Acute Cholecystitis

Gallstone-Associated (Calculous) Cholecystitis

• Prevalence: Over 90% of cases result from gallstones obstructing the cystic duct.
• Pathophysiology:
  • Obstruction leads to bile stasis, increased gallbladder pressure, inflammation, and secondary bacterial infection.
  • Chronic gallstone disease may present as episodic biliary colic, with persistent obstruction leading to acute cholecystitis.
• Risk Factors:
  • Female sex (influence of hormonal factors)
  • Increasing age
  • Pregnancy
  • Obesity and rapid weight loss
  • Certain ethnic groups, including Native American and Hispanic populations
  • Use of hormonal therapy such as estrogen.

Non-Gallstone (Acalculous) Cholecystitis

• Incidence: Accounts for approximately 5-10% of cases.
• Predisposing Conditions:
  • Severe Illness: Common in critically ill patients, particularly those in intensive care.
  • Total Parenteral Nutrition (TPN): Leads to gallbladder stasis, with a high prevalence of biliary sludge formation in prolonged cases.
  • Major Surgery & Trauma: Severe burns, major surgical interventions, and septic states increase risk due to gallbladder ischemia.
  • Cardiac Events: Myocardial infarction and shock states contribute to gallbladder hypoperfusion.
  • Infectious Causes: Epstein-Barr virus, Salmonella, cytomegalovirus, and Cryptosporidium have been implicated.
  • Medication-Induced Factors: Ceftriaxone can precipitate with calcium to form biliary sludge, while ciclosporin reduces bile acid secretion, promoting stone formation.

Bacterial Involvement

• Secondary Role: Infection is typically a consequence rather than a primary cause of gallbladder inflammation.
• Common Pathogens:
  • Escherichia coli, Klebsiella, Enterococcus, Pseudomonas, Salmonella, and Bacteroides fragilis.
  • In up to 40% of patients, cultures from gallbladder specimens may be negative despite inflammation.

Mechanisms of Gallstone Formation

• Supersaturation & Precipitation: Imbalances in bile composition, including excess cholesterol or bilirubin, predispose to stone formation.
• Biliary Stasis: Reduced gallbladder motility, often seen with fasting, TPN, or systemic illness, increases risk.
• Nucleation of Cholesterol Crystals: Mucin and biliary proteins enhance the crystallisation process.

Complications

• Gangrenous Cholecystitis: Persistent ischemia can lead to necrosis and perforation.
• Emphysematous Cholecystitis: Infection with gas-producing bacteria such as Clostridium perfringens can result in gas accumulation within the gallbladder wall, increasing the risk of rupture.

Mechanisms of Disease Development

• Cystic Duct Obstruction: The primary cause of acute cholecystitis is obstruction of the cystic duct, usually by gallstones, leading to bile stasis and inflammation.
• Acalculous Cholecystitis: This occurs in a smaller percentage of cases and is attributed to ischemia, biliary stasis, or direct bacterial invasion, often in critically ill patients.

Gallbladder Inflammation and Injury

Bile Stasis and Increased Pressure

• When the cystic duct is obstructed, bile cannot drain, resulting in increased intraluminal pressure and mucosal injury.

Prostaglandin-Mediated Inflammation

• Mechanical irritation from gallstones stimulates the release of prostaglandins (PGI₂, PGE₂), promoting vascular dilation, fluid accumulation, and neutrophil infiltration.
• These inflammatory changes cause gallbladder wall thickening, pain, and tenderness.

Ischaemic Injury and Necrosis

• As the gallbladder becomes distended, blood supply to the tissue is compromised, leading to ischaemia and, in severe cases, necrosis or perforation.

Bacterial Superinfection

• Although not always present initially, secondary bacterial infection may occur, involving common organisms such as Escherichia coli, Klebsiella, Enterococcus, and Bacteroides fragilis.
• In some cases, no bacterial growth is detected, indicating that infection is a consequence rather than the primary cause of inflammation.

Pathogenesis of Acalculous Cholecystitis

Biliary Stasis and Sludge Formation

• Common in critically ill patients, this occurs due to impaired gallbladder motility, often secondary to systemic illness, prolonged fasting, or total parenteral nutrition.
• Retained concentrated bile is highly toxic to the gallbladder mucosa, leading to inflammation.

