Diarrhea Flashcards
What is the chloride channel on crypt cells sensitive to?
intracellular calcium levels
How do chloride channels on crypt cells open?
calcium is released from intracellular stores in the cytosol
How do post-ganglionic parasympathetic or ENS fibers trigger the release of intracellular calcium?
post-ganglionic parasympathetic or ENS fibers release ACH to act on muscarinic receptors which cause the second messenger cyclic GMP to increase in the cell which triggers an intracellular Ca to rise
Normally, when are crypt cells stimulated to secrete chloride?
to get sodium to the villus when it is needed to absorb dietary components
What are the three types of diarrhea?
secretory, malabsorptive, and osmotic
What occurs to the gut in secretory diarrhea cases?
excessive chloride secreting activity of crypt cells, reduced activity of villus cells, excessive secretion of water from the cells
Explain the mechanisms that lead to increased Cl and water secretion in secretory diarrhea.
certain toxins cause production of free radicals which damage tissues resulting prostaglandin E2 and I2 production by cells in mucosa and submucosa. Prostaglandins E2 and I2 bind to Pg receptors on crypt cells and activate adenyl cyclase which increases cyclic AMP in the cells. Increased cyclic AMP will cause a rise in intracellular Ca from intracellular stores which binds to calmodulin and initiates the opening of Cl channels; Na and water will follow into the lumen.
What is the alternative pathway for Ca release in the ER during secretory diarrhea?
prostaglandins activate phospholipase A which tells IP3 to open Ca channels in the ER
What are some toxins that cause secretory diarrhea?
salmonella, cholera, and enterotoxigenic e-coli
How does salmonella cause secretory diarrhea?
white blood cells and cells damaged by salmonella within the lamina propria release prostaglandins (PGE2) which not only stimulates the secretion of Cl but also stimulates mucous secretion by goblet cells
What can slow the production of PGE2?
glucocorticoids and NSAIDs
How does salmonella use extracellular calcium to cause secretory diarrhea?
bacterial toxins have been found to cause secretion of serotonin from enteroendocrine cells, serotonin causes calcium channels in adjacent cell basolateral membranes to open which raises intracellular calcium and stimulates secretion of chloride
How does inflammation lead to hypersecretion in secretory diarrhea?
TNF-alpha and other cytokine can bind to receptors on crypt cells and activate adenyl cyclase which activates cyclic AMP which activates secretion of intracellular calcium stores
What mechanism does cholera use to cause secretory diarrhea?
it secretes enterotoxin which binds to specific receptors on enterocytes of the small intestine only linked to guanylate cyclase activity
How does the enterotoxin that cholera secretes cause secretory diarrhea?
it raises levels of intracellular calcium to rise, mostly from intracellular calcium stores, through extracellular calcium can also serve as a source; Cl leaves, Na and H2O follows
What are the two types of toxins that e-coli secrete?
ST-toxin and LT-toxin
How does ST toxin work?
it is heat stable and activates cyclic GMP just like cholera toxin
How does LT toxin work?
it is heat labile and activates adenylate cyclase via its own g-protein coupled receptor which raises intracellular cAMP which then raises intracellular calcium increasing the secretion of chloride
Why does the secretory diarrhea associated with LT toxin last until the cells slough off?
because it irreversibly binds to the receptors
How does secretory diarrhea effect villus cells?
it blocks Na coupled to Cl entery across the apical membrane so more Na and Cl stays in the gut
What does secretory diarrhea not block in villi cells?
Na absorption coupled to sugars or amino acids
What generally occurs to the gut due to malabsorptive diarrhea?
loss of villous cells or villous enzymes, loss of tight junctions, loss of plasma proteins that would normally be absorbed by lymphatics
What are some toxins that cause malabsorptive diarrhea?
Johne’s disease, rota virus, transmissable gastroenteritis coronavirus, coccidiosis, cryptosporidosis, panleiukopenia, parvo
What is protein losing enteropathy?
protein leaks out through damaged mucosa to enter the lumen of the gut instead of entering lacteals
What are some examples of disease that cause protein losing enteropathy?
