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Liver and Gallbladder Disorders in Children

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1. Biliary Dyskinesia

Definition

Causes

• Abnormal gallbladder contractile response to cholecystokinin (CCK)
• Associated functional GI disorders: delayed colonic transit, delayed gastric emptying
• Possible autonomic dysregulation or hormonal imbalance
• Often co-exists with irritable bowel syndrome or functional dyspepsia

Classification

Clinical Signs

• Right upper quadrant or epigastric pain (biliary colic) — often episodic, postprandial
• Nausea, vomiting, oral intolerance
• No fever or jaundice (distinguishes from cholecystitis)
• No stones or sludge on ultrasound
• A confounding factor: patients often have other functional GI disorders

Diagnosis

• Ultrasound: no stones/sludge — required to exclude organic causes
• CCK-stimulated HIDA scan (cholescintigraphy): ejection fraction < ~35% is diagnostic of hypomotor biliary dyskinesia
• Rome IV criteria help exclude GERD, IBS, and other functional causes
• CT, endoscopy used to rule out other diagnoses

Management

• Cholecystectomy: effective in >85% of patients, especially those with classic biliary colic and reduced ejection fraction
• In non-responders or atypical cases: ERCP with sphincterotomy
• Medical options: dietary fat restriction, antispasmodics, prokinetics
• Patients with nausea as the primary symptom respond less well to cholecystectomy

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2. Jaundice

Definition

Bilirubin Metabolism (basis for classification)

• Unconjugated (indirect) bilirubin: fat-soluble, albumin-bound, produced from RBC breakdown
• Hepatocytes conjugate bilirubin with glucuronic acid → water-soluble conjugated (direct) bilirubin → excreted in bile

Causes and Types

Pre-hepatic (Hemolytic) Jaundice

• Excess RBC breakdown overwhelms hepatic conjugation capacity
• Causes: hemolytic anemia (hereditary spherocytosis, G6PD deficiency, sickle cell disease), incompatible blood transfusion, neonatal hemolysis (Rh/ABO incompatibility)
• Bilirubin: predominantly unconjugated ↑
• Urine: normal color (no bilirubin); urobilinogen ↑
• Stools: dark (excess urobilinogen)

Hepatic (Hepatocellular) Jaundice

• Impaired uptake, conjugation, or excretion of bilirubin by damaged hepatocytes
• Causes: viral hepatitis (A, B, C, E), autoimmune hepatitis, toxic/drug-induced hepatitis, Wilson's disease, metabolic disorders (galactosemia, tyrosinemia), cirrhosis
• Bilirubin: both conjugated and unconjugated ↑ (mixed)
• AST/ALT: markedly elevated
• Urine: dark (bilirubin); urobilinogen variable

Post-hepatic (Obstructive/Cholestatic) Jaundice

• Obstruction of bile flow from hepatocytes to duodenum
• Causes in children: biliary atresia, choledochal cyst, cholelithiasis, primary sclerosing cholangitis, pancreatic mass, bile duct stricture
• Bilirubin: predominantly conjugated ↑
• ALP and GGT markedly elevated
• Urine: dark (bilirubinuria); stools: pale/clay-colored (acholic)

Neonatal Physiological Jaundice

• Appears day 2–4 of life, resolves by day 10–14; unconjugated
• Due to high RBC turnover + immature hepatic conjugation
• Pathological if: appears < 24 h, bilirubin rises rapidly, conjugated bilirubin ↑, persists > 2 weeks

Clinical Signs

• Yellow discoloration: sclerae (earliest), skin (face → trunk → extremities), mucous membranes
• Pre-hepatic: mild jaundice, pallor (anemia), splenomegaly
• Hepatic: fatigue, anorexia, hepatomegaly, tender liver, dark urine, possible fever
• Obstructive: deep yellow-green jaundice, pruritus, pale stools, dark urine, no fever (unless cholangitis)

Management

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3. Portal Hypertension

Definition

Causes — Classified by Level of Obstruction

In children specifically, the most common causes are: extrahepatic portal vein obstruction (EHPVO)/portal vein thrombosis (pre-hepatic, most common in children), biliary atresia with cirrhosis (intrahepatic), and cystic fibrosis-related liver disease.

Pathophysiology

1. Increased resistance at the sinusoidal level — from fibrosis, parenchymal nodules, myofibroblast contraction, ↓ NO production, ↑ endothelin-1
2. Increased portal venous inflow — splanchnic arterial vasodilation (mediated by NO, prostacyclin, TNF-α) → increased venous efflux into the portal system

Clinical Signs

• Splenomegaly (most prominent sign in children with pre-hepatic PH)
• Ascites
• Caput medusae (dilated periumbilical veins)
• Hematemesis (esophageal/gastric variceal bleeding)
• Rectal bleeding (hemorrhoids/rectal varices)
• Signs of hypersplenism: thrombocytopenia, leukopenia, anemia

Complications

1. Esophagogastric varices → massive hematemesis; ~40% of patients with advanced cirrhosis; ~30% mortality per bleeding episode
2. Ascites → occurs when ≥500 mL accumulates; can lead to spontaneous bacterial peritonitis, hepatorenal syndrome, hepatic hydrothorax
3. Portosystemic encephalopathy → impaired ammonia clearance; behavioral changes, confusion, coma
4. Congestive splenomegaly → hypersplenism (thrombocytopenia, pancytopenia)

• Hepatopulmonary syndrome: intrapulmonary vascular dilation → hypoxemia (worse when upright — platypnea/orthodeoxia)
• Portopulmonary hypertension: pulmonary arterial hypertension in the setting of PH

Management

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4. Interpretation of Liver Function Tests (LFTs)

Pattern Recognition Principle

"Patterns of liver test abnormalities denote the predominant type of liver injury."

