L88: pathogenesis of diarrhea

MCQ: A cow with chronic weight loss and watery diarrhea has markedly thickened intestinal folds containing foamy macrophages in the lamina propria. Which disease and mechanism BEST explain this lesion?

Paratuberculosis (Johne's disease) - infiltrative inflammation causing malabsorption

MCQ: A 3-day-old calf presents with profuse watery diarrhea, dehydration, and metabolic acidosis. Necropsy shows intact villous architecture with normal epithelial cells. Which of the following BEST explains the mechanism of diarrhea in this case?

Secretory diarrhea due to enterotoxigenic Escherichia coli (ETEC)

MCQ: A foal with Rhodococcus equi pneumonia also develops severe diarrhea. At necropsy, the colon shows ulcerative typhlocolitis with fibrinous exudate and numerous macrophages containing intracellular bacteria. Which best describes the mechanism of diarrhea in this lesion?

Exudative diarrhea due to mucosal ulceration and inflammation

MCQ: A 12-year-old cat with chronic renal failure exhibits vomiting, diarrhea, and ulceration of the tongue, stomach and colon. Microscopy of the intestine shows fibrinoid necrosis of arterioles and mucosal ulceration. Which of the following BEST describes the pathogenesis?

Endothelial damage from uremic toxins leading to mucosal ischemia

MCQ: A horse with Salmonella infection develops severe mucosal ulceration and protein-losing enteropathy. Which change at the cellular level drives this process?

Separation of apical tight junctions

MCQ: Which combination of pathophysiologic mechanisms is MOST likely to be present in a chronic small-intestine diarrheal disease characterized by weight loss, bulky watery stools, and malabsorption?

Osmotic/malabsorptive + increased mucosal permeability

MCQ: what are the main targets of injury to intestinal mucosae?

1. villi

2. enterocytes

3. crypts

4. apical junction complexes

5. lamina propria

what factors are active during intestinal inflammation?

chemotactic factors

what are examples of diarrhea due to inflammation?

1. canine histiocytic ulcerative colitis

2. Johne’s disease (ruminants)

3. amyloidosis

4. lymphoma

how does inflammation lead to diarrhea?

chronic injury of the lamina propria results in dense cellular infiltration and disruption of the epithelial barrier, leading to increased permeability and fluid secretion

endotoxemia

vascular damage and DIC leading to thromboemboli in small vessel

what leads to primary necrosis of the GALT?

1. bovine viral diarrhea

2. rhodoccoccus equi infection

lymphangiectasia

SOLs of the lamina propria leading to obstruction to outflow of lymph

disorders of innervation

alteration of the microbiota results in changes of gut-brain axis

where does small bowel diarrhea originate from?

small intestine

what are signs of small bowel diarrhea?

1. watery, large volume diarrhea

2. weight loss

3. dehydration

4. malabsorption

where does large bowel diarrhea originate from?

colon

what are signs of large bowel diarrhea?

1. frequent small-volume diarrhea

2. urgency

3. mucus in stool

4. blood in stool

5. abdominal cramping

what is the functional unit of the small intestine?

villus

what are the targets for microbial colonization or destruction of intestinal mucosa?

1. absorptive enterocytes

2. crypt cells

3. microvilli and glycocalyx

4. apical junctional complexes

5. lamina propria

what are disorders of the lamina propria?

infiltrative, necrotizing, and vascular lesions

MCQ: what intestinal function is increased in all pathological processes associated with diarrhea?

intestinal motility

diarrhea

 increased fecal fluidity, usually accompanied by

increased defecation frequency and volume of feces

what does diarrhea lead to the loss of?

1. body water

2. electrolytes 

3. bicarbonate

what are the three major categories pathogens fall into that cause diarrhea?

1. invasive

2. induce inflammation

3. induce intestinal secretion

what do we classify diarrhea based on?

