Histology: Liver, Gallbladder & Pancreas β€” Answer Key

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Built from GI Lecture 33 (LOs 1–5).

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πŸ“– Use alongside: GI Lecture 33 β€” Histology of Liver, Gallbladder & Pancreas (HoyaDocs) Focus on: classic vs portal vs acinar lobule, portal triad, zones 1/2/3 (periportal vs centrilobular), sinusoid structure, Space of Disse, Kupffer + Ito cells, gallbladder wall, Rokitansky-Aschoff sinuses, pancreas exocrine (acini + 4-level duct system) vs endocrine (islets of Langerhans).
Liver Architecture
Sinusoids & Disse
Gallbladder
Pancreas Exocrine
Pancreas Endocrine
Practice Qs
LO 1 & 2
ON EXAM β€” hexagonal classic lobule, portal triad (hepatic a., portal v., bile duct), central vein, zones 1/2/3, directionality of blood flow (triad β†’ central) vs bile flow (hepatocyte β†’ canaliculus β†’ triad), acetaminophen hits zone 3.
Three lobule models
ModelCenterPeripheryPurpose
Classic lobule
Central vein
Portal triads (hexagon corners)
Describes blood flow β€” "blood goes in at corners, out at center"
Portal lobule
Portal triad (bile duct)
3 adjacent central veins
Describes bile drainage (bile flows FROM hepatocytes TO bile duct in center)
Acinus of Rappaport
Line between 2 portal triads
Diamond shape with central veins at 2 tips
Describes metabolic zonation (zones 1/2/3) & O2 gradient
Portal triad β€” 3 components
Hepatic artery branch (bright red, thick-walled)
Portal vein branch (large, thin-walled, usually empty)
Bile duct (cuboidal/columnar epithelium)
Hepatocyte on H&E β€” key features
Polygonal (6-sided) large cells
Large, round, central; prominent nucleolus; often binucleate
Eosinophilic (lots of smooth ER, mitochondria, lysosomes, glycogen)
Plates/cords 1-cell thick radiating from central vein
Sinusoidal (basolateral, facing blood via Space of Disse) and canalicular (apical, facing bile canaliculus)
Blood flow directionality
Portal triad (hepatic a. + portal v.)
Central vein β†’ hepatic veins β†’ IVC
~5–10 mmHg (low pressure)
~90–100 mmHg (systemic)
Portal vein ~75%; hepatic artery ~25% (but each supplies ~50% of O2)
Bile flow directionality (OPPOSITE of blood)
Hepatocytes
Bile canaliculi (between adjacent hepatocytes)
Canals of Hering (transition cuboidal β†’ columnar)
Portal triad β†’ R/L hepatic duct β†’ common hepatic duct β†’ CBD β†’ duodenum
Zones 1, 2, 3 β€” function & vulnerabilities
ZoneLocationKey functionMost vulnerable to
Zone 1 (periportal)
Nearest portal triad (highest O2)
Oxidative metabolism, gluconeogenesis, urea cycle, bile formation
Viral hepatitis, ingested toxins entering from portal v. (yellow fever, iron in hemochromatosis)
Zone 2 (midzonal)
Middle of acinus
Intermediate function/vulnerability
Yellow fever specifically (midzonal necrosis)
Zone 3 (centrilobular)
Around central vein (lowest O2)
CYP450 drug metabolism, glycolysis, lipogenesis, alcohol metabolism
Ischemia ("shock liver"), acetaminophen (NAPQI), alcohol β†’ Mallory bodies, venous congestion (right HF β†’ "nutmeg liver")
Cholangiocytes
Bile ducts (interlobular β†’ hepatic β†’ common bile)
Simple cuboidal (small ducts) β†’ simple columnar (larger ducts)
HCO3⁻ (bicarbonate) β€” stimulated by secretin; also add water to bile
πŸͺ€ TRAP: Acetaminophen toxicity, ischemic injury (shock liver), and alcoholic hepatitis all hit ZONE 3 (centrilobular) β€” it is farthest from oxygenated blood. Zone 1 (periportal) is hit first by viral hepatitis and toxins entering from the portal triad.
LO 3
ON EXAM β€” discontinuous (sinusoidal) capillary with fenestrations + NO basement membrane, Space of Disse (between hepatocyte and sinusoid endothelium), Kupffer cells = liver macrophages, Ito (hepatic stellate) cells = store vitamin A + become myofibroblasts in cirrhosis.
Hepatic sinusoid β€” 5 defining features
Discontinuous endothelial cells with large fenestrations (100–200 nm)
ABSENT (no basal lamina) β€” key feature!
Mix of oxygenated (hepatic a.) + nutrient-rich deoxy (portal v.) blood
