Diarrhea is a change in one or more of the following characteristics of a bowel movement: increased frequency, increased fluidity, and/or increased volume. Diseases involving the small or large intestine, or both, may result in diarrhea. Systemic diseases or non-gastrointestinal diseases, such as hyperthyroidism in a cat, can also result in diarrhea. Many diseases produce similar pathophysiologic changes that culminate in diarrhea. The diagnosis and management of diarrhea is often based on these altered physiologic mechanisms.

Anatomic differences between the dog and the cat are minor. The primary function of the small intestine is to aid digestion, absorb nutrients, and move luminal contents aborad. The large intestine serves as a reservoir allowing the absorption of fluids and electrolytes and serves as a storage reservoir for feces. Intestinal motility functions to aid in digestion and in the absorption process while moving intestinal contents aborally. Numerous hormones and the nervous system aid in the integration of complex gastrointestinal functions.

Most of the diseases that produce diarrhea cause an increased concentration of fecal water. It takes only small increases in fecal water content to convert normal bowel movements to diarrhea. Diarrhea originating from small intestinal disorders is usually the result of fluid being delivered to the colon at a rate or volume that overwhelms normal colonic absorptive capacity (colon overload). Diarrhea originating from the large intestines usually occurs because fluid normally delivered to the colon is not absorbed due to decreased colonic absorptive capacity. Occasionally, weight loss occurs as the result of small bowel disease without diarrhea because the large bowel absorbs sufficient water to prevent diarrhea. Several pathophysiologic mechanisms, including hypersecretion, altered permeability, altered motility, and malabsorption, result in increased fecal water. Diarrhea may be acute (<7 days) or chronic (>2 weeks).

Hypersecretion

Hypersecretion occurs in several enteric bacterial diseases of domestic animals. In the normal small intestine, fluid and electrolytes are secreted by immature cells in the base of the intestinal villi. These are promptly absorbed by the mature epithelial cells lining the tips of the villi. This process is called “bidirectional flux,” and in the normal animal, absorptive flux always exceeds the secretory flux so that a net absorption of fluid and electrolyte occurs. In certain diseases, secretion of fluids is stimulated to such a degree that the absorptive capacity of the small and large intestine is overwhelmed, allowing a marked increase in fecal water. Enterotoxigenic bacteria, such as Escherichia coli, Clostridium perfringens, and Campylobacter species, produce substances that stimulate hypersecretion and watery diarrhea even though the gut appears intact structurally. In small animals, hypersecretion is of less importance than in large animals; however, in certain diseases, hypersecretion is partially responsible for increased fecal water.

Altered Permeability

The normal intestinal mucosa allows electrolytes that are absorbed to be retained in the enterocytes, creating an osmotic concentration gradient. This concentration gradient allows fluid to be absorbed from the intestinal lumen. Many enteric diseases dramatically alter gut permeability, causing absorbed electrolytes to flow back into the bowel lumen increasing fecal water. Small changes in permeability result in the secretion of electrolyte-rich, protein-poor fluid. Greater permeability changes produce the exudation of fluid containing considerable quantities of plasma proteins. An example of this process is lymphangiectasia, a protein-losing enteropathy. Characteristically, both albumin and globulin are lost in equal amounts, resulting in both hypoalbuminemia and hypoglobulinemia. Structural damage to mucosal integrity produces tremendous permeability changes. A 10,000-fold increase in gut permeability produces hemorrhagic exudates and suggests that the gut defense barriers have been greatly compromised.

Altered Motility

Very few cases of diarrhea are the result of intestinal hypermotility. Certainly, in diarrhea, luminal contents are transported aborally at an accelerated rate. However, hypermotility is not the primary cause; rather, hypomotility is the usual intestinal response when disease is present. Two major intestinal movements are normally present: rhythmic contractions or segmental contractions and peristalsis. Rhythmic segmentations slow down the passage of ingesta through the intestine, thereby aiding digestion and absorption. In diarrheal states, the strength of these contractions is greatly reduced, resulting in decreased resistance to the flow of ingesta. Anticholinergic drugs are generally contraindicated in the treatment of diarrhea since they further decrease the strength and rate of segmental contractions, which augments the hypomotile condition of the diseased gut. Peristaltic waves move ingesta in the aboral direction. There is little evidence to support the widely held concept that peristaltic activity is exaggerated in diarrheal states. In fact, when resistance to flow is decreased by lack of segmental contractions, very little peristaltic activity is required to move luminal contents a great distance. In summary, one should view the diseased gut as a hypomotile tube with decreased resistance to the aboral movement of luminal contents. Therapy regarding alteration of motility should be predicated on this assumption.

