hepatic pathology

Question 1

Liver microanatomy

Answer 1

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

Question 2

kupffer cells vs stellate cells

Answer 2

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

Question 3

Patterns of hepatic injury

Answer 3

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)

Question 4

Hepatic cirrhosis

Answer 4

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)

Question 5

Infectious disorders of the liver

Answer 5

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)

Question 6

Alcoholic hepaptitis microscopy

Answer 6

Mallory body! with necrotic hepatocytes

Hyaline bodies - just ketratin filled cytoplasm

Question 7

features of drug and toxin-induced liver disease

Answer 7

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

Question 8

Cholestasis (obstructive liver disease)

Answer 8

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)

Question 9

intra vs extra hepatic cholestasis

Answer 9

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

Question 10

cholestasis pathophysiology

Answer 10

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

Question 11

cholestasis of sepsis

Answer 11

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)

Question 12

primary biliary cirrhosis

Answer 12

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

Question 13

Secondary biliary cirrhosis (AKA ANATOMIC)

Answer 13

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

Question 14

Primary sclerosing cholangitis

Answer 14

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

Question 15

Primary sclerosing cholangitis histopathology

Answer 15

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

Question 16

Liver infarcts

Answer 16

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

Question 17

Extra hepatic portal vein obstruction

Answer 17

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

Question 18

Intrahepatic obstruction of blood flow

Answer 18

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

Question 19

Budd chiari syndrome (hepatic vein thrombosis

Answer 19

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)

Question 20

Sinusoidal obstructive syndrome

Answer 20

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)

Question 21

Chronic passive congestion of liver

Answer 21

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

Question 22

Heatocellular nodules

Answer 22

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

Question 23

dysplastic nodules

Answer 23

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

Question 24

benign hepatic neoplasms

Answer 24

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

Question 25

precursor lesions of HCC

Answer 25

Cellular dysplasia- large cell variant , not a pre malignant change, changes occur due to chronic injury

Cellular dysplasia- small cell variant- directly pre malignant

Question 26

Malignant tumors of the liver

Answer 26

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

Question 27

Hepatocellular carcinoma (HCC)

Answer 27

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)