Kupffer cells (in lumen) and pit cells (liver NK)
Wider and more irregular than typical capillaries
3 capillary types β€” compare
TypeEndotheliumBasement membraneExample organ
Continuous
Tight junctions, no gaps
Intact, continuous
Brain (BBB), muscle, lung, skin
Fenestrated
Small fenestrations (60–80 nm), often with diaphragms
Intact, continuous
Kidney glomeruli, GI mucosa, endocrine glands
Sinusoidal (discontinuous)
Large fenestrations (100–200 nm), intercellular gaps, NO diaphragms
Absent / discontinuous
Liver, spleen, bone marrow
Space of Disse (perisinusoidal)
Between sinusoidal endothelium and hepatocyte basolateral membrane
Ito (hepatic stellate) cells β€” store vitamin A
Site of plasma-hepatocyte exchange; fluid here drains via lymphatics; site where fibrosis occurs in cirrhosis
Kupffer cells β€” 4 functions
Phagocytosis of old/damaged RBCs (heme β†’ bilirubin)
Clear gut-derived bacteria and endotoxins from portal blood (first-pass)
Antigen presentation; cytokine release (TNF-Ξ±, IL-6)
Activate Ito cells in liver injury β†’ fibrosis signaling
Resident tissue macrophages (mononuclear phagocyte system; derived from yolk sac + monocytes)
Irregular shape, within sinusoidal lumen, often with phagocytosed material (brown/golden pigment)
Ito (hepatic stellate) cells β€” quiet vs activated
StateAppearanceFunction
Quiet (healthy)
Star-shaped, in Space of Disse, large lipid droplets with vitamin A
Vitamin A storage (~80% body stores); mild ECM maintenance
Activated (cirrhosis engine)
Lose lipid droplets β†’ elongated myofibroblast-like
Deposit type I collagen in Space of Disse β†’ fibrosis + portal HTN; contract sinusoids
Ito cell activation β€” 6-step cascade in cirrhosis
Chronic injury: alcohol, viral hepatitis, NASH, iron, toxins β†’ hepatocyte damage
Kupffer cells activated β†’ release TGF-Ξ², PDGF, TNF-Ξ±
Stellate cells proliferate in Space of Disse
Lose vitamin A β†’ transform into myofibroblasts
Deposit collagen (type I & III) in Space of Disse β†’ "capillarization" of sinusoids
Fibrosis β†’ cirrhosis β†’ portal HTN + impaired hepatocyte function
4 clinical consequences of cirrhosis
Portal hypertension β†’ varices, caput medusae, splenomegaly, ascites
Loss of synthetic function β†’ ↓ albumin, ↓ clotting factors (INR ↑)
Loss of detoxification β†’ hyperammonemia β†’ hepatic encephalopathy
↑ Risk of hepatocellular carcinoma (HCC)
⚠️ In cirrhosis, activated Ito cells deposit COLLAGEN in the Space of Disse β†’ "capillarization" of sinusoids (they become like regular capillaries WITH basement membrane + no fenestrations) β†’ impaired hepatocyte-blood exchange β†’ portal HTN.
LO 4
ON EXAM β€” 3-layer wall (NO submucosa, NO muscularis mucosae), simple columnar with microvilli, Rokitansky-Aschoff sinuses = mucosal diverticula, concentrates bile 5–10Γ— by NaCl/H2O reabsorption, CCK triggers contraction + relaxes sphincter of Oddi.
Gallbladder anatomy
Inferior surface of liver (between right and quadrate lobes)
Fundus, body, neck
Joins common hepatic duct β†’ forms common bile duct (CBD)
Outpouching at GB neck where gallstones commonly impact (infundibulum)
3-layer wall (atypical β€” NO submucosa, NO muscularis mucosae!)
Mucosa: simple columnar epithelium + lamina propria (NO muscularis mucosae)
Muscularis externa (smooth muscle β€” irregular/intermixed, no distinct layers)
Serosa (where free surface) / adventitia (where attached to liver)
Epithelium
Simple columnar
Microvilli (apical) β€” resemble absorptive intestine cells
↑ surface area for active Na⁺/Cl⁻ reabsorption β†’ H2O follows β†’ bile concentration 5–10Γ—
Rokitansky-Aschoff sinuses
Outpouchings (herniations) of mucosa through the muscularis externa
Marker of chronic cholecystitis; can trap bile/cholesterol β†’ "strawberry" gallbladder (cholesterolosis)
Bile concentration β€” 4-step mechanism
Na⁺/K⁺ ATPase on basolateral membrane pumps Na⁺ out β†’ Na⁺ gradient
Na⁺ enters apically from bile (Na⁺/H⁺ and Cl⁻/HCO3⁻ exchangers) β†’ Cl⁻ follows
H2O follows NaCl osmotically (via aquaporins/paracellularly)
Bile volume ↓ 5–10Γ—; bile salts, cholesterol, bilirubin concentrated
