Malabsorption syndrome

Stefano Fiorucci, MDDepartment of Surgery and Biomedical Sciences

University of Perugia

Malabsorption• 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 and are often referred to as the malabsorption syndrome.

• Malabsorption is a clinical term that encompasses defects occurring during the digestion and absorption of food nutrients

• Impairment can be of single or multiple nutrients depending on the abnormality.

• Most, but not all, malabsorption syndromes are associated with steatorrhea, an increase in stool fat excretion of >6% of dietary fat intake. Some malabsorption disorders are not associated with steatorrhea: primary lactase deficiency, a congenital absence of the small intestinal brush border disaccharidase enzyme lactase, is associated with lactose "malabsorption," and pernicious anemia is associated with a marked decrease in intestinal absorption of cobalamin (vitamin B12) due to an absence of gastric parietal cell intrinsic factor required for cobalamin absorption

CLASSIFICATION OF MALABSORPTION SYNDROMESInadequate digestion

Postgastrectomy

Deficiency or inactivation of pancreatic lipaseExocrine pancreatic insufficiency, chronic pancreatitis, pancreatic cancer, cystic fibrosis, gastrinoma

Reduced intraduodenal bile acid concentration/impaired micelle formationCholestatic liver diseasesBacterial overgrowth in small intestine:

Afferent loop /stricture/fistulasInterrupted enterohepatic circulation of bile saltsIleal resection, Crohn diseaseDrugs (bind or precipitate bile salts)neomycin, cholestyramine, calcium carbonate Impaired mucosal absorption/mucosal loss or defectCrohn’s disease

Inflammation, infiltration, or infection:Crohn’s diseaase, amyloidosis, scleroderma Lymphoma, eophionolic gastroenteritis, celiac sprue, collagenous sprueWhipple disease, radiation enterits, infection includinggiardiasis, grapht vs hostGenetic disorders

Disaccharidase deficiency, agammaglobulinemia, abetalipoproteinemia, Hartnupdisease, cystinuriaImpaired nutrient delivery to and/or from intestine:L ymphomaa Lymphangiectasia Lymphatic obstruction Circulatory disordersEndocrine and metabolic disorders

Malabsorption:Causes

Exocrine pancreatic insufficiency chronic pancreatitispancreatic cancercystic fibrosis

Inactivation of pancreatic lipase – Gastrinoma(ZES)

drugs (orlistat)bile acid (impaired

micelle formation)parenchymal liver D.cholestatic liver D.

Bacterial overgrowthAnatomic stasis(blind loop, stricture, fistula)Functional stasis(DM, scleroderma)

Interrupted interohepatic circulation of bile acid(ileal resection, crohn’s D.)

Drugs(bind or precipitate bile salt)neomycin, chlestyramine

Impaired mucosal absorbtion/mucosal loss or defectintestinal resection or bypassinflammation/infiltration/infect.(celiac sprue, tropical sprue,whippl’s disease, lymphoma,mastocytosis, eosinophilic e.,scleroderma, crohn’s D., …)

Impaired nutrient transportlymphatic obstruction(lymphoma, lymphangectasia)CHF

Genetic disordersdisacharidase defficiencyAgamaglobulinemiaAbetalipoprotinemia

Endocrine/Metabolic disordersDM

Hyperthyroidismadrenal insufficiency

carcinoid syndrome

Malabsorptive disorders can be categorized into

1-Generalized mucosal abnormalities

resulting in multiple nutrient malabsorption

2-Specific nutrient disorder

(carbohydrate, fat, protein, vitamin and mineral

malabsorption)

Malabsorptive disorders with generalized mucosal defects

• Celiac disease

• Cow’s milk allergy

• Microvillous inclusion disease

• Tufting enteropathy

• Lymphangiectasia

• Short bowel syndrome

• Chronic malnutrition

• Congenital immunodeficiency disorders

• HIV

• Parasitic infections

• Tropical sprue

• Bacterial overgrowth

Specific nutrient malabsorptive disorder

Carbohydrate malabsorption

- lactase deficiency (congenital, secondary)

- Congenital sucrase-isomaltasedeficiency

- Glucose- galactose malabsorption

Protein malabsorption- Enterokinase deficiency

- Amino acid transport defect

(eg;Hartnup disease )

Fat malabsorption

-Pancreatic exocrine insufficiency

(cystic fibrosis, shwachman

diamond syndrome, chronic

pancreatitis)

-liver and biliary disorders

- abetalipoproteinemia

Specific nutrient malabsorptive disorder

Mineral and vitamin malabsorption

-Congenital chloride diarrhea

-Congenital sodium absorption defect

-Acrodermatitis enteropathica

-Menke disease

-Vitamin D dependent rickets

-Vitamin B12 malabsorption

Mechanisms1. Luminal phase (processing defect)

– Digestive enzyme deficiency / inactivation– bile salt synthesis; Excretion; loss;

bile salt de-conjugation– gastric acid; intrinsic factor (p. anemia)– Bacterial consumption of nutrients

2. Mucosal phase– Epithelial transport defect – inflammations

infections– Brush border hydrolysis defect

congenital/acquired disacharidase deficiency

3. Post-absorptive phase– Enterocyte processing – Abetalipoproteinemia– Lymphocytic obstruction – intestinal

lymphangectasia

Clinical manifestations• History:

Diarrhea/steatorrhoea,Weight loss Symptoms of anaemia

• Diarrhoea – bulky, floating, malodorous stool –difficult to flush.

• Weight loss – may be profound, usually associated with anorexia.

• Anaemia – B12, iron, folate malabsorption.

