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| − | ==Introduction==
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| − | * Defined as "'''an increase in volume and fluidity of faeces, and increased frequency of defaecation'''".
| + | |linkpage =Alimentary System - Pathology |
| − | ** Associated with malabsorption of fluid and electroyles in the intestines.
| + | |linktext =Alimentary System |
| − | * The precise pathogenesis of diarrhoea in many individual diseases is not well defined.
| + | |maplink = Alimentary System (Content Map) - Pathology |
| − | ** Four major mechanisms are known to exist.
| + | |pagetype =Pathology |
| − | *** One or more of these may operate in many diseases.
| + | |sublink1=Small and Large Intestines - Pathology |
| − | | + | |subtext1=SMALL AND LARGE INTESTINES |
| − | ==Interference with normal mucosal cell transport processes== | |
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| − | ===Normal intestinal absorption and secretion===
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| − | * Normal intestinal water absorption and secretion is mainly due to passive osmotic forces created by active solute transport.
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| − | ** The sodium ion (Na<sup>+</sup>) is the most important solute.
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| − | *** Is actively absorbed from the intestine.
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| − | *** Is largely responsible for the passive absorption of water.
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| − | * Active Na<sup>+</sup> absorption from the intestine results from a combination of processes.
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| − | *# Na<sup>+</sup> is secreted from intestinal epithelial cells into the underlying interstitium
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| − | *#* This is ATPase dependent
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| − | *#* Creates a gradient for uptake of Na<sup>+</sup> from the intestinal lumen.
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| − | *# There is coupled Na<sup>+</sup> and Cl<sup>-</sup> absorption.
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| − | *#* Na<sup>+</Sup> and Cl<sup>-</sup> are activily absorbed at the luminal surface of the cell.
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| − | *#** The mechanism for this is dependent on adenyl cyclase activity.
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| − | *# Na<sup>+</sup> is also absorbed in association with glucose and some amino acids (i.e. coupled).
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| − | *#* This is also energy dependent.
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| − | * Once absorbed into the intestinal epithelial cells by these coupled mechanisms, Na<sup>+</Sup> is pumped out by the basal and lateral primary pumps.
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| − | ** This increases the gradient for water absorption.
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| − | * These overall absorption mechanisms operate primarily on mature villus absorptive cells and [[Colon - Anatomy & Physiology|colon]]ic surface cells.
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| − | ** The small intestinal crypts are lined by rapidly dividing and relatively immature cells.
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| − | *** 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.
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| − | **** Consequently there is an overall balance of secretion into the crypt - normal intestinal secretions.
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| − | *** The same potential secretory mechanisms probably exist in the villus cells.
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| − | **** These are grossly outweighed by absorptive mechanisms.
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| − | *** Considering both villus and crypt mechanisms, there is '''net absorption''' of Na<sup>+</sup> and H<sub>2</sub>O.
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| − | | |
| − | ===Secretory Diarrhoeas===
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| − | * The overall balance of the absorptive and secretory mechanisms above is shifted in a number of diseases.
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| − | ** There is net secretion of Na<sup>+</sup> and H<sub>2</sub>O into the lumen of the intestine.
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| − | *** '''“Secretory” diarrhoeas'''.
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| − | * The best known secretory diarrhoeas are those caused by the '''enterotoxin producing strains of bacteria'''.
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| − | ====Enterotoxin Producing Strains of Bacteria====
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| − | * E.g. ''Vibrio cholerae'', [[Escherichia coli|''E. coli'']].
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| − | * Organisms adhere to the surface of intestinal epithelial cells and secrete their enterotoxins.
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| − | ** Enterotoxins are absorbed into cells and interfere with intracellular enzymes and metabolism.
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| − | * The heat labile enterotoxin of [[Escherichia coli|''E. coli'']] and cholera toxin interfere with adenyl cyclase activity.
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| − | ** Result in increased intracellular levels of cAMP.
