Home › Pathology › Cholelithiasis

Cholelithiasis

*Cholelithiasis*

For medical students2 min readUpdated 2026-10-10

Cholelithiasis (cholelithiasis) is a pathological condition characterized by the formation of calculi (stones) in the gallbladder or biliary ducts. The disease is often asymptomatic, but it can lead to severe pain and complications when biliary outflow is obstructed.

PrevalenceGallstones occur in 10–20% of the adult population in developed countries.

Risk GroupFemales aged 55–70, individuals with obesity and diabetes mellitus.

Stone CompositionPredominantly cholesterol (80%), pigment, and calcium stones.

Asymptomatic CourseOver 80% of patients remain asymptomatic for decades.

Mechanism of Lithogenesis

The formation of calculi is based on three key processes:

Dyscholia — alterations in the chemical composition of bile.
Stasis — stagnation of bile within the gallbladder lumen.
Infectious Factor — inflammatory processes in the biliary tract.

The lithogenic process begins with the formation of an organic matrix, onto which salt crystals subsequently deposit.

Classification and Morphology

Gallstones are classified according to their chemical composition:

Cholesterol stones: the most frequent type (80%). They can be pure cholesterol (single, rounded) or mixed (multiple, layered on cross-section).
Pigment stones: dark brown or black, often irregular and polygonal with facets.
Calcium stones: less common, distinguished by high density.

In mixed gallstones, the gallbladder is often enlarged, its wall is thickened, and the mucosa acquires a granular appearance.

Clinical Manifestations

Despite frequent asymptomatic carriage, as the disease progresses patients may experience:

A sensation of heaviness in the right upper quadrant.
Spastic pain (biliary colic).
Dyspeptic disorders: nausea and a bitter taste in the mouth.
Obstructive jaundice, occurring when a stone blocks the bile duct.

Mnemonic

The "4F" rule (regarding risk factors): Female, Forty (age 40+), Fat, Fertile.

Frequently asked questions

What complications can develop in cholelithiasis?

Cholelithiasis can lead to local, inflammatory, and obstructive complications:

Local damage — pressure sores (decubitus ulcers) of the gallbladder wall leading to perforation, adhesion formation, and fistulas.
Inflammatory processes — cholecystitis, cholangitis, and cholangiolitis.
Obstructive conditions — biliary tract obstruction and biliary colic.
Involvement of adjacent organs — acute pancreatitis.

What components form the organic matrix of a gallstone?

The organic matrix of a gallstone is formed from cellular, protein, and microbial components. It includes:

Cellular elements — desquamated epithelial cells, leukocytes, and cellular detritus.
Protein substances — mucus, fibrin, collagen, and other secretory proteins.
Microorganisms — bacteria acting as an organic foundation during inflammatory processes.

Formation of the colloidal matrix is primary according to the colloidal theory of stone formation, or secondary during salt crystallization.

As a result of which pathological processes do pigment stones form?

Pigment stones form as a result of pathologies accompanied by an excess of bilirubin or infectious-inflammatory changes in the biliary tract. Two pathogenetic variants are distinguished:

Black stones — form against the background of increased hemolysis (e.g., in congenital hemolytic anemias, sickle cell disease) and in liver cirrhosis due to increased bilirubin concentration.
Brown stones — form against the background of chronic inflammation in the intra- and extrahepatic bile ducts.

What microscopic changes are observed in the gallbladder wall during the long-term course of cholelithiasis?

During the long-term course of cholelithiasis, microscopic signs of chronic calculous cholecystitis develop in the gallbladder wall. The following changes are observed:

Mucosa — atrophy, sclerosis of the lamina propria, formation of Rokitansky-Aschoff sinuses.
Muscular layer — hypertrophy or sclerosis.
Inflammatory infiltration — lymphomacrophagal infiltration (leukocytes appear during exacerbations).

Special variants reveal extensive fibrosis extending beyond the wall (xanthogranulomatous variant) or replacement of structures by dense hyaline sclerosis with possible calcification (hyalinizing variant).

What is the biochemical mechanism of dyscholia development during the formation of cholesterol stones?

The biochemical mechanism of dyscholia involves an imbalance in the lipids of bile micelles (dyslipoproteinemia). The process is driven by the following factors:

Enzymatic shifts — increased HMG-CoA reductase activity (enhances cholesterol synthesis) or decreased 7α-hydroxylase activity (suppressed by estrogens or allosterically inhibited by bile acids).
Changes in bile composition — absolute increase in cholesterol concentration and decrease in the levels of solubilizers (bile acids and phospholipids/lecithin).

As a result, the lithogenic index (ratio of cholesterol to the sum of bile acids and phospholipids) exceeds the 1:10 proportion, leading to cholesterol precipitation and crystallization.

Where is pain localized during biliary colic?

The typical localization of pain is the right upper quadrant (hypochondrium).

How do cholesterol stones appear on cross-section?

Mixed cholesterol stones have a layered structure: alternating dark layers (pigments) and light layers (cholesterol).

What factors contribute to the development of cholelithiasis?

In addition to age and sex, significant risk factors include obesity, diabetes mellitus, use of oral contraceptives, and ileal resection.

Go deeper

Pathophysiology of biliary colic during duct obstruction.
Differential diagnosis of pigment and cholesterol stones.
The role of the organic matrix in initiating crystallization.
Morphological changes of the gallbladder wall in chronic cholecystitis.
Complications of cholelithiasis (cholangitis, gallbladder hydrops).