Diagnostic Patterns

Pediatric note: ALP is physiologically elevated in children and adolescents due to bone isoenzyme during periods of growth — always interpret with age-specific reference ranges and confirm biliary origin with GGT.

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5. Ultrasound Examination of the Gallbladder (Functional Assessment)

Morphological Assessment

• Wall thickness (normal < 3 mm)
• Size: normal gallbladder in children — length 3–7 cm, width 1–3 cm
• Presence of stones, sludge, polyps
• Pericholecystic fluid (sign of cholecystitis)

Functional Assessment (Dynamic / Contraction Study)

1. Fasting scan: baseline gallbladder volume measured (child fasts 4–6 hours)
2. Fatty meal provocation: child given a fatty meal or CCK injection
3. Post-prandial scan: gallbladder volume re-measured at 30 and 60 minutes
4. Ejection fraction = (Fasting volume − Residual volume) / Fasting volume × 100%

• EF < 35% → hypokinetic biliary dyskinesia (impaired emptying)
• EF > 75–80% → hyperkinetic dyskinesia

Note: CCK-HIDA scan (cholescintigraphy) is the gold standard for ejection fraction measurement, but dynamic ultrasound is used as a simpler, radiation-free alternative particularly in children.

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6. Skin Color Assessment

Jaundice

• Assessment: examine in natural (daylight) lighting
• Earliest sign: yellow discoloration of the sclerae (visible at bilirubin ~34 µmol/L)
• Then: skin of face, trunk, palms/soles (deepest jaundice)
• Color nuances:
  • Lemon-yellow: hemolytic jaundice (pre-hepatic)
  • Bright orange-yellow: hepatocellular jaundice
  • Yellow-green / olive green: obstructive/cholestatic jaundice (prolonged)
• Check oral mucosa, hard palate (especially in dark-skinned children)

Pallor

• Indicates anemia — relevant in hemolytic jaundice
• Assess: conjunctival pallor (most reliable), palmar creases, nail beds, oral mucosa
• In children: conjunctival pallor is the most sensitive site
• Associated with pre-hepatic jaundice, hypersplenism-related anemia (in portal hypertension), or blood loss from varices

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7. Palpation of the Abdomen in Children

General Principles

• Child should be supine, relaxed, knees slightly flexed; warm hands
• Younger children: distract with conversation or have parent present; infants may be examined on parent's lap
• Begin with light palpation (to assess tenderness, guarding, superficial masses), then deep palpation

Liver Palpation

• Technique: start from the right iliac fossa, moving upward toward the right costal margin, synchronizing with breathing (feel the liver edge descend on inspiration)
• Normal findings in children:
  • Neonates/infants: liver edge palpable 1–2 cm below right costal margin (normal)
  • Children < 4 years: up to 2 cm below right costal margin
  • Older children/adolescents: normally not palpable or just at costal margin
• Characterize the liver edge: sharp vs. rounded; smooth vs. nodular; tender vs. non-tender; soft vs. firm/hard

Spleen Palpation

• Start from right iliac fossa toward left costal margin (spleen enlarges toward right iliac fossa)
• Splenomegaly: a key sign of portal hypertension in children

Gallbladder Palpation

• Murphy's sign: deep inspiration while examiner presses under right costal margin in mid-clavicular line → sudden arrest of inspiration due to pain = positive (cholecystitis)
• In children: less sensitive; gallbladder rarely palpable unless hydrops or empyema

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8. Percussion of Liver Borders — Kurlov's Method

Technique

Normal Liver Size by Kurlov (in adults):

• 1st size: 9 ± 1 cm
• 2nd size: 8 ± 1 cm
• 3rd size: 7 ± 1 cm (written as 9–8–7 cm)

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9. Pathological Percussion Signs

Ortner-Grekov's Sign (Ortner's Sign)

• Technique: the examiner percusses (taps) the right costal arch with the ulnar edge of the right hand, or taps the medial edge of the right hand placed over the right costal arch
• Positive: pain elicited by this percussion
• Significance: indicates inflammation of the gallbladder or bile ducts — positive in:
  • Acute cholecystitis
  • Cholelithiasis
  • Biliary dyskinesia (sometimes)
  • Cholangitis
• Reflects tenderness of the gallbladder/biliary tree through the overlying ribs

Mendel's Sign (Mendel's Abdominal Percussion Sign)

• Technique: the examiner percusses or taps the anterior abdominal wall with a finger (like tapping) in the right hypochondrium (over the gallbladder projection) and epigastrium
• Positive: pain elicited by percussion (unlike deep palpation, uses percussion stimulus)
• Significance: indicates local peritoneal irritation over the gallbladder/bile ducts; positive in:
  • Acute cholecystitis
  • Peritoneal involvement in biliary disease
  • Duodenal ulcer with local peritonitis (also described here)
• More sensitive for detecting localized tenderness than palpation in tense abdominal muscles

Comparison: Both signs detect biliary/hepatic tenderness. Ortner's targets the costal arch (indirect percussion); Mendel's targets the abdominal wall directly over the organ. Both are more relevant in the context of acute/inflammatory biliary disease.

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Summary Table: Key Differentials in Pediatric Jaundice by LFT Pattern

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• Sabiston Textbook of Surgery, 21st Ed. — Biliary Dyskinesia, p. 1835
• Robbins & Cotran Pathologic Basis of Disease — Portal Hypertension, p. 770–771
• Tietz Textbook of Laboratory Medicine, 7th Ed. — Liver Function Test Abnormalities, p. 2022