Lipid Digestion and Absorption (RCSI Bahrain) PDF

Royal College of Surgeons in Ireland – Medical University of Bahrain Digestion and Absorption of Lipids Module : Gastrointestinal & Hepatology Code: MED 201 Class : MedYear 2 semester 1 Lecturer : Dr Jeevan K Shetty Date : 12 Sep 2024 Learning Outcomes Describe the digestion of...

Royal College of Surgeons in Ireland – Medical University of Bahrain Digestion and Absorption of Lipids Module : Gastrointestinal & Hepatology Code: MED 201 Class : MedYear 2 semester 1 Lecturer : Dr Jeevan K Shetty Date : 12 Sep 2024 Learning Outcomes Describe the digestion of lipids in the body Describe the products of lipid digestion Explain the mechanism of the absorption of lipids in the body Explain the significance of malabsorption syndromes Case Recall What are the types of fatty acids? How many calories does each gram of fat generate? What constitutes dietary lipids? Lipids 25 – 160 g/day ingested Mostly triglycerides (triacylglycerols). Also, phospholipids, cholesterol esters Essential: fat soluble vitamins A, D, E, K essential fatty acids e.g., linoleic, linolenic Lipids Most lipids are insoluble in water – how to digest with water-soluble enzymes? How to transport in blood? A few lipid compounds are soluble in water – short chain FA < 10 carbons, some polyunsaturated complex lipids with short chain FAs Lipids - emulsification Bile salts + mixing: – emulsify aqueous and lipid components Large lipid drops are broken down into small droplets (0.5 – 1.0 mm) which can form stable suspension Much larger aqueous/lipid interface Allows enzyme access to lipid substrate Bile acids What is the precursor for bile salt? And name them Enzymes 1 Orlistat 2 Free FA Smith 8.16 Meisenberg & Simmons Enzymes 1 Pancreatic Lipase – Binds to the surface of lipid droplet in the presence of pancreatic co-lipase – Co-lipase also helps overcome bile-salt inhibition of pancreatic lipase Enzymes 2 Cholesterol esterase – pancreas Principle function is to cleave fatty acid from cholesterol esters Also able to hydrolyse triacylglycerol, monoacylglycerol, others Phospholipase – pancreas – Secreted as inactive precursor –activated by trypsin Smith 8.16 – Hydrolises phospholipid to lysophospholipid by removing one fatty phospholipase acid Lysophospholipase lysophospholipase – Removes remaining fatty acid from lysophospholipid Glycerophosphate + fatty acid Quick Review What is Orlistat? Why is it used? Colipase secreted as zymogen- pro-colipase- which compound activates pro-colipase? The contraction of the gallbladder and secretion of pancreatic enzymes are stimulated by the which gut hormone?  https://www.youtube.com/watch? Micelle formation v=tmZksHXtZtg&ab_channel=ArmandoHasudungan Free fatty acids and monoacylglycerols are insoluble in water Micelles: Lipid particles ~4-6 nm diameter. Contain ~20 lipid molecules Initially formed from bile salts, then other lipids are incorporated Dynamic equilibrium between micelles and aqueous solution Bile salts interact with long-chain fatty acids to form a mixed Smith 6.9 micelle Absorption of lipids Lipid breakdown products diffuse across the unstirred layer to the enterocyte membrane They diffuse through the membrane and into the cell Or can cross into the cell using a specific fatty acid transporter protein Smith 8.17 Bile salts are re-absorbed in the ilium Short-medium chain FAs do not require mixed micelles for absorption Short & Medium chain fatty acids Pass the enterocytes → released to the hepatic portal vein → liver → enter the general circulation and bind albumin Absorption of lipids Normal absorption of fat-soluble vitamins depends on intact fat- digesting and absorbing mechanisms A, D, E, K Vitamin deficiency syndromes may result from fat malabsorption Smith 8.17 Lipids in the enterocyte Lipid breakdown products enter the enterocyte Triglycerides, phospholipids, cholesterol esters, re-synthesized in enterocyte Combined with apolipoproteins (Apolipoprotein B-48 is the main structural component) into lipoproteins known as chylomicrons Chylomicrons are transported out of the cell into the extracellular fluid and carried to the blood through the lymphatic system. Smith 8.17 Short and medium-chain FA (4-12) can directly enter the portal circulation (transported bound to albumin) Chylomicrons Triglyceride incorporated into chylomicron particles 98-99% lipid 1-2% protein – Apolipoprotein B-48 Protein synthesised at rough ER, lipids added in smooth ER and Golgi Golgi packages them into vesicles that travel to the basolateral membrane, and release the chylomicrons into the extracellular space Collected by the lymph; this lymph has a milky appearance because of the fat and is known as ‘chyle’ Why are short and medium-chain fatty acid-containing fat preferred for dietary therapy in pancreatic insufficiency? Indigestible material Not everything can be digested... 95% of fat; 70-90 % of starch is digested Keratins and some plant proteins difficult to digest Cellulose not digested at all Anaerobic fermentation by intestinal flora produces gas (hydrogen, CO2, CH4) Indigestible material – ‘fibre’ – helps movement through GIT Summary Mouth – Mastication – Emulsification – Lingual lipase Stomach – Gastric lipase Small Intestine – Pancreatic enzymes – Emulsification Malabsorption Absorption depends on: Presence of substance in absorbable form Integrity and normal structure of absorptive area Normal ratio of speed of absorption to speed of passage through GIT Malabsorption Global malabsorption: in diseases causing diffuse mucosal damage or a reduction of the absorptive surface (e.g., celiac disease) Partial malabsorption: caused by a localized absorption impairment, resulting in deficiencies of specific nutrients (e.g., vitamin B12 deficiency in patients with diseases affecting the terminal ileum) Malabsorption causes : Pancreatic insufficiency e.g. in chronic pancreatitis – Can be seen for example in cystic fibrosis Insufficiency of brush border enzymes Eg lactase deficiency Sucrose-isomaltase deficient Inadequate mucosal surface – eg in coeliac disease – flattening of villi Inflammatory states eg. Crohn’s disease – inflammation, thickening of GIT wall, obstruction Infection Acute eg salmonella – inflammatory response Chronic eg tropical sprue ; caused by infectious agent, leads to partial villus atrophy in jejunum Surgery ( Short Bowel Syndrome) colonic resection – loss of absorptive area gastrectomy – loss of intrinsic factor (B12), loss of HCl Malabsorption Results in: Weight loss, weakness. “failure to thrive” in infants. various disorders due to vitamin deficiency states Accompanied by: eg steatorrhoea (visible fat in feces); intestinal discomfort; diarrhea Investigated by: Imaging, endoscopy, biopsy, serum enzymes (in the case of pancreatitis) Summary Reading Smith & Morton – Systems of the Body “The Digestive System” esp. Ch. 5, 8. Lippincott's 4th ed – Ch 15; Ch 7 Meisenberg and Simmons 2nd ed Ch. 19 Kumar and Clark 6th ed. pp301-306 (malabsorption) Emedicine: Malabsorption syndromes