Cholelithiasis (Gallstones): Pathogenesis and its problems

FAUZI YUSUF GastroenteroHepatologi Division, Medical Faculty SyiahKuala University/Zainoel Abidin Hospital Banda Aceh

Gallstones

Common worldwide Mostly asymptomatic Two main type : cholesterol and pigment In USA and Western countries,cholesterol stones the majority (80-90%) East Asian contries pigment stone is significant higher than Western contries

Cholesterol stones
Mayor clinical associations : Aging Female gender Obesity Pregnancy Rapid weight loss Native American ethnicity

Risk Factors associated With Cholesterol Hypersecretion in Bile

Clinical
Obesity

Patogenesis
Increasehydroxymethylglutaryl coenzyme A Inhibition of hepatic acyl coenzym A cholesterol Increase Lipoprotein receptors B and C Age related decrease in 7 -hydrolase activity

Contraceptives oral
Estrogens Age

Pigment stone

Two types :Black pigment, Brown pigment Black pigment stones : Associated with - old age - cirrhosis - hemolysis - possibly TPN Brown pigment stones : found mostly in bile ducts

Cholesterol
7 Hydroxylase 12 Hydroxylase

7 Hydroxycholesterol

26 Hydroxylase

26 Hydroxylase

Chenodeoxycholic Acid (unconjugated)

Intestinal Bacteria

Cholic Acid (unconjugated)

Intestinal Bacteria

Lithocholic Acid (unconjugated)

Deoxycholic Acid (unconjugated)

Role of the Gallbladder

Gallbladder mucosal plays an important role in pathogenic process. Gallbladder - absorb excess water and electrolyte and concetrate bile - secretes hydrogen ions and mucin. Normal : Balance proportion Cholesterol-Bile AcidLecithin. Imbalance Precipitacion Crystal Chlesterol Stone

Diagnosis

Ultrasonography
- Diagnosis of gallbladder stones( 95%) - Can also visualize the bile ducts, liver, and pancreas. - Stone in the bile ducts ( 30 %). ERCP MRCP EUS

Other Radiologic Studies

15 % of gallstones are radio-opaque on plain abdominal X-ray. CT scanning, for more information but lower sensitivity than USG. Rarely, PTC, Oral cholecystography.

Natural History

Asymptomatic gallstones
The majority of the patients with gallstones are asymptomatic Asymptomatic Symptomatic 1-2 % The consensus asymptomatic patients with gallstones Should not undergo prophylactic cholecystectomi.

Symptomatic Gallstones

Cholesterol stone, not calcified - < 5mm, patent cystic duct oral bile acid - Single stone, 5-20 mm, patent cystic duct ESWL + oral bile acid Laparoscopic or Open cholecystectomi Endoscopic Sphincterotomy Non cholesterol stones or Calcified stones

Differential Diagnosis
Many conditions

Right Upper Quadrant pain Epigastric pain

Peptic Ulcer Choledocholithiasis Pancreatitis GERD Angina Liver-related conditions

Source: Bates Jane A; Pathology of Gallbladder and Biliary Tree; in Abdominal Ultrasound: How Why and When; Second Ed; Churchill Livingstone; China; 2004

Natural History

Once experiences a first episode of biliary pain 75 % attack within a 2 years period. Serious Complications : - Acute cholecystitis - Pancreatitis - Cholangitis The risk of developing a serious complications in patients with first episode of biliary pain 12 % year

Biliary pain

1/3 patient with Gallstone are Symptomatic Biliary pain is main complaint (70%-80%). The pain of Biliary Functional spasm around an obstructed Cystic Duct. Episodic and Severe Epigastric, right upper quadrant

Acute cholecystitis

The most common of acute complications The leading indication for emergency cholecystectomy Pathogenesis : - Cyst duct obstruction (stone, mucous, sludge) - Lysolecithin, prostaglandins and others subtances stasis obstruct gallbladder inflamation the gallbladder wall.

Acute cholecystitis (cont..)

Clinical presentation - Moderate pain in the epigastium or upper right quadrant which may radiate to right sholder and scapula. - Nausea, vomiting, febrile - Right upper quadrant tenderness, - Murphys signs

Acute cholecystitis (cont..)

Laboratory findings - Leukositosis - AST,ALT, Alkaline phosphatase, bilirubin levels normal/slightly elevated - If Alkaline phosphatase Choledolithiasis? Diagnosis Base on combination of characteristic clinical findings and Radiologic studies.

Diagnosis

Hepatobiliary scanning - Injecting radiolabeled HIDA or DISIDA - Sensitivity 90% Ultrasonography - Sign : Gallstone, dilated gallbladder, thickened gallbladder wall, edema within gallbladder wall, perycholecystic fluid, sludge.

ULTRASOUND APPEARANCES

Source: Bates Jane A; Pathology of Gallbladder and Biliary Tree; in Abdominal Ultrasound: How Why and When; Second Ed; Churchill Livingstone; China; 2004

ULTRASOUND APPEARANCES

Source: Bates Jane A; Pathology of Gallbladder and Biliary Tree; in Abdominal Ultrasound: How Why and When; Second Ed; Churchill Livingstone; China; 2004

Cholangitis

Choledocholithiasis ( Common Bile Duct stones) obstructive jaundice, pruritus,acholic feces Cholangitis. Clinical picture : Charcot Triad (Biliary pain, Jaundice, Chill and Rigor) Slight hepatomegali, tenderness. BloodCulture : E. Coli, Klebsiella, Proteus dan Pseudomonas. Patogenesis : Biliary tract obstruction, Increase intralumen pressure, Bile acid infection.

ULTRASOUND APPEARANCES

Source: Bates Jane A; Pathology of Gallbladder and Biliary Tree; in Abdominal Ultrasound: How Why and When; Second Ed; Churchill Livingstone; China; 2004

Cholangitis (cont..)

Therapi 85 % response - Antibiotic (7-10 days) gram +/-, anaerob - Fluid and Electrolyte - Analgetic Drainage ERCP, sphingterotomi 15 % Directly Drainage (persistent fever, abdominal pain, sign and symptom septicemia) ERCP, PTBD

Acute Pancreatitis

= Biliary Pancreatitis Precipitate by the passage of stones or sludge in the common bile duct sludge or microscopic stones Fasting totally Total Parenteral Nutrition Urgent ERCP Sphincterotomi Antibiotic

ULTRASOUND APPEARANCES

Endoscopic cholangiopancreatography (ERCP) of a stone in a normalcalibre (5 mm) duct

Source: Bates Jane A; Pathology of Gallbladder and Biliary Tree; in Abdominal Ultrasound: How Why and When; Second Ed; Churchill Livingstone; China; 2004

ULTRASOUND APPEARANCES

Source: Bates Jane A; Pathology of Gallbladder and Biliary Tree; in Abdominal Ultrasound: How Why and When; Second Ed; Churchill Livingstone; China; 2004

Summary

The Majority patient with Gallstones are Asymptomatic Complication Gallstones symptomatic are : Acute cholecystitis, Acute cholangitis, Biliary Pancreatitis Therapy Gallstone are oral bile acid, ESWL, ERCP, Laparoscopic/Open Cholecystectomi, depend on characteristic patients.