SM_152b: Bile Salts and Absorption of Lipids

Question 1

Describe dietary composition

Answer 1

Dietary composition

• 50% carbohydrate
• 16% protein
• 98% absorbed
• Other lipids: cholesterol, phospholipids, fat soluble vitamins

Question 2

Triglycerides are composed of ____ and ____

Answer 2

Triglycerides are composed of 3 fatty acids and a glycerol backbone

Question 3

___ are the most abundant fatty acids in the human diet

Answer 3

Long chain fatty acids are the most abundant fatty acids in the human diet

• 13-21 carbons
• Less soluble than short and medium chain fatty acids

Question 5

___ fatty acids have no double bonds in the carbon chain

Answer 5

Saturated fatty acids have no double bonds in the carbon chain

Question 6

___ fatty acids have double bonds in the carbon chain

Answer 6

Unsaturated fatty acids have double bonds in the carbon chain

Question 7

Emulsification of lipids includes ____ and ____

Answer 7

Emulsification of lipids includes mechanical breakdown of solid fat (chewing, gastric churning) and fine emulsion of lipid droplets

Question 8

Minor digestion of lipids involves gastric lipase breaking down fatty acids into ____ and ____

Answer 8

Minor digestion of lipids involves gastric lipase breaking down fatty acids into diacylglycerol and free fatty acids

Question 9

Minor digestion of lipids involves pancreatic lipase breaking down fatty acids into ____ and ____

Answer 9

Minor digestion of lipids involves pancreatic lipase breaking down fatty acids into 2-monoacylglycerol and free fatty acids

Question 10

Bile acids are ____ and have a ____ and ____

Answer 10

Bile acids are amphipathic and have a hydrophilic head and hydrophobic tail

• Form micelles

Question 12

Bile salts are exported from the liver via the ___

Answer 12

Bile salts are exported from the liver via the bile canaliculus

Question 13

Describe bile secretion

Answer 13

Bile secretion

• 50% of hepatic bile passess into the duodenum and 50% is diverted into the gallbladder for storage
• Relative tone of sphincter of Oddi and gallbladder determines whether the bile enters the gallbladder or duodenum

Question 14

Gallbladder functions to ____

Answer 14

Gallbladder functions to concentrate and acidify bile

• Expands as it fills with bile during fasting
• Upon eating, intestinal cells release CCK -> stimulates gallbladder contraction -> releases bile into duodenum

Question 15

Bile salts enhance solubility of lipids by forming ____

Answer 15

Bile salts enhance solubility of lipids by forming mixed micelles

Question 16

Mixed micelles facilitate transport of lipids to ____

Answer 16

Mixed micelles facilitate transport of lipids to enterocyte brush-border membrane

• Lipids leave the micelle and are taken up into the enterocyte by passive diffusion and active transport

Question 17

Describe fatty acid absorption

Answer 17

Fatty acid absorption

1. Medium chain fatty acids and short chain fatty acids passively diffuse direcctly into the portal circulation
2. Long-chain fatty acids are re-esterified with monoacylglycerol within the enterocyte
3. The newly formed triacylglycerols are assembled with cholesterol phospholipids and apolipoproteins to form chylomicrons
4. Chylomicrons are transferred by exocytosis into lacteals (lymphatic system)
5. Enter bloodstream via thoracic duct

Question 18

Describe intestinal uptake of bile acids

Answer 18

Intestinal uptake of bile acids

1. After releasing lipid contents of mixed micelles, bile acids continue to travel through the small intestine to the distal ileum
2. Most bile acids are actively absorbed in the ileum via the apical sodium-dependent bile acid transporter (ASBT)
3. Enter the portal circulation primarily via the basolateral membrane transporters OSTalpha/beta

Question 19

Most bile acids are returned to the liver via the ____ and are taken up in hepatocytes primarily via ____

Answer 19

Most bile acids are returned to the liver via the portal vein and are taken up in hepatocytes primarily via NCTP

Question 20

Liver receives dual blood supply from the ____ and ____

Answer 20

Liver receives dual blood supply from the hepatic portal vein and hepatic arteries

• Efficient uptake of bile acids from the portal circulation prevents entry into the systemic circulation

Question 21

Describe enterohepatic circulation of bile acids

Answer 21

Enterohepatic circulation of bile acids

• Bile salt pool recirculates 4-12 times / day (up to 5 times after a single fatty meal)
• Each bile salt may be reused up to 20 tiems
• 95% of bile acids are reabsorbed in each cycle
• 5% are lost to fecal excretion
• New bile acids are synthesized in the liver to replace those lost to fecal excretion

Question 22

Describe synthesis of bile acids

Answer 22

Synthesis of bile acids

• Primary bile acids in humans: cholic acid, chenodeoxycholic acid
• Synthesized in the liver from cholesterol
• Major synthesis pathway is catalyzed by CYP7A1
• Conjugated bile acids are more potent detergents

Question 23

Bile acids are ligands that ____ and ____

Answer 23

Bile acids are ligands that bind to receptors (FXR) and activate signaling cascades

• FXR is a nuclear receptor that binds bile acids

Question 24

Bile acid binding to ____ stimulates the ____ which negatively regulates ____ to suppress bile acid synthesis

Answer 24

Bile acid binding to FXR stimulates the SHP which negatively regulates CYP7A1 to suppress bile acid synthesis

Question 25

Bile acid synthesis is subject to ___ from the gut

Answer 25

Bile acid synthesis is subject to feedback regulation from the gut

Question 26

Describe feedback regulation of bile acid synthesis

Answer 26

Feedback regulation of bile acid synthesis

1. Bile acids bind FXR in enterocytes
2. Induces fibroblast growth factor 19 (FGF19)
3. FGF19 enters the portal circulation
4. FGF19 returns to the liver
5. FGF19 binds to its receptor FGFR4
6. Inhibits CYP7A1
7. Suppresses bile acid synthesis

Question 27

Bile acids are regulators of ____

Answer 27

Bile acids are regulators of metabolic disease

• Obeticholic acid: synthetic bile acid
• NGM-282: FGF19 analogue

Question 28

Fat malabsorption results in ____ and ____

Answer 28

Fat malabsorption results in steatorrhea (excess fat in stool) and fat soluble vitamin deficiency

• Pale oily stools
• Cramping, bloating
• Fecal incontinence
• Fat soluble vitamin deficiency: Vitamins A, D, E, K

Question 29

Fat malabsorption results from ____ or ____

Answer 29

Fat malabsorption results from bile acid deficiency or exocrine pancreatic insufficiency

• Bile acid deficiency: chronic cholestasis (primary biliary cholangitis), ileal resection (Crohn disease)
• Exocrine pancreatic insufficiency: chronic pancreatitis (alcohol)

Question 30

Gallstone formation risk factors include ____, ____, ____, and ____

Answer 30

Gallstone formation risk factors include cholesterol supersaturation, gallbladder stasis, increased mucin production, and hydrophobic bile

• Gallstones can get lodged in the biliary tree impeding the flow of bile

Question 31

Cholestasis is ____ that may be ____ or ____

Answer 31

Cholestasis is impaired bile flow that may be intrahepatic or extrahepatic

• Intrahepatic: impaired flow of bile aciss out of hepatocytes into bile canaliculi
• Extrahepatic: blockage of extrahepatic bile ducts
• Consequences: liver toxicity, spill-over of compounds from the enterohepatic circulation into systemic circulation, fat malabsorption