Hepatic bile vs gallbladder bile
ComponentHepatic bileGallbladder bile
Volume/concentration
Dilute, watery, yellow; ~600 mL/day produced
Concentrated, viscous, dark green-brown; ~50 mL stored
Concentration factor
Gallbladder concentrates bile 5–10Γ— (up to 20Γ— in some texts)
CCK β€” 5 functions
Contracts gallbladder β†’ ejects bile
Relaxes sphincter of Oddi
Stimulates pancreatic acinar enzyme secretion
Slows gastric emptying
Promotes satiety
Fatty acids & amino acids in duodenum β†’ I cells release CCK
Gallstone types
Stone typeCompositionRisk factor
Cholesterol
> 50% cholesterol; radiolucent (yellow); most common in Western world (~80%)
4 F's: female, fat, forty, fertile; OCPs, Crohn (bile acid loss), obesity, rapid weight loss
Pigment (black)
Calcium bilirubinate; radiopaque; small, hard
Chronic hemolysis (sickle cell, spherocytosis), cirrhosis
Pigment (brown)
Ca-bilirubinate + cholesterol; soft, greasy
Biliary tract infection (E. coli, Ascaris, Clonorchis) β€” Ξ²-glucuronidase deconjugates bilirubin
Acute cholecystitis & porcelain GB
Stone impacts cystic duct β†’ bile stasis β†’ chemical irritation + secondary bacterial infection
US: wall thickening > 3 mm, pericholecystic fluid, gallstones, sonographic Murphy; HIDA: non-visualization of GB
Deep inspiration with palpation of RUQ β†’ inspiratory arrest due to pain
Dystrophic calcification of GB wall (chronic inflammation) β†’ ↑ risk of GB adenocarcinoma β†’ prophylactic cholecystectomy
πŸͺ€ TRAP: Gallbladder lacks a muscularis mucosae and submucosa. So any mucosal cancer invasion has direct access to the muscularis externa β†’ poor prognosis at diagnosis.
LO 5
ON EXAM β€” acinar cells (basophilic base, eosinophilic apex = zymogen granules), centroacinar cells begin duct, 4-level duct system (intercalated β†’ intralobular β†’ interlobular β†’ main pancreatic duct), sphincter of Oddi.
Pancreas β€” quick anatomy
Head (with uncinate process), neck, body, tail
Tail (intraperitoneal β€” within splenorenal ligament)
Duct of Wirsung β€” joins CBD at ampulla of Vater
Duct of Santorini β€” drains separately at minor papilla (above major)
Ampulla of Vater (hepatopancreatic ampulla) β†’ sphincter of Oddi β†’ 2nd part duodenum (major papilla)
Exocrine vs endocrine β€” % and structure
Component% of glandFunctional unitProduct
Exocrine
~85% of pancreas mass
Acinus (cluster of serous acinar cells)
Digestive enzymes + HCO3⁻-rich fluid β†’ duodenum
Endocrine
~1–2% of pancreas mass
Islet of Langerhans
Insulin, glucagon, somatostatin, PP β†’ blood
Acinus β€” histology
Pyramidal/wedge-shaped cells arranged around a small central lumen (berry cluster)
Deeply BASOPHILIC β€” abundant rough ER (rRNA binds basic dyes)
EOSINOPHILIC β€” zymogen granules (pre-packaged inactive digestive enzymes)
Round, basal position
Zymogen granule contents
Trypsinogen, chymotrypsinogen, procarboxypeptidase, proelastase
Ξ±-amylase and lipase (secreted in active form)
In duodenum β€” enterokinase (enteropeptidase) cleaves trypsinogen β†’ trypsin β†’ activates all other zymogens
Centroacinar cells
Within the acinus β€” extension of intercalated duct cells into the acinar lumen
Pale/clear cytoplasm (unlike basophilic acinar cells); small flattened cells in center of acinus
Bicarbonate (HCO3⁻) and water β€” stimulated by secretin
4-level duct system
Intercalated ducts (simple cuboidal, HCO3⁻ secretion)
Intralobular ducts (within lobule)
Interlobular ducts (between lobules; in CT septa)
Main pancreatic duct (of Wirsung) + accessory duct (of Santorini)
Regulation β€” secretin vs CCK
HormoneTriggerEffect on pancreas
Secretin
Duodenal acid (H⁺ < pH 4.5) β†’ S cells release secretin
Stimulates DUCT cells β†’ HCO3⁻ + watery secretion (neutralizes duodenal acid)
CCK
Fatty acids & AAs in duodenum β†’ I cells release CCK
Stimulates ACINAR cells β†’ enzyme secretion (+ GB contraction, relaxes sphincter Oddi)
Acute pancreatitis β€” "pancreas eats itself"
Gallstones (most common) and alcohol β€” together ~70–80% of cases ("I GET SMASHED" mnemonic)
