Basics
Description
Wide spectrum of diseases related to gallbladder dysfunction and cholelithiasis:
- Asymptomatic cholelithiasis (80%)
- Gallbladder sludge or microlithiasis
- Biliary pain: Result of a biliary distension
- Atypical pain with gallstones: Abdominal pain that is not clearly biliary-type pain is infrequently related to incidental gallstones
- Gallbladder dysmotility: Hypercontractile or hypocontractile gallbladder and Sphincter of Oddi dysfunction
- Acute cholecystitis: Inflammation of gallbladder
- Gallstone pancreatitis: Result of transient obstruction of the pancreatic duct by a stone
- Choledocholithiasis: Gallstone within the common bile duct, often causing obstruction with abnormal liver function tests (LFTs) or ductal dilation
- Acute cholangitis: Ascending bactibilia resulting in bacteremia usually related to choledocholithiasis obstructing the bile duct (1-5)
Epidemiology
Incidence
- The 5-year incidence for Danish women aged 30, 40, 50, and 60 years of age were 1.4%, 3.6%, 3.1%, and 3.7%, respectively. Likely higher in Hispanic, South American, and Native American populations and lower in African and Asian populations.
- Cholelithiasis occurs in 4.5-12% of pregnancies of whom 30% progress to biliary pain usually in women with stones >10 mm. Progression to acute cholecystitis occurs in 0.04% and gallstone pancreatitis in 0.006% of pregnancies. It is the second most common reason for nonobstetric surgery in pregnancy.
Prevalence
- High prevalence: 14.2 million adult women in the US have gallstones. The majority are asymptomatic.
- Women aged <30 years affected 3:1 compared to men
- Gender gap equalizes by age 50
Risk Factors
- Strong (OR >2)
- Multiparity, age >40, obesity, female gender when <40 years, rapid weight loss, cirrhosis
- Moderate (OR 1.5-2)
- Diabetes mellitus, family history, ileal dysfunction (e.g., Crohn's disease, resection or bypass), estrogen therapy, first 5 years of oral contraceptive use
- Weak (OR 1-1.5)
- Drugs (ceftriaxone, clofibrate), sedentary lifestyle, total parenteral nutrition
Genetics
- Patients with first-degree relative are 2-4 times more likely to have gallstones than controls.
- The prevalence in the Pima Indian population is 73%.
- Inborn errors of metabolism
General Prevention
- Avoidance of risk factors
- Dietary factors that may prevent stones:
- Ascorbic acid
- Diet rich in polyunsaturated or monounsaturated fats
- Vegetable protein
- Coffee
Pathophysiology
- Bile is critical for digestion of fats.
- Most adult gallstones are made of cholesterol.
- Small proportions are pigment stones.
- Cholesterol gallstone formation
- Cholesterol supersaturation
- Alteration in ratio of bile acids favoring hydrophobic bile acids
- Accelerated crystal nucleation
- Diminished gallbladder motility with bile stasis
- In acute cholecystitis, direct detergent action of bile salts on gallbladder mucosa stimulates inflammatory cascade and later superinfection.
- In pregnancy, altered physiology related to estrogen and progesterone exacerbates these factors leading to more lithogenic bile and hypomotility.
Diagnosis
Diagnosis and management of gallbladder disease in pregnant and nonpregnant patients is nearly identical, except for their preference to use noninvasive techniques in pregnancy.
History
- Inquire about risk factors
- Location, quality, onset, timing, and severity of pain suggestive of biliary origin should prompt further evaluation.
- Intermittent right upper quadrant pain +/- radiation to the shoulder
- Rapid onset with plateau
- Slow, gradual improvement over hours
- Fatty food intolerance
- Often associated with nausea
- Exclude more serious complications or unrelated conditions
Physical Exam
- Benign exam with uncomplicated biliary pain
- Focus on excluding complications
- Fever (abscess, cholecystitis, cholangitis)
- Hypotension or tachycardia (cholangitis)
- Murphy's sign
- Inspiratory arrest with palpation of gallbladder fossa (cholecystitis)
- Jaundice (obstruction)
- Toxic appearance (cholangitis)
Tests
Lab
- LFTs
- Congruent elevations of alkaline phosphatase, bilirubin, and gamma glutaminase suggest biliary obstruction.
