153. Pathology Gallbladder, Biliary Tract

Question 1

Bilirubin: when is it unconjugated and conjugated

Cholestasis

• etiologies
• pathophys
• histo

Answer 1

bili: breakdown product of heme
Extrahepatic: bound to albumin (unconj)
Intrahepatic: gets glucuronidated (conj) excreted in bile

Cholestasis:
Intrahepatic: Alcohol, Drug Toxicity, Viral Hepatitis, PBC, PSC, TPN
Extrahepatic: PSC, Obstruction (stone, carcinoma, congenital atresia, trauma/stricture)
Pathophys: 1. Retention of bile acids = Pruritis, 2. high serum bilirubin/lipids = Jaundice, Xanthomas, 3. Less bile entry to intestine = Fat malabsorption, vit ADEK deficiency = steatorrhea, night blindness, bone disease, neuropathy/rash, coagulopathy, 4. Hepatic accumulation of Cu, bile acids, other compounds = liver damage
Histo: bile plugs, ballooning degeneration due to toxic buildup within hepatocyte

Question 2

PBC (Primary Biliary Cholangitis)

• what is it
• epi (F or M)
• labs/dx
• sx
• histo
• management
• key pt scenario

Answer 2

Autoimmune destruction of small INTRAHEPATIC bile ducts = inflammation/fibrosis = decreased bile flow (“obstructive”) = progressive fibrosis - cirrhosis/liver failure
F>M
Labs: high Alk-P, high GGT, high bili, high IgM, AMA+ in 95% KEY!! AMA
Sx: pruritis, jaundice, xanthomas

Histo:
Stage 1: FLORID DUCT LESIONS: lymph inflammation +/- GRANULOMAS (Giant cells) - cause damage to small bile ducts and loss of shape
Stage 2: Ductular proliferations (compensate for “obstructions”)
Stage 3: Fibrosis/scarring
Stage 4: Cirrhosis

Mgmt:
Ursedeoxycholic Acid: more hydrophilic bile acid = improves itching/liver enzymes (less hydrophobic bile production), delays disease progression
Tx fat soluble vitamin deficiencies (Vit ADEK)
Cholestyramine for itching
Cirrhosis = transplant

MIDDLE AGE WOMAN WITH JAUNDICE AND ITCHING

Question 3

PSC (Primary Sclerosing Cholangitis)

• what is it
• epidemiology (M or F)
• disease assoc
• sx
• labs
• imaging
• histo
• mgmt
• pt scenario

Answer 3

Chronic cholestatic liver disease due to progressive inflammation, fibrosis, destruction of intra and EXTRAHEPATIC bile ducts
Epi: 1/60000 in US, M>F
Assoc: 70-80% have coexisting UC; 160x risk for CHOLANGIOCARCINOMA
sx: diarrhea, bloody stools, jaundice, fatigue, itching
Labs: HIGH Alk-P, high bili, AST/ALT near normal
Imaging: Ultrasound, ERCP/MRCP, Colonoscopy for UC
Histo: sclerosis - bile duct destruction, concentric ONION-LIKE FIBROSIS around small bile ducts
Cholangiocarcinoma histo: large angular glands infiltrating and mass lesion formation

Mgmt: Tx underlying disease (UC = immunosuppression), dilation/stenting of strictures, screen for cholangiocarcinoma, liver tx

Pt: YOUNG MAN WITH JAUNDICE AND DIARRHEA (HX OF UC)

Question 4

Normal histo of gallbladder

Cholelithiasis

• types of stones
• pathogenesis and RF for each stone
• complications

Answer 4

Normal: mucosal layer on muscular layer (no submucosa)

1. Cholesterol Stones: 80% in US, mainly cholesterol crystals
   PGen: 1. Bile supersaturated with cholesterol = NUCLEATION (formation of solid cholesterol monohydrate crystals), 2. Gallbladder hypomobility = accelerates nucleation, 3. Mucus hypersecretion in gallbladder traps nucleated crystals = aggregation
   RF: 5F’s: Fat (obesity, high fat diet, hyperlipidemia), Female (female sex hormones), Fair (white ppl - genetic predisposition), Fertile (pregnant/OCP/pre-menopausal: high estrogen = high cholesterol secretion and low gallbladder contraction), Forty and Above (advanced age), Rapid Weight loss and some drugs
2. Black Pigmented: 20% US, Ca salts of unconj bili (hard, radioopaque)
   PGen: Chronic Hemolysis = high unconj bili (+GB stasis) = precipitation of Ca + unconj bili
3. Brown Pigmented: 5%, Ca salts of unconj bili with cholesterol/palmitate (MIXED)
   RADIOLUCENT - not seen on imaging, soft/friable
   More common in Asia

Complications: 1. Cholecystis, 2. Choledocholithiasis (in biliary tree), 3. Gallstone ileus

Question 5

Acute Cholecystitis

• what is it
• sx
• types

Answer 5

Acute GB infection

sx: fever, leukocytosis, RUQ Pain
1. Calculous Cholecystitis: 90%, gallstone obstructs cystic duct
2. Acalculous Cholecystitis: 10%, assoc with critical conditions (surgery, burns, TPN, post-partum, trauma) due to low contractility of GB (ischemia), bile stasis, high viscosity of GB

Question 6

Chronic Cholecystitis

• what is it
• sx
• gross

Answer 6

> 90% assoc with gallstones
Repeat bouts of mild-severe acute cholecystitis
Many w/o apparent antecedant attacks
sx: recurrent attacks, with steady/colicky RUQ pain, N/V, intolerance to fatty food
Gross: thickened GB wall with stones (due to contraction against resistance)

Question 7

GB Carcinoma

• what is it
• epi (age, gender, race)
• RF
• Histo

Answer 7

MOST COMMON malignancy of extrahepatic biliary tree
F>M, age 60s-70s, common in whites
Most important RF: gallstones, chronic cholecystitis
“porcelain GB” = calcified gallbladder 2/2 chronic cholecystitis (15% risk of cancer developing)

Histo: angulated glands infiltrating + invading thru wall and proliferating