introduction malabsorption. malabsorption syndrome diminished intestinal absorption of one or more...

Introduction

Malabsorption

Malabsorption Syndrome

• Diminished intestinal absorption of one or more dietary nutrients

• Not an adequate final diagnosis• Most are associated with steatorrhea– Increase in stool fat excretion of >6% dietary fat

intake

Approach to the Patient

Malabsorption

History, Symptoms and Initial Preliminary Observation

• Extensive small-intestinal resection for mesenteric ischemia– Short bowel syndrome

• Steatorrhea with chronic alcohol intake and chronic pancreatitis– Pancreatic exocrine dysfunction

Active Transport of Site-specific Dietary Nutrient Absorption

• Throughout SI (Proximal>Distal)– Glucose, amino acids, lipids

• Proximal SI (esp. duodenum)– Calcium– Iron– Folate

• Ileum– Cobalamin– Bile acids

Adaptation

• Morphologic and functional• Due to segmental resection• Secondary to the presence of luminal

nutrients and hormonal stimuli• Critical for survival

Steatorrhea

• Quantitative stool fat determination (72 hours)– Gold standard

• Qualitative Sudan III stain– Does not establish degree of fat malabsorption– For preliminary screening studies

• Blood, breath, and isotropic test– Do not directly measure fat absorption– Excellent sensitivity only with obvious steatorrhea– Not survived transition from research laboratory to

commercial application

Laboratory Testing

• Vitamin D malabsorption– Evidence of metabolic bone disease– Elevated serum ALP– Reduced serum calcium

• Vitamin K malabsorption– Elevated prothrombin time– Without liver disease– No intake of anti-coagulants

Laboratory testing

• Cobalamin/Folate malabsorption– Macrocytic anemia

• Iron malabsorption– Iron deficiency anemia– No occult bleeding from GIT– Non-menstruating female– Exclusion of celiac sprue• Iron is absorbed in the proximal SI

Diagnostic Procedures

Malabsorption

Diagnosis of Malabsorption

• Effect of prolonged (>24h) fasting on stool output– Osmotic diarrhea• Decrease in stool output: Presumptive evidence that

diarrhea is related to malabsorption

– Secretory diarrhea• Persistence of stool output: Not due to nutrient

deficiency

Stool Osmotic Gap

• Normal: 290-300 mosmol/kg H20 • Significant osmotic gap

– Suggests the presence of anions other than Na and K are present in the stool, presumably the cause of diarrhea

• Diff >50: osmotic gap present, dietary nutrient is not absorbed

• Diff <25: dietary nutrient is not responsible for the diarrhea

Useful in differentiating secretory from osmotic diarrhea

2 x (stool [Na+] + [stool K+]) ≤ stool osmolality

Schilling Test Urinary D-Xylose Test Radiologic Examination

Use

-determine the cause for cobalamin malabsorption-assess the integrity of stomach, pancreas, and colon

-test for carbohydrate absorption-assessment of proximal small-intestinal mucosal function

-evaluation of the patient with presumed or suspected malabsorption

Procedure

-performed by administering 58Co-labeled cobalamin orally and collecting urine for 24 h

- performed by giving 25 g D-xylose and collecting urine for 5 h

-performed with the examination of the esophagus to duodenal bulb-insufficient barium is given to the patient

AbnormalFindings <10% excretion in 24 h <4.5 g excretion Ex. strictures & fistulas

(Crohn’s disease),

Disadvantage- infrequently performed because of the unavailability of human intrinsic factor

- diminished use due to ease of obtaining a mucosal biopsy by endoscopy and false-negative rate

-abnormalities are rarely seen with current barium suspensions, skilled personnel required

Cobalamin Absorption

Dietary cobalamin in

meat

Bound to R-binder protein

in stomach

Complex bound in acid milieu in

the stomach

Uptake of cobalamin in receptors in

brush border of ileal enterocytes

Pancreatic protease

enzymes split cobalamin and binding protein

Cobalamin enters the

proximal small intestine and

binds to intrinsic factor

Schilling Test• Pernicious Anemia

– Atrophy of gastric parietal cells lead to absence of gastric acid and intrinsic factor secretion

• Chronic Pancreatitis– Deficiency of pancreatic proteases to split the cobalamin-R binder

complex• Achlorydia

– Absence of another factor secreted with acid that is responsible for splitting cobalamin from the proteins in food

• Bacterial Overgrowth syndromes– Bacterial utilization of cobalamin

• Ileal dysfunction– Impaired cobalamin – intrinsic factor uptake

Schilling Test58Co-Cbl

With Intrinsic Factor

With Pancreatic Enzymes

After 5 Days of Antibiotics

Pernicious anemia Reduced Normal Reduced Reduced

Chronic pancreatitis Reduced Reduced Normal Reduced

Bacterialovergrowth Reduced Reduced Reduced Normal

Ileal disease Reduced Reduced Reduced Reduced

Biopsy of Small-Intestinal Mucosa

• Essential in the evaluation of a patient with documented steatorrhea or chronic diarrhea

• Preferred method to obtain histologic material of proximal small-intestinal mucosa

• Indications:– Evaluation of a patient either with documented or

suspected steatorrhea or with chronic diarrhea– Diffuse or focal abnormalities of the small

intestine defined on a small-intestinal series

Biopsy Lesions and Findings

Results of Diagnostic Studies in Different Causes of SteatorrheaD-Xylose Test Schilling Test Duodenal

Mucosal BiopsyChronic pancreatitis

Normal 50% abnormal; if abnormal, normal with pancreatic enzymes

Normal

Bacterial overgrowth syndrome

Normal or only modestly abnormal

Often abnormal; if abnormal, normal after antibiotics

Usually normal

Ileal disease Normal Abnormal NormalCeliac sprue Decreased Normal Abnormal:

probably "flat"Intestinal lymphangiectasia

Normal Normal Abnormal: "dilated lymphatics"

Differential Diagnosis for Chronic Diarrhea: Approach to a Patient with Malabsorption

CC: Diarrhea 1 month duration

Prolonged fast (>24h)

Osmotic Diarrhea (>50 osmotic gap

difference)

SI Mucosal Biopsy

Diagnosis: Cause of Malabsorption

Secretory Diarrhea (<25 osmotic gap

difference)