Gallstones

Gallstones (cholelithiasis) are solid concretions that form within the gallbladder from precipitated components of bile. The large majority — roughly 80% — are cholesterol stones, forming when bile becomes supersaturated with cholesterol relative to the bile salts and phospholipids that normally keep it in solution, so that cholesterol crystals precipitate and aggregate.^[1][2] The remainder are pigment stones: black pigment stones, composed of calcium bilirubinate from unconjugated bilirubin and classically associated with chronic hemolysis (e.g., sickle cell disease, hereditary spherocytosis) or cirrhosis; and brown pigment stones, associated with biliary infection or infestation.^[1][2]

This chapter covers gallstones themselves — the majority that remain entirely silent, the biliary colic that develops when a stone transiently obstructs the cystic duct, and the medical (ursodiol-based) option for patients who are poor surgical candidates or decline surgery. It deliberately does not re-explain the acute emergency presentations that gallstones can progress to — acute cholecystitis, choledocholithiasis, ascending cholangitis, or gallstone pancreatitis — which this platform covers in its dedicated Cholecystitis chapter; this chapter cross-references that content rather than duplicating it.

Gallstone disease is common. The Canadian Association of General Surgeons cites an approximate 10% incidence in the general population, with prevalence highest (over 70%) in certain Indigenous populations — including the Pima and Chippewa of North America and the Mi'kmaq of Canada — and in South American Indigenous populations; intermediate (5-21.9%) in Caucasian, Asian, and African American populations; and lowest (under 5%) in Native African populations.^[3] Canadian-specific data from the Canadian Liver Foundation puts prevalence at up to 20% in Canadian women and 10% in Canadian men by age 60, with 70-80% of the Canadian First Nations population affected.^[2] The great majority of people with gallstones — roughly 80% — never develop symptoms at all; these are called silent gallstones and generally do not require treatment (see Choose Initial Treatment).^[2][1]

Asymptomatic (silent) gallstones

Most gallstones are discovered incidentally during imaging performed for an unrelated reason and never cause symptoms.^[2][1] Progression to symptoms is genuinely uncommon: the Canadian Association of General Surgeons estimates that approximately 1-3% of individuals with asymptomatic or mildly symptomatic cholelithiasis develop significant symptoms annually,^[3] closely matching a prospective American cohort in which only 1-2% per year developed biliary symptoms or a complication.^[1] Longer-term data are reassuring in the same direction: in one 24-year follow-up of patients with incidentally discovered gallstones, only 28% still had demonstrable stones and only 6% had ever required a cholecystectomy.^[1] This natural history is the basis for the observation-only approach to silent gallstones described in Choose Initial Treatment.

Biliary colic

Biliary colic is the characteristic symptomatic presentation of uncomplicated gallstone disease. It results from a stone (or thick sludge) transiently impacting the cystic duct: intraluminal pressure within the gallbladder rises, the organ distends, its wall stretches, and pain results; pain subsides once the transient obstruction relieves itself, typically as the stone falls back from the duct.^[3] Pain is typically located in the right upper quadrant or epigastrium, often radiates to the back or right scapula, is frequently post-prandial, and is commonly triggered by a fatty meal; nausea and vomiting are common accompaniments.^[3][1] The pain follows a genuine "colic" pattern — an acute rise in severity, a plateau of persistent pain, then gradual resolution — typically lasting from about 30 minutes to several hours, with most series describing resolution within about 4-6 hours.^[3][1] Persistence of symptoms beyond about 6 hours is the single most useful clinical clue that the picture has evolved into acute cholecystitis rather than remaining simple biliary colic — see Red Flags/Refer, and this platform's dedicated Cholecystitis chapter for the full management of that presentation.^[1]

Intractable biliary colic

A distinct pattern deserves its own recognition: some patients have the clinical picture of biliary colic, but symptoms recur with every meal or every attempt at oral intake, rather than resolving and staying resolved between episodes. This usually reflects a stone impacted at the gallbladder neck rather than one that transiently obstructs and releases, and these patients cannot reliably tolerate a sustainable diet — they need admission and cholecystectomy on an expedited basis, not another outpatient trial of analgesia and dietary advice.^[3]

