Start Module 2: Physiology: Bile, Bilirubin. Liver and the Lab

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Start Module 2: Physiology: Bile, Bilirubin Liver and the Lab

Bile Physiology WYNTKFTB (Intro to Pathology) Applied Anatomy Components Function Synthesis Enterohepatic circulation Imbalance of components (i.e. lithogenesis) Marker of biliary injury

the Bile Key Players Key Players: (preview): Cannicular Markers: Alk, -GT Components: BS, Chol, Bilirubin Function: Fat Digestion, Excretion Dysfunction: Obstruction, Destruction

the Bile Key Players: Cannicular Markers: Alk, -GT Components: BS, Cholesterol, Bilirubin Function: Fat Digestion, Excretion Dysfunction: Obstruction, Destruction

Ampulla @ Duo 2 Biliary Anatomy: Hepatic Ducts + Cystic Duct = CBD

Can a stone Can a cystic hurt me? duct stone or obstruction hurt me? A. Yes B. No

Obstructive Jaundice Liver Injury with CBD stone (Choledocolithiasis) Ducts from liver are obstructed Alk, TB/DB DB: Direct bilirubin Conjugated

Gallstone Pancreatitis Alk, TB/DB Lipase, Amylase Ampulla @ Duo 2

Fistula Gallstone Ileus (lodged in ileum) If there is a fistula between the air-filled intestine and biliary ducts, what do you expect to find in the hepatobiliary tree?

Air Air Gallstone Ileus Pneumobilia Fistula If there is a fistula between the air-filled intestine and biliary ducts, what do you expect to find in the hepatobiliary tree?

Cystic Duct Common Bile Duct Fistula b/w GB & intestine with obstruction at ileocecal vv Obstruction, Ampulla

Bile Trivia for USMLE? 7 -hydroxylase.

Bile Trivia for USMLE? What is the principle mode of ridding the body of cholesterol? Excreted in bile (bile acid/salts) Secreted in bile What is the primary building block of bile acid synthesis? Cholesterol cholic and chenodeoxycholic acids What is the difference between bile acid and bile salt? Conjugation. Adding glycine/taurine to bile acids renders them bile salts and therefore water soluble. What are the main constituents of bile? Bile salts, phospholipids (PPL; hydrophilic), cholesterol (stones) Bilirubin added for color ; Water and Ions added for flavor.

Not So Trivial Bile Facts for USMLE? What is the principle mode of ridding the body of cholesterol? Excreted in bile (bile acid/salts) (think cholestyramine) Secreted in bile What is the primary building block of bile acid synthesis? Cholesterol cholic and Cholestyramine: chenodeoxycholic acids MOA: Binds bile salts LDL receptor AE: Triglycerides Conjugation. Adding glycine/taurine to bile acids renders them bile salts and therefore water soluble. What is the difference between bile acid and bile salt? What are the main constituents of bile? Bile salts, phospholipids (PPL; hydrophilic), cholesterol (stones) Bilirubin added for color ; Water and Ions added for flavor.

Not So Trivial Bile Facts for USMLE? What is the principle mode of ridding the body of cholesterol? Excreted in bile (bile acid/salts) (think cholestyramine) Secreted in bile What is the primary building block of bile acid synthesis? Cholesterol cholic and chenodeoxycholic acids 7 -hydroxylase. (think fibrates and stones) What is the difference between bile acid and bile salt? Conjugation. Adding glycine/taurine to bile Fibrates: acids renders them bile salts and therefore MOA: water PPAR soluble. LPL AE: interfere w/ 7 -OHase cholesterol stones What are the main constituents of bile? Bile salts, phospholipids (PPL; hydrophilic), cholesterol (stones) Bilirubin added for color ; Water and Ions added for flavor.

Not So Trivial Bile Facts for USMLE? What is the principle mode of ridding the body of cholesterol? Excreted in bile (bile acid/salts) Secreted in bile What is the primary building block of bile acid synthesis? Cholesterol cholic and chenodeoxycholic acids What is the difference between bile acid and bile salt? Conjugation. Adding glycine/taurine to bile acids renders them bile salts and therefore water soluble. What are the main constituents of bile? Bile salts, phospholipids (PPL; hydrophilic), cholesterol (stones) Bilirubin added for color ; Water and Ions added for flavor.

Not So Trivial Bile Facts for USMLE? What is the principle mode of ridding the body of cholesterol? Excreted in bile (bile acid/salts) Secreted in bile Delicate balance What is the primary building block of bile acid synthesis? Cholesterol cholic and chenodeoxycholic acids What is the difference between bile acid and bile salt? Bile salts Conjugation. PPL Cholesterol Adding glycine/taurine to bile acids renders them bile salts and therefore water soluble. What are the main constituents of bile? Bile salts, phospholipids (PPL; hydrophilic), cholesterol (stones) Bilirubin added for color ; Water and Ions added for flavor.

Bile Salts (PPL) Cholesterol Bilirubin Delicate balance

Bile Salts Stones Cholesterol An imbalance in these factors cholelithiasis Bilirubin They are really interested in cause/consequence of this imbalance.

Decrease: Liver failure Disease of ducts (PBC, CF) Failure of enterohepatic circulation Bile Salts Increase: Pregnancy Obesity Cholesterol Bili Increase: Hemolysis Bili Bilirubin

Enterohepatic Circulation of Bile (Salts) The most important point of this discussion is awareness that bile acid/salts are recycled. Failure to do so results in two testworthy situations: 1. Fat malabsorption 2. Gallstone formation

Enterohepatic Circulation of Bile (Salts) Primary BA: Cholic Acid Chenodeoxy-Cholic Acid 7 -hydroxylase

Enterohepatic Circulation of Bile (Salts) Secondary BA: Deoxy-Cholic Acid Litho-cholic Acid Portal Vein Ileum

You should only care about the implication of this fun little tale Ileum No bile or TI Bile salt deficiency: Stones ( BS/ Chole), Fat Vit Def, (B-12)

Bacterial Overgrowth: Bile salts deconjugated too soon. Bile acids reabsorbed (too soon) leading to incomplete absorption of fats

Don t lose your bile on the fine particulars You need to be familiar with the concept of enterohepatic circulation and implication of its failure Failure Liver (cirrhosis; no bile acids/salts) Duct destruction (PBC, PSC), obstruction Disease/loss of terminal ileum (Crohn s, resection) Implication Steatorrhea Malabsorption (including fat soluble vitamins) Stones

Bile Function??? Pancreatic Lipase Bile Salts Enterocytes Fat Absorption (3 components)

Bile Function??? Greasy, Foul Smelling Stools that Float Pancreatic Lipase Bile Salts Enterocytes Fat Absorption (3 components)

Bile WYNTKFTB Components Bile salts, cholesterol, bilirubin Function Emulsify fats, cholesterol excretion/secretion Synthesis Cholesterol, 7- hydroxylase, primary bile acids Conjugation w/ taurine/glycine yields bile salts Enterohepatic circulation Majority (85%) of bile is recycled Imbalance (pathology) Bile salt causes steatorrhea BS:cholesterol ratio associated w/ stones Marker of injury (pathology) Alk, -GT Conjugated bilirubin

We will review bile again in context of stones/obstruction This was background on bile physiology