膽結石(Gallstones)

General information

Description:

Ÿ   stone in gallbladder, usually supersaturated cholesterol

Also called:

Ÿ   cholelithiasis

Ÿ   calculus or calculi of gallbladder

Ÿ   cholecystolithiasis (used to specify gallstones in gallbladder)

Ÿ   choledocholithiasis (used to specify gallstones in common bile duct)

Ÿ   biliary colic (used to describe resulting pain)

Types:

Ÿ   cholesterol stones - most common type of gallstone in United States(2)

Ÿ   pigmented stones

1.           black pigment stones - calcium bilirubinate stones, forms in sterile gallbladder bile, calcium bilirubinate is polymerized and oxidatively degraded

2.           brown pigment stones - forms in infected bile

a.           contains unpolymerized calcium bilirubinate plus calcium fatty acid soaps resulting from bacterial hydrolysis of biliary lecithinmore likely to develop in bile ducts than gallbladder

b.          more likely to develop in bile ducts than gallbladder

Ÿ   low phospholipid-associated cholelithiasis (LPAC)

1.           rare syndrome with low biliary phospholipid levels and symptomatic recurrent cholelithiasis

2.           typically starts before age 40 years and recurs after cholecystectomy

3.           sludge or microlithiasis may occur in liver or along biliary tree

4.           associated with ABCB4 mutations which codes for hepatobiliary phospholipid-flippase MDR3

Epidemiology

Who is most affected:

Ÿ   female, increasing age (rare in children but has been reported)

Incidence/Prevalence:

Ÿ   prevalence of gallstones 13%-18% in men and 15%-25% in women

Ÿ   among patients with asymptomatic gallstones, about 1.5% per year will be treated for gallstone-related complications or symptoms

Likely risk factors:

Ÿ   family history of cholecystectomy in first-degree relative

Ÿ   female gender

Ÿ   obesity (body mass index > 30 kg/m2)

1.           abdominal circumference > 36 inches (91 cm) associated with 2 times the risk compared to < 26 inches

2.           dietary factors:

a.           higher intake of trans-fatty acids

b.          high-dietary glycemic index or glycemic load

c.           lack of physical activity (sedentary lifestyle)

Ÿ   rapid weight loss/cyclic weight loss

Ÿ   childbearing

Ÿ   increasing age

Ÿ   ethnicity - Native American (Pima Indian), Scandinavian

Ÿ   ileal disease, resection, or bypass

Ÿ   total parenteral nutrition (TPN)

Ÿ   postmenopausal estrogen

Ÿ   smoking

Ÿ   drug

1.           fibric acid derivatives such as bezafibrate, clofibrate, fenofibrate, gemfibrozil

2.           oral contraceptives (estrogen-progestin combinations)

3.           hormonal replacement therapy (HRT) or estrogen replacement therapy

Possible risk factors:

Ÿ   Cirrhosis

Ÿ   Crohn disease

Ÿ   sickle cell disease (in children)

Ÿ   genetic predisposition (ABCG8 and UGT1A1 (including Gilbert syndrome variant rs6742078)

Ÿ   elevated plasma bilirubin

Etioplogy and pathogenesis

Causes:

Ÿ   factors contributing to formation of cholesterol stones

1.           cholesterol supersaturation

2.           accelerated cholesterol crystal nucleation

3.           impaired gallbladder motility

4.           intestinal degradation of bile salts may destabilize cholesterol carriers in bile

Ÿ   black pigment gallstones

1.           related to changes in heme metabolism or bilirubin absorption

2.           increased bilirubin concentrations lead to precipitation of calcium bilirubinate

Ÿ   brown pigment stones

1.           mechanical obstruction of biliary tract

2.           leads to bacterial degradation and precipitation of biliary lipids

Ÿ   rapid weight loss in patients with obesity

History and physical

History:

Chief concern (CC):

Ÿ   most patients with gallstones are asymptomatic

Ÿ   colicky pain may occur

1.           in upper abdomen (epigestric)

2.           in right upper quadrant (RUQ)

*usually after meals

Ÿ   nausea and/or vomiting

Ÿ   patients may demonstrate Collin's sign by placing their hand behind the back and thumb pointing upwards

Present illness (PI):

Ÿ   biliary colic - pain typically < 8 hours duration

Ÿ   acute cholecystitis - pain persists for > 8 hours

Ÿ   patterns suggesting cholangitis

Ÿ   Charcot triad

1.           intermittent fever and chills

2.           right upper quadrant pain

3.           jaundice

Ÿ   Reynold's pentad suggests obstructive cholangitis

1.           intermittent fever and chills

2.           right upper quadrant pain

3.           jaundice

4.           mental status changes

5.           hypotension

*the last two features have been characterized as Longmire's classification and suggest acute obstructive suppurative cholangitis

Ÿ   acute pancreatitis - pain is classically described as

1.           epigastric

2.           constant

3.           radiating through to the back

4.           relieved by bending forward

5.           associated with vomiting

Family history (FH)

positive family history of gallstones is associated with 4.5 times risk of gallstones

Physical:

Ÿ   Skin:

Jaundice (+) indicates:common bile duct obstruction or ascending cholangitis

Ÿ   Abdomen:

