git physiology i
TRANSCRIPT
GI Physiology – I
Dr Bhawana Neupane PantLecturer, Department of Physiology
Gastrointestinal System: Processes
• Motility• Digestion• Secretion• Absorption
Structure of the GI TractInnervation of the GI Tract
GI Peptides
Structure of the GI Tract a) Layers of the GI tract b) GI muscles
Innervation of the GI Tract a) Intrinsic/Enteric nervous system b) Extrinsic/Autonomic and central NS
Hormonal Control of GI functions
Costanzo 327-335
1) Serosa - Continuous with the mesenteries
2) Muscularis- Longitudinal muscle- Circular muscle
3) Submucosa
4) Mucosa- Muscularis mucosae- Lamina propria- Epithelial cells
Layers of the GI tract
Structure of GI Tract
General Anatomy of Gut Wall
(Contains connective tissue, immune cells, capillaries, nerve endings)
(Might have role in villus movement)
1) Serosa
2) Muscularis:- Longitudinal muscle
- Circular Muscle
3) Submucosa:
4) Mucosa
Submucosal plexus (= Meissner’s plexus
Myenteric plexus (= Auerbach’s plexus)
2. Innervation of the GI Tract
a) The Enteric/ Intrinsic Nervous System
Primarily controls motility (length, intensity, frequency, velocity of peristaltic waves)Decreases tension of sphincters
Controls secretion, absorption, submucosal motility and blood flow
The Enteric Nervous System
Local Reflexes = “Short Reflexes.”
Can be influenced by CNS = “Long Reflexes.”
Parasympathetic and Sympathetic Innervation
Afferent Efferentsensory neurons from enteric NS (local afferents)
afferent sympathetic nerve fibers afferent parasympathetic nerve fibers2
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mechanoreceptors chemoreceptors thermoreceptors
nociceptors
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Integration of neuronal control of GI function
Effector system of GI innervation:
(modified from B&L)
Interaction of ANS and ENS
• The enteric nervous system coordinates digestion, secretion, and motility to optimize nutrient absorption.
• Its activity is modified by information from the CNS and from local chemical and mechanical sensors.
Enteric Nervous System
What Is "Diabetic Stomach"?
“My niece takes an oral medicine for diabetes. At least once a week, she throws up at night. The doctor calls it "diabetic stomach." I have never heard of this, and I have had diabetes for 36 years. What could be the cause of her stomach problems, and what foods may be causing flare-ups?”
Hint:Type II diabetic patients have autonomic neuropathy and motor neuropathy.
Diabetic Stomach
• Gastroparesis is a disorder affecting people with both type 1 and 2 diabetes in which gastric emptying is delayed.
• Symptoms: Nausea Vomiting of undigested food Early feeling of fullness when eating Weight loss Abdominal bloating
• Avoid high-fat and high-fiber foods.
Cholinergic (Acetylcholine) - excitatory
Adrenergic (Norepinephrine) - inhibitory
Non-adrenergic, non-cholinergic neurotransmitter (NANC)
• Vasoactive Intestinal Peptide (VIP)
• Gastrin Releasing Peptide (GRP) or Bombesin
• Enkephalins (opiates)
• Neuropeptide Y
• Substance P
Neurotransmitters and Neuromodulators in the Enteric Nervous System:
Note: There are list of putative transmitters is long; often, their physiologic significance is uncertain; but their potential pharmacological value is high.
Is a disorder caused by the absence of enteric neurons.
In the majority of affected people, the disorder affects the short segment of the distal colon.
In rarer cases it affects the whole colon or even the whole GI system.
Hirschsprung disease or congenital megacolon
In children with Hirschsprung’s disease, nerves fail to form in all or part of the large intestine (colon). Waste from digestion cannot pass through the part of the colon lacking nerve tissue. The normal colon swells with blocked stool.
Clinical Presentation: Failure to pass meconium, abdominal distension, vomiting, enterocolitis
Treatment: Surgical removal of part (Pull through procedure)
Gastrointestinal Peptides:
Gastrointestinal Hormones:
Gastrin:
• Secreted by G cells in the antrum of stomach
• Principal physiologic actions: – Gastric acid secretion– Pepsin secretion– Trophic action (growth of the mucosa of the stomach, small and large
intestine)
What happens in Zollinger-Ellison Syndrome?
What happens when gastric antrum is resected?
H+ secretion is increased
Hypertrophy of gastric mucosa
Duodenal ulcer
Steatorrhea
H+ secretion is decreased
Gastric mucosa atrophies
Gastrin Stimulation
Inhibition by:
- Somatostatin (H+ stimulates, N. vagus inhibits D-cells)
- Low pH (partly at pH 3.5, completely at pH 2)
- Secretin
Stimulation by:
- N. Vagus
- Distention of the stomach
- Protein digestion products
- Calcium, alcohol, coffee
- CNS (anticipation of meal,
olfactory stimuli) AA: phenylalanine and tryptophan Secretin
Cholecystokinin- secreted by I cells in the mucosa of the duodenum, the jejunum
• Primary functions:- Stimulation of pancreatic enzyme secretion
- The contraction of the gall bladder and relaxation of sphincter of
Oddi
- Growth of the exocrine pancreas and gallbladder
• Secondary functions:- Augments the action of secretin in producing secretion of an
alkaline pancreatic juice
- Increases the synthesis of enterokinase
- May enhance the motility of the small intestine and colon
CCK Functions
CCK Stimulation
Stimulation by:- Digestion products of fat and protein (most potent long fatty acid chains)
- Meals stimulate CCK secretions of gut and CNS simultaneously
Secretin
Secreted by S cells in upper small-intestinal mucosa.
