From the physiopathologic point of view, different mechanisms may produce diarrhea, although it is quite difficult in certain clinical conditions to distinguish among mechanisms that frequently overlap.

The assessment includes a detailed medical history, dietary history, previous surgery, medication review, physical examination, and description of stools. Frequency, amounts, and consistency of the stools should be carefully obtained. When the stools are consistently large, light in color, watery or greasy, free of blood, or contain undigested food particles, the underlying disorder is likely to be in the small bowel or the proximal colon. Indeed, small stool diarrhea, in which frequent but small quantities of feces that are dark in color and often contain mucus or blood pass in spite of a sense of urgency, is associated with a disorder of the left colon or rectum (1,13). Widespread inflammation may simultaneously produce both patterns of diarrhea, confirmed by the passage of nonbloody diarrheal fluid, pus, or exudates. Other useful information includes fecal incontinence, change in stool caliber, rectal bleeding, and small, frequent, but otherwise normal stools.

Timing and spontaneous recovery are also important. Although osmotic diarrhea typically stops or reduces after fasting or stopping the drug previously used, secretory diarrhea persists in spite of fasting. Chemotherapy-induced diarrhea typically occurs 2 to 14 days after therapy. Radiation colitis is probable in patients who have recently received pelvic radiation for malignancies of the urogenital tract and of the prostate.

A physical examination should precede any further investigation. Signs of anemia, fever, postural hypotension, lymphadenopathy, neuropathy, hepatosplenomegaly, ascites, gaseous abdominal distention or lymphadenopathy, reduced anal sphincter tone, a rectal mass or impaction, and deterioration of nutritional status are of paramount importance in defining the type of diarrhea. Some etiologies may have a typical clinical pattern. For example, carbohydrate malabsorption is typically associated with excessive flatus and mushy stools, whereas intermittent diarrhea and constipation are frequent in diabetic neuropathy, as well as in irritable bowel syndrome or subobstructive disorders. Autonomic neuropathy or anal sphincter dysfunction may be characterized by nocturnal diarrhea and fecal soiling. Alternating diarrhea and constipation suggests fixed colonic obstruction. Fecal impaction may cause apparent diarrhea because only liquids pass a partial obstruction. Symptoms of dumping syndrome after gastric surgery, such as early nausea, abdominal distention, weakness, and diarrhea after a meal followed by hypoglycemia, sweating, dizziness, and tachycardia, are typical. Secretory diarrhea combined with upper GI symptoms caused by refractory peptic ulcer disease is suggestive of a gastrin-secreting tumor. High circulating serotonin levels in carcinoid syndrome cause other effects besides diarrhea, including hypotension, sweating, flushing, palpitation, and wheeziness (19). The association of heat intolerance, palpitations, and weight loss suggests possible hyperthyroidism. Intestinal dysmotility or bacterial overgrowth due to diabetes, neoplastic conditions, or postoperative conditions should be suspected, excluding other causes.

Chronic bowel ischemia should be considered in elderly patients with the clinical features of diffuse atherosclerotic disease. Rectal examination and abdominal palpation should be performed to look for fecal masses and to exclude fecal impaction and intestinal obstruction, as well as for perianal fistula or abscess. Rectal involvement is probable in the presence of tenesmus, commonly defined as the passing of a little or no stool in spite of a sense of rectal urgency.

Of course, the site of neoplasm and metastases is of paramount importance. An abdominal x-ray will help the diagnosis. The location of the tumor will be verified by computed tomography scan, magnetic resonance imaging, angiography, or laparoscopy.

Laboratory findings should complete the investigation. If feasible, collected diarrhea stool specimen should be submitted for qualitative study. A positive finding in either the stool guaiac or the leukocyte test leads to a suspicion of an exudative mechanism, as in radiation colitis, colonic neoplasm, or infective diarrhea. Stool cultures for bacterial, fungal, and viral pathogens, as well as a formal evaluation of the GI tract, should complete the initial assessment (14). Gram stain of the stool can diagnose the presence of Staphylococcus, Campylobacter, or Candida infection. Multiple stool cultures should be obtained from patients with secretory diarrhea to rule out microorganisms producing enterotoxins that stimulate intestinal secretion. The presence of a microorganism in the stools is diagnostic.

An anionic gap of >50 mmol/L due to a reduction of stool content in sodium and potassium suggests an osmotic diarrhea, whereas lower values (<50 mmol/L) indicate a secretory diarrhea due to active secretion of salts and water.

The pancreatic secretion of lipase, amylase, and proteases breaks down fat to monoglycerides and fatty acids, carbohydrates to monosaccharides and disaccharides, and proteins to peptides and amino acids. Several processes have
been recognized to facilitate the absorption of fat from the aqueous luminal environment. Triglycerides are emulsified together with phospholipids, bile salts, and monoglycerides and diglycerides and dispersed into a variety of phases and particles. Lipid digestion begins in the mouth and in the stomach, active at a low pH, promoting emulsion stability and facilitating the action of pancreatic lipases. Gastric and pyloric motility further promotes emulsification of lipids. This effect is amplified by bile salts and biliary phospholipids, which also influence the absorption of cholesterol and sterol vitamins. Lipolysis to fatty acids and monoglycerides is mediated by pancreatic lipases (34). Protein digestion begins in the stomach. Acid denaturation leads to proteolysis, which is promoted by endopeptidases activated by an acidic environment, cleaving the internal bonds of large proteins to form nonabsorbable peptides. Pancreatic peptidases convert proteins and polypeptides into amino acids and oligopeptides. Hormonal and neural stimulation stimulates the release of proenzymes by the pancreas. Enteropeptidases and trypsin activate a cascade of events that promote the activation of chymotrypsin, elastase, and carboxypeptidases A and B in the duodenum. Digestion of carbohydrates has been described in Section Osmotic Diarrhea.

The hydrolysis of fat, protein, and carbohydrate by pancreatic enzymes, and the solubilization of fat by bile salts, may be altered by several conditions (34,45). In pancreatic carcinoma or following pancreatic resection, decreased pancreatic enzymes and bicarbonate release may limit the digestion of fat and protein leading to pancreatic insufficiency. These disorders may also be associated with malabsorption of fat-soluble vitamins. The Zollinger-Ellison syndrome is characterized by an extreme acid hypersecretion, causing a low luminal pH, which inactivates pancreatic enzymes with consequent fat malabsorption. A decrease in intraluminal bile salts due to disruption of the enterohepatic circulation is also seen in patients with Zollinger-Ellison syndrome. Biliary tract obstruction, terminal ileal resection, or cholestatic liver disease results in decreased formation of bile salts or delivery to the duodenum (46). Many postsurgical disorders have been associated with a marked proliferation of intraluminal microorganisms, including an afferent loop of a Billroth II partial gastrectomy, a surgical blind loop with end-to-side anastomosis, or a recirculating loop with sideto-side anastomosis. The final consequence depends on the extension of resection. With limited small bowel resections, malabsorbed bile acids pass into the colon and increase colon motility, while decreasing water and electrolyte absorption, resulting in diarrhea. In contrast, after massive small bowel resection, the bile acid pool will decrease because of the loss of intestinal bile salts. This phenomenon is associated with a loss of the absorptive intestinal surface and bacterial overgrowth. These processes will result in steatorrhea. Bacterial overgrowth causes catabolism of carbohydrates by gramnegative aerobes, deconjugation of bile salts by anaerobes, and the binding of cobalamin by anaerobes. Other than massive resection involving the ileocecal calve, causes of bacterial overgrowth include obstruction or strictures and autonomic neuropathy (45).