Symptomatology and General Principles of Treatment of Chronic Cholecystitis
1. Kebekova Aizat Ashimzhanovna
2. Khan Sohail
3. Karangale Om
(1. Lecturer, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic
2. Student, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic
3. Student, International Medical Faculty, Osh State University, Osh, Kyrgyz Republic)
Abstract
Chronic cholecystitis is a long-standing inflammation of the gallbladder wall, most often associated with gallstones (cholelithiasis). It is one of the most common diseases of the hepatobiliary system and a leading indication for abdominal surgery worldwide. The clinical picture is dominated by recurrent right upper quadrant pain, dyspepsia and intolerance to fatty food, with periods of remission and exacerbation. This article reviews the aetiology, pathogenesis, clinical features, diagnostic approach and the general principles of conservative and surgical management of chronic cholecystitis, with emphasis on laparoscopic cholecystectomy as the treatment of choice for symptomatic disease.
Keywords: chronic cholecystitis, cholelithiasis, biliary colic, dyspepsia, ultrasonography, laparoscopic cholecystectomy
1. Introduction
Chronic cholecystitis is a chronic inflammatory disease of the gallbladder characterised by structural changes of its wall (fibrosis, thickening, loss of contractility) and disturbed bile composition and motility. In approximately 90–95% of cases it occurs together with gallstones, and it is then called chronic calculous cholecystitis. Chronic acalculous cholecystitis, without stones, is much less common.
Gallstones are present in about 10–20% of adults in Western populations, and the disease is more frequent in women, in people over 40 years of age, and in those with obesity. The classical description of risk factors is the "five Fs": female, fertile (multiparous), forty, fat and fair. Because the disease follows a prolonged, relapsing course and may lead to complications, its early recognition and correct management are important for every future physician.
2. Aetiology and Pathogenesis
Chronic cholecystitis arises from a complex interaction of mechanical, metabolic, infectious, and structural factors that drive ongoing inflammation and progressive tissue remodeling within the gallbladder wall.
The primary mechanical driver is the persistent presence of gallstones, which induce continuous mechanical irritation of the mucosal lining and cause recurrent, low-grade, or intermittent obstruction of the cystic duct. This mechanical stress is closely linked to functional bile stasis, stemming from gallbladder hypomotility or functional dyskinesia. Elevated progesterone levels during pregnancy, rapid weight loss, prolonged physiological fasting, and total parenteral nutrition all compromise normal neurohormonal gallbladder contraction, leading to bile retention, mucosal distension, and subsequent inflammation.
Metabolic derangements significantly influence the physical properties of bile, converting it into a lithogenic medium. Supersaturation of bile with cholesterol relative to bile salts and phospholipids initiates cholesterol crystal nucleation and sludge formation. This chemical alteration is strongly tied to systemic metabolic conditions including obesity, metabolic syndrome, type 2 diabetes mellitus, and dyslipidemia, all of which alter hepatic lipid transport and biliary lipid ratios to cause direct chemical injury to the gallbladder mucosa.
Opportunistic microbial invasion often turns low-grade chemical or mechanical irritation into established inflammatory disease. Ascending migration of enteric pathogens from the duodenum—most notably Escherichia coli, Klebsiella species, Enterococcus, and various anaerobes—serves as the main route of bacterial access, though hematogenous and lymphogenous seeding during systemic or regional inflammatory processes also occurs. When acute infectious or calculous flares do not resolve completely, persistent micro-abscesses, mucosal ischemia, and intramural scarring lead directly to chronic, low-grade inflammation.
Additional systemic and lifestyle triggers sustain this chronic disease state. Diets high in saturated fats combined with irregular meal timing suppress natural postprandial gallbladder emptying, while a sedentary lifestyle promotes systemic metabolic dysregulation. Hormonal influences, congenital biliary tract anomalies, and endemic parasitic infestations—such as Giardia lamblia or Opisthorchis species—further contribute to mechanical outflow resistance, persistent immunologic reaction, and progressive gallbladder wall fibrosis.
In the pathogenesis, impaired emptying and chronic irritation lead to repeated inflammation of the mucosa. Over time the wall becomes thickened and fibrotic, the muscular layer atrophies, and the gallbladder may become shrunken, or sometimes calcified ("porcelain gallbladder"). The organ then loses its concentrating and contractile function.