- Normal LFT has a high negative predictive value.
- CBC with differential
- Leukocytosis may indicate cholecystitis or cholangitis.
- Amylase and lipase to exclude pancreatitis
- Alkaline phosphatase is expected to be elevated in third trimester often 2 times the upper limit of normal.
Imaging
- Ultrasound
- Prompt, noninvasive, safe, and cost-effective
- Approximately 84% sensitivity for cholelithiasis, but much lower for choledocholithiasis
- Evaluate for biliary ductal dilation
- Presence of pericholecystic fluid, thickened gallbladder wall or Murphy's sign indicates acute cholecystitis.
- CT
- Given its increased accuracy, it may be helpful to evaluate for hepatic duct or intrahepatic duct dilation and exclude other pathologies.
- Little role in pregnancy as majority of stones are radiolucent, unless heavily calcified
- Endoscopic ultrasound
- High sensitivity but invasive
- Consider in patients with recurrent classical biliary pain by history, but limited imaging secondary to anatomy or obesity
- Safe in pregnancy, but rarely used
- Cholecystokinin cholecystoscintigraphy (hepatobiliary iminodiacetic acid or HIDA scan)
- Nonvisualization (no uptake of tracer) of gallbladder suggests acute cholecystitis.
- Unknown safety in pregnancy; reserve for postpartum evaluation
- Diagnostic endoscopic retrograde cholangiography (ERCP) (5)
- Used only if a high probability of choledocholithiasis, as it affords the ability to diagnose and intervene on bile duct stones
- Safest in second and third trimester. Shield pelvis, monitor fetus, and keep O2 saturation >96%. Monitor dosimetry. Average fetal dose is 164 millirads (1-4).
- Magnetic resonance cholangiopancreatography
- Highly accurate for choledocholithiasis
- Safest, least invasive
- Gadolinium crosses the placenta, so safety in pregnancy is uncertain.
- Endoscopic ultrasound
- Highest sensitivity for choledocholithiasis, but invasive and limited availability (1-4)
Surgery
- Exclude cholangitis
- Failure to treat with appropriate antibiotics may result in rapid deterioration of patient leading to sepsis and death.
Differential Diagnosis
- Acute hepatitis
- Hepatic abscess
- Biliary dyskinesia
- Sphincter of Oddi dysfunction
- Congenital choledochal cyst rupture/infection
- Irritable bowl syndrome
- Dyspepsia
- Peptic ulcer disease
- Empyema or pneumonia
- Carcinoma
- Oriental cholangitis (recurrent cholangiohepatitis)
Treatment
- For uncomplicated biliary pain, conservative management with pain medications, IV fluids, and NPO
- Evaluate for sepsis
Medication
- Ursodeoxycholic acid (UDCA) 5 mg/kg PO b.i.d.:
- Dissolution if stones are <10 mm and adequate gallbladder motility is present
- Might be of benefit in recurrent pancreatitis secondary to bile microcrystals
- Indicated after bariatric surgery or in aggressive weight loss programs
- UDCA has not been studied in pregnancy.
- Ketorolac 30-60 mg IV or IM or ibuprofen 400 mg PO t.i.d. p.r.n. for acute attacks if no contraindications (age, renal failure, pregnancy)
- Broad-spectrum antibiotics with enterococcal coverage are recommended if there is evidence of cholangitis or acute cholecystitis.
- First line
- Ampicillin and gentamicin
- Piperacillin-tazobactam
- Ciprofloxacin and metronidazole
- Second line
Additional Treatment
General Measures
- Narcotic pain medication titrated to symptom control
- NSAIDs may be helpful in nonpregnant patients.
Issues for Referral
- Consult gastroenterologist if biliary obstruction (TBili > 1.8), bile duct dilation, or pancreatitis (lipase >3 — ULN)
- Consult surgery if acute cholecystitis, cholangitis, or gallstone pancreatitis for cholecystectomy
Complementary and Alternative Medicine
Rowachol (monoterpene) may have adjunctive role for medical dissolution of stones in nonoperative candidates.
