Factors influencing the efficiency of nutrient uptake:

1. Number of villus absorptive cells present

2. Presence of functional hydrolases and specific nutrient transport proteins on the brush border membrane

3. Transit time

A. Selective Brush Border Disaccharidase Deficiency

Acquired lactase deficiency

1. Most common cause of selective CHO malabsorption in adults

2. Prevalence: highest in Asians, African-Americans, Native Americans;

3. lowest in those of northern European descent

4. Quantity of lactose ingested to produce symptoms varies from individual to individual and depends on a) amount of enzyme present, and b) capacity to salvage wasted lactose in the colon by bacterial metabolism to short chain FAs (SCFAs)

5. Diagnosis depends on a) empiric treatment with lactose-free diet, b) lactose tolerance test, c) hydrogen breath test after oral administration of lactose.

Secondary lactase deficiency with reversible loss of lactase activity may follow injury to small bowel mucosa, e.g. viral gastroenteritis, giardiasis, bacterial overgrowth.

*Lactase is the disaccharidase of lowest abundance in the brush border membrane and thus is the first to be affected with diseases.

B. Congenital enteropeptidase (enterokinase) deficiency is a rare cause of severe

protein malabsorption. Affected infants present with diarrhea, growth retardation

and hypoproteinemic edema.

C. Abetalipoproteinemia is a rare autosomal recessive disease due to mutation of the microsomal triglyceride transfer protein (MTP) which is required for assembly and secretion of apoB-containing lipoproteins (chylomicrons) across the basolateral membrane of intestinal epithelial cells and into lymphatics. Affected children present with severe fat malabsorption and neurologic disorders (retinopathy and spinocerebellar degeneration due to vitamin E deficiency).

D. Diseases Associated with Mucosal Damage

Main mechanism of malabsorption in these disorders is a decrease in absorptive

surface area.

1. Mucosal inflammation and villus flattening

• celiac disease

• tropical sprue

• food allergies

• infections

• food allergies

• graft vs. host disease (GVHD)

• intestinal rejection

• early radiation enteritis

2. Mucosal ulceration

• ulcerative jejunitis

• NSAID-induced ulcer(s)

• ischemia (radiation enteritis, mesenteric ischemia)

3. Surgical resection or bypass

• short bowel syndrome (SBS)

Table 3. Impaired Mucosal Absorption

E. Celiac Disease

1. Other terms: celiac sprue, non-tropical sprue, gluten-sensitive enteropathy

2. Etiology: an inflammatory disease of small bowel caused by ingestion of gluten (wheat protein).

3. Prevalence: US 1:4500 (based on GI Sx)

US 1:300

based on serology

Ireland 1:122

4. Associated with dermatitis herpetiformis (DH), a blistering, itching, burning rash on extensor surfaces, buttocks, and back; virtually all patients with DH have abnormal intestinal biopsies.

5. Two factors contribute to the development of celiac disease.
   Ingestion of gluten, a protein found in wheat and related grains, rye, barley, and oats. Toxic portion of protein is gliadin, the alcohol-soluble fraction which is rich in proline and glutamine.

Genetic background. Celiac disease runs in families; approximately 15% of first-degree relatives of affected individuals have celiac disease. There is 70-100% concordance rate in identical twins compared to 30% for nonidentical twins. The disease has been mapped to the HLA-D region on chromosome 6.

6. Onset most commonly at age 2 (after introduction of wheat into diet) and in early adult age but the disease can present any time.

7. Involves primarily the proximal small bowel but can involve ileum and colon.

8. Pathogenesis: Gluten triggers an inflammatory response resulting in villus flattening, which decreases the intestinal surface area available for fluid, electrolyte and nutrient absorption.

9. Clinical presentation is variable:

Diarrhea, weight loss, vitamin and mineral deficiencies

Anemia (iron and/or folate malabsorption)

Bone diseases (osteoporosis)

Neurologic disorders (myopathy, epilepsy, autism)

Gynecologic disorders (infertility, spontaneous abortion)

Psychiatric disorders (depression, schizophrenia)

10. Diagnosis

1. Intestinal biopsy is the “gold standard”.

• Characteristic findings of flat villi or subtotal villus atrophy which reverts to normal with gluten-free diet (GFD)

• A spectrum of mucosal abnormalities:

1. Increased intraepithelial lymphocytes (IEL) and normal villus/crypt architecture

2. Flat/atrophic mucosa

3. Hypoplastic mucosa

2. Serologic markers

Antigliadin antibodies (IgG, IgA) sensitive

Antireticulin antibodies not specific

Antiendomysial (EMA) antibodies (IgA)

Sensitivity 90%

Specificity 100%

* Tissue transglutaminase is the antigen which recognizes the anti-endomysial antibody

Category: Gastroenterology Notes