Liver Anatomy and Histology PDF

LIVER I Liver anatomy Liver histology ▪ The normal adult liver weighs 1400 to 1600 gm. It has a dual blood supply, with the portal vein providing 60% to 70% of hepatic blood flow and the hepatic artery supplying the remaining 30% to 40%. ▪ Within the liver, the branches of the portal v...

LIVER I Liver anatomy Liver histology ▪ The normal adult liver weighs 1400 to 1600 gm. It has a dual blood supply, with the portal vein providing 60% to 70% of hepatic blood flow and the hepatic artery supplying the remaining 30% to 40%. ▪ Within the liver, the branches of the portal veins, hepatic arteries, and bile ducts travel in parallel within portal tracts. Recycler main cleaner FABRICA DEL CUERPO ▪ The most common terminology of the hepatic microarchitecture is based on the lobular model. Accordingly the liver is divided into 1- to 2-mm in diameter lobules that are oriented around the terminal tributaries of the hepatic vein (terminal hepatic veins), with portal tracts at the lobule's periphery. These are often drawn as hexagonal structures. The hepatocytes in the vicinity of the terminal hepatic vein are called “centrilobular”; those near the portal tract are “periportal.” Division of the parenchyma into zones is a useful concept since certain types of hepatic injury tend to preferentially affect particular zones. This results in part from the zonal gradient of oxygenation and metabolic activities. ▪ Within the lobule, hepatocytes are organized into anastomosing sheets or “plates” extending from portal tracts to the terminal hepatic veins. Between the trabecular plates of hepatocytes are vascular sinusoids. ▪ Beneath the endothelial cells lies the space of Disse. ▪ Scattered Kupffer cells of the mononuclear phagocyte system are attached to the luminal face of endothelial cells. ▪ Myofibroblastic hepatic stellate cells are found in the space of Disse Acinus hexagon IMPORTANT MOPST IMPORTANT CELL - HEPATOCYTE cOLLECTION AT TEH CENTRAL VEIN TODO VA AL DUODENUM Hepatocyte and Parenchymal Responses Acidophil body: Type of focal necrosis in which dead hepatocyte is identifiable as shrunken, eosinophilic round body with variable nucleus, usually not accompanied by inflammation Also called Councilman body, single cell death, apoptotic cell. Signifies nonspecific hepatocellular injury Hepatocyte necrosis: Clusters of macrophages with eosinophilic cytoplasm indicate foci where hepatocytes have undergone necrosis Ballooning (feathery) degeneration:Swelling of hepatocytes with increased and pale cytoplasm, nonspecific Bile ductules: Proliferate in pathologic conditions and can Leads to lytic necrosis and replacement by inflammatory cells differentiate into hepatocytes to repopulate a destroyed liver  Centrilobular necrosis: Bridging necrosis: Necrotic hepatocytes around central vein, usually due to May also be called confluent ischemia, drugs or toxins Necrotic cells spans adjacent lobules in portal-portal, Common finding at autopsy because it is associated with portal-central or central-central pattern circulatory failure or shock Necrosis Interface hepatitis: Inflammatory cells between inflamed portal tracts and periportal parenchyma  Mallory hyaline: Also called Mallory bodies Giant cell transformation:Hepatocyte with 6 or Irregular, rope-like, sharply defined, more nuclei intracytoplasmic eosinophilic deposits of cytokeratin, may assume C shape around nucleus, often in ballooning cells, surrounded by neutrophils in alcoholic liver disease. Microvesicular steatosis:Multiple tiny intracytoplasmic Macrovesicular steatosis:Single large intracytoplasmic fat droplets that do not displace the nucleus fat droplet that displaces nucleus May be so small that they simulate ballooning degeneration Cirrhosis distruccion del higado ▪ Diffuse nodulation of liver due to fibrous bands subdividing liver into regenerative nodules Common causes include: -Chronic viral hepatitis B (± D) and C -Fatty liver disease: alcoholic and nonalcoholic -Metabolic: genetic hemochromatosis, alpha-1- antitrypsin deficiency, Wilson disease -Immune mediated: autoimmune hepatitis, primary biliary cholangitis, primary sclerosing cholangitis -Chronic biliary obstruction -Drug induced liver injury -Cryptogenic (idiopathic) cirrhosis ▪ Although uncommon, regression of fibrosis, albeit rarely, in fully established cirrhosis, does occur; this is another reason why cirrhosis should not be automatically equated with end stage disease Alcoholic fatty liver Clinical features ◦ General (nonspecific): malaise, fatigue, anorexia, weight loss ◦ Specific (due to impaired liver function): ◦ Impaired protein synthesis (leukonychia [white nails], ascites, bruising) ◦ Impaired biliary excretion (jaundice, pruritus) ◦ Impaired nitrogen metabolism (hepatic encephalopathy) ◦ Impaired estrogen metabolism (palmar erythema, spider nevus, testicular atrophy, gynecomastia) ◦ Complications: ◦ Decompensation: development of jaundice, ascites, variceal