Cholecystitis & Cholelithiasis

The gallbladder is a pear-shaped reservoir under the liver that stores and concentrates bile — a mix of cholesterol, bilirubin, water, bile salts, phospholipids, and ions made by the liver to digest fat. When fat and protein reach the small intestine, intestinal I-cells release cholecystokinin (CCK), which contracts gallbladder smooth muscle and relaxes the sphincter of Oddi, so bile empties into the duodenum. Gallstones (cholelithiasis) form when bile components precipitate out of that concentrated fluid. About 10–15% of the general population carries them — roughly 14 million US women and 6 million men aged 20–74, and more than a quarter of women over 60 — and 20–40% of carriers eventually develop a complication.

Cholesterol stones (≈ 75% of stones in Western nations) begin when the liver secretes more cholesterol than bile salts can hold in solution: bile becomes supersaturated, cholesterol crystals precipitate, and mucin glycoprotein in the gallbladder traps them so they coalesce (nucleation). Two accomplices speed the process — hypomotility (a gallbladder that empties poorly after meals, leaving stasis and ever more concentrated bile) and neutrophils shedding DNA onto crystals that attract more crystals. Estrogen feeds the first step directly: it upregulates cholesterol synthesis and reduces bile-acid synthesis, which is why gallstone risk in women runs about 2-fold that of men.

Pigment stones run on bilirubin instead of cholesterol. Black stones are calcium bilirubinate from hemoglobin breakdown — the stones of hemolytic disease such as sickle cell disease. Brown stones form where bacterial or parasitic infection meets stasis, contain calcium bilirubinate, phosphate and cholesterol, and are the usual primary common-bile-duct stones (born in the duct itself, unlike secondary stones that migrate from the gallbladder). Most stones never announce themselves: fewer than half of carriers develop symptoms, about 1–2% per year — roughly 10% by 5 years and 20% by 20 years — which is why an incidental stone in a normal gallbladder earns reassurance, not surgery.

A stone that sits in the gallbladder body is harmless; a stone that lodges in the neck or cystic duct is the whole disease. After a fatty meal, CCK drives the gallbladder to contract against the impacted stone — that is biliary colic: crampy right-upper-quadrant or epigastric pain lasting at least 30 minutes, radiating to the back or below the right scapula, with nausea and vomiting, in a patient who is afebrile with normal labs. If the stone falls back, the attack ends. Chronic, intermittent obstruction over weeks to months produces chronic cholecystitis — a scarred, poorly emptying gallbladder with stones in more than 90% of cases, whose labs may be normal even when the disease is severe, and whose dull RUQ ache can mimic peptic ulcer, irritable bowel, pancreatitis, or cardiac disease.

When the stone stays impacted, colic becomes acute calculous cholecystitis (≈ 95% of acute cases have stones). Trapped bile raises intraluminal pressure, the gallbladder distends, wall perfusion falls, and ischemia plus chemical irritation ignite inflammation; stagnant bile is a culture medium, so bacterial colonization (E. coli, Klebsiella, anaerobes) intensifies it. Clinically the pain turns constant, progressive and unrelenting — persistent obstruction is typically confirmed when pain lasts longer than 6 hours — and fever, tachycardia, leukocytosis and Murphy’s sign (inspiratory arrest on RUQ palpation) appear; a palpable tender RUQ mass may follow, and the pain persists even when the patient has not eaten. The wall then walks a timeline: edematous (days 2–4) → necrotizing (days 3–5, with arteriolar thrombosis marking the ischemic component) → suppurative (≈ days 7–10) — and, untreated, gangrene and rupture.

Ten percent of acute cholecystitis has no stone. Acalculous cholecystitis is the disease of the critically ill: prolonged fasting or TPN removes the meal-driven CCK signal, so the gallbladder never empties and bile concentrates and pressurizes; hypoperfusion (sepsis, severe burns, trauma, cardiac events, mechanical ventilation) starves the wall; bacteria are present in 11–30% of cases. It is missed because the ventilated or sedated patient cannot report pain — the only clues may be a fever of unknown origin or grimacing during abdominal palpation — and it carries a mortality of 30–75%, with antibiotics alone usually ineffective. Either way, cholecystitis is a surgical disease: patients managed conservatively re-present with acute disease and higher operative morbidity.

