Gallstone

Aka: Gallstone, Cholelithiasis

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II. Epidemiology

  1. Cholelithiasis affects 20 million in United States
  2. Cholecystectomies per year in U.S.: 300,000
  3. Management complications result in 6000 US deaths/year
  4. Cholelithiasis Incidence increases with age
    1. However children have an Incidence of Gallstones of 1.9%
  5. Females are more often affected after Puberty
    1. Prior to Puberty, males and females have equal Incidence of Gall Bladder disorders

III. Definitions

  1. Biliary Colic
    1. Transient cystic duct obstruction
  2. Cholelithiasis
    1. Presence or formation of Gallstones
  3. Acute Cholecystitis
    1. Persistent obstruction of the cystic duct with constant pain (contrast with Biliary Colic)
    2. Results in gallbladder wall thickening, serious infection or perforation
  4. Choledocholithiasis
    1. Calculi in the common bile duct
  5. Acute Gallstone Cholangitis (Ascending Cholangitis)
    1. Acute biliary tract infection caused by Bacteria ascending from the Small Intestine

IV. Risks Factors: Cholesterol Gallstones

  1. Classic 5 F's
    1. Female
    2. Forty (age over 40 years)
    3. Fair skinned (Scandinavian)
    4. Family History (first degree relative)
      1. Specific races (e.g. Chilean Indians, Mexican Americans, Pima Indians)
    5. Fat (Obesity with BMI >30, and esp. >35 kg/m2)
      1. Obesity is also a risk factor for Gallstone development in children
  2. Dietary and lifestyle factors
    1. High calorie diet
    2. Excessive intake of refined Carbohydrates
    3. Low fiber intake
    4. Prolonged Fasting
    5. Sedentary lifestyle with low Physical Activity
    6. Rapid weight loss
      1. Post-Bariatric Surgery (Gallstones develop in 22%, esp. Sleeve Gastrectomy)
    7. Total Parenteral Nutrition (TPN) Cholestasis
      1. Common cause in children with serious comorbidity
  3. Associated Conditions
    1. Alcoholic Cirrhosis
    2. Bariatric Surgery
    3. History of ileal disease, resection or bypass
    4. Type 2 Diabetes Mellitus, Metabolic Syndrome or Hyperinsulinism
    5. Hyperlipidemia (dyslipidemia)
    6. Obesity
    7. Pregnancy
      1. Gallstones are found in 12% of pregnant women
      2. Intrapartum Cholecystectomy is needed in 3% of pregnant women with Gallstones
    8. Celiac Disease
    9. Non-Alcoholic Fatty Liver Disease (NAFLD)
    10. Hemolytic Anemia
      1. Increased Hemoglobin degradation, Unconjugated Bilirubin formation and
      2. Deposition of polymerized calcium Bilirubinate with black pigment Gallstones
  4. Congenital Causes (esp. Children)
    1. Sickle Cell Anemia (most common cause in children)
    2. Hereditary Spherocytosis
    3. Cystic Fibrosis
    4. Obesity
  5. Medications
    1. Estrogen Replacement (e.g. Premarin)
    2. Oral Contraceptives
    3. Ceftriaxone
    4. Noninsulin Therapy of Type 2 Diabetes (for >26 weeks)
      1. Dipeptidyl-Peptidase IV Inhibitor (DPP-4 Inhibitor, RR 1.2)
      2. GLP-1 Receptor Agonist (RR 1.2)

V. Pathophysiology

  1. Gall Stones
    1. Solid calculi form when there is impaired gallbladder motility
    2. Composition
      1. Cholesterol stones (80% of Gallstones in U.S.)
        1. Cholesterol and bile supersaturation which precipitates into Cholesterol monohydrate crystals
      2. Black pigment stones (10 to 15% of Gallstones in U.S.)
        1. Polymerized calcium Bilirubinate associated with Unconjugated Bilirubin deposition
        2. Chronic Hemolysis is a common cause
      3. Brown pigment stones (5%)
        1. Associated with biliary tract infections
  2. Progression to symptoms
    1. Gallbladder distention (hydrops)
    2. Serosal edema
    3. Infection secondary to obstructed cystic duct