Hypoperfusion and Ischemia

• Hypotension, sepsis, or trauma may reduce gallbladder blood flow, leading to ischemic necrosis.
• Endotoxins can further impair gallbladder contraction by inhibiting cholecystokinin (CCK)-mediated responses.
  
  

Disease Progression and Complications

Potential Outcomes

• Some cases resolve spontaneously if the impacted stone dislodges, restoring cystic duct patency.
• Persistent obstruction, however, leads to further complications.

Severe Complications

• Gangrenous Cholecystitis: Persistent ischaemia results in tissue necrosis and a high risk of perforation.
• Emphysematous Cholecystitis: Gas-forming bacteria (Clostridium perfringens) cause intramural gas accumulation, increasing the risk of rupture.
• Pericholecystic Abscess: Inflammatory spread leads to abscess formation around the gallbladder.
• Mirizzi’s Syndrome: An impacted gallstone compresses the common bile duct, leading to jaundice.

Classification of Acute Cholecystitis

Calculous Cholecystitis (90–95%)

• Caused by gallstone obstruction of the cystic duct.

Acalculous Cholecystitis (5–10%)

• Occurs in critically ill patients due to ischaemia or bile stasis.

Pathological Stages

Oedematous Stage (2–4 days)

• Mucosal inflammation with subserosal oedema.

Necrotising Stage (3–5 days)

• Vascular compromise leads to haemorrhagic necrosis, though without full-thickness wall involvement.

Suppurative Stage (7–10 days)

• Bacterial invasion results in intra-wall abscesses and pericholecystic collections.

Chronic Cholecystitis

• Recurrent inflammation leads to fibrosis and gallbladder dysfunction.

Emphysematous Cholecystitis

• Characterised by gas formation in the gallbladder wall due to anaerobic bacterial infection, frequently seen in diabetics.

Prevalence and Incidence

• Acute cholecystitis follows the epidemiological pattern of gallstone disease, its most common cause.
• Gallstone Disease: Affects approximately 10-20% of adults, though only a portion develop symptoms. Among those with asymptomatic gallstones, 1-2% become symptomatic annually.
• Acute Cholecystitis: Develops in about 10% of individuals with symptomatic gallstones.
• Surgical Interventions: Cholecystectomy is one of the most frequently performed major surgical procedures, with hundreds of thousands of operations occurring annually.

Age Distribution

• The incidence of cholecystitis increases with age, particularly after the fourth decade of life.
• Elderly populations have a greater prevalence, with a notable increase among older men, possibly related to hormonal changes, including shifts in androgen-to-estrogen ratios.

Sex Differences

• Women are 2-3 times more likely to develop gallstones and acute cholecystitis than men.
• Hormonal factors, particularly estrogen and progesterone, contribute to gallbladder stasis and gallstone formation.
• Pregnancy-Related Risk: Elevated progesterone levels during pregnancy impair gallbladder motility, predisposing women to gallstone formation and acute cholecystitis.
• Acalculous Cholecystitis: While gallstone-related cholecystitis is more common in women, acalculous cholecystitis occurs more frequently in elderly men.

Ethnic and Geographic Variations

• Higher Prevalence: Scandinavian populations, Native American groups (particularly Pima Indians), and Hispanic individuals have higher rates of gallstone disease and cholecystitis.
• Lower Prevalence: Individuals from sub-Saharan Africa and Asia have lower incidences.
• In the U.S., gallbladder disease is more common among White populations compared to Black populations.

Acalculous Cholecystitis

• Accounts for 5-14% of acute cholecystitis cases.
• More frequently observed in critically ill patients, particularly those in intensive care settings, burn units, or post-trauma care.
• Risk factors include total parenteral nutrition (TPN), prolonged fasting, sepsis, and major surgical interventions.

Primary Symptom

• Right upper quadrant (RUQ) abdominal pain is the most common presenting complaint.
• The pain often begins in the epigastric region and migrates to the RUQ.

Pain Characteristics

• Typically severe and constant, lasting several hours.
• May radiate to the right shoulder or back.
• Unlike biliary colic, which resolves within a few hours, acute cholecystitis pain persists beyond six hours.

