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==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.
==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<sup>+</sup>) is the most important solute.
*** Is actively absorbed from the intestine.
*** Is largely responsible for the passive absorption of water.
* Active Na<sup>+</sup> absorption from the intestine results from a combination of processes.
*# Na<sup>+</sup> is secreted from intestinal epithelial cells into the underlying interstitium
*#* This is ATPase dependent
*#* Creates a gradient for uptake of Na<sup>+</sup> from the intestinal lumen.
*# There is coupled Na<sup>+</sup> and Cl<sup>-</sup> absorption.
*#* Na<sup>+</Sup> and Cl<sup>-</sup> are activily absorbed at the luminal surface of the cell.
*#** The mechanism for this is dependent on adenyl cyclase activity.
*# Na<sup>+</sup> is also absorbed in association with glucose and some amino acids (i.e. coupled).
*#* This is also energy dependent.
* Once absorbed into the intestinal epithelial cells by these coupled mechanisms, Na<sup>+</Sup> 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 [[Colon - Anatomy & Physiology|colon]]ic surface cells.
** The small intestinal crypts are lined by rapidly dividing and relatively immature cells.
*** Although there is primary active Na<sup>+</sup> absorption there is also active secretion of Na<sup>+</sup>, Cl<sup>-</sup>, HCO<sub>3</sub><sup>-</sup>, and therefore H<sub>2</sub>O.
**** 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<sup>+</sup> and H<sub>2</sub>O.
===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<sup>+</sup> and H<sub>2</sub>O into the lumen of the intestine.
*** '''“Secretory” diarrhoeas'''.
* The best known secretory diarrhoeas are those caused by the '''enterotoxin producing strains of bacteria'''.
====Enterotoxin Producing Strains of Bacteria====
* E.g. ''Vibrio cholerae'', [[Escherichia coli|''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 [[Escherichia coli|''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<sup>+</sup>, Cl<sup>-</sup> and hence H<sub>2</sub>O 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<sup>++</sup> 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<sup>++</sup> levels.
====Treatment====
* Chloride coupled mechanisms of Na<sup+</sup> (and H<sub>2</sub> are affected as described above.
** However, other mechanisms remain intact provided the epithelial cells are not destroyed.
*** E.g. glucose and primary active transport.
* 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.
==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. [[Intestines - Proliferative Enteritis#Paratuberculosis (Johnes disease)|Johnes disease]]).
** Immunologically mediated reactions (e.g. [[Intestines - Inflammatory Bowel Disease And Related Conditions#Eosinophilic Enteritis|eosinophilic enteropathy]]).
** Neoplasia (e.g. [[Intestines - Proliferative Pathology#Lymphoma|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 [[Intestines - Fibrinous/ Haemorrhagic Enteritis#Salmonellosis|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.
** The presence of immature epithelial cells on villi will also cause an osmotic type of diarrhoea.
*** Lack their normal brush border enzymes.
* 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.
==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 [[Intestines - Catarrhal Enteritis#Transmissible Gastro-Enteritis (TGE)|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'''.
* 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.
* There may be inflammation in the underlying lamina propria.
** Prostaglandin is released, and
*** '''Increases intestinal motility'''.
*** Provokes '''increased secretory activity''' from remaining epithelial cells.
==Diarrhoea in Small Intestinal Disease Only==
* When disease is present only in the [[Small Intestine - Anatomy & Physiology|small intestine]], diarrhoea occurs only when the reserve capacity of the [[Colon - Anatomy & Physiology|colon]] to resorb water is exceeded.
** The [[Colon - Anatomy & Physiology|colon]] is able to resorb up to 3-4 times the volume normally presented from the [[Small Intestine - Anatomy & Physiology|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 [[Colon - Anatomy & Physiology|colon]]ic resorption (except in horses).
==Diarrhoea in the [[Large Intestine - Anatomy & Physiology|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.