Stimulates water and alkali secretions from pancreas and biliary tract
Inhibits gastrin release, suppresses gastric acids
It also augments the action of CCK in producing pancreatic secretion of digestive enzyme
The secretion of secretin is increased by the products of protein digestion and by acid bathing the mucosa of the upper small intestine.
Secretin Stimulation
- contact with acidic chyme- also stimulated by fatty acids
IV: GIPold name: Gastric Inhibitory Peptidenew name: Glucose-dependent Insulinotropic Peptide- Secreted by K-cells in duodenum and jejunum
GIP Functions
Major function:- Release of insulin
Action as enterogastrone controversial:- Inhibits gastrin release and acid secretion- Inhibits gastric and intestinal motility
??
GIP Stimulation
Stimulated by- Glucose in upper small intestine- Long-chain fatty acids- Certain AA (different than those for gastrin and CCK) Inhibited by- High levels of insulin or glucagon (unclear if physiologic?)
C. Candidate Hormones
• produced by pancreatic islet cells and endocrine cells
• released most potently by protein digestion products
• also released by vagal stimulation and Ach
I: MotilinII: Pancreatic PolypeptideIII: Enteroglucagon
II: Enteroglucagon• secreted by intestinal mucosal cells of colon and terminal ilium• stimulated by intraluminal glucose and fat• same effects as glucagon but less potent (glycogenolysis and gluconeogenesis, lipolysis)• might inhibit gastrin release and gastric acid secretion (not established)
III: Pancreatic Polypeptide• Secreted by the pancreas• Stimulated by ingestion of carbohydrates, proteins, or lipids• Inhibits pancreatic secretion of HCO3
- and enzymes • Physiologic role uncertain
I: Motilin• primarily in duodenum by M cells• physiologic stimuli not known• initiates the MMC migrating motor complex (see motility lecture)
Candidate Hormones
D. Paracrines• Secreted into the interstitial fluid
and diffuse to adjacent cells
• The site of secretion must be only a short distance from the site of action.
1. Somatostatin
2. Histamine
Somatostatin• Secreted by D-cells in gastric mucosa• Delta cells in the pyloric antrum, the duodenum and the pancreatic
islets• Both paracrine and endocrine
• Suppresses gastric secretions• Inhibits motility and tone of stomach and small intestines and gall
bladder• Inhibits formation of liver bile• Inhibits the release of ALL known GI hormones• Inhibits saliva, gastric, pancreatic, small intestinal and liver
secretions• Inhibits splanchnic blood flow• Inhibits intestinal absorption
• In brain it inhibits GH release• In pancreas, inhibitor of insulin and glucagon
Octreotide : analogue of somatostatin
Action Gastrin CCK Secretin GIP
Acid secretion
Pancreatic HCO3- secretion
Pancreatic enzyme secretion
Bile HCO3-
Gallbladder contraction
Gastric emptying
Gastric Mucosal growth
Pancreatic growth
Insulin Secretion
S = stimulates; I = inhibits
Actions of GI hormones
ISS
S
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S
SS S
I
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I
GI Motility
Skeletal muscle:• Upper esophagus• External anal sphincter
Smooth muscle: (of the visceral or unitary type): • Rest of GI tract
GI Muscles
In comparison to skeletal muscle:
Energy: Low (up to 300x less)
Force: High
Shortening: High
Time: Long (tonic)
Speed: Slow
Basic Electrical Activity
SLOW WAVES:- Due to rhythmic changes in membrane potential initiated by Interstitial cells of Cajal (pacemaker cells)- Not responsible for contractions but determine the frequency of contractions
SPIKE POTENTIALS:- Develop on top of slow waves when they reach threshold potential (~ -40mV)- The higher amplitude the more spike potentials the stronger gut motility
Membrane potential
• Frequency of electric activity determines the frequency of contractions
• Basic Electrical Rhythm in different parts• Stomach ~ 3/min• Duodenum ~ 11-12/min• Distal Ileum ~ 6-7/min
Objectives of Today’s Class:• Structure of GI Wall
• Enteric Nervous System and Its Interaction with ANS and CNS
• Understanding GI Hormones
• Electric Basis of Motility in GI – Slow Waves
MotilityMouth and Esophagus: Chewing, Swallowing,
Peristalsis
Stomach: Filling, Churning, Peristalsis, Emptying
Small Intestine: Segmental Contractions, Peristalsis
Large Intestine: Haustral Shuttling, Mass Movements, Defecation.
Sphincters: Regulation of Movement
Tonic Contractions
“Latch Mechanism” and slow myosin ATPase allow SM to maintain contraction with little energy and excitatory signal from nerves or hormones
Phasic Contractions
Peristalsis Segmentation