Distinguishing biliary colic from evolving cholecystitis

Between episodes of biliary colic, the physical examination is usually unremarkable and the patient is afebrile with a soft, non-tender abdomen. A tender, palpable gallbladder, a positive Murphy's sign, fever, or leukocytosis all point toward acute cholecystitis rather than simple biliary colic and should prompt management via this platform's Cholecystitis chapter rather than continued conservative management of "just gallstones."^[3]

Non-modifiable and modifiable risk factors combine to determine both the likelihood of forming gallstones and, to some extent, the stone type.

Medications — a genuinely pharmacist-relevant contributor

Several medication classes promote gallstone or biliary-sludge formation, and recognizing this in a patient with new gallstones or biliary-type symptoms is a real, actionable pharmacist contribution.

• Ceftriaxone forms an insoluble calcium-ceftriaxone precipitate in bile, producing biliary sludge or frank "pseudolithiasis" in a substantial proportion of treated patients (reported in 3-46% of courses, with higher rates in children, and with higher doses and longer courses) — this is usually reversible within 1-2 weeks of stopping the drug, and should be distinguished from a true, pre-existing gallstone rather than assumed to represent new chronic gallstone disease.^[4]
• Octreotide reduces gallbladder motility and cholecystokinin release with ongoing use, and is associated with new gallstone formation in roughly half of patients after a year of therapy.^[5]
• Fibrates — most clearly documented for clofibrate (an older agent no longer marketed), through inhibition of the ACAT enzyme system that renders bile more lithogenic — are a recognized, if less prominent, contributor with the fibrates still in use (gemfibrozil, fenofibrate); this does not argue against appropriate lipid-lowering therapy, but is worth considering in a patient on a fibrate who develops new gallstones or biliary colic.^[5]
• Estrogen-containing therapy (hormone therapy, combined oral contraceptives) increases cholesterol secretion into bile and carries a real but modest risk (number needed to harm of 322).^[1]
• Newer incretin-based diabetes therapies — DPP-4 inhibitors (odds ratio 1.22) and GLP-1 receptor agonists (relative risk 1.27) — carry a modest independent gallstone risk, compounded when they drive rapid weight loss; risk rises with more than 26 weeks of use.^[1]

Pigment stones specifically

Chronic hemolysis (sickle cell disease, hereditary spherocytosis, and other hemolytic disorders) and cirrhosis are the classic drivers of black pigment stones, while biliary infection or infestation is associated with brown pigment stones.^[1][2]

The "F" mnemonics

The classic bedside teaching mnemonic for gallstone risk is the "4 F's" — Female, Forty (increasing age), Fertile (multiparity/pregnancy), and Fat (obesity) — though gallstones occur across every age, sex, and body habitus. The Canadian Association of General Surgeons teaches an extended "6 F's" version that adds Fair (higher prevalence in Caucasian populations) and Family history.^[3]

History

Characterize the pain: location (right upper quadrant or epigastric), radiation (back, right scapula), timing relative to meals (classically post-prandial, often triggered by fatty food), duration, and whether it fully resolves between episodes or recurs with every meal (see Recognize the Condition). Ask specifically about fever, jaundice, pale stools, and dark urine, which point toward a complication rather than simple gallstones, and review the medication list for a gallstone-promoting agent (see Risk Factors).

