gastrointestinal physiology - bpums · gastrointestinal function motility, ... (ach): excitatory...
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General principal of General principal of
gastrointestinal functiongastrointestinal functionMotility, nervous control and Motility, nervous control and
blood circulationblood circulation
Gastrointestinal (GI) Motility
• Characteristic of the GI wall *
• Smooth muscles in GI function as syncytium
Characteristic of the GI wall
• Mucosa:• Epithelium; varies at different part of GI
• Lamina propria; connective tissue– Glands, lymph node, capillaries
• Muscularis mucosa; mucosal fold and ridges
• Submucosa: connective tissue• Submucosa: connective tissue
• Glands , large nerve trunks, blood vessels
• Muscularis externa: mix & propel content of the lumen
• Inner circular layer
• Outer longitudinal layer
• Serosa: connective tissue covered by squamous mesothelial cells
• Electrical activity of GI smooth muscle*
– Slow waves: oscillation of RMP
• Fr: 3-12/min
• Generated by interstitial cells of Cajal
• Amplitude and frequency of SW modified by ANS
– Spike potential: due to slow Na-Ca entry, Fr: 1-10/sec
• Calcium ions and muscle contraction• Calcium ions and muscle contraction
• Changes in RMP: – Depolarizing (distension, Ach)
– Hyperpolarizing (epinephrine)
• Tonic contraction of some GI muscles:
– Repeated spike potential or Hormonal
REGULATORY MECHANISMS IN THE
GASTROINTESTINAL TRACT
• Neural �Extrinsic component (sympathetic and
parasympathetic)
�Intrinsic component (Enteric nervous system)�Intrinsic component (Enteric nervous system)
• Endocrine�Entroendocrine cell (EEC)
• Paracrine
In The Clinic
Glucagon-like peptide 1 (GLP-1) is a regulatory peptide released from EC
cells in the gut wall in response to the presence of luminal carbohydrate and lipids.
GLP-1 arises from differential processing of the glucagon gene, the same gene
that is expressed in the pancreas and that gives rise to glucagon. GLP-1 is
involved in regulation of the blood glucose level via stimulation of insulin secretion
and also insulin biosynthesis. Agonists of the GLP-1 receptor improve insulin
sensitivity in diabetic animal models and human subjects. Administration of GLP-1
also reduces appetite and food intake and delays gastric emptying, responses that
may contribute to improving glucose tolerance. Long-acting agonists for the GLP-1
receptor, such as exanatide, have been approved for the treatment of type 2
diabetes.
Paracrine Regulation
• Histamine: by ECL cells.
• Serotonin: by enteric neurons, mucosal mast cells, enterochromaffin cells, regulates smooth cells, enterochromaffin cells, regulates smooth muscle function & water absorption.
• Prostaglandins
• Adenosine
• Nitric oxide (NO)
• Neural control
�Extrinsic component (sympathetic & parasympathetic)
�Intrinsic component (Enteric nervous system)
– Myenteric (Auerbach'sAuerbach's) plexus: motor
– Submucosal (Meissner'sMeissner's) plexus: secretory
�Neurotransmitters on ENS:
The Enteric nervous system (ENS)
�Neurotransmitters on ENS:
�Excitatory: Ach, VIP
�Inhibitory: NO
ENS (minibrain) consists of:
Sensory neurons
Interneurons
Motor neurons
Neurotransmitters/Neurotransmitters/neuromodulatorsneuromodulators in the ENSin the ENS
� Acetylcholine (ACh): Excitatory transmitter to smooth muscle, intestinal epithelial
cells, parietal cells, certain endocrine cells, and at neuroneuronal synapses
� Adenosine triphosphate (ATP): Inhibitory transmitter to smooth muscle
� Calcitonin gene-related peptide (CGRP):
Released by enteric sensory neurons onto interneurons in enteric ganglia and central Released by enteric sensory neurons onto interneurons in enteric ganglia and central
ganglia
� Gastric-releasing peptide: Released by secretomotor neurons onto G cells
� Nitric oxide (NO): Inhibitory transmitter to smooth muscle cells
� Substance P: Excitatory transmitter to smooth muscle cells
� Vasoactive intestinal peptide (VIP): Inhibitory transmitter to smooth muscle cells,
excitatory secretomotor transmitter to epithelial and gland cells, vasodilator.
• Autonomic control of GI tract
– Parasympathetic innervation
• Cranial (vagus n)
• Sacral (S2-S4 ): pelvic n
Afferent sensory nerve fiber from
To:1. ENS
2. Prevertebral ganglion
3. Spinal cord
4. Brain stem
Osmoreceptors
Chemoreceptors
mechanoreceptors
• GI reflexes:1. local reflex
2. Gastrocolic, enterogastric, colonoileal reflexes
3. Vagovagal reflex, defecation reflex
�Three types of
afferent signals that
originate from the GI
tract by:
- hormones
- immune system
- neurons
In The Clinic
Hirschsprung's disease is a congenital disorder of the enteric nervous
system characterized by failure to pass meconium at birth or severe chronic
constipation in infancy. The typical features are absence of myenteric and
submucosal neurons in the distal part of the colon and rectum. It is a polygenic
disorder with characteristic mutations in at least three different classes of genes
involved in neuronal development and differentiation
In The Clinic
Neurogenic secretory diarrheaSecretomotor neurons excite secretion of H2O, electrolytes, and mucus from the
crypts of Lieberkühn.
Ach and VIP are the principal excitatory neurotransmitters. The cell bodies of
secretomotor neurons are in the submucosal plexus. Excitation of these neurons,
for example, by histamine release from mast cells during allergic responses, can
lead to neurogenic secretory diarrhea. Suppression of excitability e.g. by morphine
or other opiates, can lead to constipation.
Gastrointestinal blood flow
� Anatomy of GI blood supply• Sup & inf mesenteric arteries*
� Effect of gut activity and metabolic factors on GI blood flow
– Increased blood flow during activity– Increased blood flow during activity
• Role of vasodilators: CCK, VIP, Gastrin, Secretin
• Bradykinin, Kallidin
• O2-Adenosin
� Nervous control of GI blood flow:• Hemorrhagic shock, exercise
End