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| − | ** Increased cAMP interferes with chloride coupled sodium transport
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| − | *** Promotes Na<sup>+</sup>, Cl<sup>-</sup> and hence H<sub>2</sub>O secretion from the epithelial cells.
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| − | *** The overall balance is shifted and the intestine becomes a '''net secretor''' of fluid.
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| − | ** The increased cAMP levels probably act via a number of other intracellular processes including:
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| − | *** Activation of protein kinases.
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| − | *** Increased intracellular Ca<sup>++</sup> levels.
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| − | *** Calmodulin stimulation.
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| − | * Other enterotoxins may act by other mechanisms.
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| − | ** E.g. the heat stable toxin of E. coli acts by guanyl cyclase and increased cGMP.
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| − | ====Other types of disease processes====
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| − | * Other types of disease processes may also interfere with mucosal transport.
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| − | * Prostaglandins, released during inflammation, and intestinal polypeptides (e.g. VIP) act via adenyl cyclase and increased cAMP.
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| − | * Acetylcholine stimulation from the parasympathetic nervous system promotes secretion via increased intracellular Ca<sup>++</sup> levels.
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| − | ====Treatment====
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| − | * Chloride coupled mechanisms of Na<sup+</sup> (and H<sub>2</sub> are affected as described above.
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| − | ** However, other mechanisms remain intact provided the epithelial cells are not destroyed.
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| − | *** E.g. glucose and primary active transport.
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| − | * It is therefore possible to “drive” the surviving absorptive processes.
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| − | ** Forms the basis for oral fluid and electrolyte replacement therapy.
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| − | *** A mixture of salt, sugar and water is used to treat diarrhoea.
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| − | ==Alterations in structure/permeability==
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| − | ===Inflammation/ Infiltration===
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| − | * The absorptive capacity of the intestine is dependent on intestinal surface area.
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| − | * Many diseases cause massive cellular infiltration into the small intestinal lamina propria, resulting in:
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| − | ** Stunting and fusion of villi.
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| − | ** Loss of surface area.
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| − | ** Overall decreased absorptive capacity.
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| − | * The cellular infiltrate may result from:
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| − | ** Chronic inflammation (e.g. [[Johne's Disease|Johnes disease]]).
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| − | ** Immunologically mediated reactions (e.g. [[Inflammatory Bowel Disease#Eosinophilic Enteritis|eosinophilic enteropathy]]).
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| − | ** Neoplasia (e.g. [[Lymphoma|intestinal lymphoma]]).
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| − | * Inflammatory or reactive processes immediately below the epithelium may provoke interference with epithelial transport processes and increase the tendency to diarrhoea.
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| − | ===Acute Destructive Enteropathies===
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| − | * Invasive bacterial infections such as [[Salmonellosis|Salmonellosis]] result in epithelial destruction and loss of surface area.
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| − | * There is also active exudation of extracellular fluids from the eroded/ ulcerated mucosal surface.
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| − | ** Exacerbated by the increased vascular permeability associated with inflammation.
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| − | ** Prostaglandin release associated with inflammation may also provoke secretion from surviving epithelial cells.
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| − | * The presence of blood and mucosal shreds in watery faeces is known as '''dysentery rather than diarrhoea'''.
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| − | ==Osmotic diarrhoea==
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| − | * If non-absorbable solutes accumulate in the gut lumen, there will be retardation of water and electrolyte absorption and diarrhoea will occur.
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| − | ** Large amounts of osmotically active solutes will cause net movement of water from the plasma into the lumen.
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| − | * Seen in animals deficient in specific brush border enzymes.
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| − | ** E.g. lactase deficiency.
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| − | *** 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.
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| − | **** Provokes diarrhoea.
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| − | ** The presence of immature epithelial cells on villi will also cause an osmotic type of diarrhoea.
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| − | *** Lack their normal brush border enzymes.
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| − | * Many laxatives act in this way.
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| − | ** E.g. those containing magnesium.
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| − | ==Derangement of intestinal mobility== | |
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| − | * In some cases diarrhoea is related to intestinal mobility.
