Bile Physiology: Composition, Function, and Synthesis, Slides of Physiology

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BILE PHYSIOLOGY

DIPENDRA PARAJULI

University of Louisville

BILE „^

COMPLEX LIPID-RICH MICELLARSOLUTION

„^

ISO-OSMOTIC WITH PLASMA

„^

VOLUME OF HEPATIC BILE = 500 –600 CC/DAY

University of Louisville

FUNCTION OF BILE „^

INDUCE BILE FLOW AND PHOSPHOLIPIDAND CHOLESTEROL SECRETION „^

ESSENTIAL FOR INTESTINAL ABSORPTIONOF DIETARY CHOLESTEROL , FATS ANDVITAMINS „^

BIND CALCIUM AND HELP TO PREVENT CaGALLSTONES AND OXALATE KIDNEYSTONE FORMATION „^

EXCRETION OF LIPID SOLUBLEXENOBIOTICS, DRUGS AND HEAVYMETALS University of Louisville

BILE FORMATION ANDCIRCULATION University of Louisville

BILE ACID SYNTHESIS TWO PATHWAYS 1) CLASSICAL / NEUTRAL^ - RESULTS IN THE SYNTHESIS OF

APPROXIMATELY 1:1 RATIO OFCHOLIC AND CHENODEOXYCHOLICACIDS 2)ALTERNATE / ACIDIC^ - YIELDS PREDOMINANTLY

CHENODEOXYCHOLIC ACIDUniversity of Louisville

BILE ACID SYNTHESIS^ CLASSICAL / NEUTRAL PATHWAY^ - PREDOMINANT PATHWAY IN HEALTH^ - POSTCHOLECYSTECTOMY PATIENTS

WITH BILE FISTULA - INFUSED WITH RADIOLABELLEDPRECURSORS

* [3H]

αOH CHOLESTEROL

* [3H]27-OH CHOLESTEROL

University of Louisville

BILE ACIDSYNTHESISALTERNATE / ACIDIC PATHWAY- MORE IMPORTANT IN CHRONIC

LIVER DISEASE-CIRRHOTICS

- LOW RATE OF BILE ACIDSYNTHESIS- ALMOST EXCLUSIVELYCHENODEOXYCHOLIC

University of Louisville

BILE ACID SYNTHESIS FINAL STEP = -^

CONJUGATION OF CHOLIC ANDCHENODEOXYCHOLIC ACIDS WITHGLYCINE AND TAURINE

• CONJUGATION ENHANCES THE

HYDROPHILICITY, THUS DECREASE THEPASSIVE DIFFUSION OF BILE AS IT MOVESTHROUGH THE BILIARY TREE ANDSMALL INTESTINE University of Louisville

BILE ACID SYNTHESIS REGULATION CHOLESTEROL 7A

α Η

YDROXYLASE

1. BILE ACIDS 2) CHOLESTEROL 3) HORMONES 4) INTESTINAL FACTORS 5) CYTOKINESUniversity of Louisville

BILE ACIDSYNTHESISREGULATIONCHOLESTEROL 7

α Η

YDROXYLASE

„^

BILE ACIDS

-Interruption of enterohepatic circulation-

increases bile acid synthesis -Intraduodenal reperfusion-reduces bile acid

synthesis University of Louisville

CLINICAL CORRELATION 1)Resection of Terminal Ileum

Increased bile acid secretion 2)Infants with inborn errors of bile acid

biosynthesis-Accumulation of toxic intermediates in thehepatocytes causing cholestasis andchronic liver damage-Oral bile acids supplements containinghydrophobic bile acids –decreasedaccumulation of toxic intermediates University of Louisville

2)^

CHOLESTEROL-Increased dietary cholesterolRats-Increased CYP

αOH Activity

? Humans -Decreased CYP

αOH Activity

3)^

HORMONES-Glucocorticoids-Thyroid hormones-Insulin-Glucagon University of Louisville

BILE ACID TRANSPORT -Bile acid pool is recirculated 10-20 times a

day -Bile acid pool is 1.5 to 4 gm -Circulating bile acid pool is 17 to 40 g 0.2 to 0.5 gm of bile is lost in feces =replaced

by de novo synthesis University of Louisville

ENTEROHEPATIC CIRCULATION 1) TWO PUMPS - LIVER

- INTESTINE

2)TWO RESERVOIRS

- INTESTINAL LUMEN - BLOOD

University of Louisville