Associated Symptoms

• Nausea and vomiting are frequent.
• Fever may be present due to inflammation or secondary bacterial infection.
• Some patients describe a history of biliary colic before the onset of acute symptoms.

Acalculous Cholecystitis

• More commonly seen in critically ill patients.
• Patients may lack a prior history of gallstones or biliary colic.
• Fever and signs of sepsis may be the primary presenting features.

Chronic Cholecystitis

Presentation

• Recurrent episodes of RUQ pain with postprandial discomfort, bloating, and nausea.
• Food intolerances, particularly to greasy or spicy foods, are common.
• Patients often report increased belching or gas.

Pain Characteristics

• Less intense than in acute cholecystitis but can be persistent over months or years.
• Sometimes mistaken for other gastrointestinal conditions like reflux or peptic ulcer disease.

Progression

• Recurrent episodes may lead to fibrosis and loss of gallbladder function.
• This increases the risk of complications such as gallstone pancreatitis.

Risk Factors and Predisposing Conditions

Gallstones

• Present in 90% of cases of acute cholecystitis.
• Previous biliary colic increases the risk of developing acute cholecystitis.

Severe Illness

• Critically ill patients may develop gallbladder dysmotility or ischaemia, leading to acalculous cholecystitis.

Metabolic and Drug-Related Factors

• Ceftriaxone: Can precipitate with calcium, forming biliary sludge.
• Ciclosporin: Decreases bile acid secretion, increasing the risk of bile stasis and stone formation.

Other Conditions Increasing Risk

• Diabetes mellitus
• Prolonged fasting or total parenteral nutrition
• Severe trauma, burns, or systemic vasculitis
• Atherosclerotic disease and acute renal failure
• HIV-related cholangiopathy, often associated with opportunistic infections like cytomegalovirus and Cryptosporidium

Additional Symptoms to Elicit

Fever and Chills

• Suggests secondary infection or developing complications such as empyema or perforation.

Jaundice

• Occurs in about 10% of cases.
• Can result from direct compression of the biliary tree by an inflamed or distended gallbladder.

Gastrointestinal Symptoms

• Anorexia is commonly reported.
• Vomiting may occur, particularly if there is an obstructing gallstone.

Referred Pain

• Pain may extend to the right scapular or interscapular area.

Fever and Tachycardia

• Suggests systemic inflammation or secondary bacterial infection.
• More common in moderate-to-severe cases.

Signs of Peritoneal Irritation

• Right upper quadrant (RUQ) tenderness is the most consistent finding.
• Guarding and rebound tenderness may be present in cases of advanced inflammation or perforation.

Murphy’s Sign

Definition

• An inspiratory pause due to pain when palpating the right upper quadrant (RUQ) during deep inspiration.

Sensitivity and Specificity

• Reported sensitivity ranges from 20% to 97%.
• More reliable when assessed via ultrasound (sonographic Murphy’s sign), which has a higher predictive value for acute cholecystitis.

Limitations

• Less reliable in elderly patients.
• Can be absent in gangrenous cholecystitis or in patients with altered pain perception due to diabetes or neuropathy.

Palpable Gallbladder and Mass

Gallbladder Enlargement

• A palpable, tender gallbladder is found in 30-40% of cases.
• Suggests significant bile stasis and possible obstruction.

Pericholecystic Abscess or Local Perforation

• May present as a localised RUQ mass.
• Requires imaging for further evaluation.

Jaundice and Biliary Obstruction

Jaundice (Present in ~15% of Cases)

• Mild jaundice with a serum bilirubin <60 μmol/L can result from inflammation or compression of the bile duct.
• Higher bilirubin levels may indicate choledocholithiasis or Mirizzi’s syndrome.

Differentiation

• If bilirubin >60 μmol/L, further imaging is warranted to assess for common bile duct obstruction.

Atypical Presentations

Elderly Patients

• May present without fever or localised tenderness.
• Symptoms may be vague, including generalised weakness or confusion.
• Higher risk of rapid progression to complicated cholecystitis.

Diabetic Patients

• Higher likelihood of developing emphysematous cholecystitis.
• Can present with subcutaneous emphysema in the right upper quadrant (RUQ).

