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Macrovesicular steatosis Iron stain using the Prussian Blue Reaction (x400). Hemosiderin granules stain as dark blue, coarse granules.
Patterns of Hepatic Injury Necrosis and Apoptosis
Ischemic coagulative necrosis – “mummified” liver cells with lysed nuclei
Apoptotic cell death – shrunken, pyknotic & intensely eosinophilic cells with fragmented nuclei
Lytic necrosis – outcome of ballooning degeneration (+) shards of cellular debris
Liquefactive necrosis - abscesses
Necrosis (left lower) is around the centrilobular area. The periportal area is viable.
Ischemia of centrilobular area resulting in coagulative necrosis of hepatic cords. (Preservation of cellular contour with disappearance of nucleus) Some viable hepatocytes with nucleus are seen in the upper middle and upper right areas.
Bridging confluent lytic necrosis in severe chronic viral hepatitis B. Inflamed portal tract ‘bridged’ through area of necrosis with centrilobular area (lower left). The upper right part corresponds to an area of extensive lytic necrosis.
Patterns of Hepatic Injury Necrosis and Apoptosis
Centrilobular – most common; immediately around terminal hepatic vein
Mid-zonal and periportal – rare
Degree of involvement:
Focal or spotty – limited to scattered cells within hepatic lobules
Interface hepatitis – between periportal parenchyma & inflamed portal tracts
Progressive fibrosis & re-organization of vascular micro-architecture of liver
Collagen deposition (types I & III) in the lobule Loss of fenestration of sinusoidal endothelial cells New vascular channels in the septae Create delicate or broad septal tracts Impaired hepatocellular protein secretion (albumin, clotting factors, lipoproteins) Shunting of blood around the parenchyma
Histological features of alcoholic hepatitis. (A) Low- power view demonstrating the cardinal features of steatosis, fibrosis, inflammation, and hepatocellular injury.
Histological features of alcoholic hepatitis. (B) (Black arrows) Mallory bodies are irregular eosinophilic cytoplasmic structures with a rope-like appearance. (Open arrow) Ballooning degeneration of hepatocytes.
Histological features of alcoholic hepatitis. (c) (Open arrow) Pericellular fibrosis, also termed 'chicken-wire' fibrosis surrounds individual degenerate hepatocytes; (Black arrow) Perivenular fibrosis extends from the central vein.
Histological features of alcoholic hepatitis. (d) The unit lesion (also termed satellitosis) comprises a degenerating hepatocyte with (arrow) a surrounding cuff of neutrophils. Marked steatosis is also evident.
Gynecomastia due to alcoholic cirrhosis A 32 year old male patient with normal secondary sex characteristics, no testicular mass, no hystory of drug ingestion, no other endocrine abnormalities and a normal neurological examination. Nevertheless, he had a history of more than 15 years of large amounts of alcohol intake and a liver biopsy confirm alcoholic cirrhosis (Laennec's Cirrhosis).
Inc. portal system pressure Development of by-passes Systemic & portal circulation share common capillary beds Veins around & within rectum Cardio-esophageal junction Periumbilical & abdominal wall hemorrhoids Esophageal varices Caput medusae
Photograph shows a caput medusae accentuated by a large amount of ascites in a patient being prepared for liver transplantation. An extensive plexus of veins is seen emanating from the umbilical region and radiating across the anterior abdominal wall.
Due to marked deficiency (type II) or absence (type I) of glucuronyl transferase
Type I should always be ruled out when persistent unconjugated bilirubin levels of 20 mg/dL are seen after 1 week of age without obvious hemolysis and especially after breast-milk jaundice has been ruled out.
