hepatic pathology Flashcards
Liver microanatomy
Classic lobule- unit drained by central vein (hexagon)
Portal lobule- unit supplied by one portal triad (triangle)
Acinus- short axis between 2 portal triads and a long axis between 2 central veins describes degenerative patterns and toxic effects according to vascular perfusion (zone 1 is closest to portal triad, 1st to get nutrients and toxins, zone 3 is furthest and susceptible to ischemia
kupffer cells vs stellate cells
Kupffer cells- phagocytic cells which line the hepatic sinusoids (on the endothelial cells)
Stellate cells- located in space of disse, acitivated in response to injury
Patterns of hepatic injury
Degeneration and intracellular accumulation
Necrosis and apoptosis
Regeneration- reserve “oval cells” can regenerate
Inflammation
Fibrosis- response to inflammation or direct toxic insult (periportal fibrosis–> pericellular fibrosis–> bridging fibrosis)
Cirrhosis- progressive fibrosis surrounds regenerative nodules
Ductular reaction (proliferation)
Hepatic cirrhosis
one of top causes of death, diffuse fibrosis and regenerative liver nodules
Bridging fibrous septae, Parenchymal nodules, diffuse diffuse disruption of hepatic architecture
Obesity, alcoholism, Hep B and C, biliary disease, hemochromatosis, Auto immune disease, cryptogenic (unknown)
Infectious disorders of the liver
Viral hepatitis (A B C D E and G)
Infectious Mononucleosis (EBV)
CMV/herpes- neonates, immunosuppressed
Yellow fever-trpical countries
Hep B- cell infiltrate obscures architecture (apoptotic cell- clowdy cells)
Alcoholic hepaptitis microscopy
Mallory body! with necrotic hepatocytes
Hyaline bodies - just ketratin filled cytoplasm
features of drug and toxin-induced liver disease
injury may occur as hepatocyte necrosis, cholestasis, insidious onset of liver dysfunction
Drug induced chronic hepatitis may be clinically and histologically indistinguishable from chronic viral hepatitis, hence serologic markers of viral infection required to make diagnosis
in alcohol- induced liver disease, both microvesicular and macrovesicular steatosis arise from production of excess reducing equivalents (NADH and H) resulting from metabolism of EtOH
Cholestasis (obstructive liver disease)
Cholestasis- systemic retention of not only bile but also other solutes eliminated in bile (bile salts, cholesterol)
Blockage of bile excretion from the liver
Results from hepatocellular dysfunction of biliary obstruction (intra- or extra hepatic)
Jaundice, pruritis, skin xanthomas (collection of foamy histiocytes- contain cholesterol)
Pruritis- due to action of bile acids on peripheral nerves can be presenting symptom
Elevated Alk phos and GGT
Deficiency of fat soluble vitamins (A D and K)
Unrelieved obstruction–> portal tract fibrosis–> cirrhosis)
intra vs extra hepatic cholestasis
Intra- hepatic cholestasis- drugs (oral contraceptives, anabolic steroids), neonatal hepatitis, pregnancy- related (estrogens)
Extra-hepatic cholestasts- Block of common bile duct due to gall stones, primary sclerosing (pericholangitis), Extrahepatic biliary atresia, carcinoma of head of pancreas, amenable to surgery
cholestasis pathophysiology
Bile can’t leave the liver bile canaliculi, so it accumulates in between the hepatocytes, and there fore bile/cholesterol accumulates in the hepatocytes, and causes apoptosis
cholestasis of sepsis
Canalicular cholestasis- mild portal inflammation with minimal necrosis, just accumulates in canaliculus
Ductular cholestasis- more ominous- bile ducules plugged with bile (this change may accompany or precede septic shock)
primary biliary cirrhosis
Non suppurative, inflammatory destruction of small and medium sized intrahepatic bile ducts without a bacteria
Chronic, progressive and potentially fatal
Cirrhosis eventually develops with portal hypertension
Peak at mid age, F>M, insidious onset–pruritis, jaundice late, xanthomas and xanthelasmas arise due to cholesterol retention
LABs- Alk phos high, cholesterol high, bilirubin is high, anti mitochondrial antibodies
Pathogenesis: AI disease destrosy biliary tree, needs liver transplant–> cirrhosis
Secondary biliary cirrhosis (AKA ANATOMIC)
Results from obstruction of extrahepatic biliary tree
Most common causes in adults- Extrahepatic cholelithiasis (gall stones), malignancies of the bilary tree at the head of pnacreas, strictures from surgery
Most common cause in kids: bilary atresia, cystic fibrosis, choledochal cysts (bile duct)
Cholestasis is reversibel if obstruction is corrected, prolonged cholestasis leads to inflammation, periportal fibrosis, hepatic scarring and cirrhosis, subtotal obstruction may lead to ascending cholangitis
Primary sclerosing cholangitis
Inflammatory cytokines or ischemia, progressive fibrosis and destruction of extrahepatic and large intra hepatic bile ducts
Clinical features- progressive fatigue, pruritis, jaundice
LABs: persistently elevated alk phos NO anti mito
Cirrhosis can result–> portal HTN
Increased risk for cholangiocarcinoma (bile duct Carcinoma)