Physical examination

Examination between episodes of biliary colic is usually unremarkable — a soft, non-tender abdomen with no fever. A positive Murphy's sign, a tender or palpable gallbladder, or signs of jaundice point away from simple gallstones toward acute cholecystitis or a biliary-obstruction complication (see Red Flags/Refer).^[3]

Laboratory testing

Basic labs are reasonable for any patient presenting with biliary-type pain: a complete blood count (looking for leukocytosis), an electrolyte/renal panel, and liver enzymes and function tests (AST, ALT, ALP, GGT, bilirubin, INR).^[3] In simple biliary colic these are typically normal; an abnormal white cell count, transaminases, or bilirubin should prompt evaluation for cholecystitis or a bile-duct complication rather than being attributed to simple gallstones.^[3]

Abdominal ultrasound showing a gallstone (echogenic focus with posterior acoustic shadowing), without wall thickening or other signs of cholecystitis. (Michael Macias, CC BY 4.0, Wikimedia Commons)

Imaging

Right-upper-quadrant ultrasound is first-line: it is fast, inexpensive, avoids radiation, and readily identifies gallstones as a mobile, echogenic focus with posterior acoustic shadowing, with a reported sensitivity of 90-95%.^[3] If choledocholithiasis is suspected (jaundice, dilated bile ducts, or a visible stone on ultrasound), MRCP (sensitivity 84%, specificity 92%) or endoscopic ultrasound (sensitivity 94%, specificity 89%, but invasive with a 4-10% complication rate) can further characterize the common bile duct — see the Cholecystitis chapter for the full biliary-obstruction pathway.^[1]

Differential diagnosis

Peptic ulcer disease and gastroesophageal reflux, functional dyspepsia, acute cholecystitis, choledocholithiasis and ascending cholangitis, gallstone pancreatitis, and — particularly for atypical or diaphragmatic-radiating presentations — a cardiac or right-lower-lobe pulmonary cause should all be considered; see this platform's Undifferentiated Chest Pain chapter where the presentation genuinely overlaps.

• Confirm the diagnosis and exclude a complication (cholecystitis, choledocholithiasis, cholangitis, pancreatitis) before treating a presentation as simple gallstones or biliary colic.
• Relieve acute biliary colic pain effectively, using an NSAID-first approach rather than defaulting to opioids.
• Avoid treating asymptomatic (silent) gallstones found incidentally — observation is correct for the great majority.
• Offer definitive treatment — elective laparoscopic cholecystectomy — to appropriate surgical candidates with symptomatic gallstones, since recurrence without it is high.
• Reserve pharmacologic dissolution therapy (ursodiol) for carefully selected patients who are poor surgical candidates or decline surgery, with stone characteristics genuinely suited to it.
• Set realistic expectations for anyone starting ursodiol — this is a slow process measured in months, with a meaningful recurrence rate after stopping.
• Identify and address a modifiable medication-related contributor where one exists, in partnership with the prescriber.
• Recognize promptly when a presentation has moved beyond simple gallstones and escalate via the Cholecystitis chapter's pathway.

Why surgery is generally the answer for symptomatic gallstones

Once gallstones become symptomatic, they do not resolve on their own, and the risk of recurrent biliary colic — and of eventually progressing to a complication — is genuinely high without removing the gallbladder. Elective laparoscopic cholecystectomy is definitive treatment for the great majority of patients able to tolerate surgery, and is the pathway the Canadian Association of General Surgeons' own biliary-colic algorithm defaults to once an episode resolves.^[3]

Acute pain management — NSAIDs first, not opioids

1st line an NSAID — the evidence here is genuinely strong, not simply a "safer alternative" framing: NSAIDs provide significantly greater relief of biliary pain than placebo (number needed to treat of 3) and than antispasmodics (number needed to treat of 3), with no difference in pain control compared with opioids.^[1] A randomized trial of diclofenac given early in an attack of biliary colic also reduced progression to overt cholecystitis, reinforcing that NSAID analgesia here is not purely symptomatic.^[6] Avoid defaulting to an opioid opioids carry more adverse effects than NSAIDs for equivalent pain relief in this setting; the older teaching that opioids should be specifically avoided in biliary pain because of sphincter of Oddi spasm is outdated and should not be the reason for withholding one when genuinely needed as an add-on for breakthrough pain.^[1] See Pharmacologic Treatment Options and Drug Tables for specific agents and doses.

