are often present in cirrhosis; the elevated insulin levels reflect decreased hepatic degradation rather than increased secretion, whereas the opposite is true for glucagon. Thyroid function tests must be interpreted with caution because of altered hepatic handling of thyroid hormones and changes in plasma binding proteins.

Complex derangements occur in the metabolism of sex hormones. Amenorrhea and decreased fertility are common in women with chronic liver disease. Males with cirrhosis, especially alcoholics, often have both hypogonadism (testicular atrophy, impotence, decreased spermatogenesis) and feminization (gynecomastia, female habitus). The biochemical basis is incompletely understood. Gonadotropin reserve of the hypothalamic-pituitary axis is often blunted. Circulating testosterone levels are low, resulting mainly from decreased synthesis but also from increased peripheral conversion to estrogens. The levels of minor estrogens are usually increased, but estradiol levels are variable and correlate poorly with clinical feminization. These changes are more prevalent in alcoholic liver disease than in cirrhosis of other etiologies; evidence indicates a direct toxic effect of ethanol on the testis.

HEMATOLOGIC DISTURBANCES

Many hematologic abnormalities are associated with liver disease. Anemia is frequent. Its pathogenesis may involve blood loss, nutritional folate deficiency, hemolysis, marrow suppression by alcohol, and chronic liver disease per se. Leukopenia and thrombocytopenia often accompany splenomegaly in portal hypertension, whereas leukocytosis occurs in cholangitis, tumor, alcoholic hepatitis, and fulminant liver necrosis.

Coagulation disturbances are common and complex. Liver synthesis of clotting factors is frequently impaired and results from hepatocellular dysfunction or inadequate absorption of vitamin K, which is required for the synthesis of factors II, VII, IX, and X. An abnormal prothrombin time results and, depending on the severity of hepatocellular dysfunction, may respond to parenteral phytonadione (vitamin K1) 5 to 10 mg/day for 2 to 3 days. Thrombocytopenia, disseminated intravascular coagulation, and dysfibrinogenemia also contribute to clotting disturbances in many patients.

RENAL AND ELECTROLYTE ABNORMALITIES

Renal and electrolyte abnormalities are common, especially in chronic disease with ascites. Hypokalemia is caused by excess urinary K loss from increased circulating aldosterone, renal retention of ammonium ion in exchange for K, secondary renal tubular acidosis, and diuretic therapy. Management consists of giving oral potassium chloride supplements and withholding K-losing diuretics. The kidney may avidly retain Na (see Ascites, above). Nevertheless, hyponatremia is common; it usually reflects advanced hepatocellular disease and is difficult to correct. Total body Na depletion is much less often responsible than relative water overload; K depletion may also contribute. Appropriate water restriction and K supplements may be helpful; use of diuretics that increase free water clearance is controversial. Sodium chloride solution given IV is rarely useful unless hyponatremia is life-threatening or total body Na depletion is evident; it should be avoided in cirrhotics with fluid retention, as it exacerbates ascites and has only a transitory effect on serum Na levels. Variable metabolic and respiratory derangements may produce alkalosis or acidosis in advanced liver failure. Blood urea concentrations are often low because of impaired liver synthesis; superimposed GI bleeding causes elevations because of an increased enteric load rather than true renal impairment, since creatinine values usually remain normal.

Renal failure in liver disease may reflect (1) disease directly affecting both organs (eg, carbon tetrachloride toxicity--rare); (2) circulatory failure with decreased renal perfusion, with or without frank acute tubular necrosis; or (3) functional renal failure, often called hepatorenal syndrome. This is a progressive disorder with no apparent morphologic abnormality in the kidney; it usually occurs in fulminant hepatitis or advanced cirrhosis with ascites. Its unknown pathogenesis probably involves neural or humoral alterations of renocortical blood flow. Insidiously progressive oliguria and azotemia herald its onset. Low urinary Na concentration and benign sediment usually distinguish it from tubular necrosis, but prerenal azotemia may be more difficult to differentiate; in doubtful cases, response to a volume load should be assessed. Once established, renal failure is almost invariably progressive and fatal; there is no effective therapy. Terminal hypotension with tubular necrosis may complicate the clinical picture, but the kidneys are characteristically unremarkable at autopsy.

CIRCULATORY CHANGES

A hyperkinetic circulatory state with increased cardiac output and tachycardia may accompany acute liver failure or advanced cirrhosis. Cirrhotic patients with collateral anastomoses may also develop arterial desaturation and clubbing of the fingers. Hypotension often occurs in advanced liver failure and may contribute to the development of renal dysfunction. The pathogenesis of these circulatory derangements is poorly understood, although peripheral arterial vasodilation probably plays a role in the hyperdynamic circulation and hypotension.

For specific disorders of hepatic circulation (eg, Budd-Chiari syndrome), see Ch. 46.