What are the 5 F's of gallstones?

The 5 F's are fat, female, fertile, forty and fair: the classic profile of a patient with cholesterol gallstones (cholelithiasis). Obesity, female sex and pregnancy are well-supported risk factors, and age counts as "older" rather than as a cut-off at 40. "Fair" is the shakiest F, a crude stand-in for ancestry. In a 2013 test of the mnemonic, 39.4% of patients with stones had a first-degree relative with gallstones vs 13.5% of controls, so add family history, plus fast weight loss.

Are the 5 F's for cholecystitis or cholelithiasis?

The 5 F's describe who gets gallstones (cholelithiasis), specifically cholesterol stones. They turn up in cholecystitis teaching because at least 90% of acute cholecystitis is caused by a gallstone blocking the cystic duct, so the same patients are at risk. The F's do not diagnose cholecystitis: that needs local signs such as a Murphy sign, systemic inflammation such as fever or leukocytosis, and typical imaging findings, as set out in the Tokyo Guidelines 2018.

How long does biliary colic last, and how is it different from cholecystitis?

Biliary colic starts suddenly, becomes intense within 15 to 60 minutes, stays steady (it is not truly colicky) for usually less than 6 hours and then fades over 30 to 90 minutes. Nausea is common, but fever is not, and labs are normal. Pain lasting more than 6 hours, especially with fever, a Murphy sign or leukocytosis, suggests acute cholecystitis; jaundice suggests a duct stone, and a lipase above 3 times normal suggests gallstone pancreatitis.

What are the three types of gallstones?

Cholesterol stones, more than 85% of gallstones in Western countries, form in the gallbladder from cholesterol-supersaturated bile and are usually radiolucent. Black pigment stones are small, hard calcium bilirubinate stones that form in the gallbladder with chronic hemolysis (sickle cell disease, hereditary spherocytosis), cirrhosis or ileal disease, and they may contain enough calcium to show on X-ray. Brown pigment stones are soft stones of calcium bilirubinate and fatty acid salts that form in the bile ducts with stasis and infection, including liver flukes.

What is the first test for gallstones, and when is MRCP, EUS or ERCP needed?

Right upper quadrant ultrasound comes first: it is about 95% sensitive and specific for gallbladder stones. A HIDA scan helps when cholecystitis is suspected but ultrasound is equivocal. For duct stones, the 2019 ASGE guideline sends high-risk patients (a duct stone on imaging, cholangitis, or bilirubin above 4 mg/dL with a dilated duct) to ERCP, intermediate-risk patients (abnormal liver tests, age over 55, or a dilated duct) to MRCP, EUS or intraoperative cholangiography, and low-risk patients straight to cholecystectomy.

When should asymptomatic gallstones be removed?

Usually they are left alone: up to 80% of people with gallstones have no symptoms, and only about 2% a year become symptomatic. Prophylactic cholecystectomy may be considered for stones larger than 3 cm or a calcified (porcelain) gallbladder, both linked to gallbladder carcinoma (the porcelain indication is debated), and for patients with stones who are having bariatric surgery. Once biliary colic starts, laparoscopic cholecystectomy is the treatment of choice, because pain recurs in 20 to 40% of patients a year.

Cholelithiasis Mnemonic: 5 F's, Stone Types & Workup

The cholelithiasis mnemonic is the 5 F's: fat, female, fertile, forty and fair, the textbook profile of a patient with cholesterol gallstones. Female sex, obesity and pregnancy are solid risk factors, "forty" holds only as "older", and "fair" is the shakiest, a crude stand-in for ancestry; the mnemonic also misses family history, fast weight loss and the pigment-stone causes (hemolysis, cirrhosis, ileal disease). Up to 80% of people with gallstones have no symptoms; the classic symptom is biliary colic, steady right upper quadrant pain usually lasting under 6 hours, and the first test is ultrasound. Symptomatic stones → laparoscopic cholecystectomy; silent stones → usually observe.

Cholelithiasis at a glance

Feature	High-yield fact
Who has stones	About 14% of US adults over 20; up to 80% have no symptoms
Stone types	Cholesterol (more than 85% in Western countries), black pigment, brown pigment
Classic symptom	Biliary colic: steady (not colicky) pain, intense within 15–60 minutes, usually lasting under 6 hours, without fever
First test	Right upper quadrant ultrasound, about 95% sensitive and specific for gallbladder stones
Duct stones	Ultrasound misses most: the ASGE 2019 criteria decide between ERCP, EUS or MRCP, and surgery
Complications	Acute cholecystitis, choledocholithiasis, cholangitis, gallstone pancreatitis, gallstone ileus, Mirizzi syndrome
Treatment	Symptomatic stones: laparoscopic cholecystectomy; asymptomatic stones: observe, with a few exceptions

The 5 F's: what the evidence supports

A 2013 study tested the mnemonic directly: it compared 198 patients admitted with upper abdominal pain (March 2009 to April 2010) who had gallstones on ultrasound with 200 admitted with the same complaint but no stones.

