Path 7 Intrahepatic Flashcards
Bile secreted per day
1 liter
Bile pathway
Bile canaliculi -> Canals of Hering -> bile ductules -> terminal bile ducts
Biliverdin v Bilirubin
water soluble v lipid soluble
Direct bilirubin
- Unconjugated
- Transported on Albumin
Bilirubin in liver
Conjugated with Glucaronic acid by
-UGT1A1 (Uridine diphosphate glucuronyl transferase)
Bilirubin in gun
Bilirubin diglucuronide
-Hydrolized by bacteria to Urobilinogen
Bile composition
Bile salts (90% reabsorbed)
Phospholipids
Cholesterol
Bilirubin
Bile function
- Excretion of endogenous lipids
- Absorption of dietary lipids
Jaudice
-Bilirubin above 2.0 mg/dl
Unconjugated bilirubinemia (3 causes)
- Hemolysis
- Reduced uptake (drug, genetic)
- Impaired conjugation (genetic, physiologic newborn)
Conjugated bilirubinemia (2 causes)
- Decreased excretion (cirrhosis, hepatitis)
- Impaired bile flow
Physiologic jaundice of newborn (cause, pathology, exacerbation, Tx)
- Transient low UGT1A1 activity
- Direct bilirubin deposited in basal ganglia (kernicterus)
- Exacerbated by breast feeding
- Tx with phototherapy
Dubin-Johnson syndrome
- Recessive conjugated hyperbilirubinemia
- Pigmented cytoplasmic globules
- MRP2 mutation (canalicular multidrug protein2)
- Impaired bilirubin glucuronide excretion
Rotor syndrome
- Recessive conjugated hyperbilirubinemia
- Decreased hepatic uptake and storage
Gilbert syndrome
- Recessive unconjugated hyperbilirubinemia
- Decreased UGTA1
Criglar-Najjar syndrome type 1
- Recessive unconjugated hyperbilirubinemia
- Absent UGTA1
- Fatal
Crigler-Najjar syndrome type 2
- Recessive unconjugated hyperbilirubinemia
- Decreased UGTA1
- Mild course, occasional kernicterus
Secondary biliary cirrhosis
Due to obstruction of extrahepatic biliary tree
Primary biliary cirrhosis clinical
- Obstruction symptoms
- Xanthomas, skin pigmentation
- Osteomalacia (due to vit. D malabsorption)
- Cirrhosis
Primary biliary cirrhosis labs
- Antimitochondrial Ab
- Elevated biliarubin, alkaline phosphatase
Primary biliary cirrhosis histo
- Granulomas (epithelioid histiocytes)
- Mixed inflammatory cells around ducts
- Duct proliferation, native ductopenia
Primary sclerosing cholangitis histo
-Onion-skin periductal fibrosis and inflammation
Primary sclerosing cholangitis
- 80% have Ulcerative Colitis
- Obstruction symptoms
- Cholangiocarcinoma risk
Primary sclerosing cholangitis labs
- p-ANCA
- Elevated IgG4 (autoimmune pancreatitis)
- Elevated serum alkaline phosphatase
Hilar Klatskin’s tumor
Cholangiocarcinoma (most common)
-Jaundice & pruritis
Distal peripheral bile duct tumor
Cholangiocarcinoma
- Hepatomegaly
- Weight loss, fatigue
- Abdominal pain
Cholangiocarcinoma risks (5)
- Primary sclerosing cholangitis
- Congenitally dilated bile ducts
- HCV
- Thorium dioxide
- Liver flukes
Cholangiocarcinoma histo
Big fat duct cells with fibrous stroma
Liver protein synthesis (4)
- Albumin
- Prothrombin
- Fibrinogen
- Lipoproteins
Liver metabolite storage (3)
- Triglycerides
- Glycogen
- Vitamin A
Liver metabolic functions (2)
- Gluconeogenesis
- Urea production
Liver architecture
- Reticulin
- No basement membrane
Liver clean up
-Kupffer cells (mononuclear phagocyte)
Ito cell
Perisinusoidal stellate cell
-Stores and metabolizes vitamin A
First cells to die from ischemia and toxicity
Centrilobular
(central vein)
(zone 3)
Cirrhosis mechanism
Lobular fibrosis via stellate (ito) cells in perisinusoidal space of Disse
Liver cirrhosis genetic risk
a1-antitrypsin deficiency
Cirrhosis cancer risk
Hepatocellular carcinoma
Hemangiosarcoma risks (3)
- Vinyl chloride
- Thorium dioxide
- Arsenic