Trypsinogen β†’ trypsin (inappropriately activated within pancreas)
Autodigestion of pancreas (proteolysis); fat necrosis (lipase liberates FFAs β†’ saponification); hemorrhage (elastase attacks vessels)
↑ Lipase (more specific than amylase), ↑ amylase; ↓ Ca²⁺ (fat saponification); hyperglycemia
Coagulative necrosis of acinar cells; fat saponification ("chalky" deposits); hemorrhage; neutrophilic infiltrate
LO 5
ON EXAM β€” islets of Langerhans (pale on H&E), Ξ²-cells (insulin, ~70%, central), Ξ±-cells (glucagon, ~20%, periphery), Ξ΄-cells (somatostatin). T1DM = insulitis + Ξ²-cell destruction. T2DM = amyloid deposition. Islet cell tumors: insulinoma, gastrinoma, glucagonoma, VIPoma, somatostatinoma.
Islet of Langerhans β€” spotting on H&E
PALE / lightly stained (vs deeply basophilic acini) β€” "island in a sea"
Rounded/oval clusters of cells, no lumen, surrounded by capillaries
~1 million islets total; most concentrated in the TAIL of the pancreas
Ξ²-cells central (majority); Ξ±-cells peripheral (outer rim); Ξ΄-cells scattered
Islet cell types
Cell% of isletHormoneMain action
Ξ± (alpha)
~20%
Glucagon
↑ Glucose (gluconeogenesis, glycogenolysis); released during fasting
Ξ² (beta)
~70%
Insulin + C-peptide + amylin
↓ Glucose (glucose uptake, glycogenesis, lipogenesis); released after meals
Ξ΄ (delta)
~5–10%
Somatostatin
Inhibits nearly everything β€” GH, insulin, glucagon, gastrin, secretin, CCK, etc.
PP (F cells)
~1–2%
Pancreatic polypeptide
Inhibits pancreatic exocrine secretion; regulates appetite
Ξ²-cell insulin release β€” 5-step cascade
Glucose enters Ξ²-cell via GLUT2 (insulin-independent, high Km)
Glucose β†’ glycolysis β†’ ↑ ATP/ADP ratio
ATP closes ATP-sensitive K⁺ channel (target of sulfonylureas)
Cell membrane depolarizes β†’ opens voltage-gated Ca²⁺ channels
Ca²⁺ influx β†’ exocytosis of insulin-containing granules (+ C-peptide, amylin)
Insulo-acinar portal system
Blood from islet capillaries drains INTO the surrounding acinar capillary bed (portal system) before leaving the pancreas
Islet hormones (insulin, glucagon, somatostatin) reach exocrine cells at HIGH concentration β†’ locally regulate enzyme secretion; explains why T1DM patients have exocrine insufficiency too
Diabetes β€” histology signatures
TypeIslet histologyMechanism
T1DM
Lymphocytic infiltrate (insulitis, mostly CD8+) β†’ Ξ²-cell destruction; islets atrophic
Autoimmune β€” anti-GAD, anti-islet cell, anti-insulin antibodies; HLA-DR3/4
T2DM
Amyloid (amylin/IAPP) deposition within islets; Ξ²-cell dysfunction but number preserved early
Peripheral insulin resistance + progressive Ξ²-cell secretory failure
Islet cell tumors
TumorCell of originClassic syndrome
Insulinoma
Ξ²-cell (most common, usually benign)
Whipple triad: hypoglycemia + symptoms + relief w/ glucose; ↑ C-peptide
Gastrinoma
G cell (non-Ξ², often duodenum/pancreas)
Zollinger-Ellison: recurrent PUD in unusual locations (jejunum), diarrhea; ~25% MEN1
Glucagonoma
Ξ±-cell
6 D's: Diabetes (mild), Dermatitis (necrolytic migratory erythema), DVT, Depression, Diarrhea, Declining weight
VIPoma
Non-Ξ² islet (Vasoactive intestinal peptide)
WDHA syndrome: Watery Diarrhea, Hypokalemia, Achlorhydria ("pancreatic cholera")
Somatostatinoma
Ξ΄-cell
Diabetes + steatorrhea + gallstones + achlorhydria (somatostatin inhibits everything)
Pancreatic ductal adenocarcinoma (PDAC)
Head of pancreas (~60–70%) β†’ painless jaundice from CBD obstruction
CA 19-9 (elevated); CEA less specific
Courvoisier sign (palpable, non-tender gallbladder), Trousseau sign (migratory superficial thrombophlebitis), painless jaundice
KRAS (> 90% of PDAC) β€” earliest; then CDKN2A/p16 β†’ TP53 β†’ SMAD4 loss
Grim: 5-year survival < 10%; often metastatic at diagnosis
⚠️ Insulinoma: Whipple triad = (1) symptoms of hypoglycemia, (2) documented low glucose at symptom time, (3) relief with glucose. ↑C-peptide (endogenous) distinguishes from exogenous insulin use.
LOs 1–5
Q1: Liver directionality
In the classic hepatic lobule, what is the direction of blood flow and bile flow, respectively?

