Chapter 33

### OVERVIEW OF LIVER FUNCTION

The liver plays a wide variety of roles in the overall scheme of the normal physiology of the body. The liver is involved in many aspects of metabolism, such as (1) lipid metabolism through fatty acid synthesis and lipoprotein conversion and (2) carbohydrate metabolism via glycogen storage, release. It is also the site of gluconeogenesis and amino acid metabolism. The liver is involved in synthesis of important proteins such as albumin and some of the coagulation factors. It also plays a role in immune system response, filtering out toxins and bacteria from the gastrointestinal tract, as well as amplifying the immune response via immune cells present in the liver. In addition, the liver is involved in endocrine control, via synthesis and secretion of hormones such as insulin-like growth factor 1 and angiotensinogen, as well as through inactivation of hormones such as insulin and corticosteroids. The liver also plays a major role in the coagulation system via synthesis of proclotting and anticlotting factors. Finally, it functions in modulating blood volume, acting as a reservoir for blood volume that can then be released into the bloodstream when stimulated by the sympathetic nervous system.1

### CIRRHOSIS OF THE LIVER

Because of the liver's central role in normal physiology, when the liver fails, there are wide-ranging effects on other organ systems. The degree of secondary involvement can alter dosing strategies and also influences the approach to certain parts of anesthetic use. Notable organs or organ systems at risk for secondary impairment due to liver failure are the cardiovascular system, brain, lungs, kidneys, gastrointestinal system, endocrine, immune system, and bone marrow. Liver transplant is the only definitive treatment for end-stage liver disease.2,3

The cardiovascular manifestations are arteriolar vasodilation and increased cardiac output, characterized as a hyperdynamic state due to decreased metabolism of vasoactive substances. Brain manifestations are the result of accumulation of toxic metabolites and can lead to hepatic encephalopathy and increased intracranial pressure. Possible pulmonary manifestations are restrictive lung disease, intrapulmonary shunts, pulmonary hypertension, and ventilation–perfusion mismatch, and hypoxemia in the absence of ascites or intrinsic lung disease (hepatopulmonary syndrome). The kidneys can fail in patients with end-stage renal disease without a primary cause of renal disease, known as hepatorenal syndrome. Common gastrointestinal manifestations are ascites, esophageal varices, portal hypertension, and delayed gastric emptying. Hematologic effects are anemia due to malnutrition, chronic disease, or bleeding, and coagulopathy due to platelet defects (number of platelets, function of platelets, or both), decreased number of clotting factors, decreased clearance of activated factors, and hyperfibrinolysis.3

The Child-Turcotte-Pugh (CTP) scoring system is commonly used to grade the severity of liver disease and life expectancy at 1 and 2 years. The CTP classification includes 5 factors: ascites, level of encephalopathy, prothrombin time, plasma bilirubin level, and serum albumin level (Pugh's modification of the original scoring system replaced nutritional status with prothrombin time). ...

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