Small intestinal disorders

Disorders causing malabsorbtion Celiac disease Autoimmune disorder with a prevalence of approximately 0.5 to 1 percent in the United States. (1 in every 100-200 persons) Inappropriate immune response to the dietary protein gluten, which is found in rye, wheat, and barley.

After absorption in the small intestine these proteins interact with the antigen-presenting cells in the lamina propria causing an inflammatory reaction that targets the mucosa of the small intestine.

Manifestations range from no symptoms to overt malabsorption with involvement of multiple organ systems and an increased risk of some malignancies

Pathogenesis - Immunity Gliadin protein fraction of wheat, rye, barley, and probably oats Class II HLA APC cells T-cells (lamina propria) Antigen ↑ IL-2, cytokines, IL-6, TNF  T-cell & Macrophage proliferation Mucosal injury

Pathophysiology of coeliac disease

Clinical features In infancy: After weaning: Classical features of diarrhea , malabsorbtion & failure to thrive. In older children: Nonspecific features such as delayed growth. O/E: --Features of malnutrition. --Mild abdominal distension. --Growth & pubertal delay leading to short stature in adulthood.

The Celiac Iceberg Symptomatic Celiac Disease Manifest mucosal lesion Silent Celiac Disease Latent Celiac Disease Normal Mucosa Genetic susceptibility: - DQ2, DQ8 Positive serology

In adult: Peak onset in third or forth decade. Female 2 > Male. The presentation is variable depending on the severity & extent of bowel involvement: 1-Florid malabsorbtion. 2-Nonspecific symptoms. 3-Folate or iron deficiency anemia. 4-Oral ulcerations. 5-Dyspepsia 6-Bloating.

Investigations A-**Jejunal Biopsy**:Characteristic histopathological changes but it is not specific for Coeliac disease. Other causes of villous atrophy are: 1-Dermatitis Herpitiformis 2-AIDS Enteropathy 3-Hypogammaglobulinaemia 4-Whipples disease. 5-Tropical Sprue 6-Lymphoma 7-Giardiasis 8-Radiation 9-Zollinger Ellison Syndrome

Normal small intestine Normal villi Figure 3. Endoscopic and biopsy findings in patients with and without celiac disease. (A) High-definition endoscopic photo of normal small intestine. The villi are clearly visible with no evidence of atrophy or scalloping of the folds. (B) Biopsy specimen of normal small intestine (hematoxylin-eosin; original magnification, × 100). (C) PillCam image of small intestine in a patient with celiac disease, showing scalloping of the mucosal folds (arrows) characteristic of a malabsorption pattern. There is also evidence of villous atrophy compared with normal. (D) Biopsy specimen of small intestine in a patient with celiac disease (hematoxylin-eosin; original magnification, × 100). Note the loss of villous architecture. Celiac Disease Villous atrophy

B-Antibodies: IgA anti-endomyseal antibodies are detectable by immunoflourescence in most untreated cases. They are not quantitative but are sensitive & specific for the diagnosis. IgG Abs must be analyzed in patients with coexisting IgA deficiency. The tissue transglutaminase Abs ( tTG ) assay has replaced other blood tests , is semi-quantitative & more accurate in patients with IgA deficiency. Abs used for screening for coeliac disease in diarrhea patients & for follow up of patients after treatment.

C-Haematology & Biochemistry: -Full blood count: Microcytic or Macrocytic anaemia Features of Hyposplenism: Target cells ,Spherocytes & Howell-Jolly bodies ). -Biochemical tests: Decreased Calcium, Magnesium , total protein ,Albumin or Vitamin D.

D-Other investigations: -Barium Follow through. Dilated loops of bowel Coarse or diminished folds Flocculation of contrast -Sugar tests of intestinal permeability are abnormal.

Management 1-Gluten free diet: Exclusion of WEAT, RYE ,BARLEY & OATS. Substituted by: RICE , MAIZE & POTATOS.

2-Mineral & vitamines supplement: 3-Steroid : for refractory cases.

COELIAC DISEASE

Prognosis: 1-Increased risk of malignancy ( T cell Lymphoma , Small bowel carcinoma & sequamous cell carcinoma of the oesophagus ). 2-Ulcerative Jejunoilietis. 3-Metabolic bone disease.