Malabsorption

Both structural and biochemical mechanisms may produce malabsorption. Diseases that destroy the villous integrity result in malabsorption of fluid, electrolytes, and basic nutrients. The enteric corona virus and parvovirus are examples of this mechanism. Altered permeability, hypomotility, and even hypersecretion (which occur in the recovery phase of these diseases) are also encountered. Infiltrative disease of the gut wall (inflammatory, infectious, or neoplastic) may also cause malabsorption. Forms of malabsorption have been recognized in dogs that have little structural abnormality in their gut. In these cases, biochemical malabsorption has been suspected (deficiency of brush border enzyme systems, lymphatic obstruction or malfunction, failure of active transport system). On a clinical basis, biochemical malabsorption is extremely difficult to prove. Overgrowth of the small intestine by certain bacteria may also cause malabsorption by blocking normal absorption of nutrients and fluid through the tips of mucosa villi.

There are several sequelae to intestinal malabsorption. Volume overload of the colon is a common mechanism; however, several other mechanisms come together to increase the volume of fecal water. Malabsorbed basic nutrients (e.g., carbohydrates and fatty acids) create significant osmotic effects within the gut lumen. These osmotically active substances tend to hold water in the gut lumen and may even stimulate the secretion of fluid into the lumen. Bacterial action on carbohydrate and fats in the gut lumen may produce substances (e.g., lactic acid and hydroxy fatty acids) that are osmotically active but also irritative to the intestinal mucosa. These substances aggravate the diarrheal state by enhancing gut secretion of fluid and electrolytes. Malabsorption of bile salts may contribute to hypersecretion and decreased fat digestion because the bile acid pool may become depleted.

Intestinal Resistance to Pathogens

Immunologic Mechanisms. The gastrointestinal immune system has to be versatile by eliminating injurious agents, while being tolerant of persistent harmless antigens. Because a single layer of epithelial cells separates the body from the luminal contents, normal epithelial cells are selective in what is allowed to come across. This “permselectivity” enables the body to receive adequate nutrition, but prevents overwhelming exposure to potentially deleterious antigens. Both antibody-mediated and cell-mediated immune mechanisms are important. Immunoglobulin A (IgA) is a secretory antibody produced by plasma cells in the gut-associated lymphoid tissue. This immunoglobulin contains a unique protein called “secretory component” that promotes transport across the mucosal barrier and protects the antibody from enzymatic digestion. Although IgA has little opsonic, complement-fixing, or bacteriocidal activity, it functions by preventing adherence of organisms to the intestinal mucosa. Other immunoglobulins (IgM, IgG, IgE) are present in low concentrations in the gut lumen unless inflammation of the intestinal wall allows their exudation.

The role of cell-mediated immunity in intestinal defense against pathogens is not well defined. It is known that animals with T-cell dysfunction are susceptible to gastrointestinal disease. Deficient cell-mediated immunity may play a role in the villous atrophy of chronic nonspecific enteritis and in bacterial overgrowth syndromes.

Nonimmunologic Mechanisms. Gastric acidity may render inactive a number of organisms and their toxins before they reach the lower portions of the intestine. Mucins in the mucous coat of the gastrointestinal mucosa act as receptors for organisms or their toxins, thus protecting the epithelium by competitive binding. Peristalsis helps prevent bacterial overgrowth in the gut. The role of altered intestinal motility in the pathophysiology of diarrhea has been discussed previously.

The intestinal microflora is a very important host defense mechanism against bacterial pathogens. It is normally quite stable; after disruption, it rapidly returns to its previous state. Several diarrheal conditions are treated symptomatically with antimicrobial drugs even though a primary bacterial pathogen is not suspected, thus referred to as antibiotic-responsive enteropathy. The normal gut flora serves as a primary defense barrier for the host. Bacterial pathogens must attach to the target cell before they can produce disease by either invasion or secretion of enterotoxins. Normal gut bacteria inhibit this attachment by occupying spaces available to pathogenic bacteria. Reduction of the normal gut flora with antimicrobial agents decreases this beneficial competition, allowing pathogenic bacteria to attach to target cells, proliferate, and potentially invade the gut mucosa. In certain situations, such as intestinal ileus, overgrowth of bacteria may contribute to diarrheal states. The use of antimicrobial drugs should be limited to conditions in which gut permeability has been greatly increased, as is the case with melena or hematochezia, or in those conditions where bacterial overgrowth is a significant component of the disease. Well-absorbed oral or parenteral antibiotics, such as tylosin or metronidazole, should then be used as opposed to poorly absorbed antibiotics.