Acalculous Cholecystitis

• Frequently occurs in critically ill patients.
• Can present with sepsis without localised pain.
• Associated with prolonged fasting, total parenteral nutrition, and major surgery.

First-Line Investigations

Abdominal Ultrasound (Preferred Initial Imaging)

• First-line imaging due to high sensitivity for detecting gallstones and acute cholecystitis.
• Key findings:
  • Pericholecystic fluid
  • Gallbladder distension
  • Wall thickening (>3 mm)
  • Presence of gallstones
  • Sonographic Murphy’s sign (pain elicited when the ultrasound probe is placed over the gallbladder, though this may be absent in gangrenous cholecystitis)

Liver Function Tests (LFTs)

• Elevated bilirubin suggests bile duct obstruction or acute focal cholestasis
• Increased levels of alkaline phosphatase (ALP), alanine aminotransferase (ALT), and gamma-glutamyl transferase (GGT) may indicate associated cholestasis

Full Blood Count (FBC)

• Leukocytosis with a left shift suggests infection or inflammation
• Significant elevation may indicate severe cholecystitis or sepsis

C-Reactive Protein (CRP)

• Elevated CRP is a marker of inflammation or infection
• Higher levels may indicate more severe disease or potential complications

Bilirubin

• Moderate elevation suggests gallbladder inflammation affecting adjacent liver tissue
• Significant elevation (>60 µmol/L) may indicate obstruction of the common bile duct

Investigations to Consider

Magnetic Resonance Cholangiopancreatography (MRCP)

• Indicated when ultrasound does not detect bile duct stones but there is bile duct dilation or abnormal LFTs
• Findings in acute cholecystitis:
  • Gallbladder wall thickening (≥4 mm)
  • Gallbladder enlargement (long axis ≥8 cm, short axis ≥4 cm)
  • Presence of gallstones or retained debris
  • Fluid accumulation around the gallbladder
  • Linear shadows in the surrounding fatty tissue
• More cost-effective than endoscopic retrograde cholangiopancreatography (ERCP) for diagnosing bile duct stones

Endoscopic Ultrasound (EUS)

• Considered if MRCP does not confirm bile duct stones
• Higher sensitivity for detecting distal common bile duct stones
• Can be combined with ERCP for therapeutic intervention

Computed Tomography (CT)

• Used when ultrasound is inconclusive or if emphysematous cholecystitis, gallbladder perforation, or sepsis is suspected
• Key findings:
  • Gallbladder wall thickening (>4 mm)
  • Pericholecystic fluid
  • Intramural gas (suggestive of emphysematous cholecystitis)
  • Abscess formation

Hepatobiliary Iminodiacetic Acid (HIDA) Scan

• Highly sensitive for detecting cystic duct obstruction
• Used when ultrasound is inconclusive or when acalculous cholecystitis is suspected
• Findings:
  • Non-visualisation of the gallbladder due to cystic duct obstruction

Serum Amylase and Lipase

• Ordered to exclude acute pancreatitis in patients with upper abdominal pain
• Lipase is preferred over amylase due to prolonged elevation (up to 14 days vs. 5 days for amylase)
• Levels >3 times the upper normal range confirm acute pancreatitis

Blood Cultures

• Recommended for patients with moderate to severe cholecystitis
• Useful in identifying bacteraemia in patients with sepsis

Gastrointestinal Causes

Acute Cholangitis

• Charcot’s triad—fever, jaundice, and right upper quadrant (RUQ) pain
• Reynolds’ pentad (in severe cases): hypotension and confusion
   Investigations:
• Elevated bilirubin and alkaline phosphatase (suggestive of bile duct obstruction)
• Magnetic resonance cholangiopancreatography (MRCP) or endoscopic ultrasound (EUS): identifies intraductal stones and purulent bile
• Blood cultures: to detect sepsis-related infection

Biliary Colic

• Colicky RUQ pain lasting minutes to hours, often after fatty meals
   Investigations:
• Normal inflammatory markers (no leukocytosis or raised CRP)
• Ultrasound: gallstones present without gallbladder wall thickening or pericholecystic fluid

Chronic Cholecystitis

• Recurrent postprandial RUQ pain, nausea, bloating
   Investigations:
• Ultrasound: gallbladder wall thickening, mucosal atrophy, gallstones
• Histopathology (if cholecystectomy is performed): fibrosis and chronic inflammation