1. pathogen 

2. presence of inflammation

3. pathophysiological mechanism

noninflammatory diarrhea

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

what area of the bowel does noninflammatory diarrhea affect?

 proximal portions of the bowel 

inflammatory diarrhea

Organisms that produce cytotoxins or are invasive and activate cytokines that initiate inflammatory cascades

what area of the bowl does inflammatory diarrhea affect?

ileum, cecum, or colon

what are the types of diarrhea based on their pathophysiological mechanisms?

1. malabsorption and osmotic

2. hypersecretory

3. exudation

4. hypermotility

malabsorptive/osmotic diarrhea

high osmolality of chyme leads to osmosis into the lumen, and the content and fluid accumulates, causing distention and higher motility

hypersecretory diarrhea

 Direct stimulation of secretory cells and mucus cells to secrete more fluid/mucus into the gut lumen leading to increased volume and distension

exudation diarrhea

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

hypermotility diarrhea

 Distension of the intestine wall and direct stimulation by several mediators during inflammation lead to higher motility patterns t

what causes malabsorption or osmotic diarrhea?

1. diet

2. loss of digestive enzymes

3. crypt or villus death

4. lesions of the lamina propria

what area is affected by malabsorption or osmotic diarrrhea?

small intestine

what are infections that can cause osmotic diarrhea?

1. rotavirus and coronavirus infections of neonates

2. parvovirus

3. feline panleukopenia

4. clostridium perfingens type C

5. johne’s disease in ruminants

what happens to the GI from rotavirus and coronavirus infections in neonates?

1. necrosis of villus enterocytes

2. villous atrophy

3. malabsorption

what type of disorder does rotavirus and coronavirus infections of neonates cause?

disorder of the absorptive enterocytes

what type of disorder does parvovirus and feline panleukopenia cause?

disorders of undifferentiated crypt cells

why does diarrhea result from parvovirus and feline panleukopenia?

loss of regenerative cells and enterocytes mean there are no more absorptive cells

what disorder does Johne’s disease cause?

disorder of the lamina propria

what cells accumulate in joohne’s disease?

1. macrophages

2. giant cells

3. lymphocytes

4. plasma cells 

why do cows with johne’s disese get diarrhea?

loss of surface area from destruction of villi and increased distance between enterocytes decreases absorptive ability

what does diarrhea from bacterial overgrowth lead to?

1. bile salt deficiencies

2. excessive bacterial toxins

3. overconsumption of resources from bacteria

what diseases cause hypersecretory diarrhea?

1. enterotoxic e. coli

2. vibro cholerae

how does hypersecretory diarrhea occur?

Chloride (Cl−) hypersecretion by the cystic fibrosis transmembrane regulator (CFTR)

what type of disorder is exudative diarrhea?

Separation of Apical Junctional Complexes

what leads to exudative diarrhea?

1. pathogens

2. inflammatory cytokines

3. toxins

exudation

Increased capillary permeability (protein-losing enteropathy) by leaky tight junctions between enterocytes

what pathogens cause exudative diarrhea?

1. cryptosporidium

2. clostridium

what cells regulate intestinal inflammation?

1. toll-like receptors

2. cytokines

3. macrophages

4. dendritic cells

M cells

regulate presentation of antigens to GALT

what released from mast cells can lead to diarrhea?

1. histamine

2. prostaglandins

3. serotonin

4. proteolytic enzymes

what do enterocytes release in response to pathogens releasing enterotoxins?

cytokines (IL-8) to activate resident macrophages

what do activated macrophages release?

histamine, serotonin, and adenosine to increase intestinal secretion of water and chloride to inhibit absorption and promote diarrhea to remove pathogen

what are the consequences of diarrhea?

1. Dehydration and hypovolemia

2. Electrolyte imbalance (↓Na⁺, ↓K⁺, ↑H⁺)

3. Metabolic acidosis

4. Hypovolemic shock due to circulatory collapse

5. Tissue hypoxia and lactic acidosis