Pathology of Biliary Tract and

Gallbladder

Dr. RAFIF AL SAADY

Assistant Professor
MBChB, FICMS, EBP, DipRCPath
[email protected]
 Objectives
 Cholestatic liver diseases
 Tumors of the Liver.
 Disorder of gallbladder.
 Causes of Jaundice.
 Biliary Tract Diseases/Cholestatic Liver Diseases

 Causes could be intrahepatic or extrahepatic obstruction of bile channels or defect in

hepatocyte bile secretion.

 Patient has dark urine, pale stool, and pruritus (↑ plasma bile acids), xanthomas, &
steatorrhea with malabsorption of fat-soluble vitamins.

 Cholestatic pattern of LFT: ↑conjugated bilirubin, ↑cholesterol, ↑ GTT, and ↑alkaline

phosphatase

Steatorrhea = excessive fat in feces.

Xanthoma = firm, raised waxy-appearing papules
 Extrahepatic: Bile duct obstruction
 Adult: gallstone, post surgery biliary stricture, pancreatic
carcinoma…etc).

 Children : malformation in the biliary system as biliary atresia,

choledochal cyst, & in cystic fibrosis.

 Extrahepatic biliary obstruction →↑ pressure in intrahepatic → ducts

injury/ fibrosis and bile stasis.

 Early is reversible (surgery), later develop biliary cirrhosis.

 Mic.: cholestatic feature with ductular reaction and Mallory-Denk bodies

 May be complicated by ascending cholangitis.

 Morphological Changes

 Accumulation of bile pigment in hepatocytes

(1)→ feathery degeneration
 Elongated green-brown bile plugs in dilated
bile canaliculi (2)→ rupture , bile taken by
Kuepfer cells (4).
 Extravasation of bile → bile infarcts.
 Ascending Cholangitis

• Secondary bacterial ascending infection of biliary tree due to biliary obstruction.

• Gut organisms as coliforms & enterococci (G-ve).
• Risk factors: obstructive GS, malignancy, stricture & blockage of stent.
• Present with Charcot triad: Colour (jaundice), Chills & fever, Colicky pain (RUQ).
• + mental confusion & hypotension= Reynolds pentad (o=‫)خمسة‬.
• Lab. findings: leukocytosis, ↑ bilirubin & alkaline phosphatase with mild ↑ transaminase
• Complication: suppurative cholangitis.
 Ascending Cholangitis
 Microscopic : infiltration of bile ducts by
neutrophils.
 Intrahepatic: Autoimmune Cholangitis

 Primary Sclerosing Cholangitis.

 Primary biliary Cholangitis.

 Primary Sclerosing cholangitis
 Inflammation & obstructive fibrosis of intra & extrahepatic
bile duct with dilatation of preserved segments.

 Middle age men with Inflammatory bowel disease (ulcerative

colitis).

 Patient may be asymptomatic with ↑ ALK.phosphatase or

jaundice & pruritis.

 Can lead to ascending cholangitis, secondary biliary cirrhosis,

↑ risk of cholangiocarcinoma & GB cancer.

 Lab. test : autoantibody as p-ANCA positive.

 Radiology: alternating stricture & dilatation with beading of

intra & extrahepatic bile ducts on ERCP & MRCP.

 Liver biopsy: concentric onion skin bile duct fibrosis in

intrahepatic bile duct and lymphocytic infiltration in
extrahepatic bile ducts..

MRCP image shows mild dilatation of the extrahepatic bile duct

(arrowhead), irregularity and beading of the intrahepatic ducts (short
arrows) and a normal pancreatic duct (long arrows)
 Primary Biliary Cholangitis/Cirrhosis
 Non –suppurative destruction of small & medium sized
intrahepatic bile ducts.

 Classically in middle age women.

 Associated with other autoimmune diseases as coeliac,
Hashimoto thyroiditis, rheumatoid arthritis, Sjogren
syndrome..

 Present with jaundice, pruritis, & ↑alk.phosphatase

 Lab. test: autoantibodies mainly Anti-mitochondrial
antibody.

 Liver biopsy: lymphocytes & granulomas destruction of

intrahepatic bile ducts (florid duct lesion).
Primarybiliary
Primary biliarycirrhosis. A portal
cirrhosis. tracttract
A portal is markedly expanded
is markedly
by an infiltrate
expanded by anof infiltrate
lymphocytes and plasma cells
of lymphocytes andsurrounding
plasma
 Later may end by fibrosis → cirrhosis. a destructive
cells granulomatous
surrounding reaction
a destructive centered on areaction
granulomatous bile duct
(the “floridon
centered duct lesion).
a bile duct (the “florid duct lesion).
Summary
 Tumors of the Liver
 Benign
 Malignant
I. Primary : Hepatocyte : Hepatoma= hepatocellular carcinoma

Bile duct: Cholangiocarcinoma.

