Gastroesophageal Reflux Disease

Yellow discoloration of skin, sclera, and mucous membranes from elevated serum bilirubin (typically clinically visible above 34 to 50 micromol/L, roughly 2 to 3 mg/dL).

Classified by mechanism: prehepatic (excess bilirubin production, typically hemolysis, unconjugated hyperbilirubinemia), hepatic (impaired hepatocyte uptake, conjugation, or excretion, from hepatitis, cirrhosis, or drug injury, mixed unconjugated and conjugated pattern), and posthepatic/obstructive (impaired bile flow from gallstones, stricture, or malignancy, predominantly conjugated hyperbilirubinemia).

Yellow discoloration of sclera (often the earliest visible sign) and skin, dark urine and pale stools with conjugated hyperbilirubinemia (bilirubin is water soluble and excreted renally, and reduced bile flow to the gut pales the stool), pruritus with cholestatic causes (from retained bile salts).

Associated features point toward etiology: fever and right upper quadrant pain suggest cholangitis or cholecystitis; painless progressive jaundice in an older adult suggests malignant obstruction (see Pancreatic Cancer and Cholangiocarcinoma entries); pallor, dark urine without pale stool, and splenomegaly suggest hemolysis; stigmata of chronic liver disease (spider angiomata, palmar erythema, ascites, encephalopathy) suggest underlying cirrhosis.

• Total and fractionated (conjugated versus unconjugated) bilirubin is the key initial test, immediately narrowing the differential.

• LFTs characterize the pattern: a hepatocellular pattern shows disproportionate transaminase elevation, while a cholestatic pattern shows disproportionate alkaline phosphatase and gamma-GT elevation.

• FBC, reticulocyte count, blood film, haptoglobin, and LDH are used if hemolysis is suspected (unconjugated pattern, normal LFTs otherwise).

• Coagulation profile and albumin assess synthetic liver function.

• Abdominal ultrasound is the first-line imaging study for cholestatic or mixed patterns, assessing for biliary duct dilatation and identifying gallstones.

• Viral hepatitis serology, autoimmune liver screen, and further cross sectional or endoscopic imaging (MRCP, ERCP, endoscopic ultrasound) are directed by the initial pattern and ultrasound findings.

Differentials span the full range covered in the separate Hepatitis B, Hepatitis C, Cirrhosis, Cholangitis, Cholecystitis, Cholangiocarcinoma, Pancreatic Cancer, Iron Deficiency Anaemia, and Vitamin B12 Deficiency Anaemia entries, as well as Gilbert syndrome (a common, benign, mild unconjugated hyperbilirubinemia unmasked by fasting or illness, requiring no treatment once confirmed) and drug induced liver injury.

Management is directed entirely at the underlying cause, detailed in the relevant condition specific entries throughout this atlas.

General supportive measures include pruritus control for cholestasis (cholestyramine first-line, rifampicin or naltrexone for refractory itch), nutritional support, and monitoring of synthetic function (INR, albumin) as a marker of severity and trajectory regardless of cause.

Referral: gastroenterology or hepatology for any jaundice of uncertain cause, evidence of chronic liver disease, or synthetic dysfunction; urgent surgical or gastroenterology referral for obstructive jaundice given the need for biliary decompression.