Friday, March 16, 2012

Aspek Biokimia Fungsi Absorpsi dan Sekresi Intestinal serta Hubungannya dengan Patofisiologi Diare


• Only 100 to 200 mL of water being excreted each day in formed stools.
• When net secretion exceeds its limited absorptive capacity, diarrhoea occurs.

After being absorbed, sodium is transported out of the epithelial cells byan ion pump referred to as Na+K+ ATPase -->  Na to ECF -->  Osmolality --> Water and other electrolytes to flowpassively from the bowel lumen through intercellular channels and into the ECF.

SECRETION
• cAMP, via Protein Kinase A (PKA), stimulates secretion by activating or enhancing the transport activities of three membrane proteins :
1. The apical anion channel. cAMP opens the apical anion channel thereby initiating secretion.
2. A basolateral membrane K+ channel. The opening of a basolateral membrane K+ channel repolarizes the cell, sustaining the electrical driving force for Cl– extrusion into the lumen.

Compounds that stimulate active secretion and inhibit active absorption:
a) Neurotransmitters:

  • Vasoactive intestinal peptide (VIP)
  • Acetylcholine
  • Substance P
  • ATP and UTP
b) Serotonin and Neurotensin. Released by enterochromaffin cells
c) Prostaglandins, leukotrienes and plateletactivating factor (PAF). Released by inflammatory cells.


The group of compounds that both inhibit active secretion (HCO3 – as well as Cl–) and enhance active absorption, includes norepinephrine (via α2-receptors), neuropeptide Y, enkephalins, all neurotransmitter, and somatostatin. Norepinephrine, the predominant antisecretory/proabsorptive agonist in the intestines, activates α2-receptors on both enterocytes (22) and nerves (S32, S33). The neural effect is inhibitory, blocking release of secretion-inducing neurotransmitters.


Diarrheal driving forces
• Osmosis, active secretion, exudation, and altered motility --> diarrhea.

Osmotic Diarrhea : When poorly absorbable, low–molecular weight aqueous solutes are ingested, their osmotic force quickly pulls water and, secondarily, ions into the intestinal lumen. Such as : Lactulose, sorbitol or Mg2+.

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