3. Classification
The classification of chronic cholecystitis relies on etiology, clinical activity, systemic severity, and symptomatic presentation, allowing clinicians to tailor both medical and surgical interventions.
Etiologically, the disease is categorized into calculous and acalculous forms. Chronic calculous cholecystitis represents the vast majority of cases, driven by the persistent mechanical presence of gallstones, cystic duct micro-obstructions, and chronic mucosal irritation. Chronic acalculous cholecystitis develops in the absence of gallstones, primarily stemming from functional dyskinesia, ischemia, chronic bile stasis, or previous severe acute illness that compromised gallbladder mucosal vascularization and contractility.
The clinical course oscillates between two distinct phases: active exacerbation and remission. During an exacerbation phase, the patient experiences a flare of active inflammation, manifesting with localized right upper quadrant pain, constitutional symptoms, and overt physical examination signs. In the remission phase, inflammatory markers normalize and acute pain subsides, though patients may remain entirely asymptomatic or exhibit mild, persistent digestive complaints due to irreversible structural changes in the gallbladder wall.
Severity grading stratifies the condition into mild, moderate, and severe categories based on the frequency, duration, and intensity of painful attacks, as well as the presence of systemic complications. Mild cases feature infrequent, short-lived episodes of biliary pain with negligible impact on daily activity and no structural complications. Moderate forms present with frequent, prolonged pain exacerbations, persistent laboratory or sonographic markers of inflammation, and noticeable functional impairment. Severe chronic cholecystitis is defined by frequent, intense flares accompanied by pericholecystic involvement, biliary tract complications, or secondary systemic dysfunction.
Symptom-based classification organizes the disease into functional clinical forms based on the dominant presenting complaint. The pain-predominant form centers on recurrent, sharp biliary colic triggered by dietary indiscretions or physical exertion. The dyspeptic form manifests primarily with chronic gastrointestinal discomfort, including postprandial heaviness, persistent nausea, abdominal bloating, and flatulence. Finally, atypical forms introduce diagnostic complexity by presenting with extra-abdominal symptom complexes, such as the cardiac variant featuring reflex angina-like chest pain (cholecystocardiopathies), or the intestinal and esophageal variants, which mimic lower bowel dysfunction or gastroesophageal reflux.
4. Symptomatology
The course is typically long and wave-like. Symptoms vary from minimal to severe and are often provoked by errors of diet, alcohol, stress, or physical strain.
4.1 Pain syndrome
Pain is the leading symptom. It is localised in the right hypochondrium or epigastrium and is typically dull, aching or pressing in character in the interval between attacks. During exacerbation or biliary colic it becomes severe and cramping, lasting from 30 minutes to several hours. The pain characteristically:
• appears 30–90 minutes after a heavy, fatty, fried or spicy meal, or after eggs, alcohol or carbonated drinks;
• radiates to the right shoulder, right scapula, right side of the neck and back (Kehr-type reflex irradiation);
• is often accompanied by nausea and vomiting.
4.2 Dyspeptic syndrome
• bitterness and metallic taste in the mouth, especially in the morning;
• belching of air or bitter content;
• nausea, sometimes vomiting of bile, which may bring partial relief;
• bloating, flatulence and unstable stools (constipation alternating with diarrhoea);
• intolerance of fatty foods and decreased appetite.
4.3 Asthenovegetative and other manifestations
• general weakness, irritability, fatigue and sleep disturbance;
• low-grade fever in exacerbation (usually 37.2–37.5 °C);
• mild subicteric sclera or jaundice if there is obstruction of the common bile duct or Mirizzi syndrome;
• skin itching in cases with cholestasis.
4.4 Physical examination
During an acute exacerbation of chronic cholecystitis, physical examination highlights localized peritoneal irritation in the right hypochondrium alongside neuro-reflexive tenderness markers. Deep abdominal palpation reveals focal tenderness concentrated at the anatomical projection of the gallbladder, located at the junction of the right costal margin and the lateral border of the rectus abdominis muscle.
Local inflammatory signs confirm direct involvement of the gallbladder and adjacent parietal peritoneum. Murphy's sign is elicited when deep palpation of the right upper quadrant causes an abrupt cessation of inspiration as the descending, inflamed gallbladder impacts the examiner's fingers. Ortner's (Grekov-Ortner) sign provides additional diagnostic weight when light percussion along the right costal arch using the ulnar border of the hand provokes sharp discomfort due to transmit pressure against the gallbladder and hepatic capsule.
