Liver disease often causes systemic symptoms and abnormalities.
(See also Liver Structure and Function Liver Structure and Function The liver is a metabolically complex organ. Hepatocytes (liver parenchymal cells) perform the liver’s metabolic functions: Formation and excretion of bile as a component of bilirubin metabolism... read more and Evaluation of the Patient With a Liver Disorder Evaluation of the Patient With a Liver Disorder History and physical examination often suggest a cause of potential liver disorders and narrow the scope of testing for hepatic and biliary disorders. Various symptoms may develop, but few are... read more .)
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 Cirrhosis Cirrhosis is a late stage of hepatic fibrosis that has resulted in widespread distortion of normal hepatic architecture. Cirrhosis is characterized by regenerative nodules surrounded by dense... read more 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).
For specific disorders of hepatic circulation (eg, Budd-Chiari syndrome Budd-Chiari Syndrome Budd-Chiari syndrome is obstruction of hepatic venous outflow that originates anywhere from the small hepatic veins inside the liver to the inferior vena cava and right atrium. Manifestations... read more ), see Vascular Disorders of the Liver Overview of Vascular Disorders of the Liver The liver has a dual blood supply. The portal vein (which is rich in nutrients and relatively high in oxygen) provides two thirds of blood flow to the liver. The hepatic artery (which is oxygen-rich)... read more .
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 Male Hypogonadism Hypogonadism is defined as testosterone deficiency with associated symptoms or signs, deficiency of spermatozoa production, or both. It may result from a disorder of the testes (primary hypogonadism)... read more (including testicular atrophy, erectile dysfunction, decreased spermatogenesis) and feminization (gynecomastia Gynecomastia This photo shows enlarged breast tissue in a male patient. Gynecomastia is hypertrophy of breast glandular tissue in males. It must be differentiated from pseudogynecomastia, which is increased... read more , 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 Alcohol-Related Liver Disease Alcohol consumption is high in most Western countries. According to the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), 8.5% of US adults are estimated to... read more 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 Overview of Hemolytic Anemia At the end of their normal life span (about 120 days), red blood cells (RBCs) are removed from the circulation. Hemolysis is defined as premature destruction and hence a shortened RBC life span... read more , marrow suppression by alcohol, and a direct effect of chronic liver disease.
Leukopenia Overview of Leukopenias Leukopenia is a reduction in the circulating white blood cell (WBC) count to < 4000/mcL (9/L). It is usually characterized by a reduced number of circulating neutrophils, although... read more and thrombocytopenia Overview of Platelet Disorders Platelets are circulating cell fragments that function in the clotting system. Thrombopoietin helps control the number of circulating platelets by stimulating the bone marrow to produce megakaryocytes... read more often accompany splenomegaly Splenomegaly Splenomegaly is abnormal enlargement of the spleen. (See also Overview of the Spleen.) Splenomegaly is almost always secondary to other disorders. Causes of splenomegaly are myriad, as are the... read more 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 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
Renal and electrolyte abnormalities are common, especially among patients with ascites.
Hypokalemia Hypokalemia Hypokalemia is serum potassium concentration < 3.5 mEq/L (< 3.5 mmol/L) caused by a deficit in total body potassium stores or abnormal movement of potassium into cells. The most common... read more 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 Hyponatremia Hyponatremia is decrease in serum sodium concentration < 136 mEq/L (< 136 mmol/L) caused by an excess of water relative to solute. Common causes include diuretic use, diarrhea, heart failure... read more is common even though the kidneys may avidly retain sodium (see Ascites: Pathophysiology Pathophysiology Ascites is free fluid in the peritoneal cavity. The most common cause is portal hypertension. Symptoms usually result from abdominal distention. Diagnosis is based on physical examination and... read more ); 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 Cirrhosis Cirrhosis is a late stage of hepatic fibrosis that has resulted in widespread distortion of normal hepatic architecture. Cirrhosis is characterized by regenerative nodules surrounded by dense... read more 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 Metabolic Alkalosis Metabolic alkalosis is primary increase in bicarbonate (HCO3−) with or without compensatory increase in carbon dioxide partial pressure (Pco2); pH may be high or nearly normal. Common... read more . Blood albumin nitrogen (BUN) levels are often low because of impaired liver synthesis; gastrointestinal (GI) bleeding Overview of Gastrointestinal Bleeding Gastrointestinal (GI) bleeding can originate anywhere from the mouth to the anus and can be overt or occult. The manifestations depend on the location and rate of bleeding. (See also Varices... read more 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
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
Functional renal failure, often called hepatorenal syndrome
This syndrome consists of
Progressive oliguria and azotemia in the absence of structural damage to the kidneys
Hepatorenal syndrome usually occurs in patients with alcoholic hepatitis or advanced cirrhosis with ascites Ascites Ascites is free fluid in the peritoneal cavity. The most common cause is portal hypertension. Symptoms usually result from abdominal distention. Diagnosis is based on physical examination and... read more . 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 Acute Tubular Necrosis (ATN) Acute tubular necrosis (ATN) is kidney injury characterized by acute tubular cell injury and dysfunction. Common causes are hypotension or sepsis that causes renal hypoperfusion and nephrotoxic... read more , 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 Liver Transplantation Liver transplantation is the 2nd most common type of solid organ transplantation. (See also Overview of Transplantation.) Indications for liver transplantation include Cirrhosis (70% of transplantations... read more .
Hepatopulmonary syndrome Hepatopulmonary Syndrome Hepatopulmonary syndrome is hypoxemia caused by pulmonary microvascular vasodilation in patients with portal hypertension; dyspnea and hypoxemia are worse when the patient is upright. Hepatopulmonary... read more is hypoxemia caused by pulmonary microvascular vasodilation in patients with portal hypertension Portal Hypertension Portal hypertension is elevated pressure in the portal vein. It is caused most often by cirrhosis (in North America), schistosomiasis (in endemic areas), or hepatic vascular abnormalities. Consequences... read more . Hepatopulmonary syndrome has a high mortality rate and prognosis is poor without liver transplantation Liver Transplantation Liver transplantation is the 2nd most common type of solid organ transplantation. (See also Overview of Transplantation.) Indications for liver transplantation include Cirrhosis (70% of transplantations... read more (the only cure for this condition). Thus, patients with hepatopulmonary syndrome should be referred expeditiously for liver transplantation. Risk stratification for transplant involves measuring the degree of hypoxemia with a room air arterial blood gas. If patients have a room air PaO2 between 50 and 60, they can achieve MELD (model for end-stage liver disease) exception points to boost their score on the liver transplant list and aid them in accessing transplantation more quickly.
Portopulmonary hypertension Portopulmonary Hypertension Portopulmonary hypertension is pulmonary arterial hypertension associated with portal hypertension without other secondary causes. Pulmonary hypertension occurs in patients with various conditions... read more is pulmonary arterial hypertension in patients with portal hypertension that does not have secondary causes. Careful assessment of hemodynamics with right heart catheterization is required to distinguish portopulmonary from traditional pulmonary hypertension and helps determine the role for liver transplantation.