Malabsorption Syndrome

Definition

• Disorders of absorption constitute a broad spectrum of conditions with multiple etiologies and varied clinical manifestations.

• almost all of these clinical problems are associated with diminished intestinal absorption of one or more dietary nutrients.

Functions of intestinal epithelia • nutrient digestion and absorption• Barrier and immune defense• Fluid and electrolyte absorption and

secretion• Synthesis and secretion of several

proteins• Production of several bioactive amines

and peptides

Bile Acids

• primary bile acids-synthesized in the liver from cholesterol

- cholic acid and chenodeoxycholic acid• secondary bile acids-synthesized from

primary bile acids in the intestine by colonic bacterial enzymes

- deoxycholic acid and lithocholic acid

Functions of bile acids (1)to promote bile flow, (2) to solubilize cholesterol and

phospholipid in the gallbladder by mixed micelle formation,

(3) to enhance dietary lipid digestion and absorption by forming mixed micelles in the proximal small intestine.

Enterohepatic circulation of bile acid

Lipids

lipid digestion and absorption

• (1) a digestive phase-both lipolysis and micelle formation requiring pancreatic lipase and conjugated bile acids, respectively, in the duodenum;

• (2) an absorptive phase for mucosal uptake and reesterification;

• (3) a postabsorptive phase that includes chylomicron formation and exit from the intestinal epithelial cell via lymphatics.

Carbohydrates• absorbed only in the small intestine in the

form of monosaccharides. • starch and disaccharides -digested by

pancreatic amylase and intestinal brush border disaccharidases to monosaccharides.

• Monosaccharide absorption occurs by a Na-dependent process mediated by the brush border transport protein SGLT1.

Proteins

• Present as polypeptides and requires extensive hydrolysis to di- and tripeptides and amino acids before absorption.

• Proteolysis –in stomach and small intestine• mediated by pepsin secreted as pepsinogen

by gastric chief cells and trypsinogen and other peptidases from pancreatic acinar cells.

Activation of proenzymes:• pepsinogen to pepsin-by pepsin in the presence of a pH <5

• Trypsinogen to trypsin-by the intestinal brush border enzyme

enterokinase and subsequently by trypsin

Classification and etiology:Disorders of intraluminal digestion• Pancreatic insufficiencies: -cystic fibrosis-chronic pancreatitis-carcinoma of pancreas• Bile salt insufficiency: -obstructive jaundice-bacterial overgrowth

• Enzyme inactivation-Zollinger-Ellison Syndrome• Rapid transit of food through gut-Gastroenterostomy-partial gastrectomy• Increased bile salt loss in faeces-terminal ileal disease- Crohn’s disease-terminal ileal resection• Lack of intrinsic factor-pernicious anaemia

Disorders of transport in the intestinal mucosal cell

• Defect in brush border hydrolysis-lactase deficiency• Defect in epithelial transport-coeliac disease -tropical sprue -lymphoma-Whipple’s disease

Disorders of transport from mucosal cell• Lymphatic obstruction-abdominal lymphoma-tuberculosis-lymphangiectasia• Defect in epithelial processing-abetalipoproteinaemia

Systemic diseases associated with malabsorption:

• Addison’s disease• Thyrotoxicosis• Hypothyroidism• Diabetes mellitus• Collagen vascular disease

Drugs causing malabsorption:• Colchicine-inhibits crypt cell division and

lactase• Neomycin-precipitation of bile salts in

gut,inhibition of lactase• Methotrexate-folic acid antagonist

causing inhibition of crypt cell division• Cholestyramine-binding bile salts• Laxatives

Clinical features• Diarrhoea, often steatorrhoea -Steatorrhoea-an increase in stool fat

excretion of >6% of dietary fat intake-loose,pale,bulky foul smelling stool

that float on water and difficult to flush away• bloating, flatulence and abdominal

discomfort.

• Weight loss • Growth retardation, failure to thrive,

delayed puberty in children• Swelling or edema • Anaemias, presenting as fatigue and

weakness.• Muscle cramp, osteomalacia and

osteoporosis• Bleeding tendencies

Tests for steatorrhea• Quantitative test–72hr stool fat collection – gold standard• > 6gm/day – pathologic

• Qualitative tests– Sudan lll stain• Detect clinically significant steatorrhea in

>90% of cases–Acid steatocrit – a gravimetric assay• Sensitivity – 100%, specificity – 95% , PPV

– 90%–NIRA (near infra reflectance analysis)• Equally accurate with 72hr stool fat test• Allows simultaneous measurement of

fecal fat, nitrogen, CHO

Schilling test• To determine the cause of cobalamine

(B12) malabsorption• Helps to asses the integrity of gastric,

pancreatic and ileal functions.• Abnormal cobalamine absorption in:

pernicious anemia, chronic Pancreatitis, achlorhydria,bacterial overgrowth, ileal dysfunction

• 58Co-labeled cobalamin adminitered orally & collect urine for 24 h,

• Urinary excretion of cobalamin will reflect cobalamin absorption provided that intrahepatic binding sites for cobalamin are fully occupied.

