Diarrhea

Diarrhea is defined as a decrease in stool consistency and/or an increase in stool frequency and volume. It results from a complex interplay between colonic epithelial cell function, luminal factors, intestinal motility, and other factors.

Stool consistency and volume are determined partly by dietary factors (e.g., fiber intake) and fluid and electrolyte transport. Electrolyte transport mechanisms and diffusion processes in the small intestine render the fluid milieu isotonic. Active (primary and secondary) electrolyte transport mechanisms create an electrochemical gradient by which means cotransport of additional electrolytes can occur. Sodium is the major cation involved in the process of fluid absorption. Chloride constitutes the major anion that plays a significant role in fluid transport, and its active export into the intestinal lumen is an important mechanism of intestinal fluid secretion. Potassium and bicarbonate also play a role in intestinal absorption and secretion mechanisms. Water transport is facilitated by this osmotic gradient. It is then absorbed by processes of trans-cellular passage facilitated by aquaporins as well as by solvent drag via paracellular pathway; paracellu-lar permeability is regulated by junctional complexes. Glucose transport is linked to sodium transport, as is the case for certain amino acids. Electrolyte transporter function can be influenced by glucocorticoids and mineralocorticoids.

Intestinal motility also influences stool volume and consistency. The enteric nervous system, with some modulation by the autonomic nervous system, is the primary regulator of gastrointestinal motility. Neuropeptides, gastrointestinal hormones, and lumi-nal stimuli, such as dietary factors and interactions with bacteria, influence colonic motility.

Mechanisms of diarrhea can also be viewed from the perspective of absorptive capacity of the small intestine and colon. Of the 8-101 of fluid processed by the small and large intestines daily (composed of intake as well as gastrointestinal secretions), the smaller intestine absorbs 80-90% of the net load. The normal adult colon absorbs approximately 1 l of fluid per day but has a capacity to absorb 3 or 41 per day; diarrhea results when this threshold is exceeded.

From a pathophysiological perspective, four mechanisms of diarrhea are traditionally described: osmotic, secretory, motility, and inflammatory. A degree of overlap occurs between these different types of diarrhea.

Osmotic diarrhea occurs when the failure to absorb a solute (usually a carbohydrate) in the proximal small intestine occurs, thus rendering the fluid hypertonic rather than isotonic, as would regularly occur. Whereas electrolytes may be reabsorbed, the carbohydrate is not; rather, a portion of it is metabolized by enteric flora to short-chain fatty acids, carbon dioxide, hydrogen, and methane. With sodium and other electrolytes absorbed readily by the colon, and resultant low-sodium concentration in the lumen, compounded by the presence of non-absorbed carbohydrate, the high osmotic gradient draws fluid into the lumen and results in diarrhea. This type of diarrhea is characterized by a significant osmotic gap that can be calculated; an additional clinically significant feature of this type of diarrhea is that it diminishes upon cessation of ent-eral intake. Malabsorbed carbohydrate and its metabolites effect a lowering of the pH of the stool as well. Lactose deficiency is a good example of osmotic diarrhea in both children and adults. Ingestion of nonabsorbable sugars, such as sorbitol, can also lead to osmotic diarrhea. In children, excess intake of fruit beverages or of carbohydrates when recovering from a bout of acute gastroenteritis can occur, which resolves upon cessation of consumption of the carbohydrate.

Secretory diarrhea occurs when the net secretion of fluids and electrolytes from the colon exceeds their absorption. This type of diarrhea exists independent of eating and is not influenced by fasting or bowel rest. The prototypical example of pure secretory diarrhea (i.e., in the absence of inflammation or blood present in the stool) is of congenital chloride transport defects and of gastrointestinal hormonal disorders, such as in Zollinger-Ellison syndrome and disorders of vasoactive intestinal peptide or in other neuroendocrine tumors (Figure 1).

Cholera occurs when the toxin interacts with the colonocyte stimulating chloride, potassium, and bicarbonate secretion via toxin A stimulation of cyclic adenosine monophopshate; some degree of inflammation may accompany this. Oral rehydra-tion solution, which contributes fluid, sodium, and glucose, relies on cellular mechanisms to effect rehydration and is the mainstay of therapy.

Motility disorders influence intestinal function as pertains to absorption; whereas decreased transit enhances absorption of nutrients, significant decreases in motility can result in stasis. Deconjuga-tion of bile acids by enteric flora can result in malabsorption and inflammation. Increases in moti-lity can occur in the clinical picture of an inflamed colon, such as can occur in infants and adults. Acute hormonal influences are more common in the adult population, such as those seen with thyrotoxicosis

■ Raised Cl Secretion

■ Raised Cl Secretion

Diarrhea

Small intestine epithelium

Figure 1 Chloride mechanisms of secretory diarrhea. (Reproduced with permission from Silbernagl S and Lang F (2000) p. 151 Color Atlas of Pathophysiology, p. 333. New York: Thieme.)

Diarrhea

Small intestine epithelium

Figure 1 Chloride mechanisms of secretory diarrhea. (Reproduced with permission from Silbernagl S and Lang F (2000) p. 151 Color Atlas of Pathophysiology, p. 333. New York: Thieme.)

and carcinoid syndrome. Pharmacological agents or substance abuse can also influence motility.

Inflammatory diarrhea results in secretion of mucus, typically with the presence of blood in the lumen, which is also a cathartic agent. The integrity of the epithelial barrier is often compromised, with resultant exudation of water and proteins. Bacterial invasion of the mucosa may occur and is one example of inflammatory diarrhea. Additional disorders that may cause inflammatory diarrhea include allergic colitis and inflammatory bowel disease (IBD).

Lastly, diarrhea can be categorized clinically into acute and chronic forms, with the latter being defined as persistence of symptoms for more than 3 weeks. Each type of diarrhea can be further clinically divided based on age with respect to likelihood of cause.

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