Johne’s disease in cattle and Chron’s in man
What causes Johnes disease?
paratuberculosis
What happens in johnes disease?
protein loss leads to severe emaciation and dehydration
What occurs in the chronic stage of Johnes disease?
loss of architecture followed by fibrosis and scarring of mucosa from immune response against mycobacterium obliterates most absorptive function over time from ileum down much of ascending colon
What are the symptoms of rota virus?
tip of villous is destroyed, can’t digest or absorb disaccharides and small peptides, not total loss absorptive capacity
What happens to crypt cells in animals that have rota virus?
they are still doing their secretory job
What happens to pigs with transmissible gastroenteritis coronavirus?
all villus cells destroyed, prolonged malabsorptive diarrhea, eventually virus is defeated and crypt cells divide like mad to cover villus
How do villi recover after a case of malabsorptive diarrhea?
the crypt regenerative cells divide at a more rapid pace and the muscularis mucosae shorten villi
What is the advantage of shortening the villi?
fewer cells are needed to fill in the defect = faster covering of denuded basement membrane
What is the disadvantage of shorteining villi for reparing?
less absorptive area for days to weeks afterward
What part of the gut does coccidiosis effect?
the cecum and colon
What part of the gut does cryptosporidiosis effect?
ileal cells and proximal colon cells
What is the severity of cryptosporidiosis’ effect based on?
the number of oocytes initially ingested
How does panleukopenia and parvo virus in dogs effect the gut?
it wipes out crypt cells which means in a few days no villus cells
Characterize the diarrhea associated with panleukopenia and parvovirus in dogs.
severe malabsorptive diarrhea - not unusual to see some hemorrhaging into the gut as denuded villi and crypts leak blood or are being destroyed by the bacteria that can grow in the tract
Where does dark, tarry looking blood in the stool originate from?
stomach and upper small intestine
What is dark, tarry looking blood called?
melena
Where does bright red blood originate from?
the colon or ocassionally the lower small intestine if digestive enzymes are not functional
What is bright red blood called?
frank blood
When the small intestine is undergoing malabsorptive diarrhea, what can the colon absorb?
Na, Cl, K, HCO3, water, and volatile fatty acids
What can’t the colon absorb?
sugars or amino acids because there are no colon enzymes for breaking down starches, sugars, or peptides
What is the difference in colon compensation for a pig that has coronavirus that is three weeks old or 3 days old?
the colon in the 3 week old can help keep the piglet alive if fed carbohydrates and electrolytes and because it has bacteria in the colon that will convert CHO to volatile fatty acids. The 3 day old piglet will die because it does not have the capability to turn CHO into volatile fatty acids, it will starve.
What type of diarrhea does hypermobility lead to?
malabsorptive because there is not enough time to allow for digestion and absorption
What opiates can be given to slow gut motility down?
morphine, codeine, and ioperamide
What is the disadvantage of giving opiates to slow down gut motility?
you lose the flushing action so if there is a toxin present you are keeping it in
What would should be in a solution for oral rehydration of malabsorptive diarrheas?
Na, K, Cl, glucose and amino acids
Why would you want to add glucose and amino acids to a solution for oral rehydration?
take advantage of Na-sugar and Na-amino acid transport mechanisms which are intact to get Na and chloride back into circulation; and provide energy
What causes osmotic diarrhea?
when lumen contents are not absorbed to an adequate extent or non-absorbable, osmotic particles draw water into the gut to maintain osmolatiry; when osmoles are not absorbed water stays in the lumen
What are some poorly absorbed substances?
milk of magnesia, epsom salts, and prune juice
What can cause osmotic diarrhea in dairy calves?
feeding milk replacer
Why does milk replacer lead to osmotic diarrhea?
it is made up of whey proteins which do not form a curd, this speeds up the rate at which they leave the abomasum
How is milk normally slowed down in the neonates abomasum?
casein partially digested in the abomasum by renin to form a curd to slow down passage from the abomasum
What is loose cow manure with a lot of bubbles a sign of?
acidosis and incomplete digestion/absorption of starches in the colon - usually do to vitreous corn or excess grain
How does the presence of oligosaccharides effect neonates and poultry?
it reduces feed intake
