Pathogenesis of Diarrhea

Question 1

Structure of Small Intestine

Answer 1

• Increase villi as you go distally
• • Blood vessels move through each finger like projection (villi)
• • As we move more distally, there will be more lymphoid tissue, vessels…
• Villi have a continual process of renewal that takes 3-5 days
• There are progenitor cells/stem cells in the crypt area forming new cells by division for villus tips
• Think about diseases having effect on crypt cells and villus cells

Question 2

Villi and Microvilli

Answer 2

• Villi increase SA by 10 fold, microvilli increase 20 fold
• About 200 fold higher than surface without villi/microvilli (e.g. large intestine)
• Disease process that damages enterocytes will affect carbohydrate And protein absorption: brush border enzymes on mature enterocytes are involved in final digestion to monosaccharides, amino acids, peptides (ATP dependent!)
• Uptake of monoglycerides and free FA’s is by diffusion accross the villi into the lymph lacteals: Processes that increase the width of the villi hamper this process. More effective with the shorter the distance of the lymph lacteals. Anything that makes that distance wider will affect the absorption of fats

Question 3

Fluid Balance in Digestinal Tract

Answer 3

• Fluid dynamics within intestinal tract
• in a normal healthy dog, there needs to be an absorption of fluid from the small intestine, small amt. of reabsorption from colon–> very little water/fluid in final fecal product
• water reabsorption 90% in colon (canine)
• HIND GUT FERMENTERS: reabsorption mainly happening in large intestine –> horse and rabbit

Question 4

villous tip of villi

Answer 4

• Mature enterocytes (absorptive cells with tight intercellular junctions) absorb sodium, glucose and aa’s across the brush border on the apical surface. Sodium is pumped out of the cell on the basolateral aspect. This results in a net absorption of fluid

Question 5

Crypt Base

Answer 5

• Stem cells (secreting cells with leaky intercellular junctions) allow sodium to leak back into the intestinal lumen
• This results in net secretion of fluid
• Main function is secretory than absorptive. Net secretion of fluid
• Glucose and aa transport are major forces for absorption of fluid in the duodenum.
• the sodium pump is more important in the ileum and colon
• In a normal animal, net absorption at villus tips> net secretion in crypts
• In diarrhea, either decreased absorption and/or increased secretion

Question 6

Diarrhea

Answer 6

increased volume/fluidity of faeces

• Diarrhoea is a sign of disease affecting the intestinal tract

Question 7

Pathogenesis of Diarrhea

(4 basic mechs)

Answer 7

1. Altered epithelial cell transport (secretory diarrhea)
2. Altered structure or permeability of mucosa
3. Osmotic effects
4. Altered Motility

Question 8

Altered epithelial cell transport

(secretory diarrhea)

Answer 8

• Alteration in electrolyte movement across epthelial surface–> BACTERIA (E. Coli)
• attach to brush border and inject toxin into the cell
• This toxin prevents sodium pump activity at apical surface (brush border) and promotes excretion of sodium from mature enterocyte (Gradient is changed)
• Massive fluid loss into the lumen of the intestine
• profuse and watery diarrhea
• No destruction of epithelial cells: histology and gorss appearance normal
• Time limited until new layer of epithelium is formed (3-5 days)

Question 9

Altered Structure or Permeability

(Bacteria)

Answer 9

• Most of veterinary diseases!!
• Mucosal is clearly abnormal in structure
• Other bacteria (e.g. Salmonella) produce cytotoxins that damage and kill cells
• Death of enterocytes allows blood, fluid and other contents of the villus core to leak into the intestinal lumen
• Villus will not be as absorptive as mature enterocytes have been killed off
• There is clearly altered structure and permeability–> loss of function
• Appearance of blood and shreds of intestinal tissue in diarrhea: dysentery
• Diarrhea is much more severe. May have blood or intestinal tissue
• More damage to mucosa–> more complications may occur along the line, longer recovery
• Haemorrhagic enteritis

Question 10

Altered Structure or Permeability

(cellular infiltrates)

Answer 10

• within the core of the villus
• Massive increase in cellularity of the villus core will cause the width of the villus to increase and the height of the villus to decrease –> not enough epithelial cells to cover tall and fat villus!
• there Isn’t an increase in the turnover rate for microvilli cells
• Loss of SA for absorption
• Also due to cells having to stretch to cover altered villus, flatten and lose brush border
• Presence of nutrients in intestinal lumen causes diarrhea due to loss of function and absorption
• Will have an affect on carb and protein absorption because it is the brush border, but fat absorption will be affected as well (predominantly what is seen in diagnosis)
• Undigested material in gut–> bacterial overgrowth–> compromises intestinal function
• Intestinal Lymphoma or “cobblestone gut”: Thickening of mucosal surface and formation of semi permanent folds. Cancer causing alterations in structure of gut
• Can get from inappropriate inflammatory rxn too: lmphocytes invading plasma cells. Can result from allergies to diets in animals! lymphoplasmacytic enteritis

Question 11

Johne’s Disease

Answer 11

• Villi are distorted by massive infiltrations of macrophages
• Causes more macrophages to accumulate to the same area –> villi become wider and shorter than usual–> infectious disease causing alteration in structure
• Caused by infection!

Question 12

Altered Structure or Permeability

(Viral Infections)

Answer 12

• Viruses have tropism for different areas of the gut
• TGE, Coronavirus: attack tips and middle (PIG): short, stubby villi
• Rotavirus: attacks tips (CALF)
• EDIM, Rotavirus: attacks very tips (MOUSE)
• These result in villus atrophy
• panleukopenia, Parvovirus: attack Crypt base/stem cells (CAT)–> disastrous, cannot regenerate. this results in mucosal collapse

Question 13

Feline Infectios Enteritis

(parvovirus)

Answer 13

NEAR TOTAL DESSTRUCTION of mucosa

• mucosa has collapsed as villi are no longer have been created
• secondary infection caused by damage to mucosa in primary
• may make them more prone to infection later on in life

Question 14

Osmotic Diarrhoea

Answer 14

• Lack of brush border enzymes results in accumulation of small osmotic solutes in the intestinal lumen drawing water from bloodstream into the intestine
• Vet example: milk intolerance (lack of enzymes: lactase enzyme)
• Most laxitives are also designed to induce mild osmotic diarrhoea
• Reverse osmotic gradient occurring​

Question 15

Diarrhoea of altered motility

Answer 15

• there may not be alterations to the intestinal structure, but there is altered function - disruption/disorganization/ reduced co-ordination of segmental movements of intestine
• Hypermotility of intestinal tract
• Increase–> will cause less absorption–> diarrhea
• Hypomotility: risk of microbial overload due to increased nutrient source for them in a static intestie and bacterial not kept at a lower level by excretion in faeces
• -bacterial overload can lead to secondary causes of diarrhea