Gallstone Disease & Cholecystitis

Gallstones (cholelithiasis) are one of the commonest surgical conditions worldwide and a perennial NEET PG favourite — expect questions on stone types, Murphy's sign, Charcot's triad, Mirizzi syndrome and laparoscopic cholecystectomy complications every year. This note builds the full pathway from asymptomatic stones to gallstone ileus and the dreaded bile duct injury.

Definition & basic anatomy

Cholelithiasis = stones within the gallbladder. Choledocholithiasis = stones in the common bile duct (CBD). Cholecystitis = inflammation of the gallbladder wall, usually from cystic duct obstruction by an impacted stone.

Key surgical anatomy to revise:

• Calot's triangle (cystohepatic triangle) — bounded by the cystic duct (inferiorly), common hepatic duct (medially) and inferior border of the liver (superiorly). Contents: cystic artery, right hepatic artery, cystic lymph node (of Lund), and Calot's node.
• The cystic artery is usually a branch of the right hepatic artery and lies within Calot's triangle.
• Hartmann's pouch — a pathological dilatation/outpouching at the gallbladder neck where stones classically impact.
• The sphincter of Oddi controls flow of bile and pancreatic secretion into the second part of the duodenum at the ampulla of Vater.

High-yield: The single most reliable landmark to prevent bile duct injury during laparoscopic cholecystectomy is the Critical View of Safety (CVS) — clearing Calot's triangle of fat/fibrous tissue so that only two structures (cystic duct and cystic artery) are seen entering the gallbladder, with the lower third of the gallbladder separated from the liver bed.

Classification of gallstones

Three principal types — cholesterol, pigment (black and brown), and mixed (the commonest).

Feature	Cholesterol stones	Black pigment stones	Brown pigment stones
Composition	>50% cholesterol monohydrate	Calcium bilirubinate polymers	Calcium bilirubinate + fatty acids
Usual site	Gallbladder	Gallbladder	Bile ducts (primary CBD stones)
Radiopaque?	Usually radiolucent	Often radiopaque (Ca)	Radiolucent
Key association	Obesity, female, OCPs, rapid weight loss, ileal disease	Chronic haemolysis (sickle cell, hereditary spherocytosis, thalassaemia), cirrhosis	Biliary stasis + infection (E. coli, Clostridium, Ascaris, Clonorchis)
Mechanism	Cholesterol supersaturation of bile	Unconjugated bilirubin excess	Bacterial β-glucuronidase deconjugates bilirubin

High-yield: Most gallstones are mixed. About 80–90% of gallstones are radiolucent on plain X-ray (only ~10–15% are radiopaque, mainly pigment stones), which is why ultrasound — not X-ray — is the investigation of choice.

Mnemonic for cholesterol stone risk factors — the classic 5 F's: Fat, Female, Forty, Fertile (multiparous), Fair. Add rapid weight loss / bariatric surgery, OCPs/oestrogen, terminal ileal resection or Crohn's, somatostatin/octreotide, ceftriaxone (biliary sludge/pseudolithiasis), and TPN.

Pathophysiology

Cholesterol stones form when bile becomes lithogenic — the three-pronged Admirand–Small / Small's triangle concept:

1. Cholesterol supersaturation (relative excess of cholesterol over bile salts and lecithin).
2. Gallbladder hypomotility / stasis (allows nucleation; seen in pregnancy, TPN, fasting).
3. Accelerated nucleation (mucin glycoproteins act as a pronucleating factor; bilirubinate/calcium as a nidus).

Pigment stones — black stones reflect excess unconjugated bilirubin from chronic haemolysis; brown stones reflect biliary infection where bacterial β-glucuronidase deconjugates bilirubin to its insoluble form.

Acute calculous cholecystitis sequence: stone impacts in the cystic duct or Hartmann's pouch → outflow obstruction → gallbladder distension → mucosal injury and release of phospholipase → lysolecithin and prostaglandin-mediated inflammation → wall oedema. Infection (E. coli, Klebsiella, Enterococcus) is secondary, not the initiating event.

