A 20-year-old obese woman with a 2-year history of gallstones presents to the emergency department

with severe, constant RUQ pain, nausea, and vomiting after eating fried chicken for dinner. She denies
any chest pain or diarrhoea. Three months ago she developed intermittent, sharp RUQ pains. On
physical examination she has a temperature of 38C (100.4F), moderate RUQ tenderness on
palpation, but no evidence of jaundice

1. Definition
Acute cholecystitis is acute gallbladder inflammation, and one of the major complications of cholelithiasis or gallstones. It
develops in up to 10% of patients with symptomatic gallstones. In most cases (90%), it is caused by complete cystic duct
obstruction usually due to an impacted gallstone in the gallbladder neck or cystic duct, which leads to inflammation within the
gallbladder wall. In 5% of cases, bile inspissation (due to dehydration) or bile stasis (due to trauma or severe systemic illness)
can block the cystic duct, causing an acalculous cholecystitis.

Epidemiology

The incidence of acute cholecystitis is approximately the same in western Europe as in the US, but the exact incidence
worldwide is not known. The distribution and incidence follow that of cholelithiasis because of the close relationship between
gallstones and acute cholecystitis. In the UK, 16,884 cases of cholecystitis were reported in the 1-year period between 2009 and
2010, with approximately two-thirds of the cases being in females.

More than 20 million Americans are estimated to have gallstones, with 500,000 cholecystectomies performed annually. Most
patients with gallstones do not develop symptoms. About 1% to 2% of asymptomatic gallstones become symptomatic each year

Acute cholecystitis is the most frequent complication of gallstones and occurs in 10% of symptomatic patients.

Acute acalculous cholecystitis accounts for 5% to 14% of cases of acute cholecystitis. The incidence is higher in the intensive-
care population, particularly in patients in burn and trauma units. The condition is 3 times more common in women than in
men up to the age of 50 years, and is about 1.5 times more common in women than in men thereafter.

Aetiology

At least 90% of patients with the condition have gallstones. Helminthic infection is one of the major causes of biliary disease in
Asia, southern Africa, and Latin America, but not the US. Infection with Salmonella organisms has been described as a primary
event in cholecystitis secondary to typhoid fever. AIDS-related cholecystitis and cholangiopathy may be secondary to CMV
and Cryptosporidium organisms. Various micro-organisms can be identified early in the onset of disease. These
include Escherichia coli, Klebsiella, enterococci, Pseudomonas, and Bacteroides fragilis. It has been suggested that this bacterial
invasion is not a primary perpetrator of injury, because in >40% of patients no bacterial growth is obtained from surgical
specimens. Generally, bacterial infection is a secondary feature and not an initiating event. Occasionally, acute cholecystitis
occurs in the absence of gallstones. Starvation, total parenteral nutrition, narcotic analgesics, and immobility are predisposing
factors for acalculous acute cholecystitis. Secondary infection with gram-negative flora occurs in most cases.

Pathophysiology
Fixed obstruction or passage of gallstones into the gallbladder neck or cystic duct causes acute inflammation of the gallbladder
wall. The impacted gallstone causes bile to become trapped in the gallbladder, which causes irritation and increases pressure in
the gallbladder. Trauma caused by the gallstone stimulates prostaglandin synthesis (PGI2, PGE2), which mediates the
inflammatory response. This can result in secondary bacterial infection leading to necrosis and gallbladder perforation.

The pathophysiology of acalculous cholecystitis is poorly understood, but it is probably multi-factorial. Functional cystic duct
obstruction is often present and related to biliary sludge or bile inspissation caused by dehydration or bile stasis (due to trauma
or systemic illness). Occasionally, extrinsic compression may play a role in the development of bile stasis. Some patients with
sepsis may have direct gallbladder wall inflammation and localised or generalised tissue ischaemia without obstruction.

Jaundice occurs in up to 10% of patients and is caused by inflammation of contiguous biliary ducts (Mirizzi's syndrome).

Acute cholecystitis may resolve spontaneously 5 to 7 days after symptom onset. The impacted stone becomes dislodged, with
re-establishment of cystic duct patency. If cystic duct patency is not re-established inflammation and pressure necrosis may
develop, leading to mural and mucosal haemorrhagic necrosis. Untreated acute cholecystitis can lead to suppurative,
gangrenous, and emphysematous cholecystitis.

Classification

Types of acute cholecystitis

1. Calculous - 90% to 95%.

2. Acalculous - 3.7% to 14%.

Pathological classification

1. Oedematous

2 to 4 days

Gallbladder tissue is intact histologically, with oedema in the subserosal layer.

2. Necrotising

3 to 5 days

Oedema with areas of haemorrhage and necrosis

Necrosis does not involve the full thickness of the wall.