F	Stands for	Verdict	Evidence
Female	Female sex, estrogen	Real	Estrogen from pregnancy, hormone therapy or birth control pills raises risk; 75.8% of patients with stones were women vs 55.5% of controls
Fat	Obesity, metabolic syndrome	Real	Excess cholesterol secreted into bile is the usual cause of supersaturation; BMI over 30 in 28.3% vs 9.5%
Fertile	Pregnancy, several pregnancies	Real	Progesterone reduces gallbladder contraction and pregnancy breeds sludge; 68.2% vs 25%
Forty	Older age	Real as "older", not as a cut-off	Prevalence rises with age (more than 25% of women over 60 have stones), but age over 40 did not separate the groups (41.4% vs 39.5%)
Fair	Fair skin, European ancestry	Shakiest: a crude proxy for ancestry	More common in patients with stones in the 2013 study, but the risk follows ancestry: high in northern Europeans, yet American Indians have the highest US rates; lower in Asian and African American populations

What the 2013 study found: fat, female, fertile and fair were all more common in patients with stones, forty was not, and 39.4% of patients with stones had a first-degree relative with gallstones vs 13.5% of controls, so the authors proposed "familial" in place of "forty". About a quarter of the predisposition to cholesterol stones appears to be inherited.

Why "fair" is the weakest F: the risk tracks ancestry, not skin tone. Native American and Hispanic populations are at least as affected as northern Europeans, and American Indians carry genes that raise the cholesterol in their bile, so a darker-skinned patient is not protected. Use the F's to recognize the typical patient, never to rule gallstones out.

Upgrade the mnemonic: keep all five, add familial and fast weight loss (the 7 F's), and learn pigment-stone causes separately: hemolysis, cirrhosis, ileal disease.

Risk factors the 5 F's miss

Risk factor	Why it matters
Family history	The strongest addition: 39.4% vs 13.5% in the study above
Native American ancestry	Highest US prevalence; Mexican Americans are also at higher risk
Fast weight loss	Severe calorie restriction and gastric bypass cause gallbladder stasis; semaglutide, a GLP-1 receptor agonist, carries a gallbladder warning (adult trials of the injection: gallstones in 1.6% vs 0.7% on placebo, an excess that persisted after accounting for weight loss)
Estrogen therapy	Oral contraceptives and hormone therapy; estrogen for prostate cancer raises risk in men too
Parenteral nutrition, prolonged fasting	Gallbladder stasis produces sludge, often the forerunner of stones
Ileal Crohn disease or ileal resection	Bile salts are not reabsorbed; also a black-stone risk
Chronic hemolysis, cirrhosis, cystic fibrosis	Black pigment stones (hemolysis: sickle cell disease, hereditary spherocytosis, β-thalassemia)
High spinal cord injury	Gallbladder stasis
Drugs	Octreotide and other somatostatin analogs (slow gallbladder emptying), fibrates such as fenofibrate (more cholesterol excreted into bile), ceftriaxone (calcium–ceftriaxone precipitate)
Metabolic, lifestyle	Insulin resistance, lipid abnormalities, physical inactivity

Octreotide: in clinical trials (mostly in acromegaly or psoriasis), 27% of patients developed gallstones and 24% sludge without stones; see the octreotide mnemonic.
Fibrates: stop fenofibrate if gallstones are found; clofibrate, named in older texts, is no longer sold in the US.
Ceftriaxone: precipitates are most likely in children, can mimic sludge or stones on ultrasound, and usually resolve once the drug is stopped ("pseudolithiasis").

How gallstones form and the three stone types

Cholesterol stones form in three steps: bile supersaturated with cholesterol (too much cholesterol, or too few bile salts and lecithin to keep it in solution), precipitation of microcrystals, sped up by gallbladder mucin, and growth on a mucin scaffold in a gallbladder that empties poorly. Biliary sludge (calcium bilirubinate, cholesterol microcrystals and mucin) often comes first, especially in pregnancy and parenteral nutrition. Stones grow about 1–2 mm a year and take 5–20 years to cause symptoms.

