Cirrhosis is the final phase of chronic liver disease and is defined by three characteristic changes. These are fibrotic scarring as a result of progressive damage to the liver; nodules of hepatocyctes surrounded by scar tissue that are a result of chronic scarring and tissue regeneration; and disruption of the architecture of the entire liver from diffuse injury and fibrosis. Symptoms usually develop late in the disease, and cirrhosis is a huge risk factor for the development of hepatocellular carcinoma (liver cancer).
Portal Hypertension
Cirrhosis is a major cause of resistance to portal blood blow in the liver, which results in portal hypertension. Portal hypertension is an increase in pressure in the portal vein, a major vessel that takes nutrient-rich blood from the gastrointestinal system to the liver. This has three major clinical consequences: ascites, portosystemic venous shunts and splenomegaly. Ascites is the accumulation of fluid in the abdominal cavity as a result of many factors. Portosystemic shunts are reversals of flow through collateral vessels at sites such as the esophagus (manifest as varices) and rectum (hemmorhoids). The esophageal varices can rupture, causing life-threatening bleeding. Splenomegaly, also known as enlarged spleen, results from long-standing congestion of blood that can back up into the spleen. The spleen is a highly vascular organ, and congestion can result in dramatic increases in size.
Lung Dysfunction
Lung function can be compromised due to several reasons. Cirrhosis results in an increase in vasodilators (cause blood vessel dilation) in the bloodstream, which affects pulmonary vasoconstriction (blood vessel constriction) that occurs in response to decreased oxygen. A protein called 2,3-BPG is also not cleared by the liver, and this results in blood cells holding on to oxygen instead of releasing it for the body to utilize. In addition, fluid buildup in the lungs or abdomen (ascites) can restrict lung motion, affecting how much air can be taken in.
Kidney Dysfunction
The increase in vasodilators in the bloodstream can cause decreased blood flow to the kidney, which is exacerbated by fluid losses into the abdomen (from ascites). Diuretic therapy is a mainstay for the treatment of cirrhosis and can exacerbate existing fluid losses as well.
Blood Dysfunction
Problems with bleeding and bruising are common with cirrhosis. When the liver is failing, it cannot produce the vitamin K-dependent clotting factors, which obviously affects the blood's ability to clot and prevent prolonged bleeding. Platelets can be destroyed by the antibodies produced; and the buildup of uremia (which the liver normally clears) can affect the quality of platelets and their ability to clot, which also is manifested in easy bruising or bleeding.
Endocrine Dysfunction
The liver produces and clears many hormones and metabolites in the body, such as glucagon and growth hormone. Their buildup affects body sensitivity to insulin, and resistance can follow easily. Sex hormones that are not adequately cleared result in gynecomastia, impotence, and infertility in men; in women, amenorrhea and infertility commonly result. The effects of estrogen on the blood vessels along with normal vasodilator buildup from liver failure can result in systemic vasodilation with dermatologic symptoms like "spider nevi."
Nervous System Dysfunction
Hepatic encephalopathy (brain/nervous system damage as a result of liver disorder) can result, with symptoms of confusion, altered mental status, and nervous system depression (e.g., fatigue or malaise). This results from both decreased clearance of ammonia and decreased clearance of substances that have neurotransmitter-like effects on the central nervous system. Neurotransmitters are molecules used in the nervous system that relay and modulate signals between neuron(s) and other cells.
Cardiovascular Dysfunction
Cirrhosis causes "hyperdynamic" circulation, which is characterized by a high cardiac output and low resistance in the blood vessels. The increase in endogenous vasodilators from decreased liver clearance is one reason, along with the increased blood flow through collateral vessels that also occurs in end-stage liver disease.
References
- "Robbins and Cotran Pathologic Basis of Disease, 8th Edition;" Kumar; 2009
- "Miller's Anesthesia, 7th Edition;" Miller; 2009
- Mayo Clinic: Cirrhosis