Clinical presentations — a spectrum

Asymptomatic gallstones → Biliary colic → Acute cholecystitis → complications (empyema, gangrene, perforation) → chronic cholecystitis → choledocholithiasis/cholangitis → gallstone pancreatitis / gallstone ileus / carcinoma.

Biliary colic

• Constant right upper quadrant (RUQ) or epigastric pain, often after a fatty meal, radiating to the right scapula/interscapular region.
• A misnomer — the pain is steady, lasting 30 minutes to a few hours, then settles. No fever, no peritonism.
• Caused by transient cystic duct obstruction without sustained inflammation.

Acute cholecystitis

• Persistent RUQ pain (>6 hours), fever, leucocytosis.
• Murphy's sign — palpate under the right costal margin and ask the patient to inspire; inspiratory arrest due to pain = positive. The sonographic Murphy's sign (probe over the gallbladder) is even more specific.
• Boas' sign — hyperaesthesia below the right scapula tip.
• A palpable, tender mass may be felt if an omental phlegmon walls off the inflamed gallbladder.

High-yield: Courvoisier's law — in a patient with painless obstructive jaundice, a palpable, non-tender gallbladder is unlikely to be due to stones (a chronically fibrosed gallbladder cannot distend) and suggests a malignant distal obstruction (e.g. periampullary/pancreatic head carcinoma). Stones cause a thick, contracted gallbladder → not palpable.

Acalculous cholecystitis

• ~5–10% of acute cholecystitis; no stones. Seen in critically ill, ICU, TPN, burns, trauma, sepsis patients.
• Due to biliary stasis + ischaemia; higher risk of gangrene and perforation, higher mortality. Often diagnosed on HIDA/USG; treated with percutaneous cholecystostomy if unfit for surgery.

Diagnosis & investigation of choice

Modality	Role / Findings
Transabdominal ultrasound (USG)	Investigation of choice for gallstones & acute cholecystitis. Sensitivity >95% for stones. Signs: stones with posterior acoustic shadowing, wall thickening >3 mm, pericholecystic fluid, gallbladder distension, sonographic Murphy's sign
HIDA scan (cholescintigraphy)	Most sensitive/specific for acute cholecystitis. Non-visualisation of the gallbladder at 4 h (with normal duct/duodenal filling) = cystic duct obstruction = positive. Useful when USG equivocal and for acalculous cholecystitis/biliary dyskinesia (ejection fraction <35%)
MRCP	Non-invasive gold standard for choledocholithiasis (CBD stones); maps biliary anatomy
Endoscopic USG (EUS)	Best for small CBD/distal stones; high sensitivity
ERCP	Therapeutic — stone extraction, sphincterotomy, stenting. Diagnostic role largely replaced by MRCP/EUS
CT	Less sensitive for stones; good for complications (perforation, gangrene, emphysematous changes), and to evaluate gallbladder cancer

Laboratory pointers: Acute cholecystitis → neutrophilic leucocytosis, mildly raised CRP; LFTs usually normal or mildly deranged. Markedly raised bilirubin/ALP suggests CBD obstruction (choledocholithiasis or Mirizzi). A rise in amylase/lipase suggests gallstone pancreatitis.

High-yield: Predictors of CBD stones — CBD diameter >6 mm on USG, total bilirubin >4 mg/dL, visualised CBD stone, ascending cholangitis. High-probability patients → proceed to ERCP; intermediate → MRCP/EUS first.

Diagnostic flow for suspected acute cholecystitis: RUQ pain + fever + positive Murphy's sign → USG → wall >3 mm, pericholecystic fluid, stones → diagnosis confirmed → if equivocal, HIDA scan → non-visualised gallbladder → confirms acute cholecystitis.

The Tokyo Guidelines (TG18) grade severity (Grade I mild, II moderate, III severe with organ dysfunction) and standardise diagnostic criteria (local inflammation + systemic inflammation + imaging).

Management & drug/procedure of choice

Asymptomatic gallstones

• Generally NOT operated — only ~1–2%/year become symptomatic.
• Prophylactic cholecystectomy indicated when: porcelain gallbladder (calcified wall, cancer risk), gallbladder polyp >10 mm (or rapidly growing/with stones), stones >3 cm, choledochal cyst / anomalous pancreaticobiliary junction, sickle cell disease, transplant candidates, and typhoid carriers harbouring stones.