Peptic Ulcer Disease

• Epigastric burning pain relieved by food or antacids; nocturnal pain common
   Investigations:
• Endoscopy: identifies gastric or duodenal ulcers
• Helicobacter pylori testing: urea breath test or stool antigen test

Acute Pancreatitis

• Severe epigastric or periumbilical pain radiating to the back, with nausea and vomiting
   Investigations:
• Serum amylase or lipase: elevated >3 times normal
• CT abdomen: pancreatic inflammation and peripancreatic fluid

Gastroesophageal Reflux Disease (GERD)

• Heartburn and acid regurgitation, worse when lying down
   Investigations:
• Endoscopy: may show oesophagitis
• Therapeutic trial of proton pump inhibitors (PPI): symptom relief supports diagnosis

Hepatobiliary and Vascular Causes

Hepatic Abscess

• RUQ pain, fever, hepatomegaly
   Investigations:
• CT or MRI: hypodense liver lesion with rim enhancement
• Blood cultures: may identify bacterial or amoebic pathogens

Mesenteric Ischaemia

• Severe diffuse abdominal pain, often disproportionate to examination findings
   Investigations:
• CT angiography: detects vascular occlusion or ischaemia
• Serum lactate: elevated in advanced cases

Other Abdominal and Systemic Conditions

Appendicitis

• Pain migrating from the periumbilical area to the right iliac fossa
   Investigations:
• CT scan: enlarged, inflamed appendix with wall thickening
• Ultrasound (especially in children or pregnancy): thickened, non-compressible appendix

Sickle Cell Crisis

• Acute pain episodes, which may localise to the RUQ but are unrelated to gallstones
   Investigations:
• Peripheral blood smear: shows sickled cells
• Haemoglobin electrophoresis: confirms diagnosis

Right Lower Lobe Pneumonia

• Fever, cough, and pleuritic chest pain, which may mimic RUQ pain
   Investigations:
• Chest X-ray: right lower lobe consolidation
• Blood cultures: indicated if sepsis is suspected

Acute Coronary Syndrome (ACS)

• Central or epigastric chest pain radiating to the left arm or jaw
   Investigations:
• ECG: ST-segment changes or T-wave inversions
• Cardiac enzymes: elevated troponin levels confirm myocardial infarction

Initial Management

Supportive Care

•  Intravenous fluids:
  • Essential for maintaining perfusion, particularly in patients with dehydration, sepsis, or haemodynamic instability
  • Balanced crystalloids (e.g., Ringer’s lactate) are preferred to avoid hyperchloraemic acidosis
• Analgesia:
  • Pain control should be initiated early to prevent respiratory compromise and reduce stress-related tachycardia
  • First-line: Paracetamol or NSAIDs (e.g., diclofenac, ibuprofen)
  • Second-line: Opioids (e.g., morphine) if NSAIDs are ineffective; used cautiously as they may increase sphincter of Oddi tone
• Nil by mouth (NPO) status:
  • Recommended to reduce gallbladder stimulation and prepare for possible surgery
• Early warning score monitoring:
  • Systems such as NEWS2 should be used to assess deterioration, especially in those at risk of sepsis

Sepsis and Organ Dysfunction

Sepsis management

• Broad-spectrum IV antibiotics should be started immediately in suspected sepsis
• Monitor lactate and blood pressure closely for signs of septic shock
• Transfer to intensive care if organ dysfunction develops

Organ support

• Respiratory support if distress occurs
• Vasopressors (e.g., norepinephrine) for refractory hypotension despite fluids

Antibiotic Therapy

Empirical Therapy

•  First-line options:
  • Piperacillin-tazobactam 4.5 g IV every 8 hours
  • Ampicillin-sulbactam 3 g IV every 6 hours
• For life-threatening infections:
  • Meropenem 1 g IV every 8 hours
  • Imipenem-cilastatin 500 mg IV every 6 hours
• For beta-lactam allergy:
  • Ciprofloxacin + Metronidazole
  • Levofloxacin + Metronidazole

Targeted Therapy

• Adjust regimen based on blood and bile culture results
• De-escalate to oral antibiotics once stable; continue 7–10 days to minimise resistance

