Compendium of Physiology, Marie Nováková1 GASTROINTESTINAL TRACT Introduction Compendium of Physiology, Marie Nováková2 • The GIT is a tube, specialized along its length for the sequential processing of food • Assimilation of substrates from food requires both digestion and absorption • Digestion requires enzymes, which are secreted in various parts of GIT • Food ingestion triggers complex whole-body responses (endocrine, neural, paracrine) • GIT plays an important role also in homeostasis (absorption vs. excretion, izovolemia, izoionia, etc.) and immunity THM Compendium of Physiology, Marie Nováková3 serosis (adventicia) epithelium muscularis mucosae longitudinal layer circular layer plexus submucosus (Meissner) plexus myentericus (Auerbach) ENS muscularisexterna submucosa Modified according to: J. Švíglerová: Fyziologie gastrointestinálního traktu, LF UK Plzeň, 2012 coordination of motility secretion and absorption + glands + lymphatic tissue Circular muscle layer: inhibitory fibers, contraction – gut is longer and smaller in diameter Longitudinal muscle layer : no inhibitory fibers, contraction – gut is shorter and bigger in diameter Compendium of Physiology, Marie Nováková4 GIT INNERVATION ENTERIC NERVOUS SYSTEM SYMPATICUS PARASYMPATICUS Local (short) reflex Central (long) reflex CNS +- mechanoreceptors chemoreceptors osmoreceptors thermoreceptors Vago-vagal reflex Compendium of Physiology, Marie Nováková5 GIT MOTILITY CONTRACTIONS tonic (stomach, colon) rhythmic MOVEMENTS propulsive (peristalsis, myenteric reflex) mixing Receptive relaxation. These contractions and movements are responsible for churning, peristalsis and reservoir action in GIT. Compendium of Physiology, Marie Nováková6 The regulation of GI function results from an interplay of neural and hormonal influences on effector cells that have intrinsic activities. The GI tract is innervated by the ANS, which is composed of nerves that are extrinsic and nerves that are intrinsic to the tract. Extrinsic nerves are distributed to the GI tract through both parasympathetic and sympathetic pathways. Intrinsic nerves are grouped into several nerve plexuses, of which the myenteric and submucosal plexuses are the most prominent. Nerves in the plexuses receive input from receptors within the GI tract and from extrinsic nerves. This input can be integrated within the intrinsic nerves such that coordinated activities can be effected. ACh is one of the major excitatory neurotransmitters, and NO and VIP are two of the major inhibitory neurotransmitters at effector cells. Serotonin and somatostatin are two important neurotransmitters of intrinsic interneurons. THM Compendium of Physiology, Marie Nováková7 THM Striated muscle comprises the musculature of the pharynx, the oral half of the esophagus, and the external anal sphincter. Smooth muscle makes up the musculature of the rest of the GI tract. Adjacent smooth muscle cells are electrically coupled to one another and contract synchronously when stimulated. Some smooth muscles contract tonically, whereas others contract phasically. In phasically active muscle, stimulation induces a rise in intracellular Ca2+, which in turn induces phosphorylation of the 20,000-dalton light chain of myosin. ATP is split, and the muscle contracts as the phosphorylated myosin (myosin P) interacts with actin. Ca2+ levels fall, myosin is dephosphorylated, and relaxation occurs. In tonically active muscles, contraction can be maintained at low levels of phosphorylation and ATP utilization. Periodic membrane depolarizations and repolarizations, called slow waves, are major determinants of the phasic nature of contraction. Slow wave activity results from ionic currents initiated through the interactions of the ICCs with the smooth muscle cells. Compendium of Physiology, Marie Nováková8 GI REFLEXES SYMP. Voluntary