Biliary colic / symptomatic cholelithiasis

• Elective laparoscopic cholecystectomy is the treatment of choice (gold standard).

Acute cholecystitis

• Admit, IV fluids, analgesia, IV antibiotics (cover gram-negatives & anaerobes).
• Early laparoscopic cholecystectomy within 72 hours (≤7 days of symptom onset) is preferred — lower complication and conversion rates than delayed surgery. ("Hot cholecystectomy.")
• Percutaneous cholecystostomy for the unfit/critically ill or Grade III disease as a temporising drain.

Choledocholithiasis / ascending cholangitis

• ERCP with sphincterotomy + stone extraction, then laparoscopic cholecystectomy. Alternatively single-stage lap CBD exploration.
• Acute (ascending) cholangitis = biliary emergency. Charcot's triad = fever with rigors + RUQ pain + jaundice. Reynolds' pentad = Charcot's triad + hypotension + altered mental status (suppurative cholangitis). Management: fluids + IV antibiotics + urgent biliary decompression (ERCP).

High-yield: Charcot's triad (cholangitis) vs Murphy's sign (cholecystitis) — a classic exam discriminator. Jaundice is a feature of cholangitis/choledocholithiasis, NOT of uncomplicated acute cholecystitis.

Medical dissolution (ursodeoxycholic acid) and ESWL are largely historical — reserved for small, radiolucent (cholesterol) stones in a functioning gallbladder in patients unfit for surgery; high recurrence. Drug = ursodeoxycholic acid (UDCA).

Mirizzi syndrome

• Extrinsic compression of the common hepatic duct by a stone impacted in the cystic duct or Hartmann's pouch, ± a cholecystocholedochal/cholecystobiliary fistula.
• Presents with obstructive jaundice + features of cholecystitis.
• Csendes classification: Type I = external compression only; Types II–IV = progressive cholecystobiliary fistula (II <1/3 circumference, III up to 2/3, IV entire wall).
• Strongly associated with gallbladder carcinoma — keep a high index of suspicion.

High-yield: Mirizzi syndrome markedly increases the risk of bile duct injury during cholecystectomy; MRCP delineates it and a low threshold for open conversion is wise.

Complications

Of the disease

• Empyema (pus-filled gallbladder), gangrenous cholecystitis, perforation (localised abscess, or free perforation → biliary peritonitis).
• Emphysematous cholecystitis — gas in the wall/lumen from gas-forming organisms (Clostridium welchii/perfringens, E. coli); associated with diabetics; high mortality → emergency cholecystectomy.
• Gallstone ileus — a large stone (usually >2.5 cm) erodes through a cholecystoduodenal fistula and impacts at the terminal ileum → mechanical small-bowel obstruction. Rigler's triad (on X-ray/CT) = pneumobilia + small-bowel obstruction + ectopic gallstone. Stone often lodges at the ileocaecal valve.
• Bouveret syndrome — variant where the stone impacts in the duodenum/pylorus causing gastric outlet obstruction.
• Gallbladder carcinoma — strongly linked to gallstones, porcelain gallbladder, chronic typhoid carriage, large stones, anomalous pancreaticobiliary junction. Mostly adenocarcinoma; spreads early to segments IVb/V of the liver.

Of laparoscopic cholecystectomy

• Bile duct injury (BDI) — the most feared complication (~0.3–0.5%). Often the CBD mistaken for the cystic duct ("classic laparoscopic injury"). Graded by Strasberg (Type A = cystic duct/duct of Luschka leak; Type E = main duct transection, sub-classified E1–E5 by Bismuth level).
• Bile leak (cystic duct stump, duct of Luschka), retained CBD stone, bleeding (cystic/right hepatic artery), bowel/visceral injury from trocar/diathermy, dropped/spilled stones → late intra-abdominal abscess.
• Post-cholecystectomy syndrome — persistent biliary-type pain/dyspepsia (retained stone, sphincter of Oddi dysfunction, cystic duct remnant).