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| − | * Some pharmacologically active substances stimulate intestinal motility.
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| − | ** E.g prostaglandins.
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| − | ** Decreases the transit time for intestinal contents.
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| − | *** Less absorption occurs.
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| − | ** May cause diarrhoea.
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| − | * Intestinal stasis may also stimulate diarrhoea.
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| − | ** Appears to be due to excessive bacterial multiplication in the intestinal contents.
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| − | *** "Small intestinal bacterial overgrowth" (S.I.B.O.) .
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| − | *** Results in the production of large amounts of osmotically active substances in the intestinal lumen.
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| − | ==An Example of the Mechanisms of Diarrhoea==
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| − | * In any individual disease associated with diarrhoea, a combination of two or more of the mechanisms above may be involved in the disease pathogenesis.
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| − | * For example, transmissible gastroenteritis (TGE).
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| − | ===Transmissable Gastro-Enteritis (TGE)===
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| − | * Affects pigs, cattle and dogs.
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| − | ** For more information on the pig, see [[Transmissible Gastroenteritis Virus|transmissable gastro-enteritis in the pig]].
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| − | * Caused by a coronavirus, which attacks mature absorptive cells of the intestinal villi.
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| − | * Gives excessive loss of surface epithelial cells.
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| − | ** Results in villus stunting and fusion in an attempt to maintain epithelial continuity.
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| − | *** Surface area is decreased.
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| − | **** '''Loss of absorptive capacity'''.
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| − | * The intestinal crypts become hyperplastic to increase the replacement of lost epithelial cells.
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| − | ** Crypt cells are normally net secretors- there is therefore '''increased secretion''' from this source.
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| − | * New cells move up from the crypts onto the villus more rapidly than usual.
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| − | ** Cells are immature and lack their normal brush border enzymes.
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| − | *** There is therefore an '''osmotic component''' to the diarrhoea.
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| − | * There may be inflammation in the underlying lamina propria.
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| − | ** Prostaglandin is released, and
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| − | *** '''Increases intestinal motility'''.
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| − | *** Provokes '''increased secretory activity''' from remaining epithelial cells.
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| − | ==Diarrhoea in Small Intestinal Disease Only==
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| − | * When disease is present only in the [[Small Intestine Overview - Anatomy & Physiology|small intestine]], diarrhoea occurs only when the reserve capacity of the [[Colon - Anatomy & Physiology|colon]] to resorb water is exceeded.
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| − | ** The [[Colon - Anatomy & Physiology|colon]] is able to resorb up to 3-4 times the volume normally presented from the [[Small Intestine Overview - Anatomy & Physiology|small intestine]].
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| − | * Therefore, for diarrhoea to occur, small intestinal disease must either:
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| − | ** Be severe, or
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| − | ** Occur in conjunction with large intestinal problems.
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| − | * Some small intestinal diseases cause only weight loss.
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| − | ** May see hypoalbuminaemia and oedema in very severe cases.
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| − | ** Weight loss is due to:
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| − | *** Maldigestion.
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| − | *** Malabsorption of nutrients
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| − | **** Cannot be retrieved by [[Colon - Anatomy & Physiology|colon]]ic resorption (except in horses).
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| − | ==Diarrhoea in the [[Large Intestine - Anatomy & Physiology|Large Intestine]]==
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| − | * Diarrhoea may occur because of failure of large intestine function, e.g.
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| − | ** Colitis due to ''Treponema hyodysenteriae'' in pigs.
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| − | ** Large intestinal parasitism in the horse.
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| − | * Mechanisms are similar to those described above.
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| − | ** Interference with mucosal transport processes.
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| − | ** Destruction or loss of surface area.
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| − | {{Learning
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| − | |Vetstream = [https://www.vetstream.com/canis/Content/Freeform/fre00889.asp Diarrhea: overview] | |
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| − | | + | <br> |
| − | [[Category:Intestines,_Small_and_Large_-_Pathology]]
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| − | [[Category:To_Do_-_Clinical]]
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