VI. Differential Diagnosis

  1. Typical right upper quadrant and Epigastric Pain presentations
    1. Hepatitis
    2. Hepatic Abscess
    3. Pancreatitis
    4. Gastritis
    5. Peptic Ulcer Disease (perforated or penetrating)
    6. Gastroesophageal Reflux disease
  2. Atypical presentations in the abdominal RUQ or epigastric region
    1. Fitz Hugh-Curtis Syndrome
      1. Gonorrhea or Chlamydia perihepatitis
    2. Pelvic Inflammatory Disease
    3. Appendicitis
    4. Pyelonephritis
  3. Chest conditions with radiation into abdominal RUQ or epigastric region
    1. Right lower lobe Pneumonia
    2. Myocardial Ischemia or Myocardial Infarction

VII. Types: Gallbladder Disease

  1. Biliary Colic
  2. Acalculous Cholecystitis (Biliary Dyskinesia)
  3. Acute Cholecystitis
  4. Choledocholithiasis
  5. Ascending Cholangitis
  6. Gallstone Pancreatitis

VIII. Findings: Symptoms and Signs

  1. See Biliary Colic
  2. See Acute Cholecystitis

IX. Imaging

  1. Gallbladder Ultrasound
    1. First-line study in the evaluation of Right Upper Quadrant Abdominal Pain, and gallsone disease evaluation
    2. Readily available, accurate, rapid, bedside, non-radiation and functional (sonographic Murphy Sign) study
    3. Clinician performed bedside Abdominal Ultrasound may help direct formal imaging and Consultation
      1. Ross (2011) Acad Emerg Med 18(3): 227-35 [PubMed]
  2. HIDA Scan (Hepatobiliary Iminodiacetic Acid Scan)
    1. Second-line study in suspected Acute Cholecystitis or Acalculous Cholecystitis, but with non-diagnostic Ultrasound
    2. Also, a first-line study when post-operative acute bile leak is suspected
    3. In Biliary Colic or hypofunctioning gallbladder, Cholecystokinin injection during HIDA Scan reproduces RUQ symptoms
    4. More accurate than RUQ Abdominal Pain and Abdominal CT for Acute Cholecystitis
      1. However, nuclear study that is more expensive and typically delayed hours obtaining radiotracer
      2. Only evaluates gallbladder and bile tract (in contrast with Ultrasound and CT which identify other regional pain causes)
  3. CT Abdomen and Pelvis with IV Contrast
    1. Work-horse of adult, undifferentiated Abdominal Pain in the emergency department
    2. Consider when Abdominal Pain is not isolated to the right upper quadrant, or in more complicated presentations
    3. Radiation exposure and higher cost than Ultrasound, and misses non-calcified Gallstones compared with Ultrasound
  4. Magnetic Resonance Cholangiopancreatography (MRCP)
    1. Indicated when Choledocholithiasis (Common Bile Duct Stone) is suspected
    2. Also detects non-stone causes of obstruction, as well as local masses

X. Management: Asymptomatic Gallstones

  1. Asymptomatic Cholelithiasis account for 80% of patients with stones (incidentally identified on imaging)
  2. Asymptomatic Gallstones have a benign course in a majority of patients
    1. In nearly 5 years of follow-up, only 10% develop symptoms, and only 7% require surgery
    2. Gallstones recede spontaneously on Ultrasound in more than 70% of patients over a 24 year follow-up
    3. Within one year of asymptomatic Gallstone diagnosis, <=2% of patients develop symptoms
  3. Management
    1. Watchful waiting (expectant management, no intervention) is recommended in most cases
    2. Consider prophylactic Cholecystectomy in asymptomatic patients at higher risk of progression
      1. Hemolytic disease (e.g. Sickle Cell Anemia, Hereditary Spherocytosis)
      2. Very large Gallstones (>3 cm)
      3. Neuroendocrine tumors
      4. Preparation for organ transplant
  4. References
    1. Friedman (1993) Am J Surg 165(4): 399-404 [PubMed]
    2. McSherry (1985) Ann Surg 202(1): 59-63 [PubMed]
    3. Schmidt (2011) Scand J Gastroenterol 46(7): 949-54 +PMID:21501110 [PubMed]
    4. Lee (2022) World J Clin Cases 10(29):10399-412 +PMID: 36312509 [PubMed]