3. Suppurative

7 to 10 days

WBCs present within the gallbladder wall, with areas of necrosis and suppuration

Intra-wall abscesses involving the entire thickness of the wall

Pericholecystic abscesses present.

4. Chronic

Occurs after repeated episodes of mild attacks

Mucosal atrophy and fibrosis of the gallbladder wall.

5. Emphysematous

Air appears in the gallbladder wall due to infection with gas-forming anaerobes
 Often found in diabetic patients.

Primary prevention

Primary prevention starts with preventing gallstones. Evidence from 4 cohort studies indicates that the prevalence of gallstone
disease is decreased in people who engage in moderate physical activity compared with those engaging in low levels of physical
activity, independent of BMI. Two cohort studies indicate that high fibre intake is associated with decreased incidence of
symptomatic gallstone disease. Because rapid weight loss and prolonged fasting are associated with high risk of gallstone
formation, limiting weight loss to a maximum of 1.5 kg/week (3.3 lbs/week) and adding 10 g (0.35 oz) fat to a low-calorie diet
have been shown to prevent gallstone formation. In asymptomatic and symptomatic gallstone carriers, treatment with the
hydrophilic bile salt ursodeoxycholic acid has been claimed to reduce the risk of biliary pain and gallstone complications such as
acute cholecystitis. Cholecystectomy in symptomatic gallstone patients is the most important prevention strategy.

Secondary prevention

Patients with symptomatic gallstones should be offered elective cholecystectomy to prevent development of acute
cholecystitis.

History & examination

Key diagnostic factors

previous episode of biliary pain (common)

About 50% of the patients who have had 1 episode of biliary pain will have another within 1 year.

RUQ pain (common)

Usually intense, lasting more than 30 minutes.

May begin in the epigastrium or left upper quadrant and move to the right subcostal region. Most often occurs after
eating a fatty meal.

positive Murphy's sign (common)

Palpation of the right subcostal region reveals tenderness. During deep inspiration, the tenderness suddenly becomes
worse and produces inspiratory arrest. Can also be elicited during ultrasound examination.

abdominal mass (common)

A distended, tender gallbladder may be palpable as a distinct mass in 30% to 40% of cases.

Other diagnostic factors

right shoulder pain (common)

Referred pain from the gallbladder may be felt in the right shoulder or interscapular region.

anorexia (common)

Non-specific symptom commonly associated with biliary disease.

nausea (common)
 Typically associated with constant RUQ pain in patients with biliary disease.

fever (common)

Persistent pain and fever suggest either more complicated disease such as abscess formation,
perforation, or acalculous cholecystitis.

vomiting (uncommon)

Non-specific symptom commonly associated with biliary disease.

jaundice (uncommon)

Mild jaundice present in about 10% of patients with the condition. Due to inflammation and
oedema around the biliary tract and direct pressure on the biliary tract from a distended
gallbladder, calculi within the common bile duct, or obstruction by a stone impacted in the
gallbladder neck (Mirizzi's syndrome).

Risk factors

Strong

gallstones

Gallstones cause 90% of cases, by becoming impacted within the cystic duct, leading to
gallbladder inflammation. Gallstones become more common with age in both genders. Native
Americans have the highest prevalence of gallstones compared with other ethnic groups in the
US. Studies have indicated an increased frequency of gallstone disease in families, twins, and
relatives of gallstone patients.

severe illness

Factors leading to biliary tract disease in critically ill patients include gallbladder dysmotility,
gallbladder ischaemia, and total parenteral nutrition. Vascular compromise, especially in
critically ill patients who experience episodes of hypotension, is thought to be a contributing
factor. Recent severe illness, including trauma and burns, puts the patient at risk of acalculous
cholecystitis.

total parenteral nutrition (TPN)

Fasting causes gallbladder hypomotility. Prolonged TPN causes gallbladder stasis, biliary sludge,
and gallstones due to decreased gallbladder emptying. Around 60% of patients receiving TPN
exhibit sludge after only 3 weeks. It is thought that bile stasis leads to accumulation of toxic
agents in the gallbladder lumen, causing gallbladder mucosa damage.

Weak

physical inactivity

Risk factor for developing gallstones.

low fibre intake

Risk factor for developing gallstones.

trauma

Related to bile stasis, ischaemia, bacterial infection, sepsis, and activation of factor XII.

severe burns

Patients with extensive burns commonly have multiple risk factors for developing acalculous
cholecystitis, such as sepsis, dehydration, total parenteral nutrition use, and positive pressure
ventilation.

ceftriaxone

Secreted into bile; can precipitate with calcium, forming biliary sludge and stones.

ciclosporin

Can decrease bile acid secretion, which may predispose to sludge or stone formation.

hepatic arterial embolisation

Ischaemia occurs as a primary event (e.g., small vessel vasculitis) or as a complication of hepatic
chemoembolisation, such as inadvertent embolisation of the cystic artery causing acalculous
acute cholecystitis.

infections

CMV, Cryptosporidium, and Salmonella typhi can infect the biliary system and produce
cholecystitis. Can occur in AIDS patients as part of the spectrum of AIDS-related cholangiopathy
due to infections with microsporidia species.

