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Human Form & Function 2 Physiology of the Small Intestine Dr. Neil Docherty My Teaching Objec6ves • Describe the various patterns of intestinal motility and how they contribute to digestion and absorption • Emphasise the role of both enzymatic and non-enzymatic processes and luminal and mucosal events in the digestive process • Detail the mechanisms involved in the absorption of major food groups in the small intestine and discuss the phenomenon of malabsorption Intes6nal Wall Structure (Adapta6on for Diges6on and Absorp6on) SURFACE AREA SECRETIONS MOTILITY DUODENUM Add secretions JEJUNUM digest/absorb ILEUM specialised absorption Folds, Villi and Microvilli Structure Matches Function in The Small Intestine Surface area for digestion/absorption masssively increased by folding of mucosa; -Plicae Circulari -Villous Units -Microvillous apical membrane of absorptive enterocyte Folding amplifies luminal surface area x600 Dietary Nutrients Water soluble Lipid soluble Carbohydrates Fats Proteins Vitamins (A,D,K,E) Vitamin C Vitamin B12 Trace Elements (Iron and calcium are good examples for integrated Physiology) N.B. In order to digest and absorb the intestine wall and associated glands must produce a large (>7 litres) volume of secretions which require to be reabsorbed to maintain vascular volume and pH Dietary Carbohydrate in Duodenum (Luminal Digestion) Salivary Gastric Intestinal Starch Amylose Amylopectin Amylase Disaccharides Sucrose Lactose Monosaccharides Glucose Galactose Fructose Insoluble material Dietary fibre N.B. Can be metabolised by colonic Bacteria to produce SCFAs Brush Border Hydrolysis and Absorption at Jejunal Mucosal Surface DIGESTION Membrane bound disaccharidases -Sucrase -Maltase -Lactase ABSORPTION -Glucose and Galactose (Secondary Active transport) -Fructose (GLUT 5) DELIVERY TO BLOOD -GLUT 2 N.B relevant to cholera treatment Protein Digestion = essential amino acids Not all amino acids can be de novo synthesised in body and so must be provided in the diet Gastric and Duodenal Proteolysis STOMACH Chief cells /Parietal cells Pepsin Dietary protein Large peptides Free neutral amino acids DUODENUM Generation of Peptides and Free AA’s Digestion products are amino acids and di/tri-peptides Brush border aminopeptidases derive amino acids for sodium coupled transport Short peptides can be taken up via peptide/proton symport and hydrolysed intracellularly Peptide Absorption lumen blood -For nutrient uptake, note the importance of the Na+ gradient -Component of the resting membrane potential (RMP) -N.B. Membrane potential not only important for excitable cell function! Classes of Dietary Lipid • • • • Long chain triglycerides Phospholipids Sterols Cholesterols (endogenous production 4>10 fold higher than dietary intake!) • Fat soluble vitamins Lipid Diges6on 1 Triglycerides (TAG) (Lingual, gastric and pancreatic lipases) Free fatty acids (FFA) Diglycerides (DAG) Monoglycerides (MAG) Fat Diges6on and Bile Flow Lipid droplets TAG Gastric lipase Duodenal CCK release FFA + + +++ Gall bladder contraction Pancreatic lipase and bile acid in small Intestinal lumen Acinar cell secretion More info in next lecture Lipase Activity In The Small Intestine N.B Requires colipase co-factor activity for function in bile acid coated lipid droplets Role of Micelle Forma6on • FFAs/monoglycerides are quite water soluble • However, some vitamins and other lipid moieties remain insoluble • This prevents approximation to enterocyte for absorption • Carriage in mixed micelles allows solubilisation and transport to apical membrane of enterocyte Intracellular Processing of Lipid in the Enterocyte Absorbed lipid Intracellular fatty acid binding proteins sER Re-esterification Golgi Apolipoprotein coating Chylomicron exocytosis at basolateral membrane -lymphatic system-systemic circuit-lipolysis-clearance Water soluble Vitamin Uptake • Vitamin C-‐ Sodium-‐Vitamin C co-‐transporter • Vitamin B12-‐Intrinsic factor-‐Ileal VitB12 transporter Vitamin B12 Absorption Clinical Correlate Pernicious Anaemia Destination of Absorbed Materials TAGs Via lymphatics And thoracic duct Glucose Amino acids SCFAs Soluble vitamins Malabsorp6on & Deficiencies • Transit )me (infec)ons, IBS) • Exocrine pancrea)c insufficiency (CF, see next lecture) • Gallbladder disease (gallstones) • Inflammatory damage to mucosa (IBD) • Resec)on induced deficiencies (Crohn’s Disease) • Bacterial overgrowth and deple)on of nutrient (Crohn’s Disease) Small intestinal motility in the fed state Purpose: Mixing of chyme with intestinal secretions Propulsion aborally • Two steps forward,one back • Gradual aboral propulsion of chyme • Time permitted for absorption to occur • Superimpose with peristaltic contractions Segmenta6on and Peristalsis 1. Segmentation (local back and forth mixing) 2. Peristalsis (aboral) of circular muscle Peristaltic Propulsion and Muscle Dynamics Food bolus activates afferent sensory neurones (mechanoreceptors) which, via inter-neurones affect the output of intrinsic enteric motor neurones. This consequently modulates muscle contraction PROXIMAL: CIRCULAR MUSCLE SHORTENS, LONGTIDUDINAL MUSCLE RELAXES DISTAL:LONGTIDUDINAL MUSCLE SHORTENS, CIRCULAR MUSCLE RELAXES Fasted Motility Patterns INTESTINAL MIGRATORY MOTOR COMPLEX PROPAGATION MOTILIN REGULATED Ileus • • • • • Temporary or permanent inhibi)on of mo)lity Func)onal obstruc)on Obstruc)ve symptoms, malabsorp)on Commonly induced by abdominal surgery Nil by mouth un)l mo)lity returns N.B. Make a conceptual link between ileus and gastroparesis in terms of neuropathy Your Learning from Today Should focus on being able to; • Describe how intestinal motility patterns contribute to digestion and absorption • Link enzymatic and non-enzymatic processes and luminal and mucosal events in the digestive process • Detail the mechanisms involved in the absorption of major food groups in the small intestine • Demonstrate an understanding of how various pathologies can cause malabsorption and nutritional deficiency