Surgical Management

Laparoscopic Cholecystectomy (LC)

• Gold-standard treatment for acute cholecystitis
• Early LC (within 72 hours) preferred to reduce hospital stay, complications, and open surgery conversion
• Transfer to specialist hepatobiliary unit if local expertise is lacking

Open Cholecystectomy

•  Considered when:
  • Severe peritonitis or gangrenous cholecystitis is present
  • Significant adhesions or fibrosis prevent laparoscopic dissection
  • High risk of bile duct injury due to unclear anatomy

Alternative and Adjunctive Interventions

Percutaneous Cholecystostomy (PC)

• Indicated for patients unfit for surgery
• Provides temporary drainage and symptom relief
• Follow-up:
  • If improved, consider elective cholecystectomy after 6–8 weeks
  • If symptoms persist, repeat imaging to exclude abscess or bile leak

Endoscopic Gallbladder Drainage

• Option for patients unsuitable for surgery and PC
• Performed in high-volume centres with expertise
• Can be achieved via EUS-guided transmural drainage

Management of Complications

Gallbladder Empyema

• Pus accumulation within the gallbladder with high risk of perforation and sepsis
   Management:
• Percutaneous cholecystostomy as first-line
• Early cholecystectomy once stable

Gangrenous Cholecystitis

• Ischaemic necrosis of the gallbladder wall due to severe inflammation
   Risk factors:
• Age >60
• Diabetes mellitus
• Inflammation lasting >48–72 hours
   Management:
• Urgent laparoscopic cholecystectomy
• Convert to open surgery if necrosis is extensive

Gallbladder Perforation

• Occurs in up to 10% of cases, especially with delayed treatment
   Clinical clues:
• Sudden pain relief followed by signs of peritonitis
   Management:
• Percutaneous drainage or immediate laparoscopic cholecystectomy depending on severity

Acute Cholangitis

• Infection of the biliary tree, often due to bile duct obstruction
   Clinical features:
• Charcot’s triad: Fever, jaundice, RUQ pain
• Reynolds’ pentad: Add hypotension and altered mental status
   Management:
• Urgent ERCP for biliary drainage
• Antibiotics and fluid resuscitation

Postoperative and Long-Term Care

Postoperative Pain Management

• Simple analgesia (paracetamol, NSAIDs) usually sufficient
• Opioids only if pain is severe

Dietary Recommendations

• No strict dietary restrictions after cholecystectomy
• Temporary mild diarrhoea or bloating with fatty foods may occur

Surveillance and Follow-up

• Monitor for signs of jaundice or bile duct obstruction
• Evaluate for post-cholecystectomy syndrome (bloating, pain, indigestion)

Overall Prognosis

Uncomplicated acute cholecystitis

• Favourable prognosis with recovery typically within 1 to 4 days following appropriate treatment
• Low mortality when managed early, particularly with laparoscopic cholecystectomy
• 25–30% of patients may experience complications or require emergency surgery due to disease progression

Complicated acute cholecystitis

• Significantly worse prognosis if untreated
• Perforation occurs in 10–15% of cases and is associated with increased mortality
• Gangrene and emphysematous cholecystitis contribute to high morbidity
• Sepsis and organ failure can further elevate mortality risk

Acalculous Cholecystitis Prognosis

• Carries a far higher mortality rate due to association with critical illness
• Mortality ranges from 10% to 50%, often due to delayed diagnosis and systemic disease
• In critically ill patients with perforation or gangrene, mortality may reach 50–60%

Mortality and Risk Factors

• Overall mortality for calculous cholecystitis: ~4%
• Acalculous cholecystitis: 10–50% mortality due to high rates of sepsis and organ failure
• Gallbladder perforation raises mortality risk to approximately 30%
• Severe inflammation requiring ICU care significantly worsens outcomes

Complications Affecting Prognosis

Bile duct injury

• Major complication of cholecystectomy, risk increases with active inflammation
• Moderate cholecystitis: ~2x higher risk compared to non-inflamed gallbladders
• Severe cholecystitis: >8x increased risk
• Intraoperative cholangiography reduces risk by approximately 50

Gallbladder empyema

• Results from bacterial overgrowth in an obstructed gallbladder
• Features include high fever, leukocytosis, systemic toxicity
• Often necessitates conversion to open cholecystectomy