1st investigations to order

Test Result

FBC- Suggests inflammatory process. elevated WBC

C-reactive protein- Suggests inflammatory process. >28.6 nanomol/L (>3 mg/dL)

LFTs- Show a cholestatic picture. elevated alkaline phosphatase, gamma-GT, and bilirubin

RUQ ultrasound scan- pericholecystic fluid, distended gallbladder, thickened gallbla

Investigations to consider

Test Result
cholescintigraphy (hepatobiliary failure of gallbladder filling with normal hepatic uptake and biliary
iminodiacetic acid [HIDA] scan) excretion; normal in acalculous cholecystitis
abdominal CT gallbladder wall inflammation; linear high-density areas in
pericholecystic fat tissue
abdominal MRI enlarged gallbladder with thickened wall; pericholecystic high signal
abdominal x-ray may see gallstones

cholescintigraphy (hepatobiliary iminodiacetic acid [HIDA] scan)

Directly shows cystic duct obstruction.

The absence of gallbladder filling within 60 minutes after the administration of tracer indicates obstruction of the cystic duct
and has a sensitivity of >90% for acute cholecystitis. The 'rim sign' is a blush of increased pericholecystic radioactivity, which is
present in about 30% of patients with acute cholecystitis and in about 60% with acute gangrenous cholecystitis.

Used if the diagnosis remains in doubt after ultrasound scanning.

Disadvantages include radiation exposure and no evaluation of an alternative abdominal diagnosis.

abdominal CT

Inferior to ultrasound in assessment of acute biliary disease

abdominal MRI

Appropriate for pregnant patients with abdominal pain.

abdominal x-ray

Radiographic demonstration of gas in the gallbladder wall, lumen, or pericholecystic tissues indicates emphysematous
cholecystitis (severe variant of cholecystitis). This is more common in patients with diabetes mellitus and in older patients.

Differential diagnosis
 Differentiating
Condition signs/symptoms Differentiating investigations

Acute cholangitis Classic findings Magnetic resonance cholangiography or MRI findings: intra-ductal purulent materia
are fever and intensity on fat-suppressed T1-weighted images.
chills, jaundice,
and abdominal
pain (Charcot's
triad). About
50% to 70% of
patients with
cholangitis
develop all 3
symptoms.

Chronic Repeated bouts No specific investigations.

cholecystitis of mild attacks or
chronic irritation Mucosal atrophy and fibrosis of the gallbladder wall in postoperative specimens.
by large
gallstones.

Peptic ulcer Burning Endoscopy may reveal a peptic ulcer.

disease epigastric pain
that occurs hours
after meals or
with hunger.
Often wakes the
patient at night.
Pain improves
with eating.

Acute pancreatitis Epigastric or Tripling of amylase.

periumbilical
abdominal pain Pancreatic inflammation on CT abdomen.
that radiates to
the back.

Ecchymosis in
the periumbilical
region (Cullen's
sign) or the flank
(Grey Turner's
sign) may be
present in severe
pancreatitis.

Sickle cell crises Associated with Blood film may show sickle cells.
gallstone
disease. Haemoglobin electrophoresis shows the presence of haemoglobin S or C.
 Differentiating
Condition signs/symptoms Differentiating investigations

Pain can occur

anywhere in the
body (including
RUQ), which may
be unrelated to
gallstone
formation.

Appendicitis Pain is usually Abdominal CT scan: dilated appendix with thickened, hyperenhancing wall and mur
located in the
right iliac fossa
but may start in
the periumbilical
region.

Right lower lobe Productive cough Right lower lobe consolidation on CXR.
pneumonia with fever.

Examination may
reveal bronchial
breath sounds,
crepitations, and
dullness to
percussion.

Acute coronary Typically central Ischaemic changes on ECG (ST elevation or depression, T-wave inversion, left bundl
syndrome chest pain,
squeezing in Elevated cardiac enzymes.
nature, radiation
to jaw or left
arm. Pain may be
felt in the
epigastrium.

May be a history
of angina and
risk factors for
CAD (e.g.,
smoking,
hypertension,
diabetes
mellitus,
obesity).

GORD Burning Therapeutic trial with proton pump inhibitors (PPIs) leads to symptom relief.
sensation in
chest after
 Differentiating
Condition signs/symptoms Differentiating investigations

meals, worse on Oesophagitis may be seen on endoscopy.

bending over or
lying down. May pH <4 for >4% of the time is typical.
be acid reflux
and dysphagia