A) Both flow from central vein β†’ portal triad
B) Both flow from portal triad β†’ central vein
C) Blood: triad β†’ central vein; Bile: hepatocyte β†’ triad (opposite directions)
D) Blood: central vein β†’ triad; Bile: triad β†’ hepatocyte
E) Both flow in canaliculi
Correct Answer: C

Blood flows INTO the lobule at the portal triad (from hepatic a. + portal v.), through sinusoids, out via central vein β†’ hepatic veins β†’ IVC. Bile flows OPPOSITE β€” hepatocyte β†’ canaliculus β†’ bile ductule (canals of Hering) β†’ bile duct in portal triad.
Q2: Acetaminophen zone
A 22-year-old woman presents with fulminant hepatic failure after acetaminophen overdose. Biopsy will most likely show necrosis in which region?

A) Zone 1 (periportal)
B) Zone 2 (midzonal)
C) Zone 3 (centrilobular, around central vein)
D) Space of Disse
E) Portal triad
Correct Answer: C

Zone 3 is farthest from oxygenated portal blood β†’ most susceptible to ischemic and toxic injury. Also the zone with the most CYP450 β†’ converts acetaminophen to the toxic NAPQI metabolite. Acetaminophen, ischemia ("shock liver"), and alcohol all target zone 3.
Q3: Sinusoid features
The hepatic sinusoid is classified as which type of capillary?

A) Continuous with tight junctions
B) Fenestrated with intact basement membrane
C) Sinusoidal (discontinuous) β€” fenestrations + NO basement membrane
D) Lymphatic
E) Arteriole
Correct Answer: C

Hepatic sinusoids are discontinuous capillaries β€” large fenestrations AND no basement membrane β†’ allows plasma proteins and macromolecules free access to hepatocytes across the Space of Disse.
Q4: Ito cell function
Which cell type, located in the Space of Disse, stores vitamin A in its quiescent state and transforms into collagen-producing myofibroblasts in cirrhosis?