Gallstone ileus

• Caused by erosion of a large gallstone through the gallbladder wall into the GI tract
• Leads to mechanical obstruction, often in the terminal ileum or pylorus
• Requires emergency enterotomy and stone extraction

Emphysematous cholecystitis

• Occurs in ~1% of cholecystitis cases
• Caused by gas-forming organisms such as Clostridium perfringens, E. coli, and Klebsiella
• More frequent in diabetics and elderly males
• High risk of gangrene and perforation, requiring emergency surgery

Acute pancreatitis

• Triggered by gallstone migration obstructing the pancreatic duct
• Severe cases may result in multi-organ dysfunction and ICU admission

Sepsis and multi-organ failure

• Untreated cholecystitis can progress to ascending cholangitis and septic shock
• Early antibiotics and biliary drainage are crucial for survival

Long-Term Prognosis and Preventative Strategies

Elective cholecystectomy

• Prevents recurrence of biliary colic and acute cholecystitis
• Reduces need for emergency surgery and lowers complication risk
• Recommended for patients with symptomatic gallstones

Post-cholecystectomy outcomes

• Most patients fully recover after laparoscopic removal
• Some may experience post-cholecystectomy syndrome (bloating, mild diarrhoea, or upper abdominal discomfort), which usually resolves over time

Follow-up and surveillance

• Monitor for jaundice as a potential sign of bile duct obstruction
• Assess liver function postoperatively to confirm resolution of inflammation and obstruction
• Address persistent gastrointestinal symptoms, particularly in patients who had emergency surgery or bile duct intervention

Infectious and Inflammatory Complications

Suppurative cholecystitis

• Progresses from acute cholecystitis when bacterial overgrowth and inflammation cause pus formation within the gallbladder wall
• Hallmarks include thickened gallbladder walls, intra-wall abscesses, and necrosis
• If untreated, may lead to perforation and pericholecystic abscess formation
• Requires urgent cholecystectomy or percutaneous drainage if the patient is unfit for surgery

Gallbladder empyema

• Characterised by pus accumulation within the gallbladder due to ongoing bacterial infection
• Presents with high fever, systemic toxicity, and leukocytosis
• Percutaneous cholecystostomy may be needed for temporary relief in high-risk surgical patients

Emphysematous cholecystitis

• Rare but severe form of infection caused by gas-forming bacteria (Clostridium perfringens, Escherichia coli, Klebsiella)
• More common in elderly, diabetic, and immunocompromised patients
• High risk of gangrene and perforation, necessitating emergency cholecystectomy

Biliary and Gastrointestinal Complications

Bile duct injury (post-surgical)

• Known risk of cholecystectomy, especially in cases of severe inflammation or distorted anatomy
• Can lead to biliary leakage, strictures, and obstruction
• Managed with endoscopic stenting, percutaneous transhepatic dilation, or surgical repair
• Intraoperative cholangiography significantly reduces risk

Gallstone ileus

• Caused by a large gallstone eroding through the gallbladder wall into the intestinal tract
• Leads to mechanical obstruction, most commonly at the terminal ileum
• Presents with abdominal pain, nausea, vomiting, and signs of bowel obstruction
• Managed with surgical enterotomy and stone extraction; cholecystectomy follows after 4–6 weeks

Cholecystoenteric fistula

• Abnormal communication between the gallbladder and adjacent organs (commonly duodenum or colon)
• May cause spontaneous decompression of the gallbladder and temporary symptom relief
• Can result in bile reflux gastritis or gallstone migration
• Definitive management with cholecystectomy is typically required

Bile leak and biloma

• Occurs when bile escapes into the peritoneal cavity, forming a localised collection
• May result from spontaneous perforation, trauma, or post-surgical complications
• Managed with percutaneous drainage or ERCP with stent placement

Severe and Systemic Complications

Sepsis and multi-organ failure

• Advanced cholecystitis can progress to ascending cholangitis and septic shock if untreated
• Requires urgent broad-spectrum antibiotics, fluid resuscitation, and biliary drainage (typically via ERCP)