	Cholesterol	Black pigment	Brown pigment
How common	More than 85% in Western countries	10–20% of US gallstones	Unusual in the US; fairly common in parts of Southeast Asia
Made of	Cholesterol microcrystals on mucin	Calcium bilirubinate with inorganic calcium salts; small and hard	Calcium bilirubinate with calcium salts of fatty acids; soft and greasy
Where they form	Gallbladder	Gallbladder, almost always	Bile ducts (primary duct stones)
Mechanism	Supersaturation, crystal precipitation, stasis	Excess bilirubin crystallizing as calcium bilirubinate	Bile stasis plus chronic bacterial colonization
Classic setting	The F's, rapid weight loss, estrogen, fibrates, octreotide	Chronic hemolysis (hereditary spherocytosis, sickle cell disease), cirrhosis, ileal disease, older age	Infection, liver flukes such as Clonorchis, strictures; the share of duct stones that are pigment stones rises with time after cholecystectomy
Plain radiograph	Usually radiolucent	May contain enough calcium to be radiopaque	Lie in the ducts: look with MRCP, EUS or ERCP

On ultrasound, gallbladder stones are echogenic foci that move with position and cast an acoustic shadow; sludge does not shadow. Only 10–15% of gallstones are calcified enough to show on a plain radiograph, so an X-ray never rules them out.

Biliary colic vs the complications

Condition	Key clue	Labs	Imaging	Management
Biliary colic	Steady RUQ pain, often after a heavy meal; intense within 15–60 min, usually lasting <6 h; no fever	Normal	Stones, no inflammation	Elective laparoscopic cholecystectomy
Acute cholecystitis	Pain >6 h, Murphy sign, low-grade fever; at least 90% have stones	Leukocytosis; bilirubin up to about 4 mg/dL even without a duct stone	Wall thickening, pericholecystic fluid, sonographic Murphy sign; on HIDA the gallbladder does not fill	Fluids, usually antibiotics, cholecystectomy within 7 days of admission; cholecystostomy if surgical risk is very high
Choledocholithiasis	Biliary pain plus jaundice; up to 10% of patients with symptomatic stones	High bilirubin, alkaline phosphatase, GGT and ALT	Duct >6 mm (>10 mm after cholecystectomy); ultrasound often misses the stone	ASGE pathway; ERCP with sphincterotomy, then cholecystectomy
Acute cholangitis	Charcot triad: fever or chills, jaundice, RUQ pain; Reynolds pentad adds confusion and hypotension	Leukocytosis, cholestatic liver tests; take blood cultures	Dilated duct, stone or other cause	Antibiotics plus biliary drainage: ERCP within 48 h (consider within 24 h in septic shock that does not respond to fluids)
Gallstone pancreatitis	Steady epigastric pain that can radiate to the back	Lipase or amylase >3 × upper limit of normal; rising bilirubin suggests a retained stone	Gallstones on ultrasound	Supportive care; ERCP only for cholangitis or ongoing obstruction; cholecystectomy before discharge if mild
Gallstone ileus	Older woman with small bowel obstruction	Nonspecific	Rigler triad: bowel obstruction, air in the biliary tree, ectopic gallstone (usually distal ileum)	Enterolithotomy; fistula repair and cholecystectomy may be added
Mirizzi syndrome	Jaundice or cholangitis from a stone impacted in the cystic duct or gallbladder neck that compresses the common duct	Cholestatic	MRCP: stone in the gallbladder neck, dilated ducts tapering to a normal common bile duct	Surgery; often recognized only at operation; subtotal cholecystectomy when anatomy is unclear

Gallstones are the most common cause of acute pancreatitis (40–70% of cases), and most patients pass the stone without ERCP. Mirizzi syndrome affects under 1% of patients with gallstones. Practice with the gallstone ileus breakdown and these tips on acute vs chronic cholecystitis.

Workup: which test, and when

Right upper quadrant ultrasound first: about 95% sensitive and specific for gallbladder stones; it also shows sludge and signs of cholecystitis and measures the common bile duct. In uncomplicated colic, liver tests and lipase are usually normal.
HIDA scan (cholescintigraphy) when cholecystitis is suspected but ultrasound is equivocal: if the tracer never fills the gallbladder, the cystic duct is blocked. Parenteral nutrition, critical illness, severe liver disease and a previous sphincterotomy cause false positives; morphine helps the gallbladder fill. It is also the most reliable test for acalculous cholecystitis.
MRCP or endoscopic ultrasound (EUS) for an intermediate probability of duct stones. On MRCP, stones are dark filling defects; EUS also finds gallbladder stones under 3 mm when other tests are equivocal.
ERCP when a duct stone is likely or proven, or for cholangitis: it treats as well as diagnoses.
CT is less sensitive than ultrasound for gallbladder stones but shows complications such as perforation and pancreatitis.

