Gastric Function Introduction PDF - RCSI 2024

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Gastric Function Class Year 2 Course Module GIHEP Title Gastric Function Lecturer Simon Furney Date 11/09/24 Learning Outcomes Explain the nervous control of the...

RCSI Royal College of Surgeons in Ireland Coláiste Ríoga na Máinleá in Éirinn Gastric Function Class Year 2 Course Module GIHEP Title Gastric Function Lecturer Simon Furney Date 11/09/24 Learning Outcomes Explain the nervous control of the GIT and how enteric reflexes and hormonal influences affect gastrointestinal function Explain the initiation of slow waves and describe the three main motor functions of the stomach: storage, mixing, emptying Explain the role that the stomach plays play in digestion, describe secretions of the stomach and name important substances absorbed by the stomach Describe the mediators of gastric acid secretion, biochemical pathways within the oxyntic cell and the main factors that inhibit gastric acid secretion List the main causes of gastritis and peptic ulcer disease Outline of Lecture 1) Control of the GI Tract a. intrinsic and extrinsic control 2) Motor function a. proximal and distal stomach 3) Secretory function a. gastric juice and gastric glands b. oxyntic or parietal cell c. dysregulation of acid secretion 4) Absorption from the stomach a. structural problems to absorption Control of the GI Tract Control of the GI tract occurs via a combination of neural and humoral factors Intrinsic control by the enteric nervous system (ENS) Extrinsic control by autonomic nervous system (ANS) Intrinsic & extrinsic control GI hormones – more on these in the GI hormones lecture Intrinsic smooth muscle action Enteric Nervous System (ENS) The ENS is contained entirely within the GI tract – has three types of neurons Sensory neurons, receive information from the mucosa – such as muscle stretch and chemical nature of contents Motor neurons control motility and secretions – acts on smooth muscle and endocrine/exocrine cells Inter-neurons relay information from sensory to motor neurons Enteric Nervous System (ENS) The ENS is arranged in two plexuses along the length of the digestive tract – they are innervated by ANS and sensory fibres The Plexus of Auerbach lying between the longitudinal and circular smooth muscle controls motor function – also called the myenteric plexus Meissner’s Plexus controls secretion of the mucosa – also called the submucosal plexus Some fibres are excitatory (ACh) while others are inhibitory (releasing NO / vasoactive intestinal peptide (VIP)) Extrinsic Control of GI Tract Extrinsic control via the autonomic nervous system Parasympathetic Nervous System – vagus (CN X, upper GI) and pelvic nerve (lower GI) – sensory afferents & pre-ganglionic efferents innervate plexuses – acetylcholine (ACh) increases contractions and secretions – physiological antagonism of NA - “rest and digest” Sympathetic Nervous System – arises from the prevertebral ganglion – post-ganglionic efferent fibres synapses with both plexuses, also direct innervation of GIT smooth muscle/glands – primarily noradrenaline, decrease motility & secretions Extrinsic innervation of the GI tract, consisting of the parasympathetic (A) and sympathetic (B) subdivisions of the autonomic nervous system. The integration of the extrinsic (parasympathetic and sympathetic) nervous system with the enteric (myenteric and submucosal plexuses) nervous system. The preganglionic fibers of the parasympathetic synapse with ganglion cells located in the enteric nervous system. Their cell bodies, in turn, send signals to smooth muscle, secretory, and endocrine cells. They also receive information from receptors located in the mucosa and in the smooth muscle that is relayed to higher centers via vagal afferents. This may result in vagovagal (long) reflexes. Postganglionic efferent fibers from the sympathetic ganglia innervate the elements of the enteric system, but they also innervate smooth muscle, blood vessels, and secretory cells directly. The enteric nervous system relays information up and down the length of the gastrointestinal tract, and this may result in short or intrinsic reflexes. Outline of Lecture 1) Control of the GI Tract a. intrinsic and extrinsic control 2) Motor function a. proximal and distal stomach 3) Secretory function a. gastric juice and gastric glands b. oxyntic or parietal cell c. dysregulation of acid secretion 4) Absorption from the stomach a. structural problems to absorption Smooth Muscle Slow Waves Waves of smooth muscle contraction are triggered by the Interstitial Cells of Cajal – between the circular and longitudinal smooth muscle Cycles of depolarisation that do not reach threshold – pass to the smooth muscle via gap junctions – require additional stimulation Occurs along the length of digestive tract – different frequencies at different points – duodenum fastest at about every 4-5 secs – ileum every 6-7 secs, stomach and colon every 20 secs Smooth Muscle Slow Waves Stimulated (via ACh etc) depolarisation 30 Membrane Potential (mV) 0 -30 AP ≈ -40 mV -60 -90 At rest Stimulated by SNS hyperpolarisation -120 5 10 15 20 25 30 35 40 (s)  The Stomach - Regions Secretory Motility Oesophagus Fundus Oesophagus Proximal stomach or orad