Mucosal Digestion and Adaptation PDF

Section 10: Mucosal Digestion and Adaptation I. Mucosal brush border enzymes A. At birth, all digestive enzymes (mucosal and pancreatic) are in low concentrations with the exception of lactase (in most domestic species). a brush border enzyme (disacchari...

Section 10: Mucosal Digestion and Adaptation I. Mucosal brush border enzymes A. At birth, all digestive enzymes (mucosal and pancreatic) are in low concentrations with the exception of lactase (in most domestic species). a brush border enzyme (disaccharide) a. Prevents digestion of ingested colostral immunoglobulins Low digestive enzymes prevents digestion of colostrum - contain immunglobins First 12-24 after birth: have an "open" gut to absorb maternal antibodies (colostrum) b. Lactase necessary to digest the main sugar in milk (lactose) Lactose > (lactase) > Glucose and galactose B. With increasing age, all brush border (and pancreatic) enzymes increase in concentration with the exception of lactase. Lactose intolerance - Lactase activity becomes reduced or absent with age in many species (some at very early ages). diarrhea in young: not too sick Evol: prevent adults from consuming dam's milk Fig. 42. Brush border carbohydrase development in the pig 64  II. Review of digestion and absorption of carbohydrate Fig. 43 very efficient process > portal vein > liver fructose - absorbed by facilitated diffusion on luminal membrane Final digestion of oligo - and di - saccharides at brush border thus, adjacent to monosaccharide transporter (e.g., SGLT 1) Fig. 44 III. Digestion and absorption of protein Fig. 45 less efficient process because poor access of enzymes to 3D strucutre Digestion Absorption Stomach Intestinal Intestinal Lumen Lumen Brush Border Dietary Protein Polypeptides Amino acids Oligopeptides Amino acids Di-, Tri-peptides Amino Acids Na+- and H+-coupled amino acid and peptide transport > ammino acids Acid hydrolysis Pepsin Pancreatic proteases: Peptidases > portal vein > Trypsin liver Chymotrypsin Carboxypeptidases Di, tripeptides only instance when 'digestion' broken down to amino acids by occurs within epithelial cells peptidases inside epithelial cells 65 IV. Digestion and absorption of fat Fig. 45a Triglyceride structure main dietery fate: triglycerides 3FA: typically, 16-18 long A. Micelle formation 1. Release of CCK stimulated by presence of fat in duodenal lumen backbone - 3 carbons a. Stimulates release of pancreatic proenzymes (lipases, carboxyesterases) b. Stimulates gallbladder contraction Bile released to lumen to emulsify lipds (i.e. form micelles) horse: no gallbladder, bile from biliary ducts increases with feeding Fig. 45b. Amphipathic bile salts. 2. Emulsification and lipase digestion a. Bile salts are amphipathic fat in the middle - form like a detergent micelle - allow lipase to digest =CMC b. Critical micelle concentration develops in bowel lumen. Micelles are composed of: 1) Hydrophobic interior - triglycerides, monoglycerides, free fatty acids and fat-soluble vitamins (A,D,E and K) (and hyrdophonic ends of bile acids) 2) Hydrophilic exterior - Hydrophilic domains of the bile salts c. Micelles increase surface area of ingested fat and aid access of lipases d. Lipase digestion 1) Lipases hydrolyze ester links at 1 and 3 positions on triglycerides Medium chain triglycerides: 3 FA < 16C : rare but a pharmaceutical. All 3 FA released. Used to increase E intake in pancreatic and liver disease 66 3. Absorption at brush border of intestinal epithelial cell a. Micelles disaggregate at epithelial brush border 1) Lipids passively diffuse across cell membrane 2) Bile salts remain in lumen a) 95% resorbed at terminal ileum b) Absorbed by Na+-coupled transport. enters portal vein to travel to liver = enteroheptaic recyclying B. Chylomicron formation within intestinal epithelial cell 1. Re-esterification and chylomicron assembly in intestinal epithelial cell a. FFAs, monoglycerides, and glycerol re-esterified into triglycerides. (absorbed from micelles) b. Aggregated with apolipoproteins, cholesterol and phospholipids to form chylomicrons Amphipathic: make chylomicron soluble in ECF to allow circulation 2. Exocytosis and lymph circulation a. Chylomicra are exocytosed from epithelial cells across the basolateral membrane into the lamina propria b. Chylomicra enter lymph in the central lacteals of villi chylomicra are too large to pass through capillary pores (fenestra) c. Pathway to general circulation: Lacteal Lymph circulation Thoracic duct Venous circulation (lymph collecting (vena cava) duct in thorax) thus, chylomicra initially bypass liver. Diluted in ECF when enters lver (prevents too much fat at once entering liver) 67  fat droplets from hight fat meal ICS (paracellular) with many exocytosed chylomicra Black fat droplets from high fat diet ICS = Intracellular space with exocytosed chylomicrons G= Golgi apparatus 68  lymph vessel wall chylomircon intersitial fluid below epithelium 69 diffusing from micelles re-esterified into TG packaged with apolipoproteins exocytosis lacteal 70  V. Intestinal adaptation A. Surface area of the small intestinal mucosa Fig. 46 (human) B. Adaptation to irreversible injury to small intestinal mucosa - Modeled by removal of bowel section, but applies to any irreversible damage (eg viral) rotovirus - damage epithelium 1. Response of undamaged mucosa is villous hyperplasia to regain absorptive surface area longer villi a. Limited to doubling of surf. area human = 50% Dog and Cat > 50% b. Requires intact crypt epithelium to lengethen villi more absorption per cm2 some diseases attack crypts (feline distemper) c. Luminal nutrients enhance the adaptation process less adaptation with perenteral feeding Fig. 47. 2. Consequences of intestinal resection a. Small intestinal resection 1) Digestion/absorption of carbohydrate less affected than protein Efficiency of carbohydrate digestion/absorption greater (jejunum) need to modify quality and quantity of dietary protein 71  2) Absorptive losses after resection of ileum a) Overall fat absorption decreases because main site for bile salt absorption fat may show in feces - steatorrhea bile salts in colon - risk for colitis b) Vitamin B12 absorption impaired ileum site of B12 absorption treatment: reduce dietary fat + give b12 injection b. Colon resection 1) Reduced VFA absorption important energy source for horses 2) Fluid and electrolyte absorption impaired diarrhea compensation occurs over time with partial colectomy in horse EX: cecum enlarges Objectives: 1. Be able to explain the development of lactose intolerance. 2. Describe the sequence of events in the digestion and absorption of carbohydrates and protein. 3. Describe the steps in lipid digestion/absorption from micelle fromation to chylomicra formation. 4. Understand the amphipathic nature of bile salts. 5. Be able to explain the extent to which the intestinal mucosa adapts to injury. 6. Know what are the nutritional conseqences of small and large bowel resection. Related Questions: 1. What is the rationale for feeding medium chain length triglycerides to a dog with pancreatic disease? 2. What is a cholecystectomy? 3. What are the major consequences of gallbladder removal in a human? 72