Gastrointestinal physiologyGastrointestinal physiology

forfor

medical studentsmedical students

General principal of General principal of

gastrointestinal functiongastrointestinal functionMotility, nervous control and Motility, nervous control and

blood circulationblood circulation

Physiological processes in the GI tract:

�Motility

�Secretion

�Digestion�Digestion

�Absorption

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

next

• Villus

– Microvillus

• Crypt

• 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

Endocrine control

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.

Endocrine cell in GI

tract:

� Open type

� Close type

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

- Sympathetic innervation

(T5 - L2) : celiac and mesenteric ganglions

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

A hierarchy of neural integrative centers

“Brain-gut axis”

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

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