hemorrhage or hepatic encephalopathy ◦ Portal hypertension: ascites (± spontaneous bacterial peritonitis), splenomegaly, esophageal / gastric varices ◦ Liver failure: coagulopathy, hepatic encephalopathy, hepatorenal syndrome, hepatopulmonary syndrome, portopulmonary hypertension ◦ Hepatocellular carcinoma: cirrhosis is a key risk factor and the annual incidence of HCC among cirrhotic patients is 2 - 8% Laboratory Gross images Higado cirhotico Nodulos de grasa: AMARIO Microscopic description ◦ Diffuse disruption in architecture of the entire liver (loss of normal central - portal relationship) ◦ Bridging fibrous septa ◦ Roundish parenchymal nodules of regenerating hepatocytes HE Masson trichrome Portal Hypertension ▪ Increased resistance to portal blood flow ▪ Can be divided into prehepatic, intrahepatic, and posthepatic -The major prehepatic conditions are obstructive thrombosis, narrowing of the portal vein before it ramifies within the liver -The main post-hepatic causes are severe right-sided heart failure, constrictive pericarditis, and hepatic vein outflow obstruction -The dominant intrahepatic cause is cirrhosis, accounting for most cases of portal hypertension. ▪ The four major clinical consequences of portal hypertension are (1) ascites, (2) the formation of portosystemic venous shunts, (3) congestive splenomegaly, and (4) hepatic encephalopathy Ascites. ◦ The accumulation of excess fluid in the peritoneal cavity is called ascites. ◦ In 85% of cases, ascites is caused by cirrhosis. ◦ Ascites usually becomes clinically detectable when at least 500 mL have accumulated. ◦ The fluid is generally serous and may contain a scant number of mesothelial cells and mononuclear leukocytes. ◦ Influx of neutrophils suggests infection Make a safe hole with catheter can collect up to 6 litres  Hepatic encephalopathy ▪ Is a spectrum of disturbances in consciousness, ranging from subtle behavioral abnormalities, to marked confusion and stupor, to deep coma and death. ▪ Associated fluctuating, neurologic signs include rigidity and hyperreflexia. ▪ Asterixis, a particularly characteristic sign, is manifested as nonrhythmic, rapid extension-flexion movements of the head and extremities, best seen when the arms are held in extension with dorsiflexed wrist. ▪ Is regarded as a disorder of neurotransmission in the central nervous system and neuromuscular system. ▪ Elevated ammonia levels in blood and the central nervous system correlate with impaired neuronal function and cerebral edema. HEPATITIS A VIRUS Hepatitis B Virus Hepatitis C Virus blood, sex Hepatitis D Virus ◦ Also called “the delta agent,” hepatitis D virus (HDV) is a unique RNA virus that is dependent for its life cycle on HBV. ◦ Co-infection occurs following exposure to serum containing both HDV and HBV. ◦ Superinfection occurs when a chronic carrier of HBV is exposed to a new inoculum of HDV Hepatitis E Virus food food blood Hepatitis. Morphology The morphologic changes in acute and chronic viral hepatitis are shared among the hepatotropic viruses and can be mimicked by drug reactions or autoimmune hepatitis. ▪ Microscopically, both acute and chronic hepatitis evoke a lymphoplasmacytic (mononuclear) infiltrate. ▪ Portal inflammation in acute hepatitis is minimal or absent. Most parenchymal injury is scattered throughout the hepatic lobule as “spotty necrosis” or lobular hepatitis. The hepatocyte injury may result in necrosis or apoptosis. ▪ The defining histologic feature of chronic viral hepatitis is mononuclear portal infiltration. ▪ It may be mild to severe and variable from one portal tract to the next. ▪ There is often interface hepatitis as well, in addition to lobular hepatitis, distinguished by its location at the interface between hepatocellular parenchyma and portal tract stroma. ▪ The hallmark of progressive chronic liver damage is scarring ▪ At first, only portal tracts exhibit fibrosis, but in some patients, with time, fibrous septa—bands of dense scar—extend between portal tracts. In parallel with increasing scarring there is also increasing ductular reaction, reflecting stem cell activation. In the most severe cases, continued scarring and nodule formation leads to the development of cirrhosis as described earlier In chronic hepatitis B, “ground-glass” hepatocytes—cells Chronic hepatitis C quite commonly shows lymphoid with endoplasmic reticulum swollen by HBsAg—is a aggregates or fully formed lymphoid follicles diagnostic hallmark. Immunostaining can confirm the presence of viral antigen Knodell Autoimmune Hepatitis ◦ Autoimmune hepatitis is a chronic, progressive hepatitis with all the features of autoimmune diseases in general: genetic predisposition, association with other autoimmune diseases, presence of autoantibodies, and therapeutic response to immunosuppression. ◦ Female predominance (78%) ◦ Morphology: ◦ Early phase of severe parenchymal destruction followed rapidly by scarring. Features considered typical of autoimmune