Compendium of Physiology1 GASTROINTESTINAL TRACT Introduction Compendium of Physiology2 • 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 Physiology3 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 Physiology4 GIT INNERVATION ENTERIC NERVOUS SYSTEM SYMPATICUS PARASYMPATICUS Local (short) reflex Central (long) reflex CNS +- mechanoreceptors chemoreceptors osmoreceptors thermoreceptors Vago-vagal reflex Compendium of Physiology5 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 Physiology6 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 Physiology7 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 Physiology8 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 Physiology9 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 Physiology10 SECRETION 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 Physiology11 • 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 Compendium of Physiology12 The functions of the GI tract are regulated by mediators acting as hormones (endocrines), paracrines, or neurocrines. 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 physical 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.