Ursodiol dissolution therapy — candidate selection, dosing, and genuinely important expectation-setting

Ursodiol (ursodeoxycholic acid) reduces hepatic cholesterol secretion into bile and decreases bile's cholesterol saturation, allowing small cholesterol gallstones to dissolve gradually over months.^[2][1] Best candidates small, non-calcified, radiolucent ("floating," high-cholesterol-content) stones in a functioning gallbladder with a patent cystic duct, in a patient with mild symptoms who is a poor surgical candidate or who declines surgery — dissolution therapy is appropriate for only a minority of symptomatic patients overall.^[1] Typical dosing is weight-based, around 8-10 mg/kg/day in 2-3 divided doses taken with food (per the product monograph); confirm the specific regimen against the current Drug Database entry.

Bariatric surgery / rapid intentional weight loss a separate, genuinely useful preventive indication: prophylactic ursodiol for roughly 6 months after bariatric surgery reduces new gallstone formation (number needed to treat of 5 to prevent any gallstone, 14 to prevent a symptomatic one, and 18 to prevent a cholecystectomy).^[1] This is worth flagging proactively for any patient starting a bariatric or rapid-weight-loss program.

• Elective laparoscopic cholecystectomy is definitive treatment for symptomatic gallstones in a suitable surgical candidate — see this platform's Cholecystitis chapter for the full operative approach, perioperative antibiotic stewardship, and postoperative care, which apply identically whether the indication was biliary colic or acute cholecystitis.
• Intractable biliary colic (recurring with every meal) needs admission and expedited cholecystectomy rather than elective scheduling, given the inability to tolerate oral intake.^[3]
• A low-fat diet can reduce the frequency of biliary colic episodes while a patient awaits surgery or is managed medically, though it does not treat the underlying gallstones and is not a substitute for definitive treatment.
• Weight loss, where indicated, should be gradual rather than rapid — rapid or very-low-calorie weight loss is itself a recognized gallstone risk factor (see Risk Factors); supervise significant intentional weight loss medically.
• Extracorporeal shock-wave lithotripsy is a noninvasive option that has been used for symptomatic gallstones in patients avoiding surgery, but meaningful complication and recurrence rates have limited it to a niche, rarely used role today.^[1]

Pregnancy

Gallbladder disease is the second most common cause of the acute abdomen in pregnancy after appendicitis.^[3] Estimates of how often gallstones or biliary sludge develop during pregnancy vary by source — the Canadian Association of General Surgeons reports that 1-3% of pregnant women develop gallstones and about 30% develop sludge,^[3] while an American series reports gallstones in up to 12% of pregnant women, with roughly 3% ultimately requiring an intrapartum cholecystectomy.^[1] Avoid NSAIDs, particularly from around 20 weeks' gestation onward, given fetal renal and other risks — acetaminophen is the preferred analgesic for biliary colic pain in pregnancy, with an opioid reserved for pain not controlled by acetaminophen alone. Do not start ursodiol dissolution therapy for gallstones in pregnancy — the months-long treatment course is not compatible with a time-limited pregnancy, and definitive management, if needed, is surgical; see this platform's Cholecystitis chapter for the operative approach in pregnancy, and the Cholestasis of Pregnancy chapter for the distinct, unrelated use of ursodiol in that condition.

Breastfeeding

Ibuprofen and other short-acting NSAIDs, acetaminophen, and standard opioid analgesics are generally considered compatible with breastfeeding at standard doses; confirm specifics against each drug's own Drug Database entry. Data on ursodiol in breastfeeding are limited, but available information does not suggest a significant risk; given the elective, months-long nature of dissolution therapy, deferring it is usually reasonable if surgery is a genuine alternative.

Pediatrics

Gallstones are less common in children than in adults but are rising in parallel with pediatric obesity; hemolytic disease (sickle cell disease, hereditary spherocytosis) remains a disproportionate driver of pigment stones in this population.^[1] Use weight-based NSAID/analgesic dosing per a pediatric dosing reference, and manage symptomatic disease with the same observation-versus-cholecystectomy framework used in adults.