Duct stones: ASGE 2019 risk stratification

The 2019 ASGE guideline rates the probability of a common bile duct stone in a patient with symptomatic gallstones:

Probability	Any one of	Next step
High	Duct stone on ultrasound or cross-sectional imaging; ascending cholangitis; total bilirubin >4 mg/dL plus a dilated duct (>6 mm with the gallbladder in place)	ERCP (before or after cholecystectomy), or laparoscopic duct clearance, depending on local expertise
Intermediate (10–50%)	Abnormal liver tests; age >55; dilated duct on imaging	EUS or MRCP, or laparoscopic intraoperative cholangiography or ultrasound
Low	None of these	Cholecystectomy, without preoperative duct imaging

What changed from 2010: the old scheme called a stone on ultrasound, cholangitis or a bilirubin >4 mg/dL alone "very strong" predictors, bilirubin 1.8–4 mg/dL and a dilated duct "strong", and abnormal liver tests other than bilirubin, age >55 and gallstone pancreatitis "moderate"; any very strong predictor, or both strong ones, meant high risk, so a dilated duct alone was already intermediate. The 2019 version dropped bilirubin 1.8–4 mg/dL and gallstone pancreatitis as predictors, downgraded a dilated duct from "strong" to an intermediate predictor, and counts a high bilirubin as high risk only with a dilated duct, so fewer ERCPs find no stone. ASGE also recommends against urgent ERCP (within 48 hours) in gallstone pancreatitis without cholangitis or biliary obstruction.

Tokyo Guidelines 2018 (TG18) in one table

TG18 adopted the 2013 (TG13) criteria for acute cholangitis.

	Acute cholangitis	Acute cholecystitis
A	Systemic inflammation: fever >38 °C or shaking chills; WBC <4,000 or >10,000/mm³, or CRP ≥1 mg/dL	Local signs: Murphy sign; RUQ mass, pain or tenderness
B	Cholestasis: total bilirubin ≥2 mg/dL; ALP, GGT, AST or ALT >1.5 × upper limit of normal	Systemic signs: fever, raised CRP, raised WBC
C	Imaging: biliary dilatation, or the cause (stricture, stone, stent)	Imaging findings typical of acute cholecystitis
Suspected	One A plus one B or C	One A plus one B
Definite	One each of A, B and C	One A, one B, plus C
Grade II (moderate)	Any two: WBC >12,000 or <4,000/mm³; fever ≥39 °C; age ≥75; total bilirubin ≥5 mg/dL; albumin <0.7 × lower limit of normal	Any one: WBC >18,000/mm³; palpable tender RUQ mass; symptoms >72 h; marked local inflammation (gangrenous or emphysematous cholecystitis, pericholecystic or hepatic abscess, biliary peritonitis)
Grade III (severe)	Organ dysfunction	Organ dysfunction

Organ dysfunction (grade III) means any of: hypotension needing dopamine ≥5 µg/kg/min or any norepinephrine; reduced consciousness; PaO₂/FiO₂ <300; oliguria or creatinine >2.0 mg/dL; PT-INR >1.5; platelets <100,000/mm³. Grade I is anything milder.

Cholangitis: antibiotics and fluids for all; drainage is urgent in grade III as soon as organ support has stabilized the patient, early in grade II, and considered in grade I only if there is no response to initial treatment within 24 hours. ASGE (2021) prefers ERCP to percutaneous drainage, within 48 hours, with sphincterotomy and stone extraction rather than a stent alone in stable patients. Practice with this cholangitis question on the Tokyo criteria.
Cholecystitis: TG18 limits early surgery in grades II and III to advanced centers; percutaneous cholecystostomy is the fallback for patients too sick for surgery.

Management (Step 2 CK depth)

Asymptomatic stones: observe. About 2% a year become symptomatic (10% at 5 years). Prophylactic cholecystectomy may be considered for stones >3 cm or a porcelain (calcified) gallbladder, which raise the risk of gallbladder carcinoma (the porcelain indication is debated), and for patients with stones who are having bariatric surgery.
Symptomatic stones: laparoscopic cholecystectomy. Once colic starts it recurs in 20–40% of patients a year, and 1–2% a year develop complications.
Acute cholecystitis: cholecystectomy within 7 days of admission and 10 days of onset (benefit shown in the first 24–48 hours); antibiotics such as ampicillin–sulbactam or piperacillin–tazobactam are usual, though unproven in mild cases.
Duct stones: ERCP with sphincterotomy and stone removal, then cholecystectomy; sphincterotomy alone is an alternative for patients at high surgical risk.
Mild gallstone pancreatitis: cholecystectomy in the same admission (PONCHO trial: biliary events in 17% when surgery was delayed vs 5%).
Ursodeoxycholic acid (ursodiol): works best on tiny (<0.5 cm) radiolucent stones in a functioning gallbladder, takes months, and suits patients who refuse or cannot have surgery; stones recur in up to 50% within 5 years, and it does not dissolve calcified or pigment stones. It can also prevent stones during rapid weight loss after bariatric surgery.

