Etiology of Cirrhosis
-alcohol
-viral
-bile duct damage
-metabolic
-NA fatty liver
-drugs
-autoimmune
-vascular
Histology of alcoholic liver disease
-steatosis (fat droplets)
-"chicken wire" fibrosis
-nodular regeneration
-inflammation
-mallory-denk bodies
Histology of HBV
-enlarged hepatocytes
-dense and shiny cytoplasm
-hep B surface/core antigen
Histology of HCV
-aggregates of lymphocytes in portal tract
Batts grading of inflammation/fibrosis
1
-minimal inflammation
-portal fibrosis
2
-mild inflammation
-periportal fibrosis (sticking out of portal tract)
3
-moderate inflammation
-bridging of fibrosis b/w portal tracts
4
-severe inflammation
-cirrhosis (fibrosis enters central vein)
Diseases that damage bile ducts
developmental/genetic
-extrahepatic biliary atresia
mechanical obstruction/neoplastic
-primary biliary cirrhosis (PBC)
-primary sclerosing cholangitis (PSC)
infections
toxins
ischemia
ideopathic
Characteristics of PBC
rare autoimmune disease
-mostly middle aged women
-(+) for antimitochondrial antibody (AMA)
Pathology of PBC
loss of bile ducts --> portal inflammation, scarring --> cirrhosis, liver failure
accumulation of bile in liver (green color)
Histology of PBC
florid ductal lesion
-dense portal lymphocytic infiltrate around bile duct
-granulomatous inflammation w/ damage of bile ducts
Characteristics of PSC
autoimmune disease associated w/ IBD
-mostly men < 45 yrs old
Pathology of PSC
progressive obliteration of bile duct lumen
-loss of bile ducts
-segmental stenosis of extrahepatic/intrahepatic bile ducts
-diffuse bile ductular proliferation
-beading (cholangiogram)
Histology of PSC
concentric periductal fibrosis (onion skin)
-bile duct surrounded by fibrotic fibers
-lymphocytic infiltration
Pathology of secondary biliary cirrhosis/lithiasis
gall stones build up in bile duct
-cause ischemia
-bile duct damage
Causes of Fe overload (hemochromatosis)
secondary overload
-erithropoetic disease
-increased oral intake
transfusional overload (blood disease)
Pathology/Histology of hemochromatosis
pathology
-dark green nodules
histology
-brown/black granules in cytoplasm
-prussian blue stain
Pathology of Wilson's disease
autosomal recessive
-Cu accumulates in liver
-exceeds binding capacity
-causing liver injury
-mimics acute/chronic viral hepatitis
-cirrhosis develops late
fatty change and focal hepatocyte necrosis
-fat droplets
-rhodanine stain specific to Cu
Pathology of alpha-1 antitrypsin deficiency
autosomal recessive
-low levels AAT --> emphysema + liver disease
cherry globules w/in cytoplasm
-mostly zone 1
Metabolic causes of cirrhosis
hemochromatosis
wilson's disease
AAT deficiency
Pathology of NA fatty liver disease
fat droplets
-progress from zone 3 --> zone 1
inflammatory infiltrates
-mostly lymphocytes (neutrophils in alc fatty liver)
chicken wire
Drugs that can induce liver injury
cholestasis
-erithromycin, testosterone (FL), oral contraceptives, chlorpromazine, phenothiazine, chlorpromazine
hepatitis
-acetominophen, indomethacin, isoniazid, methyl dopa, phenytoin
Pathology of drug-induced liver injury
sharply defined perivenular necrosis
-minimal inflammation
-lymphocytes, eosinophils enter portal area
cholestasis
-out of proportion to hepatocellular injury
hepatitis
-mild hep to panacinar confluent necrosis
-prominent eosinophilic infiltrate
-granulom
Pathology of autoimmune hepatitis
predominantly women
pts often have other autoimmune diseases
-and elevated IgG
Pathology of budd-chiari syndrome
vascular disease
caused by
-myeloproliferative disorders
-clotting disorders
-paroxysmal nocturnal hemoglobinuria
-estrogens (pregnancy)
-cancer
-ideopathic
hepatic congestion
-reversal of flow in portal vein
-congestion in central areas --> necrosis -->
Pathology of veno-occlusive disease
vascular disease
obstruction of terminal hepatic veins leads to
-hepatomegaly
-ascitis
-elevated LFT
caused by
-intake of pyrrolizidine alkaloids
-bone marrow transplant
Miscellaneous causes of cirrhosis
-sarcoidosis
-congenital syphilis
-parasites (schistosomiasis)
-glycogen storage disease (III, IV)
-CF
-galactosemia, tyrosinemia
-porphyrias
-indian childhood cirrhosis
-hereditary hemorrhagic telangiectasia
-cryptogenic
Complications of cirrhosis
-bleeding from esophageal varices
-splenomegaly (2-3x larger)
-spontaneous bacterial peritonitis
-encephalopathy
-hepatorenal syndrome
-hyperestrinism
-HCC
Important benign liver tumors
epithelial
-adenoma, focal nodular hyperplasia (hepatocytes)
-bile duct adenoma, biliary cystadenoma
mesenchymal (vascular)
-hemangioma
Pathology of liver cell adenoma
solitary tumor (10-30cm)
-adjacent liver non-cirrhotic
-benign but may cause hemorrhage if ruptures
associated with
-oral contraceptives
-anabolic steroids
-glycogen storage
-disease antiestrogens
women 30-50 yrs old
Histology of liver cell adenoma
loss of architecture
-no portal spaces
-isolated large arteries (with thickened walls)
Pathology of focal nodular hyperplasia
hepatocyte nodules surrounded by
-fibrous septa
-bile ductular proliferation
-malformed vessels
well-demarcated nodules
-subscapular
-brown --> yellow
-up to 5cm
-central gray/white scar
young women
-may be associated w/ oral contraceptives
Histology of focal nodular hyperplasia
thickened blood vessels
bile duct proliferation
Pathology of bile duct adenoma
proliferation of bile duct cells
-not malignant
subscapular lesion
Pathology of biliary cystadenoma
tumor arises from bile duct
-bile duct expansion
epithelium surrounded by spindle cells
-forms cyst
Pathology of hemangioma
tumor develops in blood vessels
-red, spongy appearance
-small, abnormal blood vessels
-benign cells lining spaces
Important malignant liver tumors
metastasis (most common w/out cirrhosis)
hepatocellular neoplasms
-HCC
-fibrolamellar HCC
bile duct derived
-cholangiocarcinoma
Epidemiology of HCC
more common in
-Africa/african americans
-east asia
-> 60 yrs old w/ cirrhosis
-HBV, HCV, smoking, cirrhosis
Histology of HCC
nodules throughout liver
-cells look similar (comes from hepatocytes)
-less cytoplasm
-no nucleolus
trabecular
-composed of 5-6 hepatocytes
pseudoglandular
-hepatocytes arranged as pseudoglands
solid
-cytoplasm less pink
-larger nuclei
scirrhous
fibrolame
Histology of fibrolamellar HCC
pink, eosinophilic cytoplasm
Characteristics of cholangiocarcinoma
solitary or multinodular tumor
-satellite nodules
-can occasionally accompany a HCC, cholangitis, dilated hepatic ducts
-poor prognosis
risk factors
-men > 60 yrs old
-parasites, cysts, lithiasis