Diarrhea: Causes, Types, and Mechanisms

Pathophysiology of Diarrhea Study Notes

• Diarrhea is characterized by excess water in feces, resulting from excessive secretions and/or decreased absorption.
• Diarrhea leads to severe electrolyte depletion, acid-base imbalance, and dehydration.
• A thorough history and physical examination are crucial for classifying the type of diarrhea.

Normal Intestine Function

• Fluid for normal intestine function is derived from ingested material and normal secretions from such organs as the stomach, intestine, pancreas, and gallbladder.
• Most fluid is absorbed in the small intestine, which has a limited capacity.
• Tight junctions in the small intestine allow small molecules and water to pass through.
• The cecum and colon absorb most of the water in horses.
• The normal function for intestines is when absoprtion exceeds secretion, so they can function as expected.

Mechanisms of Diarrhea

• Understanding the pathophysiology is important for categorizing diarrhea and guiding diagnoses and therapy.
• General mechanisms include secretory, malabsorptive, increased permeability, and abnormal motility processes.
• Multiple diarrhea forms can simultaneously occur with the same disease or etiologic agent.
• Salmonella enterica is one such example; it leads to secretory diarrhea by blocking chloride channels (due to effector proteins) and inducing hypersecretion of chloride via prostaglandin upregulation.
• Salmonella enterica also causes malabsorptive diarrhea as apoptosis of infiltrated enterocytes reduces mucosal surface area.
• A further mechanism of Salmonella enterica is to promote increased permeability when cytotoxins alter vascular permeability.

Secretory Diarrhea

• Secretory diarrhea is increased secretion of chloride, sodium, and other electrolytes.
• Exudation of fluid from inflammation can contribute to secretory diarrhea through prostaglandins and cytokines.
• Shifting the osmotic gradient via luminal contents can cause secondary secretory diarrhea.
• This process can lead to osmotic diarrhea and non-protein losing enteropathy.

Increased Chloride Secretion

• Cyclic adenosine monophosphate (cAMP) mediates increased chloride secretion.
• Chloride secretion can be due to reduced passive absorption of water and the promotion of chloride secretion.
• Infectious causes include Escherichia coli and Salmonella enterica.
• Non-infectious causes include vasoactive intestinal polypeptides from pancreatic islet cell tumors and histamine from mast cell tumors.

Enterotoxigenic Escherichia coli (ETEC)

• ETEC primarily affects calves, piglets, and lambs.
• ETEC uses fimbriae to adhere to microvilli; these fimbriae adhesins are age-dependent.
• Its enterotoxins bind to guanylate cyclase c receptor Gsa protein, which causes increased levels of cGMP and cAMP.
• This process causes secretion of chloride, blocks sodium absorption, and results in osmotic gradient leading to secretory diarrhea.

Malabsorptive Diarrhea

• Malabsorptive diarrhea is an impaired ability to absorb nutrients from villous damage, atrophy, or maldigested digesta.
• It is important to distinguish between protein-losing and non-protein-losing enteropathy since clinicopathologic findings can suggest prognosis and influence treatment decisions.
• This is often associated with severe hypoproteinemia and hypoalbuminemia.

Mechanisms of Malabsorptive Diarrhea

• Loss of protein due to damaged mucosa is a common mechanism; ruptured lymphatic vessels typically cause it.

• Loss of surface area for solute absorption occurs in the following ways

  • Loss of microvilli/villous enterocytes.
  • Overall villous atrophy.

• Increased thickness of lamina propria occurs through inflammatory cells, fibrosis, and neoplastic cells.

• Loss of digestive enzymes to break down food includes exocrine pancreas insufficiency (maldigestion) and loss of villous enterocytes.

Protein-Losing Enteropathies

• These are often associated with damage to lymphatic vessels
• severe hypoproteinemia.
• Infections: parasites (Cooperia, Nematodirus, Strongyloides, Trichostrongylus, cyathostomes), Johne's .
• Non-infectious causes include: lymphangiectasia, lymphoma, and inflammatory bowel disease.
• Lymphangiectasia, common in dogs, is a dilation, obstruction, and/or dysfunction of lymphatic vessels leading to their rupture, resulting in lymphatic fluid (rich in protein) leak into the intestinal lumen ultimately leading to malabsorptive diarrhea (protein loss).

Non-Protein Losing Enteropathies

• Non-protein enteropathies feature impaired absorption of electrolytes/nutrients.
• Patient's can still have hypoproteinemia.
• These include mucosa or digesta problems, where large, undigested solutes lead to osmotic diarrhea.
• Infectious etiologies to consider are rotavirus, Johne's, cryptosporidium, and coccidia.
• Non-infectious causes include laxatives, grain overload, and dietary, or antibiotic imbalances.
• Rotavirus targets villous enterocytes, thus impairing absorption of small solutes and production of enzymes.
• Rotavirus causes villous atrophy which results in malabsorptive diarrhea (a non-protein losing enteropathy).
• Rotavirus' secretory enterotoxin also increases chloride secretion, leading to secretory diarrhea

Increased Intestinal Permeability

• This can happen when there is inflammation or destruction of the mucosal barrier or vasculature; leaky tight junctions then permit macromolecules to pass through.
• Junctional complexes are sensitive to Starling forces.
• Potential infectious triggers are Clostridium perfringens, E. coli, Lawsonia intracellularis, parvovirus, and parasites.
• Non-infectious causes include amyloidosis, lymphoma, congestive heart failure, and portal hypertension.

