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home - Biliary - Gallstone Disease - Gallstone Epidemiology Written by Dr Sebastian Zeki

Knows the physiology and biochemistry of bile and the pathogenesis
of gallstones

Is familiar with the normal anatomy and the anatomical variations of
the biliary tree

Recognises the symptoms and signs of the potential complications of
galllstone disease including biliary colic acute cholecystitis jaundice
due to calculous bile duct obstruction cholangitis and carcinoma

Knows the various techniques of diagnostic imaging including
ultrasound CT MRI ERCP EUS radionuclide techniques

Knows the various treatment options the indications for operative and
non-operative management and the risks of each

Knows the current national guidelines for use of ERCP and the risks
of the technique

Knows the ways in which gallbladder polyps are diagnosed and

Knows that gallbladder and sphincter of Oddi dysfunction (SOD) may
account for otherwise unexplained abdominal pain

Recognises different types of SOD how they may present and how
they are investigated

Can select the most appropriate diagnostic and therapeutic
techniques for each clinical situation

Recognises possibility of diagnostic uncertainty in biliary dysmotility
and shows thoughtful judgement in each individual situation

Makes appropriate assessment stratifies urgency and plans
management of patients who have complications of gallstones

Gallstone Epidemiology

Factors inhibitory for gallstone formation:Ascorbic acid - only for women- Coffee-<4 cups/ day reduces risk of symptomatic gallstone disease Vegetable protein-Protectts vs cholecystectomy.Diet high in Poly- and monounsaturated fats- After age 40, 4x higher gallstone incidence The 10-year cumulative incidence of new gallstones of 4.6%. Females- due to:1. Sex steroids- Oestrogen induces cholesterol secretion Progesterone reduces bile acid secretionOestrogen Therapy- Risk increases with length of use and dosage2. Pregnancy (increased freq. and number inc. risk)-2.1 Overproduce hydrophobic bile acids (eg. chenodeoxycholate) so can’t solubilize cholesterol. 2.2 Progesterone reduces gallbladder contractility. Normalize 1-2 months following delivery -30% of small stones and 60% sludge disappears Rapid weight loss Bile mucin and calcium content inc Should all get UDCA prophylaxis ObesityDue to enhanced cholesterol synthesis and secretion . Higher in females/morbidly obese/ younger ages Gallbladder stasis eg: -Spinal cord injuries/ Prolonged fasting -TPN(44% prevalence of gallstones/ 25% get gallstones w/in 18m octreotide tx) Other risk factorsEthnicity- Native americans highest(73 % of female Pima Indians > 25 years) Family history —2X inc risk with FDR’sDiabetes mellitus —HyperTG and autonomic neuropathy (gallbladder hypomotility). Decreased physical activity — Sedentary females inc risk (RR 1.42).Crohn's disease Cirrhosis (Child B and C)1. Reduced hepatic synthesis and transport of bile salts and nonconjugated bilirubin2. High estrogen levels,3. Impaired gallbladder contraction response to meals. Biliary cholesterol Bile salts (= bile acids with cation) Mucin production Poor contractility Bile salts - dependent micellar solubiliza-tion of vesicular cholesterol so bile forms Free Cholesterol Other drugs -Fibrates- inhibition can cause biliary cholesterol supersatu-rated stones Serum lipids +ve assoc with apolipoprotein E4 phenotype and elevated serum TGs.-ve assoc with HDL’s No assoc of serum cholesterol Synthesis in the endoplasmic reticulum (ER). Insufficient bile salts with mucinresults in gallstones HDL: Selective cholesterol uptake from HDL mediated by SR-BI. Preferentially used for biliary cholesterol Chylomicrons: Receptor-mediated internalization of chylomicron remnants (CM),VLDL, and LDL Synthesis in liver Stone TypesCholesterol (20% pure + 60% impure) Pigmenta)Black Chronic haemolysis/Cirrhosis/Biliary infection/Usually sterileb)Brown (20%)Sclerosing cholangitis/Biliary parasites/Frequently recur/In Asians/Assoc with bacteria/RadiolucentBiliary sludgeBest detected by EUSCalcium 90% of ideopathic pancreatitis Cholesterol 7-alpha-hydroxylase in liver Liver secretes high biliary cholesterol level (as unilamellar phosphatidyl-cholines vesicles) and lower than normal levels of bile salts Transported via ABCB11 transporter ABCG5/G8 transporter Risk factors (in pink) Written by Dr Sebastian Zeki

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