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Liver disease often causes systemic symptoms and abnormalities (see Approach to the Patient with Liver Disease: Portal–Systemic Encephalopathy).
Circulatory
Abnormalities
Hypotension in advanced liver failure may contribute to renal dysfunction. The pathogenesis of the hyperdynamic circulation (increased cardiac output and heart rate) and hypotension that develop in advanced liver failure or cirrhosis is poorly understood. However, peripheral arterial vasodilation probably contributes to both. Factors that may contribute in cirrhosis may include altered sympathetic tone, production of nitric oxide and other endogenous vasodilators, and enhanced activity of humoral factors (eg, glucagon).
For specific disorders of hepatic circulation (eg, Budd-Chiari syndrome), see Vascular Disorders of the Liver.
Endocrine
Abnormalities
Glucose intolerance, hyperinsulinism, insulin resistance, and hyperglucagonemia are often present in patients with cirrhosis; the elevated insulin levels reflect decreased hepatic degradation rather than increased secretion, whereas the opposite is true for hyperglucagonemia. Abnormal thyroid function tests may reflect altered hepatic handling of thyroid hormones and changes in plasma binding proteins rather than thyroid abnormalities.
Sexual effects are common. Chronic liver disease commonly impairs menstruation and fertility. Males with cirrhosis, especially alcoholics, often have both hypogonadism (including testicular atrophy, erectile dysfunction, decreased spermatogenesis) and feminization (gynecomastia, female habitus). The biochemical basis is not fully 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 estrogens other than estradiol are usually increased, but the relationship between estrogens and feminization is complex. These changes are more prevalent in alcoholic liver disease than in cirrhosis of other etiologies, suggesting that alcohol, rather than liver disease, may be the cause. In fact, evidence indicates that alcohol itself is toxic to the testes.
Hematologic
Abnormalities
Anemia is common among patients with liver disease. Contributing factors may include blood loss, folate (folic acid) deficiency, hemolysis, marrow suppression by alcohol, and a direct effect of chronic liver disease.
Leukopenia and thrombocytopenia often accompany splenomegaly in advanced portal hypertension.
Clotting
and coagulation abnormalities are common and complex. Hepatocellular dysfunction and inadequate absorption of vitamin K may impair liver synthesis of clotting factors. An abnormal PT, depending on the severity of hepatocellular dysfunction, may respond to parenteral phytonadione (vitamin K1) 5 to 10 mg once/day for 2 to 3 days. Thrombocytopenia, disseminated intravascular coagulation, and fibrinogen abnormalities also contribute to clotting disturbances in many patients.
Renal
and Electrolyte Abnormalities
Renal and electrolyte abnormalities are common, especially among patients with ascites.
Hypokalemia may result from excess urinary K loss due to increased circulating aldosterone, renal retention of ammonium ion in exchange for K, secondary renal tubular acidosis, or diuretic therapy. Management consists of giving oral KCl supplements and withholding K-wasting diuretics.
Hyponatremia is common even though the kidney may avidly retain Na (see Approach to the Patient with Liver Disease: Ascites); it usually occurs with advanced hepatocellular disease and is difficult to correct. Relative water overload is more often responsible than total body Na depletion; K depletion may also contribute. Water restriction and K supplements may help; use of diuretics that increase free water clearance is controversial. Saline solution IV is indicated only if profound hyponatremia causes seizures or if total body Na depletion is suspected; it should be avoided in patients with cirrhosis who have fluid retention, because it worsens ascites and only temporarily increases serum Na levels.
Advanced liver failure can alter acid-base balance, usually causing metabolic alkalosis. Blood urea concentrations are often low because of impaired liver synthesis; GI bleeding causes elevations because of an increased enteric load rather than renal impairment. In the latter case, normal creatinine values tend to confirm normal kidney function.
Renal
failure in liver disease may reflect rare disorders that directly affect both the kidneys and the liver (eg, carbon tetrachloride toxicity); circulatory failure with decreased renal perfusion, with or without frank acute tubular necrosis; or functional renal failure, often called hepatorenal syndrome.
Hepatorenal
syndrome:
This syndrome consists of progressive oliguria and azotemia in the absence of structural damage to the kidney; it usually occurs in patients with fulminant hepatitis or advanced cirrhosis with ascites. Its unknown pathogenesis probably involves extreme vasodilation of the splanchnic arterial circulation, leading to decreased central arterial volume. Neural or humoral reductions in renocortical blood flow follow, resulting in a diminished glomerular filtration rate. Low urinary Na concentration and benign sediment usually distinguish it from tubular necrosis, but prerenal azotemia may be more difficult to distinguish; in equivocal cases, response to a volume load should be assessed. Once established, renal failure due to hepatorenal syndrome is usually rapidly progressive and fatal (type 1 hepatorenal syndrome), although some cases are less severe, with stable low-grade renal insufficiency (type 2). Liver transplantation is the only accepted treatment for type 1 hepatorenal syndrome; transjugular intrahepatic portal-systemic shunting (TIPS) and vasoconstrictors show some promise, but more study is needed.
Last full review/revision July 2009 by Steven K. Herrine, MD
Content last modified July 2009
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