Surgery
- Laparoscopic technique preferred
- Indications for nonurgent cholecystectomy
- Recurrent biliary pain
- Symptomatic biliary dyskinesia
- Calcified gallbladder
- Large gallbladder polyps
- Indications for urgent cholecystectomy
- Acute cholecystitis
- Choledocholithiasis if ERCP failed to clear bile ducts
- Recent surgical advances minimize risk to mother and fetus, but require multidisciplinary approach with perioperative fetal monitoring. Easiest to perform in the second trimester.
- Therapeutic ERCP
- Indicated if nonimproving acute cholangitis or gallstone pancreatitis
- Complications: Pancreatitis, bleeding, perforation, infection, cardiopulmonary
- Post-ERCP pancreatitis (5-7%) may cause abortion in pregnant woman.
- Extracorporeal shockwave lithotripsy
- Works best in thin patients with a small number of stones <2 cm
In-Patient Considerations
Admission Criteria
- Pain requiring IV narcotics
- Evidence of complications
- Acute cholecystitis
- Gallstone pancreatitis
- Acute cholangitis
IV Fluids
Electrolyte repletion, normal saline bolus followed by maintenance IV fluids if NPO
Nursing
- Monitor vital signs
- Supportive care
- Appropriate fetal monitoring
Discharge Criteria
- Pain controlled
- Tolerating diet
- Stable fetus
Ongoing Care
Follow-Up Recommendations
- After an acute attack, most patients may return home uneventfully.
- Education on recurrence risk and surgical management options
Diet
NPO until diagnosis is clear and pain resolved.
Patient Education
- Activity as tolerated
- Low-fat diet
Prognosis
- For all patients with asymptomatic gallstones, 2% will become symptomatic every year for 5 years, with a cumulative rate of biliary colic of 18-28% and of complications of 3% at 10 years.
- In pregnancy, after the first episode of biliary pain, 23% of women will progress to complications and 38% will have recurrent symptoms (1-4).
Complications
- Gallstone pancreatitis
- Acute cholangitis
- Rare complications:
- Gallstone ileus (erosion of stone into intestine causing obstruction)
- Fistula
- Gallbladder perforation with peritonitis
References
1Valdivieso V, Covarrubias C, Siegel F. Pregnancy and cholelithiasis: Pathogenesis and natural course of gallstones diagnosed in early puerperium. Hepatology. 1993;17:1-4. [View Abstract]2Glasgow RE, Visser BC, Harris HW. Changing management of gallstone disease during pregnancy. Surg Endosc. 1998;12:241-246. [View Abstract]3Tham TC, Vandervoort J, Wong RC. Safety of ERCP during pregnancy. Am J Gastroenterol. 2003;98:308-311. [View Abstract]4Lu EJ, Curet MJ, EL-Sayed YY. Medical versus surgical management of biliary tract disease in pregnancy. Am J Surg. 2004;188:755-759. [View Abstract]5Maple JT, Ben-Menachem T, Anderson MA. The role of endoscopy in the evaluation of choledocholithiasis. Gastrointest Endosc. 2010;71(1):1-9. [View Abstract]
Codes
ICD9
- 574.20 Calculus of gallbladder without mention of cholecystitis, without mention of obstruction
- 575.9 Unspecified disorder of gallbladder
- 576.5 Spasm of sphincter of Oddi
- 575.0 Acute cholecystitis
- 574.50 Calculus of bile duct without mention of cholecystitis, without mention of obstruction
ICD10
- K80.20 Calculus of gallbladder w/o cholecystitis w/o obstruction
- K82.9 Disease of gallbladder, unspecified
- K83.4 Spasm of sphincter of Oddi
- K81.0 Acute cholecystitis
- K80.50 Calculus of bile duct w/o cholangitis or cholecyst w/o obst
SNOMED
- 39621005 disorder of gallbladder (disorder)
- 266474003 calculus in biliary tract (disorder)
- 430887001 dysfunction of sphincter of Oddi (disorder)
- 65275009 acute cholecystitis (disorder)
- 307132003 common bile duct calculus (disorder)
Clinical Pearls
- It is a common and costly condition. Complications are rare.
- Initial conservative management works in the majority of cases of uncomplicated biliary pain.
- With complicated or recurrent disease, laparoscopic surgery or ERCP is safe in pregnant and nonpregnant patients.