Pathophysiology
P-II-5. Liver disease, Case 2
肝疾患 症例2
A 61-year-old man is presenting at the consulting room with pruritus and dull epigastric pain that radiates to the back. The pain is getting worse after meals and during the night, and antacids can also not relieve it. Over the last 2 months, he experienced frequent nausea and loss of appetite; moreover, he lost 8 kilograms. He noticed that his urine was dark, and his stool was lighter than usual. He has been an active smoker for 35 years and drinks alcohol casually.
Physical examination:
- height: 175 cm
- weight: 90 kg
- icterus
- excoriations on the limbs
- enlarged but painless gallbladder
Imaging methods:
- ultrasound: about 3.5 cm echogenic lesion in the pancreas, slightly dilated common bile duct and pancreatic duct
- CT: 3.4 x 3.8 cm hypodense, hypovascular mass in the head of the pancreas
Laboratory test — Blood:
- total bilirubin: 310 μmol/l
- direct bilirubin: 275 μmol/l
- ASAT: 110 U/L
- ALAT: 91 U/L
- GGT: 405 U/L
- alkaline phosphatase: 540 U/L
- amylase: 48 U/L
- lipase: 50 U/L
- CA 19-9: > 12000 U/mL (high)
- CEA: 34.2 ng/mL (high)
- prothrombin time: INR = 2.6
Urine:
- UBG: negative
- bilirubin: positive
Key Quotes & What They Tell Us
| Quote / Value | Interpretation |
|---|---|
| “enlarged but painless gallbladder” | Courvoisier’s sign → malignant obstruction of the bile duct (not gallstones) |
| CT: “hypodense, hypovascular mass in the head of the pancreas”; CA 19-9 > 12000; CEA high | Pancreatic head adenocarcinoma with characteristic tumour markers |
| “dark urine … stool was lighter than usual”; urine bilirubin positive, UBG negative | Conjugated bilirubin in urine with no urobilinogen reaching the gut → complete post-hepatic (obstructive) jaundice |
| Total bilirubin 310, direct 275 µmol/L; GGT 405, ALP 540 U/L | Conjugated hyperbilirubinaemia with a cholestatic enzyme pattern → biliary obstruction |
| Weight loss 8 kg, anorexia, back-radiating epigastric pain | Classic features of pancreatic head cancer infiltrating retroperitoneal structures |
| INR 2.6 | Fat-soluble vitamin K malabsorption (no bile in gut) → impaired clotting-factor synthesis |
| Amylase/lipase normal | Argues against acute pancreatitis as the cause |
Key Points
- Diagnosis: Carcinoma of the head of the pancreas causing obstructive (post-hepatic) jaundice.
- Hallmark sign: Courvoisier’s law — a painless, palpable, enlarged gallbladder with jaundice suggests malignant obstruction.
- Jaundice type: Conjugated hyperbilirubinaemia; bilirubinuria with absent urobilinogen indicates complete bile-duct obstruction.
- Pathophysiology: Tumour obstructs the common bile duct → cholestasis → pale stool, dark urine, pruritus, and vitamin K–dependent coagulopathy.
- Markers: Very high CA 19-9 (and raised CEA) support pancreatic malignancy.
一問一答
▶Why is urine bilirubin positive but urobilinogen negative in complete biliary obstruction?
Conjugated bilirubin refluxes into blood and urine, while no bilirubin reaches the gut to form urobilinogen.
▶Why does the patient have dark urine and pale (light) stool?
Biliary obstruction sends conjugated bilirubin into urine (dark) while preventing it reaching the gut (pale, acholic stool).
▶What is the diagnosis in a 61-year-old smoker with painless jaundice, weight loss, and a pancreatic head mass?
Carcinoma of the head of the pancreas causing obstructive (post-hepatic) jaundice.
▶What is Courvoisier's sign/law?
A painless, palpable, enlarged gallbladder with jaundice suggests malignant biliary obstruction rather than gallstones.
▶What type of hyperbilirubinaemia occurs in pancreatic head cancer?
Conjugated (direct) hyperbilirubinaemia from post-hepatic biliary obstruction.
▶What enzyme pattern indicates cholestasis in this case?
Markedly elevated GGT and alkaline phosphatase (with high conjugated bilirubin).
▶Which tumour marker is markedly elevated in pancreatic adenocarcinoma?
CA 19-9 (often with a raised CEA).
▶Why is the INR prolonged (2.6) in obstructive jaundice?
Absence of bile in the gut causes malabsorption of fat-soluble vitamin K, impairing clotting-factor synthesis.
▶Why does the patient have pruritus (itching)?
Cholestasis causes retention of bile salts, which deposit in skin and cause itching.
▶Why do amylase and lipase remain normal in this patient?
Normal pancreatic enzymes argue against acute pancreatitis; the picture is tumour-related obstruction, not inflammation.
▶Why does pancreatic head cancer cause epigastric pain radiating to the back?
The tumour infiltrates retroperitoneal structures and nerves behind the pancreas.
▶What does a 'double duct sign' (dilated common bile duct and pancreatic duct) suggest?
Obstruction at the pancreatic head, characteristic of a pancreatic head tumour.
▶How does pancreatic adenocarcinoma typically appear on CT?
A hypodense, hypovascular mass, usually in the head of the pancreas.
▶Why does the patient have weight loss and anorexia?
Constitutional (cancer cachexia) effects of malignancy plus impaired digestion from biliary/pancreatic obstruction.
▶What are the major risk factors for pancreatic cancer?
Smoking, older age, chronic pancreatitis, obesity, and diabetes.
▶How do you classify jaundice into the three main types?
Pre-hepatic (haemolytic), hepatic (hepatocellular), and post-hepatic (obstructive) — this case is post-hepatic.
▶Why is conjugated bilirubin (not unconjugated) found in the urine in obstruction?
Conjugated bilirubin is water-soluble and can be filtered into urine; unconjugated bilirubin cannot.
▶Why is pain worse after meals in this patient?
Eating stimulates pancreatic/biliary secretion against the obstruction, worsening pain.
▶Why might the modest ASAT/ALAT rise occur in biliary obstruction?
Back-pressure cholestasis causes some secondary hepatocellular injury, giving a mild transaminase increase.
▶What overall mechanism links the pale stool, dark urine, pruritus and coagulopathy?
Tumour obstruction of the common bile duct causes cholestasis, blocking bile flow to the gut and its downstream effects.