A) Kupffer cell
B) Hepatocyte
C) Cholangiocyte
D) Hepatic stellate (Ito) cell
E) Pit cell (liver NK)
Correct Answer: D

Ito (hepatic stellate) cells β€” store vitamin A in lipid droplets (why chronic vit A toxicity β†’ ↑ cirrhosis). When activated by Kupffer cell cytokines (TGF-Ξ², PDGF), they transform into myofibroblasts β†’ deposit type I collagen β†’ fibrosis & cirrhosis.
Q5: Gallbladder wall
Which layer is ABSENT from the gallbladder wall (distinguishing it from typical GI tract)?

A) Mucosa
B) Submucosa (and muscularis mucosae)
C) Muscularis externa
D) Serosa
E) Adventitia
Correct Answer: B

The gallbladder lacks a submucosa and muscularis mucosae. It has only 3 layers: mucosa (simple columnar w/ microvilli), muscularis externa, and serosa/adventitia. This means mucosal cancers quickly invade deep β€” one reason gallbladder adenocarcinoma has such poor prognosis.
Q6: Rokitansky-Aschoff sinuses
A cholecystectomy specimen shows mucosal herniations extending through the muscularis externa. What are these called?

A) Crypts of LieberkΓΌhn
B) Brunner glands
C) Rokitansky-Aschoff sinuses
D) Peyer patches
E) Plicae circulares
Correct Answer: C

Rokitansky-Aschoff sinuses = outpouchings of mucosa through the muscularis externa, characteristic of chronic cholecystitis. Think "cholesterolosis" or gallbladder "diverticula."
Q7: Acinar cell H&E
A pancreatic acinar cell shows intensely BASOPHILIC base and EOSINOPHILIC apex on H&E. What accounts for the basophilia at the base?

A) Zymogen granules
B) Rough endoplasmic reticulum (abundant rRNA)
C) Lipofuscin pigment
D) Mitochondria
E) Glycogen
Correct Answer: B

Basal basophilia = extensive rough ER (for protein/enzyme synthesis) β€” rRNA is acidic and binds basic dyes. Apical eosinophilia = zymogen granules (pre-packed digestive enzymes). This "polarity" is the hallmark of a serous secretory acinar cell.
Q8: T1DM histology
An autopsy of a 14-year-old boy with a 2-year history of type 1 diabetes shows islets with a lymphocytic infiltrate and profound loss of one cell type. Which cells are destroyed?

A) Ξ±-cells (glucagon)
B) Ξ²-cells (insulin)
C) Ξ΄-cells (somatostatin)
D) PP cells (pancreatic polypeptide)
E) Acinar cells
Correct Answer: B

Type 1 DM = autoimmune destruction of Ξ²-cells β†’ insulitis (lymphocytic infiltrate, especially CD8+ T cells). Ξ±, Ξ΄, and PP cells preserved. Type 2 DM β†’ amyloid deposition (islet amyloid polypeptide / amylin) within islets, Ξ²-cell dysfunction.
Q9: Zollinger-Ellison
A patient has refractory peptic ulcers in unusual locations (e.g., jejunum), chronic diarrhea, and elevated serum gastrin. Which islet cell tumor is responsible?

A) Insulinoma (Ξ²-cell)
B) Gastrinoma (non-Ξ² islet / duodenal)
C) Glucagonoma (Ξ±-cell)
D) VIPoma
E) Somatostatinoma
Correct Answer: B

Zollinger-Ellison syndrome = gastrinoma (often duodenal wall or pancreas), causing hypergastrinemia β†’ ↑ gastric acid β†’ multiple, recurrent, distally located ulcers + diarrhea. ~25% of gastrinomas occur in MEN1 (3 P's: Pituitary, Parathyroid, Pancreas).
Q10: PDAC molecular
A 68-year-old smoker presents with painless jaundice, weight loss, and a mass in the pancreatic head. Which is the most commonly mutated oncogene in pancreatic ductal adenocarcinoma?

A) BRAF V600E
B) KRAS
C) EGFR
D) APC
E) BCR-ABL
Correct Answer: B

KRAS activating mutation is present in >90% of PDAC β€” the earliest driver. Subsequent losses: CDKN2A (p16), TP53, SMAD4/DPC4. PDAC marker = CA 19-9. Classic signs: painless jaundice, Courvoisier sign (palpable non-tender gallbladder), Trousseau sign (migratory thrombophlebitis).