Neuro-reflexive signs reflect the systemic pathway of visceral pain transmission across phrenic and intercostal nerve roots. Elicitation of the Mussy-Georgievsky (phrenicus) sign produces localized tenderness upon pressure applied between the sternal and clavicular heads of the right sternocleidomastoid muscle, secondary to phrenic nerve hypersensitivity. Kehr's sign manifests as hyperaesthesia and acute pain upon localized pressure over the gallbladder point, while Boas' sign maps visceral somatic cross-talk to an area of hyperaesthesia beneath the right scapula and across the posterior ninth to eleventh thoracic dermatomes.
General abdominal and systemic examination findings complete the clinical picture during a flare. Patients frequently present with a heavily coated tongue reflecting gastrointestinal dysmotility and systemic inflammatory stress. Mild hepatomegaly may also be detected on palpation, resulting from secondary hepatic venous congestion or reactionary localized parenchymal inflammation.
A palpable, non-tender gallbladder together with painless jaundice should raise suspicion of other pathology (Courvoisier's law), such as malignancy of the pancreatic head.
5. Diagnosis
The diagnosis is based on the history, clinical picture and investigations.
• Laboratory tests: full blood count (leukocytosis and raised ESR in exacerbation); liver function tests (bilirubin, ALP, GGT, ALT, AST) to exclude biliary obstruction or cholangitis; amylase and lipase to exclude pancreatitis; lipid profile and blood glucose.
• Abdominal ultrasonography: the first-line and most informative investigation. It shows stones, wall thickening (more than 3 mm), a contracted or deformed gallbladder, sludge and poor contractility after a test meal. It also assesses the diameter of the common bile duct.
• Further imaging: MRCP or endoscopic ultrasound when common bile duct stones are suspected; oral cholecystography and CT in selected cases; HIDA scintigraphy with ejection fraction when acalculous disease or biliary dyskinesia is suspected.
• Duodenal intubation and bile microscopy have historically been used but are rarely required today.
Differential diagnosis includes peptic ulcer disease, chronic pancreatitis, hepatitis, irritable bowel syndrome, right-sided nephrolithiasis, right lower lobe pneumonia, and ischaemic heart disease with an abdominal presentation.
6. Complications
Complications arising from chronic cholecystitis reflect progressive mechanical, inflammatory, and infectious damage across the biliary tree and neighboring tissue structures. Superimposed acute inflammation represents a major structural threat, transitioning chronic low-grade disease into life-threatening intra-abdominal emergencies. Persistent obstruction of the cystic duct can rapidly trigger an acute inflammatory flare, progressing to luminal accumulation of purulent material, ischemic mural necrosis, and empyema of the gallbladder. Without urgent intervention, transmural ischemia leads to gallbladder perforation, which can present as localized pericholecystic abscess formation, free peritoneal rupture with diffuse peritonitis, or complex internal erosion.
Ductal migration of gallstones introduces severe obstructive and infectious risks throughout the main biliary tract. Choledocholithiasis occurs when stones pass from the gallbladder into the common bile duct, impeding the downstream clearance of bile. This mechanical blockage induces rapid biliary hypertension, manifesting clinically as obstructive jaundice. Secondary bacterial colonization of this stagnant bile pool precipitates ascending cholangitis, a life-threatening systemic infection defined by Charcot's triad of fever, jaundice, and right upper quadrant pain, which can swiftly evolve into septic shock.
Biliary outflow disruption also frequently damages adjacent digestive and pancreatic structures. Transient or complete impaction of a gallstone at the ampulla of Vater impairs pancreatic duct drainage and triggers intra-acinar enzyme activation, culminating in acute biliary pancreatitis. Continued stone migration or chronic pressure erosion gives rise to Mirizzi syndrome, wherein a stone impacted in the cystic duct or neck of the gallbladder causes extrinsic compression of the adjacent common hepatic duct. Long-standing inflammation can cause fistulous erosion into adjacent hollow organs, such as cholecystoduodenal fistulas, allowing large stones to pass directly into the gastrointestinal tract and lodge at the ileocecal valve, causing mechanical bowel obstruction known as gallstone ileus.