Clostridium perfringens Type C

• This form of Clostridium particularly affects piglets, foals, lambs, kids, and calves.
• It is known for it's alpha toxin (CPA) and beta toxin (CPB), the latter of which is trypsin labile. Beta2 toxin, perfringolysin, and large clostridial toxin Tpel are also seen with the disease
• There is bacterial overgrowth, and CPB, the previously mentioned beta toxin, is produced.
• It forms pores in endothelial cells, influx of Ca, Na, and Cl causes swelling; this can kill the cell.
• Increased permeability diarrhea and ischemic necrosis of mucosa can greatly contribute to the effects.

Abnormal Motility

• Abnormal motility is a minor cause/contributor to diarrhea.
• Hypermotility leads to less efficient water and nutrient absorption (the primary disease is uncharacterized in veterinary medicine).
• Hypomotility promotes bacterial overgrowth.
• Potential causes include: parasites (cyathostomes, Oesophagostomum spp.), peritonitis, drugs, dysautonomia, and behavioral related effects.

Evaluating the Gastrointestinal Tract

• Consider normal parameters for the species, such as orientation, symmetry, size, number, color, and consistency.
• Most disease comes from something "added" (inflammation, hyperplasia, metaplasia, neoplasia) or "subtracted" (atrophy, hypoplasia).
• The cecum typically has one constituent in dogs and horses and two in chickens.
• Evaluate location (serosa vs. mucosa vs. transmural, mesenteric vs. anti-mesenteric), distribution (focal, multifocal, locally extensive, diffuse)
• Further consider measurement, shape, and consistency (soft, firm, hard).

Additional Considerations

• Assess characteristics of digesta (amount, color, consistency).
• Evaluate how thick the wall of a hollow viscus is (mucosa, submucosa, muscularis, serosa).
• Consider cut surface: solid, friable, hemorrhagic, mucoid or cystic.

Case Study Points

• Veterinarians used the cases of Victor and Liesl to show how to apply the principles from this presentation.
• Victor, an 8 year old cross breed dog had clinical signs for 2 months, showing waxing and waning vomiting with diarrhea as a common presenting clinical sign. Analysis also showed hyponatremia and hyperkalemia. Ultimately was diagnosed wth Addison's.
• Siamese, 8mo, female- Chronic diarrhea, fresh blood, muscus, Clinically WNL were the presenting signs of another case named Kitty! After further testing, PCR tested ositive for Tritrichomonas fetus.
• Then in another practice case study, a 7 year old female labrador named Liesl had clinical signs for 3 months including liquid diarrhea, 4-5 times a day, showing weightloss and ascites; the clinical sign of the other cases in contrast to their previous case. Ultimately, the dog was having the clinical issue because of a protein lose issue involving the animals lymphatic system.

Diarrhea Overview for Cats and Dogs

• Differentiate between acute vs chronic small animal diarrhea cases and with or without systemic signs.
• Determine if the diarrhea is small intestinal, large intestinal, or mixed.
• Develop logical approaches to your small animal workup, using know treatments and diagnoses.
• Diarrhea signs are: increased frequency, volume or fluidity.
• Melena signs can include tarry feces and flatulance from gas.
• In some cases, Dyschezia can be difficult or bring pain to the patient when defecating.
• Hematochezia will cause fresh blood in stool and Tenesmus will cause straining.
• Chronic cases can have intermittant signs greater than or equal to 3 weeks old.
• Acute signs may be self resolving, symptomatic with a need for some treatment, whereas chronic signs may lead the practice to determine more diagnostic investigations.
• For treating acute cases, highly digestible foods with lower residue count and moderate fat are important.
• With chronic, the patient history is very important at determining the overall outcome and diagnosis, alongside the workup results.

Antibiotics for Diarrhea

• Metronidazole creates a significant shift in the normal microbiome; illustrated by dysbiosis index.
• C. Hiranonis is a key species important for converting primary to secondary bile acids.
• Dysbiosis from Antibiotic overuse could lead to problems down the line.
• In cases where secondary bile acids cannot survive due to presence of Dysbiosis bacteria- this pro inflammatory with chronic inflammation changes and permiability increase

Protein Losing Enteropathy Definition

• Syndrome of intestinal diseases with non-selective protein losses via albumin and globulins reduction.
• Some causes of this clinical issue can stem from IBD (inflammatory bowel disease), Neoplasia (Lymphoma)- and Lymphangiectasia. These often present as Clinical issues.

Cased Studies

• The lecture uses various case studies to show how a new practitioner can approach each unique set of symptoms.
• Two major diseases are commonly tested for, Inflammatory Bowel Disease vs Chronic Inflammatory Enteropathy.
• Long term outcomes are found to vary based on long term clinical signs.
• Some examples of common drugs prescribed include: Metronidazole, Tylosin and prednisolone.

Explore the different types and causes of diarrhea including osmotic, secretory, exudative, and motility-related diarrhea. Learn about the underlying mechanisms of diarrhea caused by bacterial overgrowth and infections such as Salmonella enterica and ETEC.