From the Guidelines
Cholecystitis is primarily caused by obstruction of the cystic duct, most commonly by gallstones, leading to increased pressure, chemical irritation, and potential bacterial infection. The pathophysiology of cholecystitis involves a complex interplay of factors, including mechanical obstruction, chemical inflammation, and secondary bacterial infection. When a gallstone becomes lodged in the cystic duct, bile cannot exit the gallbladder, leading to increased pressure and chemical irritation of the gallbladder mucosa 1. This initial chemical inflammation triggers the release of inflammatory mediators like prostaglandins, cytokines, and reactive oxygen species. As inflammation progresses, the gallbladder wall becomes edematous and thickened, with neutrophil infiltration, and blood flow may become compromised, leading to ischemia, necrosis, and potential perforation in severe cases 1. Secondary bacterial infection often follows the initial chemical inflammation, with common organisms including E. coli, Klebsiella, Enterococcus, and anaerobes from the gut. Some key points to consider in the pathophysiology of cholecystitis include:
- The role of gallstones in causing obstruction of the cystic duct and triggering chemical inflammation 1
- The importance of early diagnosis and treatment to prevent complications such as perforation and sepsis 1
- The potential for secondary bacterial infection to occur, which can worsen the clinical course of the disease 1
- The need for a comprehensive approach to management, including surgical intervention, antimicrobial therapy, and supportive care 1. It is worth noting that the management of cholecystitis has evolved over time, with a shift towards early laparoscopic cholecystectomy as the preferred treatment for acute cholecystitis, as recommended by the 2017 WSES guidelines for the management of intra-abdominal infections 1.
From the Research
Pathophysiology of Cholecystitis
- Acute cholecystitis is a progressive inflammation of the gallbladder usually caused by gallstones obstructing the cystic duct 2.
- The pathogenesis of gallbladder hypomotility and inflammation may be caused by lithogenic bile that can deliver high cholesterol concentrations to the gallbladder wall, creating a permissive environment that allows normal concentrations of hydrophobic bile salts to inflame the mucosa and impair muscle function inhibiting gallbladder emptying 3.
- High concentrations of cholesterol increase its diffusion rates through the gallbladder wall where they are incorporated into the sarcolemmae of muscle cells by caveolin proteins, inhibiting tyrosine-induced phosphorylation of caveolin proteins required to transfer receptor-G protein complexes into recycling endosomes 3.
- The sequestration of these receptor-G protein complexes in the caveolae results in fewer receptors recycling to the sarcolemmae to be available for agonist binding, explaining gallbladder hypomotility 3.
Phases of Acute Cholecystitis
- Congestion and edema are evident symptoms during the first 2-4 days, also known as the phase of edematous cholecystitis 2.
- Necrotizing cholecystitis, a phase characterized by bleeding and necrosis, is seen at 3-5 days 2.
- From 7-10 days, the disease progresses to its purulent phase, also known as suppurative cholecystitis 2.
- If the disease is still left untreated at this point, it progresses to subacute cholecystitis and it eventually becomes chronic cholecystitis 2.