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Small Intestine
a) Segmentation - Circular muscle contracts with relaxation of muscle either side-Mixes and is propulsive b) Peristalsis Short burst of longtitudinal contraction which isnt continuous. c) Interdigestive Period: MMC
Enteric Reflexes: The enterogastric reflex is activated by intestinal receptors sensitive to hydrogen ion, distension, and osmolarity. This causes a decrease in gastric motility and slows the rate of gastric emptying, protecting the intestine from excessive acidity. The ileocaecal, or ileocolic, reflex is stimulated by distension of the ileum. Increases motility of the ileum and relaxes the ileocaecal sphincter, allowing chyme to pass from the ileum to the caecum. Also, distention of the colon causes the ileocaecal sphincter to contract reflexly, providing protection against reflux of colonic contents. The gastroileal reflex is initiated when the stomach is distended, causing increased ileal motility. The intestino-intestinal inhibitory reflex is caused when a segment of intestine is distended and results in relaxation of the remaining intestine. The colocolic inhibitory reflex is a similar reflex observed in the colon. These are mediated via sympathetic pathways.
Defecation is a complex, neurally controlled act that includes voluntary and involuntary elements. Mass movements or coordinated segmental contractions of the colon deliver faecal matter to the rectum. Stretch receptors in the wall of the rectum and anal canal respond and trigger the rectosphincteric reflex. Afferent signals are sent to the cerebral cortex, where the urge to defecate is recognized, to the autonomic ganglia, and to the spinal centers, which provide the efferent innervation of the sphincters. As distension increases, rectal contractions are reflexly induced. When the rectum is distended, the immediate reflex response is relaxation of the internal sphincter and contraction of the external sphincter. If conditions are perceived to be appropriate (ie, socially acceptable) for defaecation, the external sphincter is voluntarily relaxed and defaecation occurs. If conditions are inappropriate, contraction of the external sphincter is voluntarily maintained, the rectal stretch receptors adapt, and the rectum relaxes to accommodate the contained faecal matter. The act of defaecation is facilitated by assuming a squatting or seated position to align and dilate the recto-anal junction and by employing the Valsalva maneuver to increase intra-abdominal pressure
1.5 L per day. High [HCO3-] and low [Cl-]. Secretions come from Glands of Lieberkuhn: Produce viscous mucus to protect mucosa Paneth Cells: Produce enterokinase to activate pancreatic zymogen Goblet cells: Produce mucus: Lubricates food
pH of 8.0 to 8.4 and is secreted at about 60 ml/d. High [K+] and [HCO3-] Low [Na+ and Cl-]. Secretion stimulated by mechanical irritation. Inhibited by sympathetic nerve.
------Gastric accommodation : Mediated by vagus and CCK.
Parietal cells
G cells
Cephalic phase: Vagal stimulation of secretion and motility
Gastric phase: Food in the stomach stimulates mechanoreceptors to stimulate G and parietal cells and motility
Intestinal Phase: Gastrin secreted if ph <3 Gastric secretion and motility (via enterogastric reflex inhibited if chyme ph<2
On eating: )Peristalsis : Occurs proximal to distal- mixes and grinds the chyme- the pylorus opens as the wave approaches 3)Retropulsion- the wave goes back on itself to continue the mixing In fasting: Migrating Motor Complex: Antral contraction for 10-20 minutes every 2 hours- the electrical activity starts in the stomach and ends in the ileum- sweeps up debris
Gastric motility and secretion
Secretin
Vagus nerve
+
Cephalic Phase (sight and smell stimulates vagus nerve)
The degree of enzyme secretion in the cephalic phase is about 50% of the maximal response elicited with exogenous CCK and secretin.
Vagus nerve modulates secretion by means of cholinergic fibers, which innervate pancreatic acinar cells. The vagus also modulates peptidergic nerve fibers, which innervate duct cells.
Gastrin
+
Evokes a small volume of pancreatic juice containing a high enzyme content.
