Liver disease often causes systemic symptoms and 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 but is in part a compensatory mechanism for extensive peripheral splanchnic vasodilation. 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).
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. Levels of estrogens other than estradiol are usually increased, but the relationship between estrogens and feminization is complex. These changes are more prevalent in alcohol-related 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.
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.
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 prothrombin time (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 are common, especially among patients with ascites.
Hypokalemia may result from excess urinary potassium loss due to increased circulating aldosterone, renal retention of ammonium ion in exchange for potassium, secondary renal tubular acidosis, or diuretic therapy. Management consists of giving oral potassium chloride supplements and withholding potassium-wasting diuretics.
Hyponatremia is common even though the kidneys may avidly retain sodium (see Ascites: Pathophysiology); it usually occurs with advanced hepatocellular disease and is difficult to correct. Relative water overload is more often responsible than total body sodium depletion; potassium depletion may also contribute. Water restriction and potassium supplements may help; diuretics that increase free water clearance can be used in severe or refractory cases. Saline solution IV is indicated only if profound hyponatremia causes seizures or if total body sodium depletion is suspected; it should be avoided in patients with cirrhosis and fluid retention because it worsens ascites and only temporarily increases serum sodium levels.
Advanced liver failure can alter acid-base balance, usually causing metabolic alkalosis. Blood urea nitrogen (BUN) levels are often low because of impaired liver synthesis; gastrointestinal (GI) bleeding causes elevations because of an increased enteric load rather than renal impairment. When GI bleeding elevates BUN, normal creatinine values tend to confirm normal kidney function.
Renal failure in liver disease may reflect
This syndrome consists of
Hepatorenal syndrome usually occurs in patients with alcoholic hepatitis or advanced cirrhosis with ascites. Pathogenesis is thought to be due to extreme vasodilation of the splanchnic arterial circulation, leading to decreased central arterial volume and subsequent renal vessel vasoconstriction. Neural or humoral reductions in renocortical blood flow follow, resulting in a diminished glomerular filtration rate. Low urinary sodium concentration and benign sediment usually distinguish it from acute 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 untreated hepatorenal syndrome is usually rapidly progressive and fatal (type 1 hepatorenal syndrome), although some cases are less severe, with stable milder renal insufficiency (type 2).
Combination therapy with vasoconstrictors (typically, midodrine, octreotide, or terlipressin) and volume expanders (typically, albumin) can be effective. Norepinephrine infusion can be used in refractory cases and titrated to urine output and mean arterial pressures.
If hepatorenal syndrome does not respond to medical therapy, patients should be referred for liver transplantation.
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