• 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 GASTROINTESTINAL TRACT Mechanical and chemical processing of food Absorption and excretion of products Protection of internal environment (toxins, microbes…) GIT motility – mainly nervous control Secretion in GIT – mainly humoral control Transport mechanisms, liver function + PARASYMPATICUS (preganglionic cholinergic fibres) n.VII, n.IX, n.X, nn.pelvici (S2-S4) - SYMPATICUS (postganglionic adrenergic fibres) Th5-L2 (tonus and motility –) (vasoconstriction) (musc.mucosae, sphincters +) Motility, secretion, digestion, absorption, storing, excretion 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 ENTERIC NERVOUS SYSTEM (plexuses + endings of sympathetic and parasympathetic nervous system + other GIT neurons) Local (short) reflexes Control of: •GIT motility •GIT secretion •GIT vasomotor control Mediators and modulators: Ach, peptides and bioactive amines Ach, VIP, NOR, DOPA, serotonin, histamine, AT II, PG somatostatin, enkephalin, GABA, TRH, neuropeptide Y, substance P secretin, GIP, glucagon, gastrin, CCK, G-releasing peptide (Secretin group) (Gastrin group) Chemoreceptors, mechanoreceptors, thermoreceptors… (mucosa, musc. externa) Central reflexes Continuous tonus of S, PS FORWARD SIGNALS : SPEED UP, OPEN THE WAY BACKWARD SIGNALS: SLOW DOWN, CLOSE THE WAY GIT INNERVATION ENTERIC NERVOUS SYSTEM SYMPATICUS PARASYMPATICUS Local (short) reflex Central (long) reflex CNS +- mechanoreceptors chemoreceptors osmoreceptors thermoreceptors Vagovagal reflex ELECTROPHYSIOLOGY OF GI SMOOTH MUSCLE Resting potential: from - 40 to - 80mV ( gNa : gK) Lower activity of Na+/K+-ATPase Slow waves (oscillation of rest.MP) 3 (stom.) – 12(duod.)/min – basal electric rhythm Spike (AP) low voltage, depolarisation – Na+ and Ca2+, 1-10/sec Pacemaker cells in ENS automacy Variability neurohumoural regulation Innervations: nexus, innervations of circular muscle >> longitudinal muscle No motor endplate Ach, ENS, exceptions 0 -40 ICa direct activation of contraction (binding to calmodulin) 0 -40 5s Basal muscle tonus, basal rhythm (time summation) Spike -10 -20ms F E 5s Contractions triggered by slow waves (no AP!!!) F E Stomach Modulation of slow waves – amplitude (less by frequency) 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. SWALLOWING•Oral phase (voluntary) •Pharyngeal phase (reflex)<1s •Oesophageal phase (peristaltic) Food – chewing (voluntary and reflex) Saliva (1.5 litres / day) Frequency of swallowing – approx. 600x / day SWALLOWING CENTRE (oblongata, pons) X., …. REC (touch) Plexus myentericus Parasympathetic NS (VIP) Sympathetic NS V.X. Proximal sphincter (somat.motoneurons – X. striated muscles) Peristalsis – 3-5cm/s (primary - swallowing centre, secondary - ENS) Mouth Pharynx Centr. Junction Distal sphincter (cardia) (smooth muscle) – opened by secondary peristalsis Local reflexes Reflex relaxation of cardia (PS) Achalasia (cardiospasmus) Gastrooesophageal reflux IX. Oesophagus GASTRIC MOTILITY Reflex relaxation of distal oesophageal sphincter Receptive relaxation of fundus and body (X. – VIP) (Laplace: P = T . R) Pacemaker zone (3/min) Motoric gradient (F <<< A) Chyme stratification 1,5 l A B F D P C O Migrating myoelectric complex („hungry“ contractions) Reservoir Mixer (3/min) 1-2 hour: rest 10-20 min: activity, during fasting is stronger PYLORUS = sphincter ??? Common ENS with bulbus duodeni Smooth muscle sympaticus +++, n.X. --- (VIP) N. vagus + Plexus cealicus prominent circular layer 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 A/D reciprocal activity - VOMITING (PROTECTION) HIGHER CENTRES CENTRE FOR VOMITING IN MEDULLA OBLONGATA Afferentation: X., symp. Taste Smell Vision Labyrinths Central Mechanoreceptors of pharynx Peripheral Mechano- a chemoreceptors of stomach and duodenum Peripheral Trigger zone – bottom of 4.chamber Area postrema – circ. ventric. organisation •Antiperistalsis in jejunum and duodenum •Relaxation of pylorus and antrum •Contractions of diaphragm (increased intraabdominal pressure) •Inverse Valsalva manoeuvre (decreased intrathoracal pressure) •Contractions of pylorus and antrum •Relaxation of cardia •Relaxation of upper pharyngeal sphincter Emetics: central peripheral Antiemetics MOTILITY OF SMALL INTESTINE •Slow waves – approx.11-13/min in duodenum, 8-9 - ileum •„Minute“ rhythm (jejunum) – salvos approx. every minute •Hour rhythm (migrating myoelectric complex) hours 100% 1 2 3 fasting food 5 10 12/min duodenum jejunum ileum Distance from pylorus in vitro 7/min in situ Segmentation >>> peristalsis (up to 10 cm) LAW OF INTESTINE INTESTINO-INTESTINAL REFLEX GASTRO-ILEAL R. GASTRO-COLIC R. MOTILITY OF COLON • Slow waves with frequency 4 – 6 / min •Segmentation = haustra; 5-10 cm/hour– pendulum movements •Mass peristalsis; 1-3/day – „sweeping“ •Reverse peristalsis – in proximal colon („delay“ – absorption of water and ions) •Control of anal sphincter: int. – reflex, ext. – voluntary (+reflex) •Defecation: abdominal muscles +++, muscles of pelvic bottom – •Reflex: colono-colonic, gastro-colic •Parasympaticus + (X. till FL) •Sympaticus – (L2 – L4) 4-8 hod 12-72 hod VIC PS. SAKR. PARAS Int. Ext. sfinkter GI REFLEXES SYMP. Voluntary control Voluntary control pharynx oesophagus stomach small intestine colon rectum A Continuous tonus S, PS 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 GI REFLEXES Voluntary control Voluntary control F E G D J I C A T D R Superposed on basal tonus PS and S (sphincters S PS) swallowing r. Receptive relaxation of fundus (X.) Intestino-intestinal r. (distension) R. lower oesophagus Pyloric r. (X.) Colono-colonic r. Colono-ileal r. (+) R. of internal anal sphincter Enterogastric r. (chemoreceptors) 10´´ 2-3 hrs 2-4 hrs 10-20 hrs bolus + PS and S - - - - - - - - + + Gastro-colic r. Gastro-ileal r. Local r. Reciprocal function of long. and circ. muscle Innervations of only circ. muscle Motility is increased: •CCK •Substance P •Gastrin •Mass peristaltic movements •Haustra, segmentation •Reverse peristalsis