CHAPTER 22
Disorders of epithelial transport, metabolism, and digestion in the small intestine

Richard J. Grand

Boston Children’s Hospital, Boston, MA, USA

Phenotypically, disorders of intestinal epithelial transport demonstrate similar symptoms irrespective of the specific molecular basis of the defect in absorption. Symptoms include abdominal distension and/or pain, flatulence, and diarrhea. These disorders are usually classified by the specific nutrient that is malabsorbed, and many of them are quite rare. For some, clinical tests are available that may yield clues to the specific diagnosis. These will be discussed in this chapter.

Lactose malabsorption

Lactose malabsorption may occur whenever the level of small intestinal lactase is compromised either as a consequence of genetically regulated reductions in the expression of lactase enzyme or secondary to small intestinal injury (e.g., viral infection, giardiasis, celiac disease, and other insults). During intestinal development, fetal lactase mRNA and enzyme activity reach mature levels in the third trimester of gestation, and remain relatively constant until age 3–5 years. Subsequently, in the majority of the world’s population, lactase levels then fall by about 85–90% and remain low thereafter (known as lactase nonpersistence). In contrast, in peoples of northern European ancestry and in localized groups elsewhere, lactase activity remains at the infantile level for life (known as lactase persistence). Lactase nonpersistence has also been called “lactase deficiency” or “adult hypolactasia,” terms which are no longer in use. In a rare syndrome, congenital lactase deficiency, the enzyme fails to develop, and affected infants exposed to lactose immediately after birth develop severe watery diarrhea and failure to thrive (Figure 22.1). Although lactase nonpersistence leads to intestinal complaints of varying intensity, known as lactose intolerance, it is not strictly speaking a disease. Symptoms are induced by the osmotic effects of nonabsorbed lactose, increased intraluminal fluid, and increased intestinal transit. Lactic acid produced in the colon by colonic flora may exacerbate symptoms. This phenomenon is also the basis for the lactose breath hydrogen test (Figure 22.2).

The simplest screening test to identify lactase nonpersistence is withdrawal of dietary milk and milk products. Should this maneuver produce confusing results, the next screening test should be a breath hydrogen test (see Figure 22.2). Breath hydrogen content of greater than 10–20 ppm over baseline after ingestion of a lactose load consisting of 2 g/kg bodyweight up to 25 g is considered diagnostic for lactose malabsorption.

Sucrase–isomaltase deficiency

Of all the disorders of congenital carbohydrate absorption, the altered cellular events associated with sucrase–isomaltase deficiency have been best characterized. Seven genetic forms of this disorder have been defined, five of them leading to absent functional sucrase or isomaltase. Examples of the first three of these molecular abnormalities described are shown in Table 22.1. Clinical symptoms are characteristic of carbohydrate malabsorption, as noted above for lactase nonpersistence. A presumptive diagnosis of sucrase deficiency can be made after a clinical response to sucrose exclusion from the diet. The diagnosis can be confirmed by means of breath hydrogen testing after administration of 2 g/kg bodyweight (maximum 25 g) oral sucrose (Figure 22.3), or by means of mucosal disaccharidase assays that show low sucrase activity in biopsy specimens with normal mucosal histological features. Some patients with this condition lack any isomaltase activity. The associated decreased maltase activity is attributable to the fact that sucrase–isomaltase accounts for a substantial amount of normal maltose hydrolysis.

Cystic fibrosis

Cystic fibrosis is the most commonly occurring lethal genetic disorder in the world, and is associated predominantly with pulmonary and pancreatic disease but may affect multiple organs. With modern treatment programs, most affected people survive to adulthood (median age of survival is currently about 40 years). Effects on extrapulmonary organs, including the intestine, are variable. Intestinal symptoms are caused by the presence of thick mucus produced by altered chloride secretion (Figure 22.4) with prominent goblet cells and luminal retention of mucus (Figure 22.5

Only gold members can continue reading. Log In or Register to continue