Gastric phase
Overlaps the cephalic phase.
pH<3
CCK
Secretin
Phenylalanine and tryptophan and fatty acids of 8 to 10 carbons
+
Intestinal Phase
Secretin potentiates the effect of CCK
Phases of Pancreatic Secretion
CCK
5 amino acid seqquence at carboxy end that is the same as gastrin
Structure
Several CCK lengths produced as a result of post translation modification
CCK
Receptors Types: CCK1 receptors (aka CCK-A) CCK2 receptors (aka CCK-B) identical to the gastrin receptor and is present in the stomach and brain
Stimulated by: Ingestion of a meal due to fat and protein; less so with carbs. Controlled by: Negative feedback from pancreatic secretions
Increases transient lower oesophageal sphincter relaxations (tLESRs) via the CCK1 receptor
27 amino-acid Amidated at C-terminus
Inhibits gastric acid release, gastric motility, and gastrin release Stimulation of pancreatic fluid and bicarbonate secretion
Somatostatin-14
Somatostatin-28
Cyclic peptides
G protein-coupled receptor
Distributed thourghout entire GI tract and body In GI tract produced by D-cells t1/2 in blood of 3 minutes
Stimulated By: Meal ingestion and gastric acid secretion
Inhibitory Decreases endocrine and exocrine secretion Decreases blood flow Reduces GI motility Resduces gallbladder contraction Inhibits secretion of most GI hormones
Synthetic peptides Ocreotide (90 min half life) Somatosatin LAR Lanreotide-PR Uses : secretory diarrhoea High output fitula/ stomes GI bleeding Diagnostic imaging of neuuroendocrine tumours Inhibition of tumour growth
Somatostatin
Pre-pro-gastrin
rER
G astrin is synthesized on rER, processed in the Golgi apparatus and packaged in secretory granules,
Golgi apparatus
Secretory granules
G-34 G-17
2 Major gastrin forms
Protein, peptides, and amino acids stimulate G-cells
G-cells in antrum
+
H+
-
ECL
Parietal cell
+
D-cells
Hista - mine
Causes of hypergastrinemia — Chronic atrophic gastritis PPI Zollinger-Ellison syndrome
Complications of chronic hypergastrinaemia Gastric carcinoids (occur in gastrinoma (30%) and PA (5%). Doesn’t happen with prolonged PPI use Colon and Pancreatic tumours (experimental data) Gastric polyps Trophic effects on the stomach and intestine
CCK2 receptor is present on parietal cells and enterochromaffin-like cells (ECL cells) of the stomach. CCK1 receptor is abundant in the pancreas and gallbladder and has a 1000x higher affinity for CCK than for gastrin
G-protein linked receptor
Gastrin
Gallbladder contraction. CCK also relaxes the sphincter of Oddi
Limited stimulation of pancreatic secretion directly and indirectly via vagus stimulation.
Delays gastric emptying
Overall role is to optimise small bowel absorption and giving it time
Regulates bowel motility
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Duodenum
Ileum
+
G protein coupled receptors
Receptors
Secreted by intestine
Receptor Location: Duct and acinar cells pancreas Brain cells and vagus Secreted from: small intestine and CNS
Overall role: As CCK- Overall role is to optimise small bowel absorption and giving it time
Role:
Somatostatin
1)Receptive relaxation . Distended oesophagus causes vagally mediated distention of orad stomach. Orad stomach distention only lasts as long as LES relaxation.
Hormonal Control Of Gastric Acid Secretion
Gastrin Synthesis
Cephalic phase
Gastric phase
Intestinal Phase
Colon Segmentation (most common)- haustrations take 30 seconds to peak then relax for 60seconds. Peristalsis also occurs but less common Can take stool 8-15 hours to reach transverse as above movements are slow. Mass movement - predominant in the transverse to sigmoid colon.- occurs for 15 mins during first hour after eating a meal. Stimualted by gastro and duodenocolic reflexes Rectum- segmental and peristaltic contractions
Oesophagus