Week 5: Pathology of biliary tract diseases

Question 1

Extrahepatic bile duct obstruction: etiology

Answer 1

1. Acute
   - choledocholithiasis
   - acute pancreatitis
   - early stages of acute stricture of CBD
   - mass lesions
2. Chronic
   - long term-stricture (chronic pancreatitis)
   - extrahepatic biliary atresia ( neonate)
   - parasitic infection (clonorchis sinensis)

Question 2

Signs and symptoms of extra hepatic bile duct obstruction

Answer 2

• abdominal pain
• fever
• leukocytosis
• jaundice
• AST, ALT 100-200 IU/L
• markedly elevated alk phos

Question 3

Pathology of extra hepatic bile duct obstruction

Answer 3

1. Gross
   - early stage: enlarged liver, stains green with bile
   - dilated intrahepatic bile ducts
   - cirrhosis: smaller liver, mottled green/brown, granular, firm
2. Micro
   - early: cholestasis in perivenular area. Periductal edema, with PMNs around duct and invading BM (acute cholangitis).
   - weeks-months: bile duct proliferation and dilatation. Less tubular and more tortuous. Dilated canaliculi filled with bile. Bile infarct (lytic necrosis-center of necrotic liver cells and bile surrounded by histiocytes, degenerating hepatocytes). Bile lakes. Mallory bodies.
   - years: secondary biliary cirrhosis. Common bile duct stricture. Regeneration nodules, bridging fibrosis, periductal fibrosis.

Question 4

Primary biliary cirrhosis -definition

Answer 4

• chronic, slowly progressive cholestatic liver disease
• characterized by non-suppurative destructive cholangitis
• progression to biliary cirrhosis with manifestations of portal HTN
• middle aged women 30-70 years old

Question 5

Presentation of primary biliary cirrhosis

Answer 5

LABS
-Elevated alk phos
-AST, ALT 2-3x normal
-selective IGM elevation
-M2 autoantigen (AMA-antimitochondrial antibody): positive
-hypercholesterolemia
-initially albumin, prothrombin normal
SYMPTOMS: pruritus, usually preceding jaundice
-signs: hepatomegaly, splenomegaly
-may develop ascites, esophageal varies, GI bleeding

Question 6

Pathophysiology of primary biliary cirrhosis

Answer 6

• defect in immune system: lymphocytes target duct epithelium
• antigen to mitochondria: unknown how antigen is responsible for disease

Question 7

Pathology of primary biliary cirrhosis

Answer 7

Stage I -Florid duct lesion
-infiltration of lymphocytes through duct BM (non suppurative duct damage). Granulomas can be seen
Stage II Ductular proliferation
-mild portal fibrosis
Stage III Scarring
-fibrosis with portal to portal riding
-decrease in interlobular bile ducts
Stage IV Cirrhosis
-may have “piecemeal” necrosis- hepatitis like rxn
-mallory bodies
-cholestasis
-regenerative nodules with periseptal fibrosis
-decrease/absence of small to medium bile ducts, sparing of larger ducts

Question 8

Treatment of primary biliary cirrhosis

Answer 8

1. immunosuppressives
   - corticosteroids, azathioprine, cyclosporin
2. antifibrogenic agents: colchicine
3. bind bile acids
   - cholestyramine
4. Ursodiol -dissolution of gallstones
5. Surgical
   - portacaval shunts
   - transplantation

Question 9

Primary sclerosing cholangitis- definition

Answer 9

• chronic cholestatic liver disease characterized by diffuse fibrosing obliterative cholangitis and inflammation of intra and extra hepatic bile ducts
• men in middle age, usually associated with chronic ulcerative colitis
• usually progressive with biliary cirrhosis and portal HTN

Question 10

Clinical presentation of primary sclerosing cholangitis

Answer 10

• asymptomatic with abn. liver tests
• pruritus, hepatomegaly, splenomegaly
• recurrent bouts of cholangitis: fever, ab pain, intermittent jaundice
• complications of chronic liver disease: ascites, bleeding from esophageal varices
• associated diseases: commonly ulcerative colitis. Also Sjogrens syndrome, autoimmune hepatitis, RA, vasculitis

Question 11

Lab findings in primary sclerosing cholangitis

Answer 11

• alk phos > 3x normal
• slightly elevated AST, ALT
• elevated bili
• atypical ANCA - sensitive but not specific
• imaging: “beading” of bile ducts-alternating areas in ducts of dilation and stricture

Question 12

Pathophysiology of primary sclerosing cholangitis

Answer 12

• unknown specific cause
• genetic predisposition: HLA genes
• acute insult of biliary system: infection, colon toxins, ischemic duct injury
• alteration in bile ducts that mark them as foreign, leading to their destruction by autoimmune mechanisms: cytotoxic T cells, immune complexes

Question 13

Pathology of primary sclerosing cholangitis

Answer 13

GROSS
-CBD and common hepatic ducts thickened irregularly
MICRO
-large duct fibrosis, epithelial injury, surrounding lymphocytic infiltrates. Predicate fibrosis and destruction. decreased number of ducts in portal areas as disease progresses. Mallory bodies. Extra hepatic bile duct can have inflammation and fibrosis.

Question 14

Treatment of primary sclerosing cholangitis

Answer 14

1. medical
   - cholestyramine for pruritus
   - ursodeoxycholic acid for gallstone dissolution
   - D-penicillamine: prevent increase Cu absorption
   - Chochicine: anti fibrotic
2. immunosuppressives
3. Surgical
   - biliary tract reconstruction/stent, temporary
   - transplantation

Question 15

Acute cholecystitis

Answer 15

• persistant impaction of stones
• ab pain and guarding
• low grade fever, neutrophilic
• usually resolves after a few days but can have serious complications with jaundice, high fever and leukocytosis, ascending cholangitis, severe abdominal tenderness, acute pancreatitis, severe cases rupture

Question 16

Chronic cholecystitis

Answer 16

• thickened, rubbery wall of gallbladder
• may be asymptomatic, but also present with bouts of colic
• Rokitansky-Aschoff sinuses: pockets in wall of gallbladder/ pseudodiverticuli.