1.           exclude abdominal mass or hepatomegaly

2.           presence of right upper quadrant (URQ) tenderness is

a.           NOT consistent with uncomplicated biliary colic

b.          most commonly indicative of either/or

I.            acute cholecystitis

II.          ascending cholangitis

Ÿ   Murphy's sign:
arrest of inspiration while physician palpates gallbladder during a deep breath suggests acute cholecystitis

Ÿ   Courvoisier sign:

an enlarged, palpable gallbladder in patients with obstructive jaundice caused by tumors of the biliary tree or by pancreatic head tumors:

1.           biliary tumor (cholangiocarcinoma);

2.           periampulary carcinoma (adenocarcinoma of Vater papila or duodenum)

3.           pancreatic head cancer

4.           lymph node metastasis in the porta hepatis

Ÿ   Back:

1.           Boas sign:

a.           originally described as point tenderness in area right of 10th to 12th thoracic vertebrae

b.          more recently described as hyperesthesia to light touch in right upper quadrant or infrascapular area

Ÿ   Extremities:

green, sweating spots on hands and feet as manifestation of hyperbilirubinemia

Ÿ   Rectal:
pale stools may indicate common bile duct obstruction/ascending cholangitis

Ÿ   Miscellaneous physical:

presence of dark urine (from urobilinogen) may indicate common bile duct obstruction/ascending cholangitis

Diagnosis:

Making the diagnosis:

Ÿ   presence of gallstones identified by abdominal imaging (sono)

Ÿ   may be suspected with clinical history consistent with biliary colic, acute cholecystitis, or obstructive jaundice

Differential diagnosis:

Ÿ   gastrointestinal causes of upper abdominal pain

1.           peptic ulcer disease

2.           functional dyspepsia/ irritable bowel syndrome (IBS)

3.           acute pancreatitis

4.           acute hepatitis including autoimmune hepatitis, hepatitis A, hepatitis B

5.           Fitz Hugh Curtis syndrome
a rare complication of pelvic inflammatory disease (PID) involving liver capsule inflammation[1] leading to the creation of adhesion, mostly in women, caused by Chlamydia trachomatis (Chlamydia) or Neisseria gonorrhoeae (Gonorrhea) though other bacteria such as Bacteroides, Gardnerella, E. coli and Streptococcus

Ÿ   non-gastrointestinal causes

1.           acute pyelonephritis

2.           pneumonia (right-sided)

3.           sickle cell disease - acute painful crisis

4.           acute coronary syndrome or ST-elevation myocardial infarction (STEMI)

5.           Herpes zoster shingles before eruption of vesicles

6.           referred pain from radiculopathy

see Abdominal pain - differential diagnosis for more information

see abnormal liver function tests - differential diagnosis for more information

Testing overview:

Ÿ   blood tests if suspected gallstone disease:

1.           liver function tests

2.           serum amylase, lipase

3.           complete blood count (CBC)

Ÿ   imaging for detection:

1.           abdominal/right upper quadrant ultrasound:

a.           gallstones (cholelithiasis)

b.          thickened gallbladder wall or fluid around the gallbladder

2.           magnetic resonance cholangiopancreatography (MRCP)
if ultrasound has not detected common bile duct stones but bile duct is dilated or liver function tests are abnormal

3.           endoscopic ultrasound

4.           endoscopic retrograde cholangiopancreatography (ERCP) may be used to diagnose and treat ductal stones

Urine studies

Ÿ   urobilinogen may indicate common bile duct obstruction/ascending cholangitis

Treatment

Ÿ   Medication:

provide analgesia with nonsteroidal anti-inflammatory medications (NSAIDS) and/or opioids; diclofenac (Voltaren) 75 mg intramuscularly is effective for alleviating pain of biliary coli

Ÿ   cholecystectomy

1.           indicated for patients with symptomatic gallstones

a.           associated with decreased morbidity if done

I.            within 24-72 hours in mild acute cholecystitis

II.          within 48 hours for mild gallstone pancreatitis

III.        within 24 hours for biliary colic

b.          delayed cholecystectomy recommended in severe acute cholecystitis or severe gallstone pancreatitis (> 2 weeks)

2.           not indicated for asymptomatic gallstones
*nless immunosuppressed or risk for gallbladder cancer

3.           laparoscopic cholecystectomy:
associated with shorter hospital stay and period of convalescence than open cholecystectomy

4.           small-incision cholecystectomy
quicker convalescence compared to open cholecystectomy and similar to laparoscopic cholecystectomy for symptomatic cholelithiasis

5.           open cholecystectomy:
indicated if untreated coagulopathy, Child class C cirrhosis, suspected gallbladder cancer, or hostile abdomen

6.           prophylactic antibiotics prior to elective laparoscopic cholecystectomy do not decrease rate of perioperative infection

Ÿ   nonoperative management has lower long-term cholecystectomy rate but may increase risk of gallstone-related complications compared to cholecystectomy in patients with symptomatic gallstones

Ÿ   oral dissolution therapy (ursodiol or chenodiol) may increase dissolution of gallstones but may not affect symptoms; clinical role is for patients unwilling or unable to have surgery

Ÿ   endoscopic retrograde cholangiopancreatography (ERCP) not routinely recommended in gallstone disease management, but may be considered (especially for therapy) if diagnostic suspicion of ductal stones

Reference: DynaMed