Liver pathology Flashcards
Normal Liver
Portal triad (blue arrow)
Central vein (green arrow)
Zone 1 (A) High O2 tension
Zone 2 (B)
Zone 3 (C) Low O2 tension
Portal Triad:
Hepatic artery (red arrow)
Bile duct (green arrow)
Portal vein (blue arrow)
Bile ducts; canals of Herring (blue arrows)
Normal liver, Trichrome stain; very minimal collagen (blue) in the normal liver, mostly around central vein and portal triad.
Hepatic inflow obstruction; obstruction of hepatic artery results in diffuse necrosis around portal vein and complete devastation around bile duct.
Portal vein thrombosis–>periportal necrosis (diffuse to focal)
Outflow obstruction/Venoocclusive dz–sinovascular obstructive dz (VOD-SOS); see sinusoid congestion due to obstruction (blow arrow) and hepatocyte drop-out towards central vein.
Peliosis Hepatis; diffuse dilation and congestion of sinusoids; caused by steroid use, azathioprine, danazol, B. Henselae, Castleman’s, and vinyl chloride exposure—all rare
Most often found at autopsy, can lead to fatal hemorrhage
Chronic passive congestion (secondary to CHF); central vein’s have sinusoidal congestion and hepatocyte atrophy; grossly see “nutmeg liver” (upper left photo)
Nodular regenerative hyperplasia; presents clinically as cirrhosis, see parenchymal nodules on bx, but no fibrosis.
Nodular regenerative hyperplasia; cauesd by MANY MANY things, see parenchymal nodules on bx; tx underlying cause
Focal nodular hyperplasia; a vascular anomaly (not neoplastic); grossly see lobulated nodules with central stellate scar
Focal nodular hyperplasia, a vascular anomaly; see prominent arteries with reactive adjacent tissue; cytology bland and normal plate thickness
Focal nodular hyperplasia, a vascular anomaly; can stain for with glutamine synthetase which reflects vascular flow anomalies
Cirrhosis; characterized by extensive bridging fibrosis around regenerative nodules; cirrhosis is the end-stage for many processes (alcohol, Hep C, autoimmune hepatitis, etc)
Ductular rxn; development of multiple “worm-like” bile ducts around the portal triad.
Ductular rxn with bile duct injury; see “worm-like” bile ducts that develop around the portal triad.
Cholestasis; on bx see accumulation of material in bile ducts and canaliculi
Ductular rxn wiht bile duct injury; nuclei are not round and weirdly spaced
Copper deposits around the portal triad; cause ductular reaction with bile duct injury
Ductopenia; obliterative fibrosis around portal triad; can see in normal liver (up to 20% ductopenia), also can be the final common endpoint of chronic obstruction/biliary injury
Primary biliary cirrhosis; granulomatous destruction of medium-sized bile ducts leading to chronic cholestasis, fibrosis, and cirrhosis. See dense lymphocytic plasma infiltrate around the portal trial and damage to bile ducts.
More common in females, peak age of onset 40-50 y.o., labs: +AMA, increasing Alk Phosph, itching, increase total bilirubin, normal LFT’s.
Tx with ursodeoxycholic acid or transplant
Primary biliary cirrhosis; see portal-based granulomas
Primary Sclerosing Cholangitis; inflammation and fibrous obliteration of large bile ducts, including extrahepatic ducts, leading to obstructive cholestasis, fibrosis, and cirrhosis. On bx see concentric fibrosis of bile duct. on ERCP see dilation and stricturing along the bile duct.
More common in males, peak age of onset 25-35 y.o., 70% of pts will have ulcerative colitis, 10% have Crohn’s Dz; markely increased risk of cholangiocarcinoma
Primary sclerosing cholangitis; see inflammation and fibrous obliteration of large ducts; see lymphocytes in biliary epithelium (image right)
Biliary cirrhosis
Biliary cirrhosis; see bridging fibrosis around regenerating nodules
Fulminant herpetic hepatitis; see irregular parenchyma and hemorrhaging
Acetaminophen toxicity; bright pink areas indicate dead hepatocytes (loss of nuclei)
Acetaminophen toxicity; see hepatocyte death (loss of nuclei)–cells appear bright pink
Steatosis; see large vacuoles (were filled with fat pre-processing of tissue); absence of inflammation; grossly liver appears yellow/tan and greasy
Microvesicular steatosis, seen in Reye’s syndrome; tiny foamy vacuoles
Alcoholic hepatitis; see steatohepatitis-pattern of injury on biopsy (steatosis + inflammation); see ballooning degeneration of hepatocytes (filled with grainy cytoplasm); also see Mallory’s hyaline deposition (bright pink deposites inside of vacuoles), acute/chronic inflammation in portal areas, and sinusoidal fibrosis.
