A 52-year-old man with cirrhosis presents with jaundice. Laboratory tests show: serum bilirubin 5.2 mg/dL (direct 4.1 mg/dL), ALP 110 U/L, ALT 68 U/L, albumin 2.8 g/dL, INR 1.8. Ultrasound shows cirrhotic liver with patent portal vein. A 35-year-old woman with painless progressive jaundice for 3 weeks presents with: serum bilirubin 8.4 mg/dL (direct 7.9 mg/dL), ALP 420 U/L, ALT 95 U/L, albumin 3.8 g/dL, INR 1.0. Ultrasound shows dilated intrahepatic and extrahepatic bile ducts with a mass at the pancreatic head. Which single finding best distinguishes intrahepatic cholestasis (cirrhosis) from extrahepatic obstruction (pancreatic cancer)?

Explanation

## Distinguishing Intrahepatic from Extrahepatic Cholestasis ### Clinical and Biochemical Patterns **Key Point:** The combination of preserved hepatic synthetic function (normal albumin, normal INR) with dilated extrahepatic bile ducts on imaging is the gold-standard discriminator between extrahepatic obstruction and intrahepatic cholestasis. | Feature | Intrahepatic Cholestasis (Cirrhosis) | Extrahepatic Obstruction (Pancreatic Cancer) | |---------|--------------------------------------|----------------------------------------------| | **Synthetic function** | **Impaired (↓ albumin, ↑ INR)** | **Preserved (normal albumin, normal INR)** | | **Bile duct dilation** | **Intrahepatic only** | **Both intra- and extrahepatic** | | Bilirubin (direct) | Elevated | Elevated | | ALP | Mildly elevated | Markedly elevated | | ALT/AST | Mild elevation | Mild elevation | | Prognosis | Chronic liver disease | Potentially resectable if early | ### Clinical Pearl **High-Yield:** In intrahepatic cholestasis (cirrhosis), hepatocyte dysfunction impairs both bilirubin excretion AND synthetic protein production, resulting in coagulopathy and hypoalbuminemia. In extrahepatic obstruction (pancreatic cancer), the liver parenchyma is initially intact, so synthetic function remains normal — only bile flow is obstructed. This distinction has critical prognostic and therapeutic implications. ### Imaging Correlation **Warning:** Both conditions can show dilated intrahepatic bile ducts. The key differentiator is: - **Extrahepatic obstruction:** dilated extrahepatic bile duct (CBD) + normal synthetic function = mechanical obstruction (potentially resectable) - **Intrahepatic cholestasis:** intrahepatic dilation only + impaired synthetic function = parenchymal liver disease (not surgically correctable) ### Mnemonic **EXTRA-INTACT** = **EXTRA**hepatic obstruction leaves liver **INTACT** (normal albumin, normal INR, dilated extrahepatic duct) **INTRA-IMPAIR** = **INTRA**hepatic cholestasis **IMPAIR**s synthetic function (low albumin, high INR) [cite:Harrison 21e Ch 297]