The document discusses the gallbladder and bile, their functions in digesting fats, and cholelithiasis (gallstones). It describes the three main types of gallstones, the pathophysiology of cholesterol gallstone formation, and common causes like obesity. Symptoms of gallstones are explained as well as methods for medical diagnosis. Treatment options include bile acid therapy using Ursodiol, which works to dissolve small cholesterol gallstones by altering bile composition and reducing cholesterol secretion from the liver. Ursodiol is an effective alternative to surgery for some patients with symptomatic gallbladder disease.

1. Dr. Syed Baqir Naqvi
(Pharm-D, M. Phil)
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2. Gallbladder
• The gallbladder stores and
concentrates bile from the liver.
The bile is then released into the first
section of the small intestine (the
duodenum), where it helps the body
to break down and absorb fats
from the food.
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3. Bile
“Bile is a yellow, brownish or olive-green
liquid that helps our body to digest fats.”
• The liver cells secrete bile into small canals
that lead to the common bile duct. From there,
a smaller duct branches off and leads to the
gallbladder. The common bile duct ends at the
small intestine.
• The cells of the liver produce about 800 to
1,000 ml of bile every day.
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4. Functions of bile
“Bile is a fluid that is made and released by the liver and stored in the
gallbladder.”
• Bile helps with digestion. It breaks down fats into fatty acids, which can be
taken into the body by the digestive tract.
• Bile is the greenish-yellow fluid (consisting of waste products, cholesterol,
and bile salts) that is secreted by the liver cells to perform two primary
functions:
1). To carry away waste. 2). To break down fats during digestion.
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5. • Bile is mainly made up of water, but also has bile salts, cholesterol, certain
fats (lecithin) and bile pigments in it.
• The most important bile pigment, bilirubin, is made when red blood cells
are broken down in the liver. Bilirubin is what makes urine yellow and stool
brown.
• Bile salts break down larger fat globules in food into small droplets of
fat. Smaller fat droplets are easier for the digestive enzymes from the
pancreas to process and break down. The bile salts also help the cells in the
bowel to absorb these fat droplets.
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6. Cholelithiasis
 Cholelithiasis is derived from the
Greek word;
 chol means "bile" + lith means
"stone”
 Presence of stones in the gall bladder is
referred as cholelithiasis.
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7. Complications of Cholelithiasis
 Cholecystitis.
 Perforated Gallbladder.
 Gallbladder Cancer.
 Cholangitis.
 Pancreatitis.
 Gangrene or Abscesses.
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8. Types of gallstones
There are three types which is given below.
1. Cholesterol Stones (80% cholesterol by weight)
vary in color from light-yellow to dark-green or brown
and are oval 2 - 3 cm in length, often having a tiny dark
central spot.
2. Pigment Stones are small, dark stones made of
bilirubin, calcium salts and 20% cholesterol that are
found in bile.
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9. Conti…
3. Mixed Gall Stones typically contains
20–80% cholesterol.
Other common constituent are calcium carbonate,
palmitate phosphate, bilirubin and other bile
pigments. Because of their calcium content, they are
often radio graphically visible.
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10. Pathophysiology
“Cholesterol gallstones develop when bile contains too much cholesterol
and not enough bile salts.”
Two other factors are important in causing gallstones are;
 Incomplete and infrequent emptying of the gallbladder may cause
the bile to become over concentrated and contribute to gallstone
formation.
 The second factor is the presence of proteins in the liver and bile that
either promote or inhibit cholesterol crystallization into gallstones.
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11. Etiology/Causes
Cholelithiasis is mainly caused by
i. Obesity
ii. Pregnancy
iii. Gallbladder stasis
iv. Drugs
v. Heredity
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12. Signs and symptoms
 Gallstones may be asymptomatic, even for years. These
gallstones are called "silent stones" and do not require treatment.
 Symptoms commonly begin to appear once the stones reach a
certain size (>8 mm).
 A characteristic symptom of gallstones is
a "gallstone attack", in which a person may experience intense
pain in the upper-right side of the abdomen.
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13. Conti….
Often, attacks occur after a particularly fatty meal and almost
always happens at night. Other symptoms include;
 Abdominal bloating.
 Intolerance of fatty foods.
 Belching.
 Gas.
 Indigestion.
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14. Medical Diagnosis
 Abdominal Ultrasounds.
 History and Physical
examinations.
 Abdominal CT Scan.
 Plain X-ray.
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15. Treatments
Some drugs are available which symptomatically
reduce the symptoms of disease, but the ultimately
treatment is by;
 Surgical Removal of Gallbladder.
 Laparoscopic cholecystectomy.
 Bile acid therapy (Ursodiol)
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16. BILE ACID THERAPY FOR GALLSTONES
 Ursodiol (ursodeoxycholic acid) is a naturally occurring bile acid that makes
up less than 5% of the circulating bile salt pool in humans.
 After oral administration, it is absorbed, conjugated in the liver with glycine or
taurine, and excreted in the bile.
 Conjugated ursodiol undergoes extensive enterohepatic recirculation.
 The serum half-life is approximately 100 hours.
 With long-term daily administration, ursodiol constitutes 30% – 50% of the
circulating bile acid pool.
 A small amount of unabsorbed conjugated or unconjugated ursodiol passes into
the colon, where it is either excreted or undergoes dehydroxylation by colonic
bacteria to lithocholic acid, a substance with potential hepatic toxicity. 16

17. Pharmacodynamics
 The solubility of cholesterol in bile is determined by the relative proportions of
bile acids, lecithin, and cholesterol.
 Prolonged ursodiol therapy expands the bile acid pool, this does not appear
to be the principal mechanism of action for dissolution of gallstones.
 Ursodiol decreases the cholesterol content of bile by reducing hepatic
cholesterol secretion.
 Ursodiol also appears to stabilize hepatocyte membranes, possibly through a
reduction in the concentration of other endogenous bile acids or through
inhibition of immune-mediated hepatocyte destruction.
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18. Clinical Uses
 Ursodiol is used for dissolution of small cholesterol gallstones in patients
with symptomatic gallbladder disease who refuse cholecystectomy.
 At a dosage of 10 mg/kg/d for 12–24 months, dissolution occurs in up to 50%
of patients with small (< 5–10 mm) noncalcified gallstones.
 It is also effective for the prevention of gallstones in obese patients undergoing
rapid weight loss therapy.
 Ursodiol 13–15 mg/kg/d is helpful for patients with early-stage primary biliary
cirrhosis, reducing liver function abnormalities and improving liver histology.
 Ursodiol is practically free of serious adverse effects.
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