Hepatic and small bowel injury

• May occur during difficult cholecystectomies involving dense adhesions or severe inflammation
• Requires surgical repair, either laparoscopic or open, depending on the extent of injury

Postoperative bleeding

• Typically results from vascular injury (e.g. cystic artery) during cholecystectomy
• Managed by endovascular embolisation or surgical haemostasis

Management Strategies for Complications

Early diagnosis and surgical intervention

• Timely laparoscopic cholecystectomy reduces the risk of complications
• Delaying surgery beyond 72 hours increases the risk of gangrene, perforation, and sepsis

Alternative drainage options

• Percutaneous cholecystostomy for high-risk surgical candidates
• Endoscopic ultrasound-guided gallbladder drainage in specialised centres

Preventing bile duct injury

• Intraoperative cholangiography significantly lowers the risk
• Referral to hepatobiliary specialists is advised for complex cases

1. Aune D, Leitzmann M, Vatten LJ. Physical activity and the risk of gallbladder disease: A systematic review and meta-analysis of cohort studies. J Phys Act Health. 2016;13(7):788-95.
2. Burmeister G, Hinz S, Schafmayer C. Acute Cholecystitis. Zentralbl Chir. 2018;143(4):392-399.
3. Clavien PA, Richon J, Burgan S, Rohner A. Gallstone Ileus: A Review of 36 Cases and Proposed Classification. Eur J Surg. 1990;156(10):541-546.
4. Cullen JJ, Maes EB, Aggrawal S, et al. Effect of endotoxin on gallbladder motility: A model of acalculous cholecystitis. Ann Surg. 2000;232(2):202-7.
5. European Association for the Study of the Liver (EASL). EASL clinical practice guidelines on the prevention, diagnosis and treatment of gallstones. J Hepatol. 2016;65(1):146-81.
6. Friedman GD. Natural history of asymptomatic and symptomatic gallstones. Am J Surg. 1993;165(4):399-404.
7. Gupta N, Trivedi A, Kumari S. Surgical management and outcomes of gallstone ileus: A systematic review. J Clin Med Res. 2020;12(4):215-224.
8. Kim E, Bashir R, Lahham S. Point-of-care ultrasound diagnosis of cholecystitis vs adenomyomatosis. Clin Pract Cases Emerg Med. 2019;3(2):158-9.
9. Kohga A, Suzuki K, Okumura T, et al. Is postponed laparoscopic cholecystectomy justified for acute cholecystitis? Asian J Endosc Surg. 2019;12(1):69-73.
10. Shaffer EA. Gallstone disease: Epidemiology of gallbladder stone disease. Best Pract Res Clin Gastroenterol. 2006;20(6):981-96.
11. Strasberg SM, Hertl M, Soper NJ. An Analysis of the Problem of Bile Duct Injury During Laparoscopic Cholecystectomy. J Am Coll Surg. 1995;180(1):101-125.
12. Stinton LM, Shaffer EA. Epidemiology of gallbladder disease: Cholelithiasis and cancer. Gut Liver. 2012;6(2):172-87.
13. Thangavelu A, Rosenbaum S, Thangavelu D. Timing of Cholecystectomy in Acute Cholecystitis. J Emerg Med. 2018;54(6):892-897.
14. Walsh K, Goutos I, Dheansa B. Acute Acalculous Cholecystitis in Burns: A Review. J Burn Care Res. 2018;39(5):724-728.
15. Wertz JR, Lopez JM, Olson D, Thompson WM. Comparing the diagnostic accuracy of ultrasound and CT in evaluating acute cholecystitis. AJR Am J Roentgenol. 2018;211(2):W92-7.
16. Wiggins T, Markar SR, Mackenzie H, Faiz O. Association between surgical modality and subsequent biliary complications in cholecystectomy: A population-based cohort study. Ann Surg. 2020;271(5):827-833.
17. Wilkins T, Agabin E, Varghese J, Talukder A. Gallbladder Dysfunction: Cholecystitis, Choledocholithiasis, Cholangitis, and Biliary Dyskinesia. Prim Care. 2017;44(4):575-597.
18. Yokoe M, Hata J, Takada T, et al. Tokyo guidelines 2018: Diagnostic criteria and severity grading of acute cholecystitis. J Hepatobiliary Pancreat Sci. 2018;25(1):41-54.