digestivephysiology! - mt. san antonio collegefaculty.mtsac.edu/mpresch/36_lecture_files_unit_4/23...
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DIGESTIVE PHYSIOLOGY
Physiology Unit 4
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Func1ons
• Mo1lity – Inges1on – Mas1ca1on – Deglu11on – Peristalsis
• Secre1on – 7 liters/day! – Exocrine/endocrine
• Diges1on • Absorp1on
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Diges1on of Carbohydrates
• Average intake is 250-‐300 g/day
• Amylase • Salivary, pancrea1c • Products: maltose, short chains of glucose
• Brush border enzymes • Products: glucose, galactose, fructose
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Absorp1on of Carbohydrates • Luminal absorp1on • Glucose/galactose cotransport with Na+ into enterocytes
• Fructose facilitated diffusion into enterocytes
• Basolateral absorp1on • Monosaccharides enter blood via facilitated diffusion
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Diges1on of Proteins • Require 40-‐50g of protein/day
– Supply essen1al amino acids – We consume 70-‐90 g/day
• Stomach – Pepsin
• Products are short chain polypep1des • Small intes1nes from pancreas • Trypsin, chymotrypsin
• Products are short chain polypep1des • CarboxypepAdase
• Products are free amino acids • Small Intes1nes from brush border enzymes • AminopepAdase
• Products are free amino acids
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Absorp1on of Proteins
• Luminal absorp1on – Free amino acids enter enterocytes by counter-‐transport with Na+
– Short polypep1des (2 or 3 amino acids) enter enterocytes by counter-‐transport of H+
• Basolateral absorp1on – Free amino acids enter blood by facilitated diffusion
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Diges1on of Fat
• Daily intake 70-‐100 g/day (mostly triglycerides)
• Emulsifica1on by bile salts • Pancrea1c lipase – Monoglyceride + 2 fa[y acids
• Forma1on of micelles by bile salts
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Absorp1on of Fat • Luminal Absorp1on – Monoglycerides and fa[y acids enter enterocytes by diffusion
• Basolateral absorp1on into lacteals – Exocytosis of chylomicrons
– Chylomicrons contain triglycerides, phospholipids, cholesterol, fat-‐soluble vitamins
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Lipid Transport
• From lympha1cs to thoracic duct • Free fa[y acids and glycerol into 1ssues • Le]overs to liver – Remnant par1cles contain cholesterol – Combined with apoproteins (lipid binding protein) to produce VLDL’s – Deliver triglycerides to other organs
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Lipoproteins • Lipid & protein complexes – Transport cholesterol & triglycerides in blood – Protein allows hydrophobic lipids to remain in suspension
• Five classes: Based on density, molecular weight, size, chemical composi1on
• Chylomicrons • VLDL • IDL • LDL
– High levels associated with increased risk CVD • HDL
– Low levels associated with increased risk of CVD – Best profile = high HDL, low LDL
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Absorp1on of Vitamins
• Fat-‐soluble vitamins – Vitamins A, D, E, K – Exocytosis in chylomicrons
• Water-‐soluble vitamins – Vitamins B, C – Absorbed by diffusion or mediated transport
• Vitamin B12 – Binds to intrinsic factor – Endocytosis (in ileum) into enterocytes
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Absorp1on of Water and Minerals
• Water is most abundant substance in chyme – 8 L of ingested and secreted water enter the small intes1ne each day!
– 1.5 L make it to the large intes1ne – 80% absorbed in small intes1ne
• Minerals – Na+ – HCO3
-‐
– Cl-‐ – Small concentra1ons K+, Mg2+, Ca2+, Fe3+, Zn2+, I-‐
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Regula1on of Gastrointes1nal Processes
• Regula1on of the condi1ons of the lumen of the tract (the outside of the body)
• Governed by the volume and composi1on of the luminal contents rather than the nutri1onal state of the body (the inside of the body)
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Basic Principles
1. Disten1on of the lumen wall (volume of contents)
2. Chyme osmolarity (solute concentra1on) 3. Chyme acidity 4. Chyme concentra1ons – Monosaccharides – Fa[y acids – Pep1des – Amino acids
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Neural Regula1on
• Enteric Nervous System (ENS)
• Myenteric plexus – Influences smooth muscle ac1vity
• Submucosal plexus – Influences secretory ac1vity
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Neural Regula1on
• Neural ac1vity in one plexus influences the ac1vity of the other
• S1mula1on at one point in the plexus can lead to impulses that are conducted both up and down the tract
• Neural reflexes independent of CNS • CNS can influence mo1lity and secre1on of the tract
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Hormonal Regula1on
• Hormones that control the GI system are secreted by cells sca[ered throughout the epithelium of the stomach and small intes1ne
• One surface of each endocrine cell is exposed to the lumen of the tract
• Chemicals in chyme s1mulate the cell to secrete its hormones from the opposite side of the cell into the blood
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Hormonal Regula1ons
• Each hormone par1cipates in a feedback control system that regulates some aspect of the the luminal environment
• Most GI hormones affect more than one type of target cell
• Best understood pep1de GI Hormones – Gastrin – Cholecystokinin (CCK) – Secre1n – Glucose-‐dependent insulinotropic pep1de (GIP)
