# Liver Divided into 8 segments or 2 main lobes (Left and Right) and 2 smaller lobes (Caudate and Quadrate) ## Grossing * Cirrhosis appears as firm wrinkling on surface * Look for cysts (micro) * liver parenchyma can look congested, irregular “congested” liver is more passive, “nutmeg” appearance * well defined heterogeneous foci can be seen when liver is regenerating (not cancer) *Always review with pathologist if identified as a Liver Primary*Edit ### Jaundice and Cholestasis * retention of bilirubin, bile acids and cholesterol * hepatitis and intra or extrahepatic obstruction of bile flow are most common causes (accumulation of of conjugated bilirubin) * Hemolytic anemias are most common cause of jaundice involving unconjugated bilirubin * Intrahepatic Cholestasis would be worsened by surgery (Intrahepatice biliary tree or hepatocellular secretory failure) * Skin xanthomas sometimes appear Hepatocyte Cytosolic hepatocellular enzymes * AST * ALT * LDH * Bilirubin (Total, direct, delta-covalently linked to albumin) * Urine bilirubin * Serum bile acids Plasma membranes enzymes (from damage to bile canaliculi) * ALP * γ-glutamyl transpeptidase * 5′-nucleotidase * Prothrombin Time (factors V, VII, X, prothrombin, fibrinogen) Bilirubin metabolism and elimination 1. breakdown of RBCs 2. bilirubin bound to albumin, brought to liver 3. Glucuronidation by glucuronsyltransferase, now water soluble (bilirubin mono- and diglucuronides) 4. excreted into bile 5. Gut bacteria deconjugate bilirubin into urobilinogens ### Gilbert syndrome * 7% of population * benign, decreased levels of glucuronsyltransferase, therefore transient unconjugated hyperbilirubinemia ### Dubin-Johnson syndrome * autosomal recessive defect in transport protein ### Cirrhosis * diffuse process, most or all of liver * Fibrous septa, delicate bands or broad scars around multiple lobules * Nodules (parenchymal) < 3 mm to > 1 cm encircled by fibrous bands, originate from 2 sources: 1. newly formed hepatocytes capable of regeneration 2. preexistent hepatocytes that have doesn't replicate well anymore due to cirrhosis * alcoholic cirrhosis shows diffuse nodularity on the serosal surface induced by underlying fibrous scarring * Mallory bodies are keratins that are collapsed * damaged hepatocytes or stimulated Kupffer cells and endothelial cells produce growth factors, cytokines and Collagen I and III are deposited in the Space of Disse (pseudo 'basement membrane', usually has a delicate framework of type IV collage) Collagen deposition blocks the endothelial fenestrations and prevents the free exchange of materials from the blood * most common causes are HBV an HCV and alcoholic and non-alcoholic steatohepatitis (NASH) * less frequently, autoimmune, biliary diseases, metabolic conditions (hemochromatosis), nonalcoholic fatty liver disease (NAFLD) metabolic syndromes, obesity, type 2 diabetes * NAFLD may show all changes associated with alcoholic liver disease (steatosis, NASH, cirrhosis) but less prominent * decreased liver function, portal hypertension, increased risk for liver cancer * α1-antitrypsin deficiency leading to both cirrhosis and emphysema * drugs, particularly acetaminophen most common cause of acute liver failure (caused by metabolite produced by cytochrome P-450 system in acinus zone 3 hepatocytes; zone 2 hepatocytes take over) ### Portal Hypertension * Increased resistance to portal blood flow * Pre-, intra-, or posthepatic * Cirrhosis is most common intrahepatic cause * Less common schistosomiasis, massive fatty change, diffuse granulomatous diseases (sarcoidosis, miliary tuberculosis) * increased Venus pressure results in shunts between systemic and portal capillary beds (hemorrhoids, esophagogastric varices, retroperitoneum, falciform ligament involving periumbilical and abdominal wall collaterals; caput medusae) * Esophagogastric varices are most important, 65% of persons with advanced cirrhosis, causes massive hematemesis and death ### Hepatitis * grossly, acute hepatitis appears normal to mildly mottled, enlarged, reddened * massive hepatic necrosis may shrink to 500g and become limp, red, covered in baggy capsule * may involve the entire liver, or only patchy areas * Acute vs. Chronic hepatitis is determined by pattern of cell injury and severity of inflammation (acute has less inflammation and more hepatocyte death) ### Viral hepatitis * The vowels (hepatitis A and E) never cause chronic hepatitis, only acute hepatitis. * Only the consonants (hepatitis B, C, D) have the potential to cause chronic disease (C for consonant and for chronic). * Hepatitis B can be transmitted by blood, birthing, and “bonking” (as they say in the United Kingdom). * Hepatitis C is the single virus that is more often chronic than not (almost never detected acutely; 85% or more of patients develop chronic hepatitis, 20% of whom will develop cirrhosis). * Hepatitis D, the delta agent, is a defective virus, requiring hepatitis B coinfection for its own capacity to infect and replicate. * Hepatitis E is endemic in equatorial regions and frequently epidemic. * The inflammatory cells in both acute and chronic viral hepatitis are mainly T cells; it is the pattern of injury that is different, not the nature of the infiltrate. * Biopsy assessment in chronic viral hepatitis is most impor- tant for grading and staging of disease, which are used to decide whether a patient undergoes often arduous anti-viral treatments. * Patients with long-standing HBV or HCV infections are at increased risk for the development of hepatocellular car- cinomas, even in the absence of established cirrhosis. Ground-glass hepatocytes in chronic hepatitis B, caused by accumulation of HBsAg in cytoplasm, have large, pale, finely granular, pink cytoplasmic inclusions on hematoxylin-eosin staining; immunostain- ing (inset) confirms that the endoplasmic reticulum is ballooned with surface antigen (brown). HBsAg, hepatitis B surface antigen. ransmission by blood products is now for- tunately rare, accounting for only 4% of all acute HCV infections. Occupational exposure among health care workers accounts for another 4% of case HCV is subclassified into six genotypes, based on the genetic sequence