Quiz Which of the following statements about small bowel biopsy in the diagnosis of celiac disease is/are correct? A. It is recommended for all patients with suspected celiac disease. B. It is not required if serology results are positive. C. It is never required if serology results are negative. D. False-negative results may occur.

Quiz Which of the following statements about the treatment of celiac disease is/are correct? A. Supplementation of iron may be required. B. Oats can never be part of a gluten-free diet. C. Serologic values for celiac disease typically return to normal with successful treatment. D. Most patients should have a second small bowel biopsy to confirm treatment success.

Dermatitis Herpitiformis Characterized by croups of intensely itchy blisters over extensor surface of the limbs & back. Immunoflourecence: granular or linear IgA deposition at dermo-epidermal junction.

-Jejunal biopsy:100% partial villous atrophy even without GI symptoms. -< 10% of Coeliac patients have evidence of DH. Treatment: The rash respond to gluten free diet , but some patients required Dapson ( 100- 150 mg/d ).

Tropical Sprue Chronic & progressive malabsorption in patients from / in tropics associated with abnormality in small intestine structure & function. Aetiology: Small intestinal bacterial overgrowth with E.Coli , Enterobacter & klebsiella.

Pathology: Partial villous atrophy Subtotal villous atrophy Clinical features: Diarrhea & abdominal distension. Anorexia , fatigue ,& weight loss. Acute diarrhea & fever. Chronic condition: features of malabsorption. Remission & relapse.

Differential diagnosis: -- Infectious diarrhea & Giardiasis. Management: Tetracycline 250mg 6 hourly for 28 days + 5 mg folic acid/day.

Small Bowel Bacterial Overgrowth (( Blind loop Syndrome )) >104 /ml of bacteria in duodenum & jejunum due to impairment of normal physiological mechanism controlling bacterial overgrowth in the intestine.

Causes of small bowel bacterial overgrowth Mechanism Example Hpo or Achlorhydria Pernicious anaemia Partial gastrectomy Long term PPI therapy Impaired intestinal motility Scleroderma Diabetic autonomic neuropathy Chronic intestinal pseudo-obstruction Structural abnormalities: Gastric surgery Jejunal diverticulosis Entero-colic fistulae. Extensive small bowel resection. Stricture Impaired immune function Hypogammaglobulinaemia

Clinical features Watery diarrhea with or with out Steatorrhea. Anaemia due to B12 deficiency. Symptoms of underlying intestinal cause.

Investigations Decrease serum B12 concentration. Normal or increased serum folate. Barium follow through or small bowel enema: Blind loop or fistulae. Endoscopic duodenal biopsy. Glucose Hydrogen or C14 - glycocholic acid Breath test.

Management Treatment of underlying cause. Tetracycline 250 mg 6 h for 1 week or Metronidazole 400 mg 12 h or Ciprofloxacin 250 mg 12 h I.M B12 may be needed in some cases.

Specific causes of bacterial overgrowth Jejunal Diverticulosis: Usually asymptomatic seen by Barium Follow through. Patients > 50 y when bacterial overgrowth lead to malabsorption. Complications: Perforation, obstruction.

Diabetic Diarrhea Causes: Treatment: Autonomic neuropathy: decrease motility & decrease enterocyte secretion. Coexisting pancreatic insufficiency. Associated Coeliac disease. Treatment: Antibiotic +Antidiarrheal ( Diphenoxylate 5mg 8h or loperamide 2mg 6h or opiates, alpha adrenergic agonist Clonidin or Octeriotide may be used.

Progressive Systemic Sclerosis ( scleroderma ) Circular & longitudinal small muscle fibrosis. Malabsorption due to bacterial overgrowth. Features of intestinal pseudo obstruction.

Hypogamaglobulinaemia Due to decrease or absent IgA & IgM in the serum & Jejunal secretion. Clinical presentations: Chronic diarrhea due to bacterial overgrowth& Giardiasis. Diagnosis: Serum IG & intestinal biopsy: decrease or absent plasma cell& nodules of lymphoid tissue ,some have histological picture of Coeliac disease. Treatment: regular parantral IG replacement +treatment of Giardiasis.