How USMLE tests it: traps

Biliary colic is not colicky: the pain is steady, fatty food is not a specific trigger, gas and bloating are not specific gallstone symptoms, and gallstones do not cause dyspepsia.
A normal ultrasound does not exclude a duct stone: transabdominal ultrasound detects only 15–40% of them.
A mildly raised bilirubin in cholecystitis (up to about 4 mg/dL) does not prove a duct stone; a lipase above 3 times normal suggests duct obstruction.
Acalculous cholecystitis: critically ill patient (burns, sepsis, trauma, parenteral nutrition), no stones, and a distended, thick-walled gallbladder with sludge.
Brown stones form in the ducts; black stones form in the gallbladder. Ileal disease turns up as a gallstone risk in Crohn disease questions.

Worked vignettes

Vignette 1 (Step 1). A 15-year-old boy with hereditary spherocytosis has had two episodes of right upper quadrant pain after meals. Ultrasound shows several small gallbladder stones, faintly visible on a plain radiograph. What are they made of?

Answer: black pigment stones (calcium bilirubinate). Chronic hemolysis floods bile with bilirubin, which crystallizes as calcium bilirubinate in the gallbladder; the calcium salts they contain can make black stones visible on X-ray. Not cholesterol: he has no metabolic risk factors, and cholesterol stones are usually radiolucent. Not brown: brown stones form in infected bile ducts.

Vignette 2 (Step 2 CK). A 60-year-old man has had three attacks of right upper quadrant pain; the last settled yesterday, and he is now afebrile and pain-free. Total bilirubin is 2.4 mg/dL, alkaline phosphatase 260 U/L and ALT 180 U/L; lipase is normal. Ultrasound shows gallbladder stones, a normal wall, a 7-mm common bile duct and no visible duct stone. Best next step?

Answer: MRCP or EUS (intraoperative cholangiography or ultrasound at cholecystectomy is the guideline's surgical alternative). He is intermediate risk under ASGE 2019 (abnormal liver tests, age over 55, dilated duct) with no high-risk feature: no stone seen, no cholangitis, bilirubin under 4 mg/dL. Under the 2010 criteria (bilirubin 1.8–4 mg/dL plus a dilated duct) he would have gone straight to ERCP. A stone means ERCP, then cholecystectomy; no stone means cholecystectomy. HIDA answers a different question (cholecystitis).

Vignette 3 (Step 2 CK). A 79-year-old woman has 2 days of right upper quadrant pain, rigors and jaundice. Temperature is 39.4 °C and blood pressure 118/70 mm Hg; she is alert and comfortable on room air. WBC is 16,800/mm³, total bilirubin 4.6 mg/dL and alkaline phosphatase 3 times normal; creatinine, platelets and INR are normal. Ultrasound shows an 11-mm common bile duct containing a stone. Diagnosis, grade and next step?

Answer: definite acute cholangitis, TG18 grade II → blood cultures, IV antibiotics (such as piperacillin–tazobactam) and early ERCP (within 48 hours) with sphincterotomy and stone extraction, then cholecystectomy if she is fit for surgery. She has A (fever, high WBC), B (bilirubin ≥2 mg/dL) and C (dilated duct with a stone). Grade II needs two of five predictors; she has three: WBC >12,000/mm³, fever ≥39 °C and age ≥75 (bilirubin is under 5 mg/dL). With no organ dysfunction she is not grade III. Emergency cholecystectomy would not drain the duct.

Key takeaways

5 F's: female, fat and fertile hold up, forty means "older", and fair is the shakiest; add family history and fast weight loss.
Cholesterol stones dominate; black stones form in the gallbladder (hemolysis, cirrhosis, ileal disease); brown stones form in infected ducts.
Colic is steady pain under 6 hours with normal labs; fever, longer pain, jaundice or a high lipase signals a complication.
Ultrasound first, HIDA for equivocal cholecystitis, ASGE 2019 for duct stones, TG18 to grade cholangitis and cholecystitis.
Treat symptoms, not stones: cholecystectomy for symptomatic gallstones, observation for most silent ones.