Older adults

Gallstone prevalence rises with age, and older adults are more likely to present atypically or to already have a complication (cholecystitis, choledocholithiasis) by the time they are assessed — maintain a lower threshold for imaging and for considering a complication rather than assuming simple biliary colic.

Cirrhosis and hepatic impairment

Pigment gallstones are common in cirrhosis, and surgical risk is meaningfully elevated in this population — cholecystectomy decisions should involve a surgeon experienced with cirrhotic patients. Avoid or use cautiously NSAIDs in cirrhosis, given bleeding and renal risk; acetaminophen, used cautiously with a lower total daily dose, is generally the safer default analgesic. Note that mild transaminase or bilirubin elevation can reflect the underlying liver disease itself rather than a gallstone complication — interpret labs in that context.

Bariatric surgery / rapid intentional weight loss

This population deserves proactive counselling rather than reactive management: prophylactic ursodiol for roughly 6 months after bariatric surgery meaningfully reduces new gallstone formation, symptomatic gallstones, and eventual cholecystectomy (see Choose Initial Treatment for the specific numbers).^[1]

Renal impairment

Avoid or use ketorolac and other NSAIDs cautiously in significant renal impairment; dose-adjust hydromorphone and other opioids as needed. Ursodiol is primarily hepatically handled and generally does not require specific renal dose adjustment, but confirm against the current product monograph.

Populations with a higher baseline prevalence

Certain Indigenous populations — including several Canadian First Nations communities — have a substantially higher prevalence of gallstone disease than the general population (see Clinical Snapshot and Risk Factors).^[3][2] This is a genuine epidemiologic reality worth knowing, not a reason to alter the clinical approach to an individual patient — the same observation-versus-treatment framework applies regardless of ethnicity, and the higher population prevalence should not translate into either under- or over-investigating an individual patient's actual symptoms.

• For a patient managed with observation alone (asymptomatic gallstones): no routine monitoring is needed beyond ensuring the patient knows the return precautions below — repeat imaging "just to check" is not indicated for stable, asymptomatic disease.
• For acute biliary colic managed as an outpatient with NSAID analgesia: confirm pain resolves within the expected several-hour window, and give explicit return precautions — pain lasting beyond about 6 hours, fever, jaundice, or inability to tolerate oral intake — rather than leaving follow-up entirely to the patient's discretion.^[3][1]
• For a patient started on ursodiol: schedule a repeat ultrasound at around 6 months to assess dissolution progress, and again at 12 months if therapy continues; discontinue if there has been no meaningful reduction in stone size/number by 12 months, or sooner if symptoms progress or a complication develops (see Treatment Failure/Next Step).^[2][1] Confirm the patient still understands the recurrence risk after any eventual stop.
• For a patient scheduled for elective cholecystectomy: counsel on what to expect afterward, since patients often ask a pharmacist rather than their surgeon about minor postoperative symptoms — postcholecystectomy diarrhea (reported in roughly 13% of patients, thought to reflect excess bile acid delivery to the colon, usually improving over time and responsive to cholestyramine if persistent) and a broader postcholecystectomy syndrome of ongoing GI symptoms (abdominal pain, bloating, dyspepsia) in roughly 5-10% of patients are common enough to mention proactively.^[1] Full postoperative monitoring is covered in this platform's Cholecystitis chapter.
• For any patient on a gallstone-promoting medication (see Risk Factors) who develops new biliary-type symptoms: reassess the ongoing need for that medication with the prescriber rather than only treating the gallstone in isolation.

