Laboratory Studies
Measurements of stool electrolytes and osmolality enable rapid and accurate assessment of the pathogenesis of this important chronic diarrhea (osmolar vs secretory) and greatly narrow the differential diagnoses of microvillus inclusion disease.
In assessing the nature of diarrhea, remember that stool samples should be sent for electrolyte and osmolarity measurements only if patients have liquid stools.
Fecal electrolytes demonstrate a typical pattern of secretory diarrhea. Fecal sodium levels are high (approximately 60-120 mEq/L), and no osmotic gap is found. In patients with secretory diarrhea, the following formula applies: 2(Na concentration + K concentration) = stool osmolarity ± 50. In osmotic diarrhea, stool osmolarity exceeds 2(Na concentration + K concentration) by 100 or more.
In osmotic diarrhea, findings on stool microscopy are negative for WBCs, blood (exudative diarrhea), and fat (steatorrhea).
Secretory diarrhea occurs in the fasting state and is associated with large output losses that cause dehydration and metabolic acidosis.
The stool culture is likely negative in prolonged diarrhea, as well as in a diarrhea that lacks blood, a finding that suggests no invasive bacteria.
Serum electrolyte levels may be very useful in the management but add little information to establish a diagnosis.
Cystic fibrosis, the most common cause of pancreatic insufficiency, is best confirmed or ruled out by performing the sweat test.
Other Tests
Findings from duodenal biopsy must not be considered diagnostic. Histologic results of duodenal biopsy samples can range from essentially normal to mildly abnormal, showing the following:
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Thin mucosa caused by hypoplastic villus atrophy
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Diffuse villus atrophy (loss of villus height)
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Crypt hypoplasia
The diagnosis rests on findings demonstrated by electron microscopy (see Histologic Findings).
Rectal biopsy findings demonstrate microvillous involutions and an increased number of secretory granules. This test has been proposed as a relatively easy method for making an early diagnosis.
Histologic Findings
Electron microscopy demonstrates well-preserved crypt epithelium with abundant microvilli. Villus enterocytes are severely abnormal, particularly toward the apices of the short villi. The microvilli are depleted in number, short, and irregularly arranged. Some of the enterocytes contain the typical microvillus involutions, which are intracellular vacuoles where microvilli are observed lining the inner surface. A striking feature is a number of small, membrane-bound vesicles containing electron-dense material.
A few cases have been described in which the classic microvillous inclusions are shadowed by other features, such as large aggregates of electron lucent, vermiform membranous vesicles in enterocyte cytoplasm. [14, 15]
PAS staining of the intestinal biopsy sample reveals PAS-positive material in the apical cytoplasm. The normal linear staining of the glycocalix is absent. PAS accumulates in low crypts in atypical microvillus atrophy, in upper crypts in congenital microvillus atrophy, and in low villi in late-onset microvillus atrophy.
Anti-CD10 immunohistochemistry shows a marked enlargement of the stained band that appears doubled compared with controls. [16, 17] CD10 is a neutral membrane-associated peptidase; thus, abnormal stain findings with PAS or anti-CD10 immunohistochemistry are expressions of the abnormalities in microvillar structure.