liver trans
Primary sclerosing cholangitis histopathology
Inflammation and obliterative fibrosis of intrahepatic and extrahepatic bile ducts
Inflammatory bowel disease (ulcerative colitis)- coexists in 70% of pts (People who have PSC also have Ulc col, but people with ulc col rarely get psc)
30s-50s in males, immune mediated
ONION skin bile duct
Liver infarcts
hepatic infarcts (rare) typically subcapsular are rare due to the dual blood supply to the liver Hepatic artery thrombosis in transplanted liver leads to infarct and loss of organ
Extra hepatic portal vein obstruction
Peritoneal sepsis (acute diverticulitis or appendicitis leading to pylephlebitis in splanchnic circulation)
pancreatitis- initiates splenic vein thrombisis which propagates into portal vein
Thrombogenic diseases
Post surgical thromboses
Vascular invasion by tumor, including hepatocellular carcinoma
Banti syndrome- subclinical thrombosis of portal vein produces a fibrotic recanalized vascular channel
Intrahepatic obstruction of blood flow
Cirrhosis, sickle cell disease, disseminated intravascular coagulopathy, centrilobular hemorrhagic necrosis, peliosis hepatis
Nutmeg liver
Centrilobular hemorrhagic necrosis- most common cause is heart failure
Peliosis hepatitis- primary sinusoidal dilatation, anabolic steroids, oral contraceptives
Budd chiari syndrome (hepatic vein thrombosis
Obstruction of one or more major hepatic veins due to thrombosis, caused by polycythemia vera, pregnancy, post partum state, oral contraceptives, hepatocellular carcinoma
Clinical- hepatomegaly wt gain, ascities, abdominal pain
Acute form- high mortality if untreated (portosystemic shunt)
Sinusoidal obstructive syndrome
Damaged endothelial cells create thromboemboli, resulting in fibrosis of terminal branches of hepatic vein
occurs primarily a month after BM transplantation in up to 20% of recipients (Cyclophosphamide and radiation)
Most patients recover spontaneosly but death rates are significant
usually a clinical diagnosis (hepatomegalu, ascites, wt gain, and jaundice)
Chronic passive congestion of liver
Pathophys- RHF with back of venous blood into the liver, combination of hypoperfusion and retrograde congestion, can lead to cardiac sclerosis (cirrhossis)
Histology- centrilobular necrosis- the centrilobular zone (3, closest to the cental vein) gets the most deoxygenated blood and therefore necrosis occurs first, RBCs are prominent in the zone
Nutmeg
Heatocellular nodules
Focal nodular hyperplasia- young to middle aged adults, female preponderance- poorly encapsulated lesion with central fibrous scar and hyperplastic hepatocyte nodules ( nodular regeneration in response to vascular injury)
Clinically- epigastric fullness and discomfort
No associated increased risk of malignancy, significance- must distinguish from malignancy
20% of the cases coexist with cavernous hemangioma
Really large lesions are typically bening but the small lesions under 1 cm have malignant potential
dysplastic nodules
Lesions> 1 cm diameter in cirrhotic livers
Atypical features and proliferation
Distinctive chromosomal aberrations, high grade (small cell) dysplastic lesions felt to be precursors of hepatocellular carcinoma, large cell dysplastic lesions are not malignant precursors
benign hepatic neoplasms
Cavernous hemangioma- most common, subcapsular, consists of endothelial cell lined vascular channels, must distinguish from malignat lesion- lots of blood vessels that bleed when the biopsy
Hepatic adenoma- females using orl contraceptives, regress when contraceptives stopped- tend to rupture, mistaken for hepato cellular Ca- adenomas with b catenin mutations that carry a risk of becoming malignant
precursor lesions of HCC
Cellular dysplasia- large cell variant , not a pre malignant change, changes occur due to chronic injury
Cellular dysplasia- small cell variant- directly pre malignant
Malignant tumors of the liver
Metastatic carcinoma- brease, lung, and colon much more frequent than primary carcinoma of the liver
Hepatoblastoma- most common malignant liver tumor of young childhoold, fatal within years if not resected, 2 major anatomic variatns- Epithelial type (structures resemble normal liver), Mixed epithelial and mesenchymal type (foci of osteoid, cartilage, muscle)
angiosarcoma- associated with exposure to vinyl chloride, arsenic and/thorotrast- long latency
Hepatocellular carcinoma (HCC)
Most common primary liver malignancy, cirrhosis is present in 90%, usually old people,
Asia and africa (HBV, alfatoxins from aspergilis)
Develops from small cell high grade dysplastic nodules in cirrhotic livers, arise from mature hepatocytes and progenitor (oval cells)
nodule vascularization is indication for malignancy
uni or multifocal
structural and numeric chromosome abnomalities are almost univeral
tumerigenic capacity- HBV and HCV linked to their capacity to cause continuing cell death - chronig inflammation and regeneration
AFP (alpha feto protein can be increased)