Blood vessels: Angiosarcoma (industrial materials: vinyl chloride

monomer).

II. Secondary : Most common tumors of the liver

 Tumors of the Liver
Benign tumors

 Cavernous hemangiomas:
most common benign tumour.
Histologically: vascular channels in
bed of fibrous connective tissue
 Tumors of the Liver
• Hepatocellular Adenoma: women
(estrogen-rich oral contraceptives), usually
are well-demarcated but unencapsulated
tumors that may be pale, yellow-tan, or
bile-stained and up to 30 cm in diameter.
Histologically: cords of hepatocytes with
vascular supply ↓. Risk of rupture with
intraperitoneal hemorrhage.

• D.Dx: Focal Nodular Hyperplasia: middle

age adult, lobulated mass with central
stellate scar. Histologically : central scar
contain large blood vessels & ductular
reaction.
Malignant Tumors: Hepatocellular Carcinoma (HCC)
 Malignant tumor of hepatocytes. More in male

 Risk factors: Chronic viral hepatitis (HBV & HCV).

Aflatoxins derived from Aspergillus (induce p53 mutations) Ex. corps as corn,
grain & nut..

Alcohol Liver Disease.

NASH.

Metabolic diseases : hemochromatosis, Wilson disease, and A1AT deficiency.

 Tumors are often detected late because symptoms are masked by cirrhosis. Patient may present
with jaundice, tender hepatomegaly, ascites, polycythemia, anorexia.

 Spreads hematogenously with poor prognosis.

 Serum tumor marker is alpha-fetoprotein.

 Diagnosis: U/S, CT, MRI with biopsy.

Hepatocellular Carcinoma Pathological Features
Macroscopic: unifocal neoplasm replacing most
of the right hepatic lobe. Multiple!! Or Microscopic: malignant hepatocytes growing in
infilterative. distorted versions of normal architecture,
 Cholangiocarcinoma
 2nd most common after hepatoma.
 Arise from intrahepatic or extrahepatic bile ducts.
 More in Southeast Asia related to↑ liver flukes.
 Risk factors: Primary sclerosing cholangitis.
Liver flukes infestation (Clonorchis sinensis).
Hepatolithiasis.
Fibropolycystic liver disease.
Hepatitis B & C.
NASH
Cholangiocarcinoma Pathological Features
Macroscopic: multifocal tumour Microscopic: invasive malignant glands in
reactive sclerotic stroma
 Malignant Tumors: Metastasis
 More common than primary tumors.
 The liver is the most common site of
metastatic cancers from colon, lung and
breast.

 Usually cause multiple nodules.

 Present usually as hepatomegaly.
Summary
Pathology of Gallbladder
 Gallstones (Cholelithiasis)
 ↑ cholesterol &/or bilirubin, ↓ bile salts → gall bladder stasis
and stone formation.

 Two types of stones: Cholesterol and Pigmented.

 Cholesterol stones: Most common type, contain crystalline
cholesterol monohydrate, usually radiolucent, 10-20%
radiopaque due to calcification.

 Pigmented stones: contain bilirubin & calcium, usually

radiopaque and black. Some times brown & radiolucent due
to infection.
Pathogenesis of Gallstones
 Cholesterol stone causes
 Increase cholesterol synthesis (hypercholesteremia): diet, genetics,
DM, medication (OCP) and obesity.
 GB hypomotility (stasis cause excess water resorption from bile &
concentration of cholesterol : biliary sludge): pregnancy, medication
(somatostatin), prolong fasting (Cholecystokinin), parental nutrition, spinal
cord injury.
 ↓Bile acid synthesis as in medication (fibrates) or ↓recirculation as in
crohn’s disease.
 ↑ Calcium or mucin concentration in bile leading to trapment of
cholesterol crystals: rapid weight loss.
 Pigmented stones causes
 ↑ bilirubin production ( excess bilirubin taken by liver and
excreted in bile): chronic hemolysis as SCA, spherocytosis, thalassemia.

 Altered enterohepatic circulation of bilirubin (bile acids not

reabsorbed and spill in colon → bile acids will solubilize
unconjugated bilirubin allowing its reabsorption and concentrated
in bile): crohn’s disease or resection of bowel.
Gallstones Risk Factors

Risk Factors (4F) :

Female, Fatty,
Fertile (pregnant)
and Forty.
 Gallstones (Cholelithiasis) Complications
 Can present with biliary colic ; neurohormonal activation
(ex. After fatty meal), triggers contraction of GB forcing stone
into cystic duct, usually present with Rt sided abdominal pain
radiate to shoulder, nausea and intolerance to fatty meals.
Diagnosis by U/S and treated by cholecystectomy.