XI. Management: Symptomatic Gallstones

  1. See Biliary Colic
  2. See Acute Cholecystitis
  3. Watchful waiting of Symptomatic Gallstones is a safe option when complications are absent
    1. Pregnancy and Symptomatic Gallstones
    2. Symptomatic Gallstones (e.g. Biliary Colic) without complications (Cholecystitis, Ascending Cholangitis)
      1. Up to 25% will undergo Cholecystectomy within 18 months
      2. Symptoms resolve in 50% of patients without surgery
      3. Hudson (2023) BMJ 383: e075383 [PubMed]
      4. Verhus (2002) Scand J Gastroenterol 37:834-9 [PubMed]
  4. Cholecystectomy indications
    1. Recurrent bililary colic
    2. Acute Cholecystitis
      1. Cholecystectomy within 72 hours of onset
    3. Gallstone Pancreatitis
      1. Cholecystectomy prior to Pancreatitis hospitalization discharge
    4. Gallbladder Calcification (porcelain gallbladder)
      1. Risk of gallbladder cancer
    5. Hemolytic Anemia
      1. Chronic Hemolysis is high risk for formation of black pigmented stones (calcium Bilirubinate Gallstones)
    6. Large Gallstones (>3 cm)
      1. High risk of gallbladder cancer
    7. Pending Bariatric Surgery for morbid Obesity
      1. High risk of symptomatic gallbladder disease related to rapid weight loss
    8. Native american ethnicity
      1. Higher risk of gallbladder cancer
    9. Pending transplant (with Immunosuppression)
      1. Chronic Immunosuppression risks blunted gallbladder symptoms and increased risk of Ascending Cholangitis
    10. Gallbladder dysmotility and small Gallstones
      1. Increased risk of Gallstone Pancreatitis
    11. Pregnancy and recurrent or intractable biliary pain (or associated complications)
      1. Symptomatic management is preferred
      2. However Laparoscopic Cholecystectomy is indicated if uncontrolled, persistent symptoms
    12. Child-Pugh Class A or B Cirrhosis
      1. Laparoscopic Cholecystectomy is indicated for Symptomatic Gallstones (despite the increased complication risk)
  5. ERCP and Cholecystectomy indications
    1. Choledocholithiasis
  6. Percutaneous cholecystostomy drainage indications (with delayed Cholecystectomy)
    1. Older or critically ill patients with gallbladder empyema (and associated Sepsis)

XII. Complications

  1. Overall complication rate in those with Gallstones: 20%
  2. Cystic
    1. Biliary Colic
    2. Acute Cholecystitis
  3. Common Bile Duct
    1. Choledocholithiasis (affects 6 to 12%, up to 20% of patients with Symptomatic Gallstones)
    2. Acute Gallstone Cholangitis (Ascending Cholangitis)
    3. Gallstone Pancreatitis

XIII. Complications: Post-Cholecystectomy

  1. See Cholecystectomy

XIV. Course: Asymptomatic Gallstones

  1. Symptoms developing in Cholelithiasis: 2% per year (average)
  2. Symptoms within 5 years of diagnosis: 10%
  3. Symptoms within 10 years of diagnosis: 20%

XV. References

  1. Abraham (2014) Am Fam Physician 89(10): 795-802 [PubMed]
  2. Patel (2024) Am Fam Physician 109(6): 518-24 [PubMed]
  3. Portincasa (2006) Lancet 368(9531):230-9 [PubMed]

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