control Voluntary control pharynx oesophagus stomach small intestine colon rectum A Continuous tonus S, PS BALANCE - DYSBALANCE a1 10´´ 2-3 hrs 2-4 hrs 10-20 hrs Signalling: relax, move on! slow down! PARASYMP. VI P Achswallowing lower oesophagus local pyloric gastroileal enterogastric internal anal sphincter gastrocolic receptive relaxation of fundus colonoileal colonocolonic Compendium of Physiology, Marie Nováková9 SECRETION •Salivary glands •Gastric glands •Small glands of esophagus and intestine •Exocrine pancreas •Liver STIMULATION OF SECRETION 1. Neurocrine 2. Endocrine 3. Paracrine • Lubrication of food • Swallowing •Articulation • Mechanical protection of GIT • Chemical protection of GIT • Enzymes • Immune function(s) Common features of secretion: water, ions, HCO3-, mucin Compendium of Physiology, Marie Nováková10 SECRETORY FUNCTION OF GIT AND ITS HUMORAL CONTROL HCl G Ach H peptides H2 receptors (mast cells) GRP subst.P (axon. reflex) (motility) ENS VIP GIP glucose lipids INSULIN (b-cells, endocrine pancreas) enzymes HCO3 - CCK,GIP peptides AA, FA HCl SS (d-cells) motility electrolytes H2O exocrine pancreas * CEPHALIC PHASE (taste, smell…) * GASTRIC PHASE (Ach, H, S, G, CCK stimulation of production INTESTINAL PHASE OF FOOD INTAKE (SECRETION) * mediated by gastrin Compendium of Physiology, Marie Nováková11 The functions of the GI tract are regulated by mediators acting as hormones (endocrine), paracrine, or neurocrine substances. Two chemically related families of peptides are responsible for much of the regulation of GI function. These are gastrin/CCK peptides and a second group containing secretin, VIP, GIP, and glucagon. The GI hormones are located in endocrine cells scattered throughout the mucosa and released by chemicals in food, neural activity, or mechanical distention. The GI peptides have many pharmacologic actions, but only a few of these are physiologically significant. Gastrin, CCK, secretin, GIP, and motilin are important GI hormones. Somatostatin and histamine have important functions as paracrine agents. Neurocrines VIP, bombesin (or GRP), and the enkephalins are released from nerves and mediate many important functions of the digestive tract. 12 Compendium of Physiology, Marie Nováková EMPTYING OF STOMACH CNS PACEMAKER CONTRACTIONS OF ANTRUM CONTRACTIONS OF PYLORUS DUODENUM: pH < 3,5 Lipids Peptides secretin CCK, GIP gastrin Oddi gastrin chemoreceptors osmoreceptors slowed emptying (entorogastric reflex) Symp Paras FA, H+, osmotically active substances, tryptofan Modulation: •Peristaltic movements •Continuous tonus (summation of contractions of antrum – relaxation) pressure, distension, pH, pain VIP Ach SYMP. x. Coordination of contractions of antrum and relaxation of bulbus Duodenogastric reflux - 13 Compendium of Physiology, Marie Nováková SECRETION OF GASTRIC JUICE Mucin (pH 7-8) Gastric pits (glands) pH 2, high concentration of K+ (vomiting) a ClSurface epithelia Lamina propria Mucose cells of neck Parietal cells (HCl, intrinsic factor) Main cells - zymogenic granula (pepsinogen) G cells (gastrin) Area: •Subcardial (mucin) •Fundus (HCl) •Pyloric (mucin, G) Gastric juice: water, salts, HCl, pepsin, intrinsic factor, mucin Production increases after meal Higher secretion – lower pH, lower secretion – more Na+, (always more K+ than in plasma) pepsinogen pepsin HCl Gastric mucose barrier Stimulation of a-receptors – decreased secretion of HCO3 Gastric ulcers NSA – decreased secretion of HCO3 - and mucine Ach, G, CCK, secretin + (individual number!!!) 