1. Biliary colic pain not resolving within the expected several-hour window despite adequate analgesia: reassess for acute cholecystitis rather than simply escalating the analgesic — follow this platform's Cholecystitis chapter pathway.^[3]
2. Recurrent biliary colic episodes despite conservative (analgesia-only) management: offer elective laparoscopic cholecystectomy rather than repeating analgesic courses indefinitely — recurrence without surgery is genuinely high.
3. Intractable biliary colic (recurring with every meal): this needs admission and expedited cholecystectomy, not another outpatient trial of oral analgesia or dietary modification.^[3]
4. Ursodiol therapy with no meaningful reduction in stone size or number on repeat ultrasound at 12 months: discontinue and reassess surgical candidacy rather than continuing an ineffective course indefinitely.^[1]
5. New fever, jaundice, or pain persisting beyond several hours at any point during observation or ursodiol therapy: this is no longer simple gallstone disease — escalate via the Cholecystitis chapter's pathway rather than continuing the current plan.
6. Stone recurrence after a successful course of ursodiol and a period off therapy: reassess for definitive cholecystectomy rather than defaulting to a second dissolution course, given the substantial recurrence rate already built into the original counselling.^[2][1]

• Treating asymptomatic (silent) gallstones found incidentally with cholecystectomy or ursodiol "just in case" — observation is correct for the great majority.
• Reaching for an opioid first-line for biliary colic pain, based on the outdated assumption that NSAIDs are inadequate or that opioids are somehow safer for biliary pain — the evidence shows NSAIDs are at least as effective with fewer adverse effects.
• Starting ursodiol without confirming the stone is genuinely suited to it (small, non-calcified, radiolucent, in a functioning gallbladder with a patent cystic duct) — most symptomatic patients are not good candidates.
• Starting ursodiol without explicitly counselling on the months-long timeline and the meaningful recurrence risk after stopping — a patient who expects a quick, permanent fix is being set up for disappointment and potentially for silently discontinuing an otherwise-appropriate therapy.
• Treating pain persisting beyond several hours, fever, or jaundice as "just a bad episode of biliary colic" rather than recognizing evolution to cholecystitis, cholangitis, or pancreatitis.
• Missing intractable biliary colic (recurring with every meal) as a distinct pattern needing admission and expedited surgery, rather than another round of outpatient analgesia.
• Missing a medication-induced contributor (ceftriaxone, octreotide, a fibrate, or a GLP-1 receptor agonist/DPP-4 inhibitor, especially alongside rapid weight loss) in a patient with new gallstones or biliary-type symptoms.
• Overlooking pigment-stone risk factors (hemolysis, cirrhosis) in a patient who does not fit the classic "4 F's" cholesterol-stone profile.
• Prescribing or continuing NSAIDs for biliary colic pain in a patient who is late in pregnancy, or in significant renal impairment or active GI bleeding risk, without considering acetaminophen or another alternative.

How to use this table: Doses are adult doses and require patient-specific confirmation (renal/hepatic function, weight, allergy history). Pediatric dosing is weight-based per the current product monograph unless stated. Drug pricing is intentionally omitted. Select any drug name to open its complete Pharmasist Drug Database page.

Analgesia for Acute Biliary Colic

NSAIDs relieve biliary pain at least as effectively as opioids, with fewer adverse effects — use as first-line therapy rather than defaulting to an opioid.

Opioid Analgesia — Reserve for Breakthrough Pain

The older concern about opioid-induced sphincter of Oddi spasm is outdated and not a reason to withhold one when genuinely needed; reserve for pain not controlled by scheduled NSAID/acetaminophen, given more adverse effects than NSAIDs at equivalent efficacy.

Antiemetic

For nausea and vomiting accompanying acute biliary colic.

Oral Dissolution Therapy — Selected Non-Surgical Candidates

For symptomatic patients who are poor surgical candidates or decline surgery, with stone characteristics genuinely suited to dissolution (small, non-calcified, radiolucent, functioning gallbladder with a patent cystic duct). Also used as bariatric-surgery gallstone prophylaxis. Confirm candidacy and counsel explicitly on the slow timeline and meaningful recurrence risk before starting.

Medications Associated with Gallstone or Biliary Sludge Formation — Review, Not Routine Discontinuation

Recognizing a medication-related contributor is a genuine pharmacist contribution; weigh against the drug's own benefit and involve the prescriber rather than stopping unilaterally.