Chronic structural remodeling of the gallbladder wall produces distinct pathological end-states with variable clinical outcomes. Complete obstruction of the cystic duct without bacterial infection leads to hydrops of the gallbladder, where trapped mucosal secretions progressively distend the lumen with clear, mucoid fluid. Conversely, persistent fibrotic scarring can cause marked shrinkage and atrophy of the organ, rendering it non-functional. Intramural dystrophic calcification driven by severe chronic inflammation culminates in a porcelain gallbladder, a condition characterized by a rigid, brittle wall that carries a significantly elevated risk for malignant transformation into gallbladder carcinoma.
Finally, persistent biliary tract dysfunction imposes secondary parenchymal damage onto the liver. Chronic low-grade biliary stasis and recurrent ascending micro-infections promote secondary reactive hepatitis within adjacent hepatic lobules. If ductal obstruction or chronic cholangitis remains uncorrected over extended periods, ongoing hepatocellular injury and periductal fibrotic scarring can culminate in secondary biliary cirrhosis.
7. General Principles of Treatment
Treatment is individualised according to the phase of the disease, presence of stones, severity of symptoms and the patient's general condition. Its aims are to relieve symptoms, prevent exacerbations and complications, and, where indicated, remove the diseased organ.
7.1 Treatment during exacerbation
Mild exacerbations may be managed on an outpatient basis; moderate and severe ones require hospitalisation, preferably in a surgical department. The principal measures are:
1. Rest and diet: initial fasting or a very sparing diet for 1–2 days, then gradual extension.
2. Analgesia and spasmolysis: antispasmodics (drotaverine, hyoscine butylbromide, mebeverine) and, if needed, NSAIDs (e.g. diclofenac or ketorolac). Opioids that cause spasm of the sphincter of Oddi should be used with caution.
3. Antibacterial therapy when signs of infection are present, with agents achieving good biliary concentration (e.g. cephalosporins, fluoroquinolones, or amoxicillin-clavulanate, often combined with metronidazole), chosen according to local resistance patterns.
4. Antiemetics (e.g. metoclopramide) and infusion therapy for dehydration.
5. Detoxification in severe cases.
7.2 Treatment during remission
• Diet therapy (Pevzner's Table No. 5): regular small meals 4–5 times daily; exclusion of fried, fatty, smoked and spicy food, alcohol, and carbonated drinks; reduction of animal fat and egg yolks; increased dietary fibre and vegetable oils in moderate amounts. Regular meals also support gallbladder emptying.
• Lifestyle modification: weight reduction (gradual rather than rapid), regular physical activity and avoidance of stress.
• Choleretics and cholekinetics: used selectively. Choleretics (e.g. preparations containing bile acids) are contraindicated in obstruction of the biliary tract and should not be used in patients with large or obstructing stones.
• Ursodeoxycholic acid (UDCA): may be used for dissolution of small, radiolucent cholesterol stones in a functioning gallbladder with a patent cystic duct, or for prevention of stone formation during rapid weight loss. It requires months of therapy, and recurrence after stopping is common (about 50% within five years).
• Physiotherapy and spa treatment: in remission only, in the absence of stones or complications.
• Treatment of associated conditions: helminthic infection, dyslipidaemia, diabetes, and gastrointestinal diseases.
7.3 Surgical treatment
Surgical intervention for gallbladder disease, primarily executed via laparoscopic cholecystectomy, is guided by distinct anatomical, clinical, and oncological indications to mitigate recurrent symptoms and prevent catastrophic structural complications.
The primary clinical driver for definitive surgical removal is the presence of symptomatic gallstones, particularly in patients experiencing recurrent episodes of biliary colic or frequent flares of chronic cholecystitis. Once a patient transitions from asymptomatic stone carriage to experiencing painful postprandial attacks, the likelihood of progressive, severe complications increases significantly, making elective surgery the definitive management strategy.
A history of prior severe biliary complications serves as an absolute indication for surgery due to the high rate of recurrence and associated mortality. Patients who have survived acute cholecystitis, choledocholithiasis, or acute biliary pancreatitis face a substantial risk of secondary, often more severe, obstructive or infectious episodes. Removing the gallbladder eliminates the primary anatomical reservoir for stone formation and debris, effectively severing the underlying pathophysiological chain responsible for recurrent ductal and pancreatic inflammation.