• Patient may complain of dizziness, dyspnoea and fatigue

Symptom or Sign MechanismWeight loss/malnutrition Anorexia, malabsorption of nutrientsDiarrhea Impaired absorption or secretion of water and electrolytes; colonic fluid

secretion secondary to unabsorbed dihydroxy bile acids and fatty acids

Flatus Bacterial fermentation of unabsorbed carbohydrate

Glossitis, cheilosis, stomatitis Deficiency of iron, vitamin B12, folate, and vitamin A

Abdominal pain Bowel distention or inflammation, pancreatitisBone pain Calcium, vitamin D malabsorption, protein deficiency, osteoporosis

Tetany, paresthesia Calcium and magnesium malabsorptionWeakness Anemia, electrolyte depletion (particularly K+)

Azotemia, hypotension Fluid and electrolyte depletionAmenorrhea, decreased libido Protein depletion, decreased calories, secondary hypopituitarism

Anemia Impaired absorption of iron, folate, vitamin B12

Bleeding Vitamin K malabsorption, hypoprothrombinemia

Night blindness/xerophthalmia Vitamin A malabsorptionPeripheral neuropathy Vitamin B12 and thiamine deficiency

Dermatitis Deficiency of vitamin A, zinc, and essential fatty acid

Signs, symptomsCaloric Weight loss with normal appetite

Fat Pale,voluminous,greasy offensive diarrhea

Protein Edema, muscle atrophy, amenorrhea

carbohydrate Abdominal bloating, flatus, w. diarrhea

B12 Macrocytic anemia

Subacut combined degeneration of sp.cord

Folic acid Macrocytic anemia

Vit B (general) Cheliosis, glossitis,A.stomatitis, Acrodermatitis

Iron Microcytic anemia

Ca & Vit D Osteomalacea (bone pain,pathologic#), Tetany

Vit A Follicular hyperkeratosis, Night blindness

VIt K Bleeding diathesis, Hematoma

Malasportion syndrome

Diagnosis

Endoscopy

• Gross morphology – gives diagnostic clue– Reduced duodenal folds and scalloping

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

• Biopsy – to establish Dx– For patients with documented steatorrhea

or chronic Diarrhea

• Lesions seen – classifid in to three– Diffuse,specific e.g. whippl’s Disease– Patchy, specific – crohn’s D., lymphoma

infectious causes– Diffuse,non-specific – celiac sprue, Tropical sprue

autoimmune enteropathy

• Suspected distal pathology - push enteroscopywireless capsule endoscopy

Causes of villous atrophy in the duodenum

• Celiac disease

• Tropical sprue

• Small-bowel bacterial overgrowth

• Autoimmune enteropathy

• Hypogammaglobulinemic sprue

• Drug-associated enteropathy (e.g., olmesartan)

• Whipple disease

• Collagenous sprue

• Crohn's disease

• Eosinophilic enteritis

• Intestinal lymphoma Intestinal tuberculosis

• Infectious enteritis (e.g., giardiasis)

• Graft versus host disease

• Malnutrition

• Acquired immune deficiency syndrome enteropathy

Small Bowel Biopsy

Wireless video-capsule

Barium studies

• Important information about the gross anatomy and morphology of SB– Upper GI series with small

bowell follow through

– Duodenal tube

• double contrast study by passing a tube into proximal SB and injecting barium+ methylcellulose

• Normal study doesn’t exclude small bowell disease

Functional tests for malabsorption(excluding pancreatic causes)

• Steatorrhea

• Shilling test

• Lactose test

• Xylose test

• Hydrogen breath test

Tests for steatorrhea• Quantitative test

– 72hr stool fat collection – gold standard• > 6gm/day – pathologic• P’ts with steatorrhea - >20gm/day• Modest elevation in diarrheal disease

(may not necessarily indicate Malabsorption)

• 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) malabsorbtion

– Helps to asses the integrity of gastric, pancreatic and ilealfunctions.

• Abnormal cobalamine absorbtion in:pernicious anemia, ch. Pancreatitis, Achlorohydria, Bacterial overgrowth, ileal dysfunction

– The test • Administering 58Co-labeled cobalamine p.o.

– Cobalamine 1mg i.m. 1 hr after ingestion to saturate hepaticbinding sites

• Collecting urine for 24 hr(dependant on normal renal & bladder function)

• Abnormal - <10% excretion in 24 hrs

D-xylose test• D-xylose

– A Pentose monosacharide absorbed exclusively at the proximal SB

– Used to asses proximal SB mucosal function

• The test

– After overnight fast, 25 gm D-xylose p.o.

– Urine collected for next 5 hrs

– Abnormal test - <4.5 gm excretionshow duodenal / jejunal mucosal D.

– False +ve results:

Renal dysfunction

Inadequate urine sample

Impaired gastric empyting,

Ascites

Drugs(ASA, indometacin, Neomycin)

Steatorrhea and D-Xylose Test Discriminate Maldigestionfrom Malabsorption

MALDIGESTION

(pancreatic insufficiency)

MALABSORPTION

(celiac sprue)

Fecal Fat

D-Xylose

Excretion Normal

Jejunal BiopsyNormal Abnormal “flat”

• Carbohydrate malabsorbtion– Lactose tolerance test

• P.o. 50 gm lactose• Blood glucose at 0,60,120 min.• BG <20mg/l + dev’t of Sxs – diagnostic

• Breath tests hydrogen (also detects bacterial overgrowth)

The hydrogen breath tests and lactose tolerance tests have Sensitivity and Specificity >95% in detecting in lactose intolerancei-

H2 breath test is easier