 Can induce acute cholecystitis due to stone in GB neck or

cystic duct (Murphy's sign +, → empyema & gangrene)

 Chronic cholecystitis due to chemical irritation from

cholelithiasis → herniation of GB mucosa into muscular wall
(Rokitansky-Aschoff sinus) .

 GB rupture with peritonitis.

 GB perforation with abscess formation.

 Fibrosis & dystrophic calcification→ Porcelain GB

 Gallstones Complications: continue

 Choledocholithiasis: stone in CBD → ↑alkaline phosphatase, ↑GGT, ↑

Direct bilirubin and AST/ALT.

 May cause acute pancreatitis and ascending cholangitis .

 Fistula between GB & GIT→ air in biliary tree (pneumobilia).
 Passage of stone into intestinal tract obstruction of ileocecal valve (
obstructive ileus).

 May predispose to GB adenocarcinoma .

 Acute acalculus cholecystitis
 10% Acute cholecystitis with no stone.
 Seen in seriously ill patients.

 Predisposing factors: Severe trauma (motor vehicle crash).

Severe burns.

Major surgery.

Sepsis.

other: dehydration, stasis, hypoperfusion & infections CMV)

 Gallbladder Carcinoma
 More in women, 7th decade of life.
 Risk factors: Gallstones,
Infection,

Chronic inflammation,

Porcelain GB,

Primary sclerosing cholangitis.

 Present as cholecystitis in old females.

 Gallbladder Carcinoma
 Can be:- infiltrative growth: indurated thick
area in the wall.

exophytic growth: cauliflower mass

inside lumen.

 Most common type is Adenocarcinoma.

 Poor prognosis due to delayed presentation.
Summary
 Jaundice
❑ Yellow discoloration of skin and sclera (icterus)

❑ Systemic retention of bilirubin produces serum levels above 2.0 mg/dL

❑ Arises with disturbances in bilirubin metabolism (↑ production or ↓ clearance).

❑ Causes can be:

 Prehepatic

 Hepatic

 Posthepatic
 (↑UCB) Pre-hepatic Causes of Jaundice
Results from overproduction of bilirubin → unconjugated hyperbilirubinemia.

 Hemolytic anemias (SCA, spherocytosis, Immune hemolytic anemia).

 Ineffective erythropoiesis (like thalassemia, pernicious anemia).

 Resorption of blood from internal hemorrhage (GIT bleeding & hematoma).

 (↑UCB) Hepatic Causes of Jaundice
❑ Impair uptake by liver

• Hepatocellular injury as viral hepatitis.

• Drugs that interfere with bilirubin uptake as rifampicin & probenecid.

• Newborn.

❑ Decrease ability of liver to conjugate bilirubin (glucuronyl transferase activity):

• Newborn (hepatic machinery for conjugating & excreting bilirubin does not fully mature until about 2 weeks.
Exacerbated by breast milk due to bilirubin deconjugating enzymes. Effect? Treatmen?

• Gilbert syndrome: AR with mildly low UGT activity & impair bilirubin uptake; asymptomatic or mild
Jaundice during stress (fasting, stress, infection). ↑Unconjugated bilirubin.

• Crigler-Najjar syndrome: AR, absence of UGT in type I and low level in type II. Unconjugated bilirubinemia
early life ( require phototherapy and liver transplant).

• Hepatocellular disease (viral induced hepatitis, drug & cirrhosis).

 ( ↑ CB ) Hepatic Causes of Jaundice continue
❑ Impaired transport into canaliculus:
• Hepatocellular injury (viral, alcoholic hepatitis and toxins).
• Dubin-Johnson syndrome: AR, deficiency of bilirubin canalicular transport protein. ↑Conjugated
bilirubin & Dark black liver. No treatment

• Rotor syndrome: AR, same as Dubin-Johnson syndrome but no black liver (Regular looking).
❑ Result from canalicular cholestasis:
• Hepatocellular injury (viral, alcoholic hepatitis and toxins).
• Drugs (isoniazid, rifampicin, amoxicillin/clavulanic acid, allopurinol, and cimetidine).
• Pregnancy.
• Inflammatory destruction of intrahepatic bile ducts ( primary biliary cirrhosis & primary sclerosing
cholangitis).
 Hereditary Hyperbilirubinemia

1. Gilbert syndrome.

2. Crigler-Najjar syndrome.

3. Dubin-Johnson syndrome.

4. Rotor syndrome.
 (↑CB) Post-hepatic Causes of Jaundice
Unable to excrete conjugated bilirubin→ conjugated bilirubinemia.

Extrahepatic biliary obstruction

• Intra-luminal causes as gallstones

• Mural causes as cholangiocarcinoma, strictures and drug-induced

cholestasis.

• Extra-mural causes as pancreatic cancer & abdominal masses (e.g.

lymphomas).
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Questions??