What is the pathophysiology of biliary diseases in pregnancy?

Pathophysiology of Biliary Diseases in Pregnancy

The pathophysiology of biliary diseases in pregnancy involves physiological changes that increase the risk of gallstone formation, altered bile composition, and hormonal influences that affect biliary motility and function. 1

Normal Physiological Changes Affecting the Biliary System in Pregnancy

• Hormonal influences:

  • Elevated estrogen levels lead to increased cholesterol secretion into bile
  • Progesterone causes decreased gallbladder contractility and bile stasis
  • These hormonal changes result in supersaturation of bile with cholesterol

• Gallbladder function:

  • Decreased gallbladder motility and emptying
  • Increased residual volume
  • Bile stasis promotes gallstone formation

• Bile composition changes:

  • Increased cholesterol saturation index
  • Altered bile salt composition
  • Decreased bile salt synthesis and secretion

Specific Biliary Diseases in Pregnancy

1. Gallstone Disease

• Pathophysiology:

  • Pregnancy is associated with an increased risk of developing gallstones 1
  • Hormonal changes (estrogen and progesterone) decrease gallbladder contractility
  • Bile stasis and increased cholesterol secretion lead to lithogenic bile
  • Decreased intestinal motility increases bilirubin absorption and excretion

• Clinical manifestations:

  • Biliary colic (right upper quadrant pain)
  • Nausea and vomiting
  • Symptoms may be confused with normal pregnancy discomforts

2. Acute Cholecystitis

• Pathophysiology:

  • Usually results from gallstone impaction in the cystic duct
  • Obstruction leads to gallbladder distension, inflammation, and potential infection
  • Chemical inflammation from trapped bile salts damages gallbladder mucosa
  • Secondary bacterial infection may occur

• Management considerations:

  • Conservative management resolves symptoms in >90% of cases 2
  • Surgical intervention (laparoscopic cholecystectomy) may be necessary for complicated cases
  • Timing of intervention depends on trimester and severity

3. Choledocholithiasis and Cholangitis

• Pathophysiology:

  • Common bile duct obstruction by gallstones
  • Increased biliary pressure leads to bacterial translocation
  • Biliary stasis promotes bacterial growth
  • Endotoxin release can lead to systemic inflammatory response

• Diagnostic approach:

  • Ultrasound is first-line imaging modality 3
  • MRCP can be safely performed at any gestational age if biliary obstruction is suspected

4. Intrahepatic Cholestasis of Pregnancy (ICP)

• Pathophysiology:

  • Multifactorial etiology involving genetic predisposition, hormonal factors, and environmental triggers 4
  • Impaired bile acid transport across canalicular membrane
  • Estrogen metabolites impair bile salt export pump function
  • Elevated serum bile acids cause maternal pruritus and potential fetal complications

• Risk factors:

  • Women with pre-existing hepatobiliary disease have higher risk for ICP 1
  • Genetic susceptibility (variants in ABCB4, ABCB11, ATP8B1 genes)
  • Prior history of ICP (high recurrence risk)
  • Multiple gestations

• Fetal implications:

  • Increased risk of stillbirth, particularly with bile acids >100 μmol/L 1
  • Proposed mechanisms include fetal arrhythmias and vasospasm of placental vessels induced by high bile acid levels

Pathophysiological Changes in Pre-existing Cholestatic Liver Diseases

Primary Biliary Cholangitis (PBC)

• Pathophysiological changes during pregnancy:

  • Immune-mediated damage to biliary epithelium 1
  • Complex pathogenesis involving environmental, immunogenetic, and epigenetic factors
  • Altered cholangiocyte physiology with impaired defenses against toxic bile acids
  • Reduction in immunoglobulin M levels and anti-mitochondrial-M2 antibody titers during pregnancy
  • Return to baseline levels postpartum

• Clinical course:

  • Up to 70% of women with PBC have stable or improved liver tests during pregnancy 1
  • 50% experience new or worsening pruritus during pregnancy
  • 60-70% experience increased liver disease activity postpartum

Primary Sclerosing Cholangitis (PSC)

• Pathophysiological changes during pregnancy:

  • Progressive biliary strictures affecting intra- and extrahepatic bile ducts
  • Often associated with inflammatory bowel disease (60-80% of cases)
  • Potential for recurrent bacterial cholangitis due to biliary strictures
  • Risk of developing relevant bile duct strictures during pregnancy

• Clinical course:

  • Most women have stable liver tests during pregnancy, especially those on ursodeoxycholic acid
  • Up to one-third experience deterioration in liver tests postpartum

Diagnostic Challenges

• Normal pregnancy changes can mimic liver disease:

  • Spider angiomas and palmar erythema (due to hyperestrogenic state)
  • Increased alkaline phosphatase (placental origin)
  • Hypoalbuminemia (hemodilution)
  • Liver displacement upward by gravid uterus 1

• Important laboratory considerations:

  • Serum aminotransferases, bilirubin, and bile acids should remain normal throughout pregnancy
  • Any elevation requires investigation 1
  • Clotting factors II, V, VII, X, XII, and fibrinogen are increased during pregnancy, creating a hypercoagulable state

Management Principles

• Ultrasound is the safest initial imaging modality at any gestational age 3
• MRCP can be safely performed if biliary obstruction is suspected
• Laparoscopic cholecystectomy can be performed safely in any trimester for symptomatic gallstones 3
• For high-risk surgical cases, percutaneous cholecystostomy or gallbladder aspiration can serve as bridging therapy 5

Understanding the complex pathophysiological changes in biliary diseases during pregnancy is essential for appropriate diagnosis and management to optimize both maternal and fetal outcomes.