This document discusses gallstones, including their types, prevalence, etiology, and pathogenesis. It notes that gallstones form when bile components like cholesterol and bilirubin crystallize in the gallbladder. There are three main types: mixed, cholesterol, and pigmented. Factors that contribute to cholesterol gallstone formation include genetics, sex/estrogen levels, obesity, diabetes, and impaired gallbladder function. The formation involves an altered bile composition, cholesterol crystal nucleation, mucus hypersecretion, and gallbladder hypomotility.

1. Gallstones. Etiology.
Pathogenesis.
Narmina Alakbarova
CHOLELITHIASIS (GALLSTONES)

2. • Gallstones. The gallstone types and
Prevalence
• Etiology
• Pathogenesis

3. Epidemiology
• One of most common abdominal organs requiring
surgery
• Over 95% of biliary tract disease is attributable to
cholelithiasis (gallstones)
• Population prevalence 5-20% of which majority
(70-80%) remain asymptomatic
• 1-4% develop symptoms each year

4. It is estimated that more than 20 million persons in the
United States have gallstones, totaling some 25 to
50 tons in weight!

5. What are
gallstones?

6. Gallstones are pieces of hard solid
matter in the gallbladder. They form
when the components of bile—
including cholesterol and bilirubin
— precipitate out of solution and
form crystals, much as sugar may
collect in the bottom of a syrup jar.

7. Types of Gallstones
 Mixed
 Cholesterol
 Pigmented
–Black stones
–Brown stones

8. Location: GB, ducts
Major constituents: cholesterol
Consistency: Crystalline with nucleus
Radio-opaque: 15%
Associations:
infection: rare
other diseases:
Cholesterol GS

9. Major factors in cholesterol
GS formation

10. Pigment GS
Location: GB, ducts
Major constituents: bilirubin pigment polymer
Consistency: hard
Radio-opaque: 60%
Associations:
infection: rare
other diseases: cirrhosis and hemolysis
Location: ducts
Major constituents: calcium bilirubinate
Consistency: soft, friable
Radio-opaque: 0%
Associations:
infection: usual
other diseases: chronic partial biliary obstruction

12. RESULTS:
23 %of cholesterol stones and 68%of pigment stones contained
bacteria (P < 0.0001). Stone culture correlated with scanning electron
microscopy results. Pigment stone bacteria were more often present in
bile and blood.
Cholesterol stone bacteria caused more severe infections (19%)than
sterile stones (0%),but less than pigment stone bacteria (57%)(P <
0.0001). Serum and bile from patients with cholesterol stone bacteria
had less bacterial-specific immunoglobulin G. Cholesterol stone bacteria
produced more slime. Pigment stone bacteria were more often killed by
a patient's serum. Tumor necrosis factor-alpha production of the groups
was similar

13. Formation of
gallstones

14. (1) Altered composition of hepatic bile. The bile must be
upersaturated with cholesterol;
(2) Cholesterol nucleation in the bile is accelerated;
(3) Hypersecretion of mucus in the gallbladder traps the nucleated
crystals, leading to their aggregation into stones.
(4)Impaired gallbladder function . Hypomotility of the gallbladder
promotes nucleation;
Cholesterol gallstone formation involves four
simultaneous conditions :

16. 1.ALTERED COMPOSITION OF
HEPATIC BILE.

18. Genetics
The variant is known as D19H, and
it is estimated that it may
contribute 8% to 11% of the risk for
the formation of cholesterol
gallstones. (The odds ratios are 2-3
for heterozygous carriers of D19H,
and 7 for homozygous carriers).
Individuals with the D19H variant
absorb less, but synthesize more,
cholesterol, suggesting that HMG-
CoA inhibitors (statins) may
decrease the risk of gallstone
formation in these individuals.

19. “Fat, Female, Forty, Fertile”
•Sex and oestrogens
•GSs are twice as common in women as in
men, and this is particularly so before the age
of 50.
• The incidence is higher in multiparous than in
nulliparous women.
•Women on long - term oral contraceptives
have a twofold increased incidence of GB
disease over controls.
•Postmenopausal women taking oestrogen -
containing drugs have a significant increase
frequency (around 1.8 times) of GB disease. In
men given oestrogen for prostatic carcinoma
the bile becomes saturated with cholesterol
and GSs may form.

20. •Obesity
50% of markedly obese patients
have gallstones at surgery
• Age
There is a steady increase in
gallstone prevalence with
advancing years, probably due to
the increased cholesterol content
in bile. By age 75, around 20% of
men and 35% of women in some
Western countries have GSs.
•Rapid weight loss

21. Diabetes mellitus
•Obesity
•“a diabetic neurogenic
gallbladder”
•Insulin-tolerance
Diabetics have a higher prevalence of gallstones (or a history of
cholecystectomy) than non - diabetics, particularly females (42 versus 23%).

22. On the basis of their studies in LIRKO mice, which have selective insulin resistance in the
liver, Biddinger et al.2 propose two mechanisms that underlie predisposition to
gallstone formation in individuals with the metabolic syndrome.
First, LIRKO mice show reduced formation of bile acids.
Second, the absence of hepatic insulin signaling in these mice increases the
transcriptional activity of FoxO1, through inhibition of Akt-mediated phosphorylation. As
a result, ABCG5/ABCG8 expression is induced.
Katie Ris-Vicari

23. • Biliary protein concentration is increased in
lithogenic bile. Proteins that accelerate
nucleation (pronucleators) include GBGB mucinmucin
and IgIgGG. Cholesterol GSs have bilirubin at their
centre, and a protein pigment complex might
provide the surface for nucleation of
cholesterol crystals from GB bile.
• Factors that slow nucleation (inhibitors)
include apolipoprotein A1apolipoprotein A1 and A2A2 and a 120 -
kDa glycoproteinglycoprotein. Ursodeoxycholic acidUrsodeoxycholic acid, as
well as decreasing cholesterol saturation, also
prolongs the nucleating time.
• AspirinAspirin reduces mucus biosynthesis by GB
mucosa which explains why this drug and other
non - steroidal anti - inflammatory drugs inhibit
GS formation.
2. Nucleation of cholesterol crystals
and 3. Hypersecretion of mucus

24. 4. Impaired gallbladder function
Gallbladder contraction is under
cholinergic and hormonal control.
Cholecystokinin (CCK),Cholecystokinin (CCK), derived from the
intestine, contracts and empties the
gallbladder and increases mucosal fluid
secretion with dilution of gallbladder
contents. AtropineAtropine reduces the
contractile response of the gallbladder to
CCK. Other hormones found to have an
influence on the gallbladder include
motilinmotilin (stimulatory) and somatostatinsomatostatin
(inhibitory).
Immune processes and inflammationImmune processes and inflammation in the
gallbladder also appear to effect
contraction and promote the production
of pronucleators.

25. Thanks for attention!! 