hepatitis include: ◦ -Severe necroinflammatory activity indicated by extensive interface hepatitis ◦ -Plasma cell predominance in the mononuclear inflammatory infiltrates ◦ -Hepatocyte “rosettes” in areas of marked activity BENIGN Alcoholic Liver Disease ◦ Excessive alcohol (ethanol) consumption is the leading cause of liver disease ◦ There are three distinctive, albeit overlapping forms of alcoholic liver injury: ◦ -hepatocellular steatosis or fatty change ◦ -alcoholic (or steato-) hepatitis ◦ -steatofibrosis (patterns of scarring typical for all fatty liver diseases including alcohol) up to and including cirrhosis in the late stages of disease Morphology ▪ All changes in alcoholic liver disease begin in acinus zone 3 and extend outward toward the portal tracts with increasing severity of injury. ❑ Hepatic Steatosis (Fatty Liver):After even moderate intake of alcohol, lipid droplets accumulate in hepatocytes Degeneracion grasa del higado Steatosis increasing with amount and chronicity of alcohol intake. The lipid begins as small droplets that coalesce into large droplets which distend the hepatocyte and push the nucleus aside. Macroscopically, the fatty liver in individuals with chronic alcoholism is a large (as heavy as 4 to 6 kg), soft organ that is yellow and greasy. Fatty change is completely reversible if there is abstention from further intake of alcohol. ❑ Alcoholic (Steato-) Hepatitis - Hepatocyte swelling and necrosis: Single or scattered foci of cells undergo swelling (ballooning) and necrosis - Mallory-Denk bodies: These are usually present as clumped, amorphous, eosinophilic material in ballooned hepatocytes. They are made up of tangled skeins of intermediate filaments such as keratins 8 and 18 in complex. - Neutrophilic reaction: Neutrophils permeate the hepatic lobule and accumulate around degenerating hepatocytes, particularly those having Mallory-Denk bodies. ❑ Alcoholic steatofibrosis. Alcoholic hepatitis is often accompanied by prominent activation of sinusoidal stellate cells and portal fibroblasts, giving rise to fibrosis. Fibrosis begins with sclerosis of central veins. Perisinusoidal scar then accumulates in the Fibrosis space of Disse of the centrilobular region, spreading outward, encircling individual or small clusters of hepatocytes in a chicken wire fence pattern These webs of scar eventually link to portal tracts and then begin to condense into central-portal fibrous septa Perisinusoidal scarring leads to a classic micronodular or Laennec cirrhosis (3 mm) Complete regression of alcoholic cirrhosis, while reported, is rare  asbesto Hemo cromatosa, hemosiderina, Hemochromatosis ▪ Hemochromatosis is caused by excessive iron absorption, most of which is deposited in parenchymal organs such as the liver and pancreas, followed by heart, joints, and endocrine organs. Una inferemedad en relacion con deposistos de hemosiderina ▪ Morphology: -golden-yellow hemosiderin granules in the cytoplasm of periportal hepatocytes that stain with Prussian blue -micronodular pattern of cirrhosis Mucho copper deposited all ove rthe body problema genetico anillo de wilson Wilson Disease ◦ Wilson disease is an autosomal recessive disorder caused by mutation of the ATP7B gene, resulting in impaired copper excretion into bile and a failure to incorporate copper into ceruloplasmin. ◦ This disorder is marked by the accumulation of toxic levels of copper in many tissues and organs, principally the liver, brain, and eye. ◦ The biochemical diagnosis of Wilson disease is based on a decrease in serum ceruloplasmin, an increase in hepatic copper content (the most sensitive and accurate test), and increased urinary excretion of copper (the most specific screening test). ◦ Liver: acute fulminant hepatitis, chronic hepatitis… ◦ Toxic injury to the brain primarily affects the basal ganglia, particularly the putamen, which shows atrophy and even cavitation. Nearly all patients with neurologic involvement develop eye lesions called Kayser-Fleischer rings, green to brown deposits of copper in Descemet membrane in the limbus of the cornea. α1-Antitrypsin Deficiency Inclusions ▪ α1-Antitrypsin deficiency is an autosomal recessive disorder of protein folding marked by very low levels of circulating α1-Antitrypsin (α1AT). ▪ The major function of this protein is the inhibition of proteases, particularly neutrophil elastase, cathepsin G, and proteinase 3, which are normally released from neutrophils at sites of inflammation ▪ α1AT deficiency leads to the development of pulmonary emphysema, because the activity of destructive proteases is not inhibited ▪ It also causes liver disease as a consequence of hepatocellular accumulation of the misfolded protein ▪ Morphology: α1AT deficiency is characterized by the presence of round-to-oval cytoplasmic globular inclusions in hepatocytes, which on routine hematoxylin and eosin stains are acidophilic, but are strongly periodic acid–Schiff (PAS)-positive and diastase-resistant