Liver Pathology PDF

LIVER Liver Failure The liver is responsible for the detoxification of ammonia, a bi-product of protein and amino acid metabolism. When enough liver tissue is destroyed or non-functional the normal quick metabolism of ammonia is lost or is insufficient to keep it at safe levels. The increasing bloo...

LIVER Liver Failure The liver is responsible for the detoxification of ammonia, a bi-product of protein and amino acid metabolism. When enough liver tissue is destroyed or non-functional the normal quick metabolism of ammonia is lost or is insufficient to keep it at safe levels. The increasing blood ammonia levels become toxic and the patient develops what is called “hepatic encephalopathy”. This is metabolic and one sees minimal brain pathology. Clinically one experiences impaired cognition and asterixis following decreasing levels of consciousness, coma, and death. Liver failure has three classes of causes: 1. Massive hepatic necrosis. This is usually drug-induced (e.g. acetaminophen toxicity, halothane, carbon tetrachloride, mushroom poisoning). Hepatitis A&B. 2. Chronic liver disease with cirrhosis. Alcoholic liver disease, hepatitis B&C. 3. Hepatic dysfunction without overt necrosis. Reye syndrome, tetracycline toxicity, acute fatty liver of pregnancy. Cellular hepatic injury The liver responds to injury with 5 categories of cellular changes: 1. Degeneration and cellular accumulation. Liver cells can swell. As the accumulate cytoplasmic fluid they may appear lighter. Triglyceride droplets may accumulate and result in steatosis (AKA fatty change). Small droplets that do not displace the nucleus is called microvesicular fatty change (acute fatty liver of pregnancy, valproic acid toxicity) while larger droplets are called macrovesicular fatty change (obesity, diabetes, hepatitis C). Alcoholic liver disease can cause both types. 2. Necrosis. Individual liver cells may undergo necrosis and/or apoptosis in various conditions. They may also swell so much that they burst (lytic necrosis). In chronic passive congestion the hepatocytes surrounding the central vein as oxygenation is decreased in the stagnant pooling blood (centrolobular necrosis). This can also be seen in certain drug reactions and toxins. During inflammation necrotic hepatocytes can span from one inflamed portal tract to other (bridging necrosis). Liver cells are engulfed by resting hepatic macrophages called Kupffer cells and so the identification of necrotic/apoptotic hepatocytes reflects very recent damage (hours). 3. Inflammation (hepatitis). This may consist of acute or chronic inflammation. The inflammation may be preceeded by hepatocyte damage/death or it may follow as a result. A common example is that of viral hepatitis in which lymphocytes accumulate in the portal triad and then spill over into the parenchyma and finally involve all of the liver tissue as fulminant hepatitis. 4. Regeneration. Hepatocytes are very effective in regeneration and large volumes of lost liver could potentially be replaced by hyperplasia of the residual hepatocytes if it were not for interference by fibrosis (see below). 5. Fibrosis. Liver fibrosis is caused by chronic inflammation or direct toxic insult. Fibrosis usually begins in the portal tracts and is irreversible. With continued collagen deposition the fibrosis begins to divide the liver into nodules. At this point the process is called cirrhosis. Fibrosis and cirrhosis traps and interferes with the regeneration of lost hepatocytes. They can also interrupt the usual vascular blood flow. As areas of regenerating liver expand in a balloon-like fashion in between the fibrous tissue bands they take on a nodular appearance (regenerative nodules). The leading causes of cirrhosis are shown below. The portal tracts and the area around central veins contain types II and III collagen. The Space of Disse contains a small amount of type IV collagen. In cirrhosis the perisinusoidal stellate cells are stimulated by the Kupffer cells to make types II and III collagen which accumulate in the Space of Disse and eventually bridges the portal tracts and central veins to form a honeycombed patteren of fibrosis. The stellate cells also begin to synthesize intracytoplasmic myofibers and can result in contraction of the stellate cells with constriction of the sinusoidal blood flow and resistance of blood flow through the liver. The fibrosis can also interfere with the communication between the liver parenchyma and the bile outflow tracts so that patients may develop jaundice and/or hepatic failure even though the weight of liver parenchyma has not been significantly decreased. Alcoholic liver disease 60% to 70% Viral hepatitis 10% Biliary diseases 5% to 10% Primary hemochromatosis 5% Wilson disease Rare α1-Antitrypsin deficiency Rare Cryptogenic cirrhosis 10% to 15% Portal Hypertension Portal hypertension can be pre-hepatic, intrahepatic, or post hepatic. Examples of prehepatic would be the shunting of blood to the liver in a case of massive spleenomegally or thrombosis of the portal vein. The dominant intrahepatic cause is cirrhosis and the dominant post-hepatic cause is right sided heart failure. In the case of posthepatic portal hypertension the blood pools around the central veins and produces a pattern similar to the cut surface of a nutmeg. Hepatitis The three major varieties of hepatitis are types A, B, and C. As you probably already know hepatitis A is acquired via a fecal oral route often from contaminated water or food. Type A causes an acute hepatitis that runs its course but does not cause a persistent infection. It also doesn’t predispose to cirrhosis or cancer. Types B and C, on the other hand, can result in smoldering persistent infections that cause cirrhosis and increase the risk of liver cancer. This doesn’t mean that types B and C can’t cause an acute hepatitis…they can but often do not. The various courses that these two later types of hepatitis can take are shown below (Type B above and type C below). Hemosiderosis/Hemochromatosis Another potential cause of liver cirrhosis is hemosiderosis. Hemosiderin is the terminal iron containing breakdown product of hemoglobin when it is being digested by macrophages in the tissues (not normal hemoglobin turnover). This deposition in the tissues occurs when there is too much hemoglobin that can be metabolized in this way. Multiple blood transfusions can cause hemosiderosis. A primary condition that causes the same thing in the tissues but is genetic is called “hemochromatosis”. Patients with hemochromatosis have abnormally increased absorption of iron without an increased ability to excrete it. The iron becomes deposited in the tissues. Both conditions can result in a tannish bronze color to the skin and body organs. Both can also cause cirrhosis of the liver. Liver Tumors In this country the most common variety of liver cancer is metastatic disease, often from the GI tract via the portal vein. The most common primary malignancy of the liver is hepatocellular carcinoma (AKA malignant hepatoma). Cirrhosis and whatever causes cirrhosis predispose one to develop hepatocellular carcinoma. The prognosis depends on the tumor grade and the success of surgical removal but most cases have a poor prognosis. The histology of the tumor often looks much like that of normal liver but without the usual lobular architecture with portal triads etc. Hepatocellular adenomas (AKA benign hepatomas) are benign liver tumors almost always associated with oral contraceptive use (birth control pills). If the term “hepatoma” is used by itself without a benign or malignant prefix it is referring to the hepatocellular adenoma. The histology is much like that of low grade hepatocellular carcinomas but even more low grade and bland in appearance. An unusual liver cancer is the cholangiocarcinoma, a tumor arising from the small intrahepatic bile ducts. One curious association that everyone likes to mention is that cholangiocarcinoma is associated with parasitic liver fluke infection. The prognosis of cholangiocarcinoma is very bad. Below is a gross and microscopic image of cholangiocarcinoma. Note that it is similar to other adenocarcinomas in appearance.