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Gastrin
• Endocrine cell loca1on: – G cells of the antrum of stomach
• S1mulus for release – Protein in stomach – Parasympathe1c nervous system
• Ac1ons – S1mulates
• Stomach: (+) acid secre1on and mo1lity • Pancreas: (+) enzyme secre1ons • Intes1nes: (+) mo1lity in ileum and colon
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Cholecystokinin (CCK)
• Endocrine cell loca1on: small intes1ne • S1mulus for release – amino acids, fa[y acids in small intes1ne
• Ac1ons – S1mulates
• Pancreas: (+) enzyme secre1on • Gall bladder: (+) contrac1on
– Poten1ates • Pancreas: (+) bicarbonate secre1on • Liver: (+) bicarbonate secre1on
– Inhibits • Stomach: (-‐) acid secre1on, gastric mo1lity
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Secre1n
• Endocrine cell loca1on: small intes1ne • S1mulus for release – Acid in small intes1ne
• Ac1ons • S1mulates
• Pancreas: (+) bicarbonate secre1on • Liver: (+) bicarbonate secre1on
• Inhibits • Stomach: acid secre1on, gastric mo1lity
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Glucose-‐Dependent Insulinotropic Pep1de
• Endocrine cell loca1on: small intes1ne • S1mulus for release – glucose, fat in the small intes1ne
• Ac1ons – S1mulates
• Pancreas: (+) insulin secre1on
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Stomach
• Func1on – Ini1ates protein diges1on
– Kills bacteria – Intrinsic factor
• Secreted by parietal cells • Needed for Vitamin B12 absorp1on in ileum
– Absorp1on • Water • Alcohol • Aspirin
• 3 func1ons of pH in stomach – Denature ingested protein
– Convert pepsinogen to pepsin • Digests proteins
– Destroy bacteria
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Gastric Glands • Goblet cells
– mucus • Parietal cells
– HCl – Intrinsic factor
• Chief cells – Pepsinogen
• Argentaffin cells – Serotonin – Regulate intes1nal movements
• G cells – Gastrin
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Pancreas • Pancrea1c acini – Pancrea1c juice
• water • bicarbonate • diges1ve enzymes
– Ac1va1on by enterokinase
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Pancrea1c Enzymes
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Energy Regula1on by Islets of Langerhans
• Three cell types produce pep1de hormones – Beta cells: insulin
• S1mulates cellular uptake of glucose • In liver, ac1vates glycogenesis • S1mulates lipid synthesis • S1mulates cellular uptake of amino acids
– Alpha cells: glucagon • Encourages libera1on of reserves • Prevents glucose uptake by liver, muscle, adipose
– Delta cells: somatosta1n • Not sure
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Regula1on of Insulin and Glucagon Secre1on
• Effects of glucose and amino acids – Increase in plasma glucose
• S1mulates b cells • Inhibits a cells
– Decrease in plasma glucose • decreased insulin produc1on • increased glucagon produc1on
– Meals high in protein • s1mulates insulin
– Meals high in protein and low in carbohydrate • s1mulates glucagon • result: increase in blood glucose and increased incorpora1on of amino acids into 1ssues
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Regula1on of Insulin and Glucagon Secre1on
• Effects of autonomic nerves – Parasympathe1c ac1va1on
• increased insulin – Sympathe1c ac1va1on
• increased glucagon, inhibits insulin • stress hyperglycemia = glucagon + epinephrine
– Goal: Keep blood glucose between – 50-‐170mg/100ml
• higher = glycosila1on; lower = brain damage
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Func1ons of the Liver
• Exocrine • Endocrine • Clopng func1ons • Synthesizes plasma proteins • Organic metabolism • Cholesterol metabolism • Excretory and degrada1ve func1ons
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Exocrine & Endocrine Func1ons
Exocrine FuncBons • Synthesis and secre1on of
bile salts – 250-‐1500ml/day
• Adds bicarbonate rich solu1on to bile
Endocrine FuncBons • Secretes IGF-‐1
– promotes cell division
• Forms T3 from T4 • Secretes angiotensinogen
– Increases BP – S1mulates aldosterone
secre1on
• Metabolizes hormones • Secretes immune cytokines
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Clopng and Plasma Proteins
• Produces – Prothrombin – Fibrinogen – Plasma albumin
• Regulates blood volume
– Acute phase proteins – Binding proteins – Lipoproteins
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Organic Metabolism
• Converts plasma glucose to glycogen and triglycerides
• Converts amino acids to fa[y acids • Produces triglycerides and secretes them as lipoproteins
• Gluconeogeneisis and glycogenolysis • Converts fa[y acids into ketones • Produces urea
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Cholesterol Metabolism/Excretory & Degrada1ve Func1ons
• Synthesizes cholesterol • Converts plasma cholesterol into bile salts – Bile salts needed for vitamin K absorp1on
• Excretes toxins via bile • Destroys old erythrocytes • …and lots, lots more!
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Absorp1ve State
• High insulin and low glucagon • Insulin – cellular uptake of glucose – uptake & incorpora1on of amino acids – conversion of glucose to glycogen – addi1onal glucose to fat – incorpora1on of glucose into adipose 1ssue – suppression of liver glycogenolysis
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Postabsorp1ve State
• Low insulin, high glucagon – low insulin encourages movement of amino acids out of the muscles
• Cor1sol -‐-‐ s1mulates produc1on of enzymes to convert pyruvic acid to glucose
• Glucagon – s1mulates glycogenolysis – s1mulates gluconeogenesis – s1mulates lipolysis – s1mulates ketogenesis