Liver in Disease

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The Liver in Disease As you have learned, the liver is responsible for many essential functions. Because of these activities, it is exposed to a wide variety of insults and is therefore one of the most frequently injured organs in the body. The impairment of these vital functions by hepatic disease leads to clinical manifestations that are often similar, regardless of the specific cause. This section first explores the numerous causes of liver disease and then describes the signs and symptoms of hepatic dysfunction. Objectives These objectives will focus your attention on expected learning outcomes. After you complete this section, you should be able to: 1. Identify the major causes of hepatitis. 2. Describe the major causes and potential consequences of portal hypertension. 3. Identify three major metabolic diseases involving the liver. 4. Describe acute, fulminant, and chronic hepatitis. 5. Describe the significance of the designations chronic persistent hepatitis and chronic active hepatitis in chronic viral hepatitis. 6. Describe the classification and major clinical features of jaundice. 7. Identify the clinical features and significance of cirrhosis, hepatocellular carcinoma, and hepatic failure. Key Concepts 1. Hepatitis, or inflammation of the liver, has numerous potential causes: infections with viruses, bacteria, fungi, or protozoa; exposure to toxins such as alcohol, drugs, or chemical poisons; and autoimmunity. 2. Portal hypertension involves an increase in portal blood pressure due to obstruction of, or increased resistance to, blood flow, and it can lead to ascites, rupture of esophageal varices, and portosystemic shunting. 3. Metabolic diseases such as Wilson's disease, hemochromatosis, and alpha 1 - antitrypsin deficiency can lead to liver damage. 4. The liver can compensate for a significant amount of damage, but eventually liver function will decline markedly (decompensation), as manifested by diminished synthesis, abnormal clearance and excretion, ascites, and portal hypertension. 5. Acute hepatitis may resolve without significant sequelae, but unresolved inflammation that persists for longer than six months is termed chronic hepatitis. Chronic hepatitis may be caused by ongoing infection and associated inflammation or by repeated exposure to toxins, such as alcohol. Whatever the offending agent, chronic inflammation may lead to irreversible liver scarring and fibrosis, a condition known as cirrhosis of the liver. Occasionally, acute infection results in massive tissue destruction and high risk of death (fulminat hepatitis). 6. Chronic persistent hepatitis and chronic active hepatitis are histologic designations developed for autoimmune chronic hepatitis; they do not carry any prognostic value in chronic viral hepatitis. 7. Jaundice is related to increased levels of serum bilirubin (hyperbilirubinemia) that lead to a yellow appearance of the skin and whites of the eyes. 8. Jaundice may involve unconjugated or conjugated hyperbilirubinemia; the latter may be due to hepatocellular or cholestatic disorders. 9. Cirrhosis is pathologically defined as irreversible, diffuse fibrosis (or scarring) of the liver that is a common endpoint for many chronic liver diseases; it carries an increased risk of liver decompensation, hepatic failure, and the development of hepatocellular carcinoma. 10. Hepatocellular carcinoma is often associated with cirrhosis and with chronic viral hepatitis; it is usually diagnosed at an advanced stage, with very poor prognosis. 11. Hepatic failure is marked by severe impairment of liver functions and is usually accompanied by encephalopathy; death occurs in over 50% of cases. 12. Cirrhosis, hepatocellular cancer, and hepatic failure can all occur as a result of chronic viral hepatitis. A. Causes of Liver Dysfunction Liver disease has numerous causes, ranging from microbial infections and neoplasms (tumors) to metabolic and circulatory problems. I. Inflammatory Disorders (Hepatitis). Hepatitis involves inflammation and damage to the hepatocytes. This type of insult may result from infectious agents, toxins, or immunologic attack see Figure 8. In addition, other disorders such as Wilson's disease can cause hepatitis, and some diseases such as alpha 1 -antitrypsin deficiency can imitate hepatitis. However, the most common cause of hepatitis is viral infection. Firgure(8) a. Infection. Infection is a very important cause of hepatitis, since primary viral infection of the liver is common and viruses cause the majority of liver infections. Three major viruses cause hepatitis in the United States: hepatitis viruses A, B, and C. Together, they infect nearly 500,000 people in the United States every year. Viral hepatitis will be discussed in detail in Module 2. In addition, bacteria, fungi, and protozoa can infect the liver, and the liver is almost inevitably involved to some extent in all blood-borne infections. b. Toxins. Toxins such as alcohol, drugs, or poisons can cause hepatitis directly (by damaging liver tissue) or indirectly (by reducing defenses or stimulating an autoimmune response), but the exact mechanism is not always clear. Alcohol. Alcohol is primarily metabolized by the liver, and these metabolites can cause liver damage. The risk of hepatic toxicity increases if more than 40 grams, or about four drinks, are consumed per day. Drugs. Numerous medications can damage the liver, ranging from mild, asymptomatic alteration in liver chemistries to hepatic failure and death. Liver toxicity may or may not be dose-related. Dilantin (an anti-convulsant) and isoniazid (an anti-tuberculosis agent) are examples of drugs that can cause "viral-like" hepatitis. Chemicals/Poisons. Both environmental and industrial toxins can cause a wide variety of changes in the liver. Hepatic damage is not necessarily dose-dependent and can range from mild, asymptomatic inflammation to fulminant failure or progressive fibrosis and cirrhosis. c. Immunologic mechanisms. The immune system functions primarily to recognize "foreign" or 'non-self" antigens, for example, invading viruses, bacteria, and their proteins. These antigens may be recognized by antibodies, proteins that can specifically bind to them and help remove them from the body. Occasionally, autoimmunity develops, whereby the immune system incorrectly reacts against "self" antigens, (one's own cells). This occurs in autoimmune hepatitis and primary biliary cirrhosis, two diseases in which the immune system attacks and destroys portions of the liver. If unchecked, persistent inflammation can eventually lead to cirrhosis. 2. Vascular Disorders. Obstruction of portal blood flow that drains the intestines, stomach and spleen results in portal hypertension (elevation in portal blood pressure). Think of the liver as a sieve that filters portal blood; with scarring from repeated injury, the holes of the sieve become progressively smaller, resisting flow. Resistance to blood flow can also occur before the portal blood reaches the liver, or after leaving the liver see Figure 9. Firgure(9) Portal hypertension can lead to ascites, an accumulation of fluid that fills and distends the abdomen. Two serious consequences of portal hypertension include: ?rupture of dilated esophageal blood vessels ( varices) causing massive bleeding ?portosystemic shunting, in which substances from the gut (including drugs, bacteria, and toxic substances such as ammonia) bypass the liver and thus have access to other body tissues (for example, hepatic encephalopathy due to brain exposure to ammonia or other nitrogen-containing materials) 3. Metabolic Disorders. Problems