14 Compendium of Physiology, Marie Nováková HCl PRODUCTION IN PARIETAL CELL AP SP SP H2O+CO2=HCO3-+H+ (CA) Cl- Cl- Na+ Na+ K+ K+ H+ K+ Cl- HCl Tubulovesicular system (rest, 10% – secretion) Pepsinogen (together with HCl) Pepsin (protease) Proton pump Basolateral membrane Apical membrane blood „alkaline tide“ (1 000 000 : 1 ) 15 Compendium of Physiology, Marie Nováková CONTROL OF HCl PRODUCTION IN PARIETAL CELL H+K+ (cholinergic fibres) Ach H G (antrum, duodenum) (mast cells) PK IP3 cAMP ? Ca2+ Potentiation of stimulation!!! muscarin rec H2 PGE, somatostatin – inhibition of HCl secretion 16 Compendium of Physiology, Marie Nováková Component Liver Bile Gallbladder Bile Na+ (mmol/L) 150 300 K+ (mmol/L) 4.5 10 Ca2+ (mmol/L) 4 20 Cl− (mmol/L) 80 5 Bile salts (mmol/L) 30 315 pH 7.4 6.5 Cholesterol (mg/100 mL) 110 600 Bilirubin (mg/100 mL) 100 1000 Compendium of Physiology, Marie Nováková17 • Both active and passive mechanisms participate in GIT absorption • Both paracellular and transcellular movements are involved • Absorption area is enlarged by folds, villi and microvilli (mostly in small intestine) • Absorption of water and electrolytes occurs in both small and large intestine, absorption of nutrients occurs only in small intestine • Small intestine absorbs water and electrolytes and secretes HCO3 -, large intestine absorbs water and electrolytes and secretes potassium and HCO3 • Water „follows“ electrolytes, eventually is „drafted“ by osmotically active substances • Numerous absorption mechanisms depend on sodium gradient THM 18 Compendium of Physiology, Marie Nováková DIGESTION AND ABSORPTION OF LIPIDS Triglycerides (TAG) Sterols (-esters) Phospholipids (lecithin) LIPID DROPS EMULSIFICATION (+lecithin, +monoglycides) Ø 1mm BILE ACIDS SALTS DEESTHERIFICATION PANCREATIC LIPASE (colipase) CHOLESTEROL-ESTHERASE PHOSPHOLIPASE A2 ENTERIC LIPASE Glycerol FA MAG CH LFL MICELLES Ø 5nm, 20-30 molecules polar stratification, hydrophilic disintegration of micelles TAG unstirred water layer 200-500mm bile acids resorption (diffusion) reesterification (FA >12c, in endopl.retic.) CHE PL PROT. EXOCYTOSIS CHYLOMICRA Ø 10nm LYMPHATIC CIRCULATION NEFA (<12c) GLYCEROL capillaries (fenestration) Na+ DIGESTION AND ABSORPTION OF 19 Compendium of Physiology, Marie Nováková REST OF CHYME 1. Cellulose, collagen 2. Bile acids, epithelia, mucin, leucocytes • Bacteria fermenting: fibre (pectin, cellulose) – lactate, alcohol, acetate, CO2, methane • Bacteria putrescent: residues of AA – NH3, SH2, phenol, indole, solatol (carcinogenic) Production of vitamin K and vitamins of B group, HOWEVER cannot be absorbed here NUTRITION PASSAGE EUMICROBIA 20 Compendium of Physiology, Marie Nováková FEELING OF SATIETY FOOD INTAKE Chewing movements Receptors in nose, mouth, oesophagus, intestine Mechanoreceptors of stomach GIT chemoreceptor s SATIETY PRERESORPTIVE FEEDING RESORPTIVE FEEDING Central gluco- thermo- lipo- receptors COMPILING THE INFORMATION IN CNS (CENTER OF SATIETY = ncl. ventromedial in hypothalamus) 21 Compendium of Physiology, Marie Nováková FEELING OF HUNGER LACK OF FOOD Hungry contractions of stomach Decreased glucose availability Decreased heat production Changes of lipid metabolism MechanoreceptorsGlucoreceptorsInternal termoreceptors (hypothalamus) „Liporeceptors“ HUNGER SHORT-TERMED REGULATION LONG-TERMED REGULATION Compensation of dietary mistakes 22 Compendium of Physiology, Marie Nováková Hormone Source Site of Action Effect Insulin Pancreatic beta cells Hypothalamus ↓Appetite ↑Metabolism Leptin Fat cellsEndocrine cells of the stomach Hypothalamus ↓NPY, AgRP ↑POMC Vagal afferents ↓Appetite ↑Metabolism ↓Ghrelin release CCK I cells of the duodenum Vagal afferents ↓Appetite ↓Gastric emptying PYY L cells of the ileum and colon Hypothalamus ↓NPY, AgRP ↑POMC Stomach ↓Appetite ↑Metabolism ↓Gastric emptying Ghrelin Endocrine cells of the stomach, hypothalamus, large and small intestines Hypothalamus ↑NPY, AgRP Vagal afferents ↑Appetite ↓Metabolism ↓Leptin release ↓, Inhibits; ↑, stimulates AgRP, agouti-related peptide; CCK, cholecystokinin; NPY, neuropeptide Y; POMC, proopiomelanocortin; PYY, peptide YY.