Lesson 88 - Pathogenesis of General Diarrhea

What is acute diarrhea?

sudden onset, lasting less than 2 weeks, often caused by infections, toxins, or dietary indiscretion

What is chronic diarrhea?

persistent for more than 2-3 weeks, often linked to inflammatory, metabolic, or neoplastic conditions

What are examples of dietary indiscretion?

spoiled or contaminated food, non-food items, excessively fatty or rich foods, sudden diet changes that disrupt gut microbiota and digestion

What are causes of exudative (inflammatory) diarrhea?

mucosal ulceration, leukocyte infiltration, protein-losing enteropathy

What are causes of hypermotility diarrhea?

peristalsis, ileus, serotonin-mediated motility

What is melena?

black, tarry feces due to digested blood from upper gastrointestinal tract

What is hematochezia?

presence of fresh blood in feces, indicating bleeding from the lower GI tract

What is dyschezia?

painful or difficult defecation, often due to rectal inflammation, anal sac disease, or tumors

What is tenesmus?

straining to defecate, commonly seen with large intestinal diseases like colitis

What causes fecal urgency?

colonic irritation

What is steatorrhea?

presence of excess fat in feces, seen in malabsorptive conditions like EPI

What is mucorrhea?

excess mucus in feces, usually due to colonic inflammation

What is borborygmi?

audible gut sounds caused by movement of gas and fluid in the intestines

What are Treg cells?

T regulatory lymphocytes

What are T regulatory lymphocytes?

subtype of CD4 T cells expressing high levels of CD25 and the transcription factor FoxP3

What is the function of T regulatory lymphocytes?

suppress excessive immune responses to prevent autoimmunity and excessive inflammation by releasing inhibitory cytokines and direct cell-to-cell interactions

What are inhibitory cytokines?

IL-10, TGF-beta

What are microfold cells?

M cells

What are M cells?

specialized epithelial cells found in Peyer's patches and other GALT; lack microvilli and have a folded surface to facilitate antigen transport

What is the function of M cells?

capture antigens from the intestinal lumen and deliver them to underlying immune cells to initiate an immune response

What cells are crucial for mucosal immunity?

M cells

What are mast cells?

granulated immune cells found in tissues, especially near blood vessels, skin, and connective tissue with large granules of histamine, heparin, and cytokines

What is the function of mast cells?

key players in allergic reactions, parasites, and inflammation, when activated release histamine and other mediators

What are the eosinophils?

granulocytes with bilobed nuclei and cytoplasmic granules containing toxic proteins like major basic protein, eosinophil peroxidase, eosinophil-derived neurotoxin

What are functions of eosinophils?

primarily involved in parasite defense and allergic reactions; release cytotoxic granules that kill large parasites and modulate immune responses by secreting inflammatory mediators like IL-5 and leukotrienes

What are the main dysfunctions/responses to injury for the small intestine?

inflammation, necrotizing processes, lymphangiectasia, disorders of innervation, diarrhea

What are the types of diarrhea?

small bowel diarrhea and large bowel diarrhea

What causes inflammation of the intestines?

chronic injury of the lamina propria

How does inflammation cause diarrhea?

dense cellular infiltration causes disruption of the overlying epithelium which increases permeability and swelling of the lamina propria which causes blunting and fusion of the villi reducing absorptive surface area

What type of dysfunction does canine histiocytic ulcerative colitis cause?

inflammation

What type of dysfunction of Johne's disease cause?

inflammation, lymphangiectasia

What type of dysfunction does amyloidosis cause?

inflammation

What type of dysfunction does lymphoma cause?

inflammation, lymphangiectasia

What does swelling of the lamina propria cause during inflammation?

blunting and fusion of intestinal villi which reduces the absorptive surface area of the intestinal mucosa

What does physical impairment of mucosal diffusion by space-occupying cells cause during inflammation?

disruption of the overlying epithelium which increases its permeability

What are the mechanisms of necrotizing processes in the intestine?

primary necrosis of the GALT and endotoxemia

What does primary necrosis of the GALT cause?

extension to the overlying epithelium

What are some infectious examples causing primary necrosis of GALT?

bovine viral diarrhea of cattle and Rhodococcus equi infection of horses

How does endotoxemia cause necrosis?

vascular damage, DIC, and thromboemboli in small vessels cause hemorrhage, necrosis, ulceration of the intestine

What is the pathogenesis of lymphangiectasia?

obstruction of flow in lymph vessels which can be caused by space occupying lesions in the lamina propria

What are examples that can cause lymphangiectasia?

Johne's disease in ruminants and lymphoma

How does Johne's disease cause lymphangiectasia?

granulomatous lymphangitis and lymphadenitis obstruct the lymph vessels

What are disorders of innervation?

agangliosis and dysautonomia

What are some issues that can cause disorders of innervation?

botulinum toxin, inflammatory diseases, idiopathic, hereditary, dysbiosis, interstitial cells of cajal

How are the microbiota and brain connected?

bidirectional neurohormonal interchange between intestinal microbiota and brain

What is dysbiosis?

state of microbial imbalances in the alimentary system

What does dysbiosis affect?

early brain development in mice, IBS, Crohn's disease, ulcerative colitis, demyelination in multiple sclerosis, hepatic encephalopathy, psychiatric disorders

How can interstitial cells of cajal affect the intestines?