Due to defective transport of bilirubin-glucuronide through hepatocytes into canaliculi
Characterized by mild, recurrent jaundice
Hepatomegaly and RUQ pain may be present
Jaundice may be produced by estrogens, birth control pills, or last trimester of pregnancy
May resemble mild viral hepatitis
Differential Diagnosis of Hereditary Jaundice with Normal Liver Chemistries & No Signs or Symptoms of Liver Disease Unconjugated Hyperbilirubinemia Crigler-Najjar Syndrome Gilbert’s Type I Type II Incidence Inheritance mode Serum bilirubin usual total (mg/dL) Defect Age at onset of jaundice <7% of pop’n Very rare Uncommon AD AR AD <3; < 6 >20 <20 Mostly B1; inc. All indirect All indirect with fasting Hepatic UDP-glucuronyl transferase activity Decreased Absent Marked dec. Adolescence Infancy Childhood, adolescence
Differential Diagnosis of Hereditary Jaundice with Normal Liver Chemistries & No Signs or Symptoms of Liver Disease Unconjugated Hyperbilirubinemia Crigler-Najjar Syndrome Gilbert’s Type I Type II Usual clinical features Liver biopsy Treatment Appear in early Jaundice, Asymptomatic adulthood; kernicterus in jaundice, often 1 st re- infants, kernicterus cognized w/ young adults rare fasting Normal Normal Normal Not needed Liver transplant Phenobarbital
Differential Diagnosis of Hereditary Jaundice with Normal Liver Chemistries & No Signs or Symptoms of Liver Disease Conjugated Hyperbilirubinemia Dubin-Johnson Rotor’s Syndrome Incidence Inheritance mode Serum bilirubin usual total (mg/dL) Defect Urine total coproporphyrin Age at onset of jaundice Usual clinical features Oral cholecystogram Liver biopsy Treatment Uncommon AR 2-7; < 25 Direct ~ 60% Impaired biliary excretion Normal Childhood, adolescence Asymptomatic jaundice in young adults GB not visualized Charac. pigment Not needed Rare AR 2-7; < 20 Direct ~ 60% Impaired biliary excretion Increased Adolescence, early adulthood Asymptomatic jaundice Normal No pigment None
Comparison of Jaundice (Cholestatic & Hepatocelllular) *Serum bilirubin > 10 mg/dL is rarely seen with CBD stone and usually indicates carcinoma. Hepatocellular Cholestasis Infiltration Disease example Acute viral hep. CBD stone Metastatic tumor Serum bilirubin (mg/dL) 4 – 8 6 – 20* Usually <4, often normal AST, ALT (U/mL) Markedly inc., often 500-1,000 May be sl. Inc., < 200 May be slightly inc., < 100 Serum ALP 1-2x normal 3-5x normal 2-4x normal PT Inc. in severe disease Inc. in chronic cases Normal Response to parenteral vit. K No Yes
Liver Function Tests: Normal Values & Changes Tests Normal Values Hepatocellular Jaundice Uncomplicated Obstructive Jaundice Bilirubin Direct Indirect 0.1-0.3 mg/dL 0.2-0.7 mg/dL Increased Increased Increased Increased Urine bilirubin None Increased Increased Serum albumin/ total protein Alb, 3.5-5.5 g/dL Tot, 6.5-8.4 g/dL Albumin decreased Unchanged Alk phos 30-115 IU/L Increased (+) Increased (++++) Prothrombin time INR of 1.0-1.4; 10% inc. after vit K in 24 hrs No response to parenteral vit. K; prolonged Prolonged but responds to parenteral vit. K ALT, AST ALT: 5-35 IU/L AST: 5-40 IU/L Inc. in hepato- cellular damage, viral hepatitis Minimally increased
Young women on oral contraceptives regress on discontinuance of use
Present as intrahepatic mass mistaken for HCC
If subcapsular (+) rupture intraperitoneal hemorrhage
May harbor HCC – rare
Morphology: cords of hepatocytes with clear cytoplasm (w/ glycogen), absent portal tracts & prominent arterial vessels and draining veins
The hepatic adenoma is composed of cells that closely resemble normal hepatocytes with disorganized hepatocyte cords and does not contain a normal lobular architecture. At the upper right is a well-circumscribed neoplasm that is arising in liver. This is an hepatic adenoma. Normal liver Adenoma
Intrahepatic cholangiocarcinomas are classified as either peripheral or hilar. The hilar variety are located in the hepatic hilum region and appear as discrete masses.
Peripheral cholangiocarcinoma is the most common and develops in the interlobular ducts of the liver, where the interlobular bile duct branches within the portal triads. They may be a single or multiple masses.
Patterns of Liver Chemistry Test Abnormalities Pattern Bilirubin Alkaline phosphatase Amino- transferase Albumin Prothrombin time Hemolysis Inc. (usu. B1) Normal Normal Normal Normal Acute hepatocellular +/- inc. (B1 and B2) Normal or < 3x normal Usu. >400 (ALT>AST) Normal Normal Chronic hepatocellular +/- inc. (B1 and B2) Normal or < 3x normal Usu. <300 U/L May be dec. Often prolonged; doesn’t correct with vit. K Cholestasis Usually inc. (B1 and B2) > 4x normal Usually < 300 U/L Usually normal Normal; corrects with vit. K if prolonged Infiltrative Usually normal > 4x normal; inc. GGT < 300 U/L Usually normal Normal