Advanced end-stage structural pathology of the gallbladder wall also warrants prompt operative management, regardless of whether symptoms are currently active. A non-functioning, shrunken, or severely atrophied gallbladder represents a diseased, fibrotic organ that no longer contributes to digestive physiology and serves as a continuous nidus for localized inflammation. Similarly, a calcified or porcelain gallbladder presents a clear indication for resection, as intramural dystrophic calcification reflects severe long-standing tissue injury and carries a documented association with primary malignant transformation.
Finally, specific structural features and oncological concerns necessitate surgical intervention to prevent or treat gallbladder carcinoma. The presence of exceptionally large gallstones increases mechanical mucosal friction over decades, creating a chronic inflammatory state linked to malignant degeneration. Likewise, mucosal gallbladder polyps—especially those exceeding ten millimeters, exhibiting rapid growth, or presenting with a sessile morphology—carry a high risk of harboring dysplasia or invasive adenocarcinomas. Any strong clinical or radiological suspicion of primary gallbladder cancer requires immediate surgical exploration and staging to achieve therapeutic oncological margins.
Asymptomatic gallstones usually do not require surgery and are managed by observation, except in selected high-risk groups (for example, porcelain gallbladder, or very large stones).
Methods:
• Laparoscopic cholecystectomy is the gold standard. It is associated with less pain, shorter hospital stay, quicker recovery and better cosmetic results. Elective operation in the "cold" period is preferred.
• Open cholecystectomy is used when laparoscopy is not possible or when conversion is needed (severe adhesions, anatomical uncertainty, intraoperative complications).
• Intraoperative cholangiography or preoperative ERCP/MRCP is used if common bile duct stones are suspected, and the stones are removed endoscopically or surgically.
Possible postoperative complications include bile duct injury, bile leakage, bleeding, and wound infection. Some patients develop postcholecystectomy syndrome, with persistent dyspepsia or pain, most often due to other causes that should then be sought.
7.4 Prevention and follow-up
Prevention includes a balanced diet, control of body weight, regular physical activity, treatment of metabolic disorders and avoidance of rapid weight loss. Patients treated conservatively should be followed up regularly with ultrasonography and liver function tests, and receive guidance on diet and early signs of complications.
8. Prognosis
The prognosis is favourable with timely diagnosis and appropriate treatment. Without treatment the disease follows a relapsing course, with a risk of complications that grows with the duration of symptomatic stones. After laparoscopic cholecystectomy most patients are relieved of their symptoms and return to normal activity within one to two weeks.
9. Conclusion
Chronic cholecystitis is a common, mostly stone-related disease with typical symptoms: right upper quadrant pain after fatty meals, dyspepsia, and a relapsing course. Diagnosis rests on clinical features supported by ultrasonography. Treatment consists of dietary and lifestyle measures, symptomatic and antibacterial therapy during exacerbations, and elective laparoscopic cholecystectomy for symptomatic or complicated disease, which remains the definitive and most effective option. Awareness of its symptoms and a systematic approach to its management allow doctors to prevent serious complications and improve patients' quality of life.
References
1. European Association for the Study of the Liver (EASL). EASL Clinical Practice Guidelines on the prevention, diagnosis and treatment of gallstones. Journal of Hepatology. 2016;65(1):146–181.
2. Lammert F, Gurusamy K, Ko CW, et al. Gallstones. Nature Reviews Disease Primers. 2016;2:16024.
3. Gurusamy KS, Davidson BR. Gallstones. BMJ. 2014;348:g2669.
4. Yokoe M, Hata J, Takada T, et al. Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholecystitis. Journal of Hepatobiliary and Pancreatic Sciences. 2018;25(1):41–54.
5. Williams NS, O'Connell PR, McCaskie AW (eds). Bailey & Love's Short Practice of Surgery. 27th ed. CRC Press; 2018.
6. Townsend CM, Beauchamp RD, Evers BM, Mattox KL (eds). Sabiston Textbook of Surgery. 21st ed. Elsevier; 2021.
7. Kasper DL, Fauci AS, Hauser SL, et al. (eds). Harrison's Principles of Internal Medicine. 21st ed. McGraw-Hill; 2022.