inflammation or loss of these cells affects coordinated movement of the alimentary system

Where does small bowel diarrhea originate from?

small intestine

What type of diarrhea does malabsorption syndromes cause?

small bowel

What type of diarrhea does irritable bowel syndrome cause?

small and large bowel

What type of diarrhea does small bowel bacterial overgrowth cause?

small bowel

What type of diarrhea does medications cause?

small and large bowel

What type of diarrhea does neoplasia cause?

small bowel

What type of diarrhea does infectious colitis cause?

large bowel

What type of diarrhea does inflammatory bowel disease?

large bowel

What type of diarrhea does histiocytic ulcerative colitis cause?

large bowel

What type of diarrhea does food intolerances cause?

large bowel

What type of diarrhea is water with large volume?

small bowel

What type of diarrhea is small volume?

large bowel

What type of diarrhea can be nocturnal?

small bowel

What type of diarrhea causes weight loss?

small bowel

Where does large bowel diarrhea originate from?

colon

What are disorders of the intestinal epithelium?

absoprtive enterocytes, undifferentiated crypt cells, microvilli, glycocalyx, apical junctional complexes

What are the lesions of disorders of lamina propria?

infiltrative, vascular, necrotizing

What are the defense mechanisms of the intestine?

indigenous flora, secretions, gastric acidity, intestinal motility, epithelial cell turnover, bile salts

What is a secondary defense response for the intestines?

kupffer cells in the liver

What do we lose in diarrhea?

water, electrolytes, and bicarbonate

What are the ways to classify diarrhea?

by pathogen, by presence of inflammation, and by mechanisms

What are the major categories of pathogen classified diarrhea?

invasive, inflammation, secretion

What is secretion pathogen diarrhea?

caused by pathogens that induce intestinal secretion

What organism causes secretion diarrhea?

Enterotoxic Excherichia coli

What organism causes inflammation diarrhea?

Lawsonia, Brachyspira, Salmonella

What organism causes invasive diarrhea?

Salmonella

What type of diarrhea does Salmonella cause?

Invasive and inflammatory

What organisms cause noninflammatory diarrhea?

enterotoxic E. coli, rotavirus, Cryptosporidium parvum

What is noninflammatory diarrhea?

organisms that disrupt the absorptive or secretory mechanisms of the enterocytes without destroying the cells

What parts of the bowel are affected in noninflammatory diarrhea?

proximal portions mainly

What is inflammatory diarrhea?

organisms that produce cytotoxins or are invasive and activate cytokines that initiate inflammatory cascade

What parts of the bowel are affected in inflammatory diarrhea?

ileum, cecum, colon

What are the mechanisms type of diarrheas?

malabsorption/osmotic, hypersecretory, exudation, hypermotility

What is the pathogenesis of malabsorption and osmotic diarrhea?

molecules that are poorly absorbed increase the osmolality of chyme leading to osmosis into the lumen which causes distention and higher motility

What is the pathogenesis of hypersecretory diarrhea?

direct stimulation of secretory cells and or mucus cells to secrete more into the lumen leading to distension and higher motility

What is the pathogenesis of exudation diarrhea?

severe mucosal damage leads to massive fluid, electrolyte, and protein loss

What is the pathogenesis of hypermotility diarrhea?

distension of the intestine wall and direct stimulation during inflammation lead to higher motility patterns

What are the causes of malabsorption or osmotic diarrhea?

dietary, exocrine pancreatic insufficiency, crypt or villous death, space occupying lesions of the lamine propria, rotavirus, coronavirus, decreased surface area

What part of the intestine is usually affected in malabsorption or osmotic diarrhea?

small intestine

What issue is usually associated with large intestine malabsorption or osmotic diarrhea?

malabsorption of bile salts and fatty acids

What kind of disorder does rotavirus and coronavirus cause?

disorders of the absorptive enterocytes

How does rotavirus and coronavirus cause malabsorption/osmotic diarrhea?

necrosis of villous enterocytes on the tip and villous atrophy can decrease surface area and enzymes that regulate the osmotic state of the lumen

What type of diarrhea does parvovirus and feline panleukopenia cause?

malabsorption and osmotic diarrhea

What disorder does parvovirus and feline panleukopenia cause?

disorders of undifferentiated crypt cells

How does parvovirus and feline panleukopenia cause malabsorption diarrhea?

targets crypt stem cells so there is a loss of regenerative cells and enterocytes which results in lack of absorptive cells

What type of diarrhea does lactose intolerance cause?

malabsorption and osmotic diarrhea

What disorder does lactose intolerance cause?

abnormalities of the microvilli and glycocalyx

How does lactose intolerance cause malabsorption or osmotic diarrhea?

lack of lactase in the glycocalyx means unable to digest lactose and it is fermented by bacteria increasing osmolality in the lumen

What type of diarrhea does Clostridium perfringens type C cause?

malabsorption or osmotic diarrhea

What disorder does Clostridium perfringens type C cause?

epithelial targets unknown or nonspecific

How does Clostridium perfringens cause malabsorption or osmotic diarrhea?

produces a nonspecific cytotoxin which causes necrosis of villous absorptive cells which extends into the lamina propria and blood vessels causing massive and acute necrohemorrhagic enteritis

What type of diarrhea does mycobacterium paratuberculosis cause?

malabsorption or osmotic diarrhea