Pyloric Pyloric sphincter sphincter Distal stomach or caudad Body Antrum Gastric Motor Function The stomach performs three mechanical functions These are: The (short term) storage of ingested food – the reservoir function The mixing of contents The emptying into intestines Receptive Relaxation Swallowing relaxes the lower oesophagus and proximal stomach – receptive relaxation This is a vagovagal reflex, relaxing the stomach so pressure remains stable despite the increased volume – may involve the release of NO Gastric accommodation and dilation of the proximal stomach also allows for an increased volume without increase in pressure – controlled by enteric nervous system – beyond certain volumes a marked increase in pressure  Volume vs. Pressure 80 absence of vagal nerve Pressure (cmH2O) 60 40 normal 20 200 400 600 800 1000 volume (ml) Mixing & Emptying The distal stomach is similar to small intestine and shows spontaneous or basal electrical rhythm Contractions start mid-stomach and spread distally The force and speed of contractions increase as they reach the pyloric sphincter/gastroduodenal junction The effect of this is contractions overtake contents – small amount of food emptied due to narrow pyloric sphincter – most is pushed back for the next wave (i.e. mixing)  Mixing & Emptying Motility 1 Oesophagus Proximal stomach or orad 2 Pacemaker 3 region 1 Pyloric sphincter 2 4 3 Spread of contraction 4 5 5 Distal stomach or caudad Factors Affect Contractions In the fasted state, stomach is quiescent – although depends on the phase (e.g. cephalic phase - Pavlov) In the fed state contractions are fairly continuous These are controlled by various neurohumoral and mechanical stimuli – mechanical stimuli such as distension – ACh (vagus) increases the number and force of contractions – hormones such as gastrin increase contractions – hormones such as secretin decrease contraction Emptying Emptying is due to coordinated contraction – peristaltic contractions in the stomach, relaxed pylorus and lack of contraction in duodenum Time spent in the stomach is dependent on composition – liquid empties quickly – solids have to be reduced in size so take longer in the stomach Composition of food entering the duodenum activates receptors leading to hormone release that alter gastric motility – properties such as acidic, lipid, osmotic pressure Outline of Lecture 1) Control of the GI Tract a. intrinsic and extrinsic control 2) Motor function a. proximal and distal stomach 3) Secretory function a. gastric juice and gastric glands b. oxyntic or parietal cell c. dysregulation of acid secretion 4) Absorption from the stomach a. structural problems to absorption Gastric Phases Cephalic phase – initiated by sight, smell or thoughts of food – release of gastrin into blood – secretion of mucous, HCl and pepsinogen Gastric phase – stretching of stomach activates stretch receptors – stimulation of peristalsis (mixing) and gastric emptying Intestinal phase – begins with activation of receptors in the small intestines – inhibition by Cholecystokinin (CCK) and secretin slows gastric emptying  The Stomach - Regions Secretory Motility Oesophagus Fundus Oesophagus Proximal stomach or orad Pyloric Pyloric sphincter sphincter Distal stomach or caudad Body Antrum Gastric Juice The stomach secretes ~1,500 ml/day of gastric juice This is predominantly water but also includes – HCl, HCO3-, other ions (Na+, K+), mucus, pepsin, intrinsic factor This also includes swallowed saliva and reflux duodenal fluids such as bile and pancreatic juice It is the gastric juice that mediates the digestion occurring in the stomach Gastric Digestion All digestion is the breaking of large macromolecules into smaller parts that are easier to absorb Carbohydrate digestion starts in the mouth with salivary amylase – which is largely inactivated by the acidic stomach Lipid digestion starts in the stomach by gastric lipase – activated by the low stomach pH Protein/peptide digestion also starts in the stomach by the enzyme pepsin /acid – also activated by the low pH from inactive precursor Gastric Glands Surface epithelial cells throughout stomach – secrete thick mucous with mucin HCO3- – lubricates and protects against low pH and enzymes Pyloric Glands in the antrum of the stomach – mostly mucous cells – Gastrin or G cells secrete gastrin peptide hormone released into the blood (endocrine) – also Delta or D-cells release somatostatin peptide hormone that has endocrine and paracrine actions Gastric Glands Oxyntic Glands are located in the fundus and body Oxyntic or Parietal Cells – secrete HCl (kills bacteria, lower pH for digestion) – also secrete Intrinsic Factor (Vitamin B12 absorption) Peptic or Chief Cells – secrete pepsinogen, the inactive precursor of pepsin Enterochromaffin-like Cells (similar to mast cells) – secrete local hormone histamine (paracrine) Also mucous neck cells and D cells – secrete a thin mucus and somatostatin respectively Regulation of Gastric Secretion Vagal stimulation via ACh – release of all gastric secretions from the various cell types – acid, pepsinogen, water, mucus, gastrin (via GRP) – also increases gastric motility Gastrin stimulated by gastrin releasing peptide (GRP) – also stimulated by amino acids and inhibited by low pH (