High-yield: A patient with fever, jaundice and bile in the drain days after lap chole = suspect bile duct injury / leak → investigate with HIDA/MRCP/ERCP; manage leaks endoscopically (ERCP + stent), major transections need hepaticojejunostomy (Roux-en-Y).

Key differentials

Condition	Discriminating clue
Acute cholecystitis	RUQ pain >6 h, positive Murphy's sign, no jaundice, USG wall thickening
Ascending cholangitis	Charcot's triad (fever+pain+jaundice), CBD stone, deranged LFTs
Acute pancreatitis (gallstone)	Epigastric pain to back, raised lipase/amylase, gallstones on USG
Peptic ulcer / perforation	Epigastric burning, free gas under diaphragm if perforated
Acute appendicitis (high/retrocaecal)	Migratory pain to RIF, McBurney tenderness
Right basal pneumonia / inferior MI	Referred RUQ/epigastric pain, ECG & CXR clinch it
Hepatitis / liver abscess	Tender hepatomegaly, deranged LFTs, serology/USG

Recently asked / exam angle

• Investigation of choice for gallstones? → Ultrasound (radiolucent stones, posterior shadowing).
• Most sensitive test for acute cholecystitis? → HIDA scan (non-visualisation of gallbladder).
• Best non-invasive test for CBD stones? → MRCP.
• Stone impacted in cystic duct compressing CHD with jaundice → Mirizzi syndrome (Csendes classification).
• Pneumobilia + SBO + ectopic stone → Rigler's triad → gallstone ileus (stone usually lodges at terminal ileum/ileocaecal valve).
• Painless palpable gallbladder + jaundice → Courvoisier's law → think malignancy, not stones.
• Black pigment stones → chronic haemolysis (hereditary spherocytosis, sickle cell, thalassaemia, prosthetic valve); brown stones → biliary infection/stasis, Ascaris/Clonorchis.
• Drug causing biliary sludge/pseudolithiasis → ceftriaxone; drug for medical dissolution → ursodeoxycholic acid.
• Most important step to avoid bile duct injury → Critical View of Safety.
• Gallbladder cancer associations → porcelain gallbladder, large stones (>3 cm), chronic typhoid carriers, polyp >10 mm, anomalous pancreaticobiliary junction.
• Timing of surgery in acute cholecystitis → early lap chole within 72 h / ≤7 days.
• Reynolds' pentad → Charcot's triad + hypotension + confusion = suppurative cholangitis → urgent ERCP.

Rapid revision

1. Mixed stones are commonest; 80–90% of gallstones are radiolucent → USG is the investigation of choice.
2. Cholesterol stones = 5 F's; black pigment = haemolysis; brown pigment = biliary infection/stasis (only stones that form primarily in the bile duct).
3. Murphy's sign = inspiratory arrest = acute cholecystitis (no jaundice).
4. Charcot's triad (fever+RUQ pain+jaundice) = cholangitis; Reynolds' pentad adds shock + confusion.
5. Courvoisier's law — painless palpable gallbladder + jaundice → think malignancy, not stones.
6. HIDA scan (non-visualised gallbladder) = most sensitive test for acute cholecystitis; best for acalculous cholecystitis.
7. Acalculous cholecystitis — ICU/TPN/burns/trauma patients; high gangrene/perforation risk; treat with percutaneous cholecystostomy if unfit.
8. Mirizzi syndrome — cystic duct stone compresses common hepatic duct → obstructive jaundice; Csendes classification; raises BDI and cancer risk.
9. Gallstone ileus — Rigler's triad (pneumobilia + SBO + ectopic stone); stone at terminal ileum via cholecystoduodenal fistula; Bouveret = gastric outlet variant.
10. Lap cholecystectomy is gold standard; do it early (≤72 h) in acute cholecystitis; Critical View of Safety prevents bile duct injury.
11. Bile duct injury — Strasberg/Bismuth classification; major transection → Roux-en-Y hepaticojejunostomy.
12. Prophylactic cholecystectomy for porcelain gallbladder, polyp >10 mm, stones >3 cm, sickle cell, anomalous pancreaticobiliary junction — all raise gallbladder carcinoma risk.