Alcoholic hepatitis; looks like steatohepatitis; with Trichrome stain can see paracellular/sinusoidal fibrosis wrapping around ballooning hepatocytes
Chronic hepatitis; see lymphocytic infiltration and “interface activity” (damage to surrounding hepatocytes); can be due to viral, autoimmune, or drug hepatitis.
Acidophil bodies; are dead/shrunken hepatocytes; also see ceroid-laden macrophages (unsaturated lipids)
Chronic hepatitis; on the right see portal triad filled with lymphocytes and interface activity; on the bottome left see normal-appearing hepatocytes
Interface activity; hepatocyte injury bordering lymphocytic infiltration, aka “piecemeal necrosis”
Ground glass hepatocytes; characterized by viruses packing into vacuoles in hepatocytes; dx’stic of chronic Hep B usually, but also seen in some other conditions.
Echinococcal cyst; a canine tapeworm that invades the lungs and liver, forming cysts; cyst rupture can cause anaphylaxis; example of non-viral infectious hepatitis
Alpha-1 Antitrypsin Deficiency; an AR mt in A1AT gene, an inhibitor of neutrophil elastase (released during inflammation). Deficiency seen in ~10% of PiZZ homozygous pts who have reduced ability to degrade mutant proteins, so see accumulation of large, eosinophilic globule of antitrypsin in hepatocytes which undergo necrosis –> fibrosis, nodular regeneration and cirrhosis.
PAS/D stain detects globules of mt A1AT protein in hepatocytes.
Gaucher’s dz; defect in glucocerebrosidase which accumulates in small aggregates of liver macrophages in the sinuosoids. On high-power microscopy appears as crumpled “tissue paper.” Can also affect spleen and bonemarrow. Most common among Jews of European descent.
Von Gierke Dz, a glycogen storage dz, defect in glucose-6-phosphatase leads to accumulation of glycogen in hepatocytes and subsequent hypoglycemia, failure to thrive, skin xanthomas, gout, and bleeding disorders. Liver transplant needed to prevent fatality.
Hemachromatosis, an AR mutation in HFE gene, leading to excess absorption of dietary iron, accumulation of iron in the liver, leading to toxicity, fibrosis, and cirrhosis.
Extrahepatic manifestations include CHF (Fe accumulation in heart), and DM (Fe accumulation in pancreas).
Epidemiology: males, >40 y.o., less often seen in women due to iron loss with menses.
Labs: see elevated serum ferritin and transferrin-iron saturation.
Tx with phlebotomy, good prognosis if Fe levels reduced/normalized.
Hemochromatosis; extrahepatic manifestations include CHF (deposition in heart, left image) and DM (pancreatic deposition, right image).
Hepatic hemangioma
Hepatic adenoma; clonally-derived benign growths, usually seen in women, often with a 5+ yr hx of OCP use; uncommonly seen in men w/ hx of anabolic steroid use, rare life-threatening complications include rupture and hemorrhage.
Subtypes include HNF1A mt’d, b-catenin activated, inflammatory and unclassified
Hepatic adenoma, HNF1A mutated subtype; more common in females, 35-40% of hepatic adenomas, see a decrease in FABP1 expression, tend to have more steatosis
Hepatic adenoma, Inflammatory type; make up 50% of hepatic adenomas, associated with alcohol and obesity, see numerous thick walled arteries, inflammatory infiltrates, and sinusoidal dilation.
Stain strongly for CRP and Serum Amyloid A
Hepatocellular carcinoma; cirrhosis is main risk factor (~80% of HCC cases in cirrhotic pts); other risk factors include chronic Hep B or C, and aflatoxins produced by mold in spoiled food; most common primary malignant tumor of the liver; usually advanced with dx’d; primary tx with surgery (chemo and radiation largely ineffective).
Hepatocellular carcinoma
Hepatocellular carinoma; tumor looks like sinusoidal spaces, hypercellularity
