Difference between revisions of "Diarrhoea"
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** Interference with mucosal transport processes. | ** Interference with mucosal transport processes. | ||
** Destruction or loss of surface area. | ** Destruction or loss of surface area. | ||
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[[Category:Intestines,_Small_and_Large_-_Pathology]] | [[Category:Intestines,_Small_and_Large_-_Pathology]] | ||
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Revision as of 12:56, 7 September 2010
Introduction
- Defined as "an increase in volume and fluidity of faeces, and increased frequency of defaecation".
- Associated with malabsorption of fluid and electroyles in the intestines.
- The precise pathogenesis of diarrhoea in many individual diseases is not well defined.
- Four major mechanisms are known to exist.
- One or more of these may operate in many diseases.
- Four major mechanisms are known to exist.
Interference with normal mucosal cell transport processes
Normal intestinal absorption and secretion
- Normal intestinal water absorption and secretion is mainly due to passive osmotic forces created by active solute transport.
- The sodium ion (Na+) is the most important solute.
- Is actively absorbed from the intestine.
- Is largely responsible for the passive absorption of water.
- The sodium ion (Na+) is the most important solute.
- Active Na+ absorption from the intestine results from a combination of processes.
- Na+ is secreted from intestinal epithelial cells into the underlying interstitium
- This is ATPase dependent
- Creates a gradient for uptake of Na+ from the intestinal lumen.
- There is coupled Na+ and Cl- absorption.
- Na+ and Cl- are activily absorbed at the luminal surface of the cell.
- The mechanism for this is dependent on adenyl cyclase activity.
- Na+ and Cl- are activily absorbed at the luminal surface of the cell.
- Na+ is also absorbed in association with glucose and some amino acids (i.e. coupled).
- This is also energy dependent.
- Na+ is secreted from intestinal epithelial cells into the underlying interstitium
- Once absorbed into the intestinal epithelial cells by these coupled mechanisms, Na+ is pumped out by the basal and lateral primary pumps.
- This increases the gradient for water absorption.
- These overall absorption mechanisms operate primarily on mature villus absorptive cells and colonic surface cells.
- The small intestinal crypts are lined by rapidly dividing and relatively immature cells.
- Although there is primary active Na+ absorption there is also active secretion of Na+, Cl-, HCO3-, and therefore H2O.
- Consequently there is an overall balance of secretion into the crypt - normal intestinal secretions.
- The same potential secretory mechanisms probably exist in the villus cells.
- These are grossly outweighed by absorptive mechanisms.
- Considering both villus and crypt mechanisms, there is net absorption of Na+ and H2O.
- Although there is primary active Na+ absorption there is also active secretion of Na+, Cl-, HCO3-, and therefore H2O.
- The small intestinal crypts are lined by rapidly dividing and relatively immature cells.
Secretory Diarrhoeas
- The overall balance of the absorptive and secretory mechanisms above is shifted in a number of diseases.
- There is net secretion of Na+ and H2O into the lumen of the intestine.
- “Secretory” diarrhoeas.
- There is net secretion of Na+ and H2O into the lumen of the intestine.
- The best known secretory diarrhoeas are those caused by the enterotoxin producing strains of bacteria.
Enterotoxin Producing Strains of Bacteria
- E.g. Vibrio cholerae, E. coli.
- Organisms adhere to the surface of intestinal epithelial cells and secrete their enterotoxins.
- Enterotoxins are absorbed into cells and interfere with intracellular enzymes and metabolism.
- The heat labile enterotoxin of E. coli and cholera toxin interfere with adenyl cyclase activity.
- Result in increased intracellular levels of cAMP.
- Increased cAMP interferes with chloride coupled sodium transport
- Promotes Na+, Cl- and hence H2O secretion from the epithelial cells.
- The overall balance is shifted and the intestine becomes a net secretor of fluid.
- The increased cAMP levels probably act via a number of other intracellular processes including:
- Activation of protein kinases.
- Increased intracellular Ca++ levels.
- Calmodulin stimulation.
- Other enterotoxins may act by other mechanisms.
- E.g. the heat stable toxin of E. coli acts by guanyl cyclase and increased cGMP.
Other types of disease processes
- Other types of disease processes may also interfere with mucosal transport.
- Prostaglandins, released during inflammation, and intestinal polypeptides (e.g. VIP) act via adenyl cyclase and increased cAMP.
- Acetylcholine stimulation from the parasympathetic nervous system promotes secretion via increased intracellular Ca++ levels.
Treatment
- Chloride coupled mechanisms of Na<sup+ (and H2 are affected as described above.
- However, other mechanisms remain intact provided the epithelial cells are not destroyed.
- E.g. glucose and primary active transport.
- However, other mechanisms remain intact provided the epithelial cells are not destroyed.
- It is therefore possible to “drive” the surviving absorptive processes.
- Forms the basis for oral fluid and electrolyte replacement therapy.
- A mixture of salt, sugar and water is used to treat diarrhoea.
- Forms the basis for oral fluid and electrolyte replacement therapy.