• To ensure saturation of hepatic cobalamin binding sites, 1 mg cobalamin is administered intramuscularly 1 h following ingestion of the radiolabeled cobalamin.

• <10% excretion in 24 h-abnormal

Urinary D-xylose test• assessment of proximal small-intestinal

mucosal function• a pentose,absorbed almost exclusively in the

proximal small intestine• Give 25 g D-xylose and collecting urine for 5 h.• abnormal test (<4.5 g excretion) primarily

reflects the presence of duodenal/jejunal mucosal disease.

• Can also be abnormal in patients with blind loop syndrome (as a consequence primarily of abnormal intestinal mucosa)

• false-positive-patients with large collections of fluid in a third space (i.e., ascites, pleural fluid).

• Tests for pancreatic insufficiency–Stimulation of pancreas through

administration of a mealor hormonal secretagogues , then analysis of duodenalfluid–Indirect tests – schilling test

• Tests for protein malabsorption Enteral protein loss measuring alpha-1 antitirypsin clearance

Endoscopy• Gross morphology – gives diagnostic clue–Cobblestone appearance – Crohn’s

disease.–Reduced duodenal folds and scalloping

of duodenal mucosa – celiac disease•Use of vital dyes to identify villous

atrophy

Biopsy of Small-Intestinal Mucosa

• primary indications (1) evaluation of a patient either with

documented or suspected steatorrhea or with chronic diarrhea

(2) diffuse or focal abnormalities of the small intestine defined on a small-intestinal series

• Lesions seen – classified into three1. Diffuse,specific– Whipple’s disease,– Agammaglobulinemia, – Abetalipoproteinemia

2. Patchy, specific– Crohn’s disease,– Intestinal lymphoma

• Suspected distal pathology - push enteroscopy wireless capsule endoscopy

3. Diffuse,non-specific – celiac sprue, – Tropical sprue– Bacterial overgrowth

Barium studies• evaluation of the patient with presumed or

suspected malabsorption• small-bowel series -a useful examination to

look for anatomical abnormalities, such as strictures and fistulas (as in Crohn's disease) or blind loop syndrome (e.g., multiple jejunal diverticula), and to define the extent of a previous surgical resection

Treatment• Replacement of nutrients, electrolytes and

fluid may be necessary. • In severe deficiency, hospital admission may

be required for parenteral administration.• Pancreatic enzymes are supplemented orally

in pancreatic insufficiency.

• Dietary modification is important in some conditions: –Gluten-free diet in coeliac disease.– Lactose avoidance in lactose intolerance.

• Antibiotic therapy will treat Small Bowel Bacterial overgrowth.

CELIAC SPRUE

• Etiology–Hypersensitivity to Gliadin portion of

gluten (wheat, barley, rye)–IgA antigliadin, IgA antiendomysial,

and IgA anti-tTG antibodies• Familial clustering–HLA-B8, DQw2 on Chromosome 6

• Classic flat mucosal lesion

Tropical Sprue

• manifested by chronic diarrhea, steatorrhea, weight loss, and nutritional deficiencies, including those of both folate and cobalamin

• affects 5–10% of the population in some tropical areas

• etiology and pathogenesis of tropical sprue are uncertain

• Klebsiella pneumoniae, Enterobacter cloacae, or E. coli

Short Bowel Syndrome

• clinical problems that occur following resection of varying lengths of small intestine

• any age from neonates through the elderly.• Following resection, the residual intestine

undergoes adaptation of both structure and function that may last for up to 6–12 months.

• Continued intake of dietary nutrients and calories is required to stimulate adaptation

• . Thus, enteral nutrition and calorie administration must be maintained

Bacterial Overgrowth Syndrome

• a group of disorders with diarrhea, steatorrhea, and macrocytic anemia whose common feature is the proliferation of colonic-type bacteria within the small intestine

• due to stasis caused by • impaired peristalsis (functional stasis),changes

in intestinal anatomy (anatomic stasis), direct communication between the small and large intestine

Whipple's Disease

• a chronic multisystem disease associated with diarrhea, steatorrhea, weight loss, arthralgia, and central nervous system (CNS) and cardiac problems

• caused by the bacteria Tropheryma whipplei.