ACUTE ACALCULOUS CHOLECYSTITIS

"Bekhudi besabab nahi ghalib,
Kuchh to hai jis ki pardadari hai"
                             - Mirza Ghalib 

Acute acalculous cholecystitis (AAC) is defined as acute necroinflammatory disease of gallbladder (GB), in the absence of cholelithiasis, and has multifactorial pathogenesis. It is clinically indistinguishable from acute calculous cholecystitis.

AAC is the epiphenomenon (secondary manifestation) of various primary disease pathophysiology. It is typically seen in critically ill patients, though it is also reported in outpatient setting.

PHYSIOLOGY OF BILIARY SYSTEM:

Liver normally produces 600 ml bile per day (0.4 ml/min). Cholecystokinin (CCK) regulates functioning of this system. CCK release is stimulated by food bolus, which causes contraction and emptying of GB, relaxation of sphincter of Oddi, increased intestinal motility, and stimulation of pancreatic enzyme secretion. These all events allow normal emptying of GB to promote digestion

.

During fasting, approximately half of this (0.2ml/min) enters the GB and the rest flows directly into duodenum. GB fills by concentration and pressure gradient. Normally GB selectively removes and increases bile salt concentration 5 to 6 fold, thereby creating an osmotic gradient drawing bile into the GB. The pressure gradient is created mainly from contraction of sphincter of Oddi. Low level of cholecystokinin (CCK) during fasting, causes a high to low pressure gradient from sphincter of Oddi to GB, respectively. Therefore, fasting favors a pressure gradient for bile collection into GB.

The cystic artery supplying to GB, is an end artery, with no significant source of collateral supply, therefore predisposing GB to ischemia.

PATHOPHYSIOLOGY:

Bile stasis and GB ischemia are the nidus that leads to AAC.  Inspitated bile is directly toxic to GB epithelium, which stimulates inflammatory cascade and resulting GB wall edema, increased permeability, microvascular occlusion, ischemia and translocation of bacterial.

AAC occurs in approximately 0.2 to 0.4 percent of all critically ill patients, usually in elderly patients (above 60 years). Risk factors associated are sepsis, shock, burn, trauma, recent surgery (non GB related, abdominal or extra abdominal), fasting and total parenteral nutrition (TPN).

Critically ill patients have many risk factor that may cause AAC. Ongoing SIRS, hypovolemia, hypotension, decreased splanchnic blood flow, vasopressors, absent enteral nutrition and total parenteral nutrition lead to increased bile viscosity, decreased GB contraction, bile stasis, inflammation and ischemia of GB.

Complications of AAC are secondary bacterial infection, empyema, gangrene and perforation of GB.

AAC in critically ill patients is associated with high mortality, around 30%, ranging from 10-90 percent. Early diagnosis and intervention the key to reduce mortality.

Mortality in AAC is related to critical illness predisposing to AAC, and resulting complications.

Diagnosis of AAC is elusive in critically ill patients, as patients are unconscious, sedated or ventilated, therefore unable to express symptom. Also there are many confounding factor that may mimic fever, leukocytosis and elevated liver enzymes.

Incidence of AAC occurring in outpatient setting is not well defined. In this setting AAC usually developed in the absence of acute illness. There is no defined risk factor in these patients but usually reported in patients with diabetes, atherosclerosis, vasculitis and drugs. It is indistinguishable from acute calculous cholecystitis clinically.

AAC encountered in outpatient setting has a straightforward diagnosis and excellent prognosis with prompt cholecystectomy.

DIAGNOSIS:

In critically ill patients, diagnosis rests on imaging studies, which may demonstrate distended GB, echogenic bile (sludge), increased GB wall thickness (3-4mm), pericholecystic fluid, subserosal edema, intraluminal gas and sloughed mucosal membrane.

USG is the modality of choice, because of bedside availability, rapidity and repeatability, as critically ill patient have multiple transportation risks. Sensitivity and specificity of USG range from 30 to 100 percent.

CT scan is useful to diagnose other associated abdominal pathologies. But it need transportation to radiology department. Sensitivity is similar to USG.

HIDA SCAN (hepato-biliary iminodiacetic acid scan) is a nuclear scan, which diagnoses non motility of GB. Various modalities are used in HIDA scan. Radionuclide cholescintigraphy (RC), morphine cholescintigraphy (MC) and cholecystokinin (CCK) augmented HIDA scan.

RC: Radiolabeled technetium is injected and if GB is not visualized after 1 hour, it is considered positive.

MC: If RC is positive, morphine is injected, if still GB is not visualized after 30 min, it is considered positive.

CCK HIDA SCAN: CCK is injected and if GB is not visualized, it is considered positive.

MC and CCK HIDA scan is done in indeterminate RC study or to rule of false positive result.

TREATMENT:

Treatment includes empirical broad spectrum antimicrobial to cover enteric gram negative pathogens and anaerobes, after drawing blood culture. Gam positive and fungal coverage should be added if there is risk of these pathogens, like immunosuppression, previous antibiotic use, and abdominal surgery.

Cholecystectomy with drainage, is the definitive therapy of AAC. Cholecystostomy is sometimes preferred, as it is less invasive and many patients are too sick to undergo cholecystectomy.

Early intervention is the key to good outcome. Timely cholecystectomy is associated with 90 percent survival rate.

References:

Acute Acalculous Cholecystitis: A review. Clinical gastroenterology and hepatology, 2010.

Acalculous cholecystitis presenting in an outpatient with no risk factor. SA Journal of Radiology. 2012.

Acute Acalculous Cholecystitis: Challenging the myths. HPB 2007.

Acute Acalculous Cholecystitis in critically ill patients. S Afr Med J, 1987.