Alterations in structure/permeability
Inflammation/ Infiltration
- The absorptive capacity of the intestine is dependent on intestinal surface area.
- Many diseases cause massive cellular infiltration into the small intestinal lamina propria, resulting in:
- Stunting and fusion of villi.
- Loss of surface area.
- Overall decreased absorptive capacity.
- The cellular infiltrate may result from:
- Chronic inflammation (e.g. Johnes disease).
- Immunologically mediated reactions (e.g. eosinophilic enteropathy).
- Neoplasia (e.g. intestinal lymphoma).
- Inflammatory or reactive processes immediately below the epithelium may provoke interference with epithelial transport processes and increase the tendency to diarrhoea.
Acute Destructive Enteropathies
- Invasive bacterial infections such as Salmonellosis result in epithelial destruction and loss of surface area.
- There is also active exudation of extracellular fluids from the eroded/ ulcerated mucosal surface.
- Exacerbated by the increased vascular permeability associated with inflammation.
- Prostaglandin release associated with inflammation may also provoke secretion from surviving epithelial cells.
- The presence of blood and mucosal shreds in watery faeces is known as dysentery rather than diarrhoea.
Osmotic diarrhoea
- If non-absorbable solutes accumulate in the gut lumen, there will be retardation of water and electrolyte absorption and diarrhoea will occur.
- Large amounts of osmotically active solutes will cause net movement of water from the plasma into the lumen.
- Seen in animals deficient in specific brush border enzymes.
- E.g. lactase deficiency.
- Feeding lactase deficient animals on milk means that lactose will remain in the lumen as an osmotically active solute rather than being broken down to glucose and galactose.
- Provokes diarrhoea.
- Feeding lactase deficient animals on milk means that lactose will remain in the lumen as an osmotically active solute rather than being broken down to glucose and galactose.
- The presence of immature epithelial cells on villi will also cause an osmotic type of diarrhoea.
- Lack their normal brush border enzymes.
- E.g. lactase deficiency.
- Many laxatives act in this way.
- E.g. those containing magnesium.
Derangement of intestinal mobility
- In some cases diarrhoea is related to intestinal mobility.
- Some pharmacologically active substances stimulate intestinal motility.
- E.g prostaglandins.
- Decreases the transit time for intestinal contents.
- Less absorption occurs.
- May cause diarrhoea.
- Intestinal stasis may also stimulate diarrhoea.
- Appears to be due to excessive bacterial multiplication in the intestinal contents.
- "Small intestinal bacterial overgrowth" (S.I.B.O.) .
- Results in the production of large amounts of osmotically active substances in the intestinal lumen.
- Appears to be due to excessive bacterial multiplication in the intestinal contents.
An Example of the Mechanisms of Diarrhoea
- In any individual disease associated with diarrhoea, a combination of two or more of the mechanisms above may be involved in the disease pathogenesis.
- For example, transmissible gastroenteritis (TGE).
Transmissable Gastro-Enteritis (TGE)
- Affects pigs, cattle and dogs.
- For more information on the pig, see transmissable gastro-enteritis in the pig.
- Caused by a coronavirus, which attacks mature absorptive cells of the intestinal villi.
- Gives excessive loss of surface epithelial cells.
- Results in villus stunting and fusion in an attempt to maintain epithelial continuity.
- Surface area is decreased.
- Loss of absorptive capacity.
- Surface area is decreased.
- Results in villus stunting and fusion in an attempt to maintain epithelial continuity.
- The intestinal crypts become hyperplastic to increase the replacement of lost epithelial cells.
- Crypt cells are normally net secretors- there is therefore increased secretion from this source.
- New cells move up from the crypts onto the villus more rapidly than usual.
- Cells are immature and lack their normal brush border enzymes.
- There is therefore an osmotic component to the diarrhoea.
- Cells are immature and lack their normal brush border enzymes.
- There may be inflammation in the underlying lamina propria.
- Prostaglandin is released, and
- Increases intestinal motility.
- Provokes increased secretory activity from remaining epithelial cells.
- Prostaglandin is released, and
Diarrhoea in Small Intestinal Disease Only
- When disease is present only in the small intestine, diarrhoea occurs only when the reserve capacity of the colon to resorb water is exceeded.
- The colon is able to resorb up to 3-4 times the volume normally presented from the small intestine.
- Therefore, for diarrhoea to occur, small intestinal disease must either:
- Be severe, or
- Occur in conjunction with large intestinal problems.
- Some small intestinal diseases cause only weight loss.
- May see hypoalbuminaemia and oedema in very severe cases.
- Weight loss is due to:
- Maldigestion.
- Malabsorption of nutrients
- Cannot be retrieved by colonic resorption (except in horses).
Diarrhoea in the Large Intestine
- Diarrhoea may occur because of failure of large intestine function, e.g.
- Colitis due to Treponema hyodysenteriae in pigs.
- Large intestinal parasitism in the horse.
- Mechanisms are similar to those described above.
- Interference with mucosal transport processes.
- Destruction or loss of surface area.