A gallbladder stone that migrates into the common bile duct (CBD) is choledocholithiasis — present in roughly 1–15% of people with gallstones. The duct is now dammed, and everything upstream backs up. Conjugated bilirubin regurgitates into the blood: skin and sclera yellow once levels reach about 3 mg/dL, the urine turns dark, "tea-colored" (conjugated bilirubin is water-soluble, so the kidney excretes it), stools turn clay- or pale-colored (bilirubin never reaches the gut), and pruritus follows bile-acid deposition in the skin. The labs read cholestatic: ↑ bilirubin, ↑ alkaline phosphatase (ALP), ↑ GGT, transaminases up as well. A bilirubin above 2 mg/dL suggests a duct stone and above 3–4 mg/dL strongly suggests one — yet WSES warns against using labs as the only evidence, because ultrasound sees a dilated duct (> 6 mm) with 90% accuracy but the stone inside it only 15–40% of the time.

The dam has two lethal neighbors. Upstream, rising intra-biliary pressure breaks the duct’s defenses (its epithelium normally secretes IgA to keep bacteria from adhering), and gram-negative gut organisms — E. coli, Klebsiella, Enterobacter, Pseudomonas — plus anaerobes colonize the stagnant bile and translocate into the bloodstream: acute (ascending) cholangitis, endotoxemia, sepsis, multi-organ failure. Untreated mortality runs about 50%. The textbook cue is Charcot’s triad — fever, RUQ pain, jaundice — but it is present in only 26.4% of cases (specificity 95.9%), so its absence excludes nothing; the Tokyo Guidelines 2018 criteria (systemic inflammation + cholestasis + imaging), reported by StatPearls at 100% sensitivity, have replaced it. Add altered mental status and hypotension and you have Reynolds’ pentad: septic cholangitis. Downstream, a stone lodged at the ampulla blocks the pancreatic duct as well — gallstone pancreatitis, epigastric pain boring to the back — which is why amylase and lipase are drawn on every cholecystitis admission (depth on the Pancreatitis page).

Obstructive jaundice also reaches the bedside through the clotting cascade. Without bile salts in the gut, fat-soluble vitamin K is malabsorbed, the liver cannot complete factors II, VII, IX and X, and the prothrombin time lengthens — parenteral vitamin K is recommended before procedures, and a coagulation profile is part of every cholangitis work-up (an INR above 1.5 counts as hepatic organ dysfunction in the TG18 severity scheme). Kidney injury complicates 5–16% of obstructive jaundice, malnutrition with fat-soluble-vitamin deficiency follows prolonged obstruction, and chronic obstruction can end in secondary biliary cirrhosis.

Laparoscopic cholecystectomy is the standard of care for symptomatic stones (≈ 1 million a year in the US) and "the best treatment" for cholecystitis: most patients are symptom-free after the gallbladder is removed (post-cholecystectomy symptoms persist in 5–30%), while delay invites recurrence, duct stones and pancreatitis. Every guideline owner says operate early, during the same admission — they differ on the clock. StatPearls reports that surgery within 72 hours of symptom onset carries 30-day morbidity of 6.6% and mortality of 1.1%; the Tokyo Guidelines 2018 (as reported in J Clin Med 2023 and EClinicalMedicine 2024) say "as soon as possible, preferably within 72 h of the onset of symptoms, but also after this time interval"; the World Society of Emergency Surgery (WSES) 2020 says within 7 days of admission and 10 days of symptom onset, otherwise delay beyond 6 weeks. Meta-analyses agree surgery within 3 days lowers biliary complications, but waiting up to 10 days did not raise them — so "early" means this hospitalization, not this hour. Delay does have a cost: inflammation matures, dissection gets harder, and bile-duct-injury risk climbs.

The TG18 severity grade (as reported by the carriers) decides who gets that early operation. Grade I (mild) has no organ dysfunction and minimal inflammation; Grade II (moderate) has any of WBC > 18,000, a palpable tender RUQ mass, symptoms > 72 h, or marked local inflammation such as gangrene, abscess, biliary peritonitis or emphysematous change; Grade III (severe) has dysfunction of any one organ — hypotension needing vasopressors, decreased consciousness, PaO₂/FiO₂ < 300, oliguria or creatinine > 2.0 mg/dL, INR > 1.5, platelets < 100,000. Grades I–II go to early laparoscopy; Grade III only with favorable predictors, and WSES says no laparoscopy in septic shock. Patients too sick or frail for anesthesia get a percutaneous cholecystostomy drain as a bridge (surgery 4–8 weeks later) or as definitive care — but it is a rescue, not an equal: drained patients had more complications, more recurrent biliary events (recurrence up to 47% after drain removal) and more than three times the mortality of early surgery. Antibiotics, finally, are not automatic: required for complicated disease and cholangitis, debated for uncomplicated cholecystitis, and — with adequate source control — withdrawn within 24 h of cholecystectomy.