Malabsorption syndrome: pathophysiology and diagnosis. Teaching slides

1. Malabsorption syndrome
Stefano Fiorucci, MD
Department of Surgery and Biomedical Sciences
University of Perugia

2. 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

3. CLASSIFICATION OF MALABSORPTION SYNDROMES
Inadequate digestion
Postgastrectomy
Deficiency or inactivation of pancreatic lipase
Exocrine pancreatic insufficiency, chronic pancreatitis, pancreatic cancer, cystic fibrosis, gastrinoma
Reduced intraduodenal bile acid concentration/impaired micelle formation
Cholestatic liver diseases
Bacterial overgrowth in small intestine:
Afferent loop /stricture/fistulas
Interrupted enterohepatic circulation of bile salts
Ileal resection, Crohn disease
Drugs (bind or precipitate bile salts)
neomycin, cholestyramine, calcium carbonate
Impaired mucosal absorption/mucosal loss or defect
Crohn’s disease
Inflammation, infiltration, or infection:
Crohn’s diseaase, amyloidosis, scleroderma Lymphoma, eophionolic gastroenteritis, celiac sprue,
collagenous sprue
Whipple disease, radiation enterits, infection includinggiardiasis, grapht vs host
Genetic disorders
Disaccharidase deficiency, agammaglobulinemia, abetalipoproteinemia, Hartnup
disease, cystinuria
Impaired nutrient delivery to and/or from intestine:
L ymphomaa Lymphangiectasia Lymphatic obstruction Circulatory disorders
Endocrine and metabolic disorders

4. Malabsorption:Causes
Exocrine pancreatic insufficiency
chronic pancreatitis
pancreatic cancer
cystic fibrosis
Inactivation of pancreatic
lipase – Gastrinoma(ZES)
drugs (orlistat)
bile acid (impaired
micelle formation)
parenchymal liver D.
cholestatic liver D.
Bacterial overgrowth
Anatomic 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 defect
intestinal resection or bypass
inflammation/infiltration/infect.
(celiac sprue, tropical sprue,
whippl’s disease, lymphoma,
mastocytosis, eosinophilic e.,
scleroderma, crohn’s D., …)
Impaired nutrient transport
lymphatic obstruction
(lymphoma, lymphangectasia)
CHF
Genetic disorders
disacharidase defficiency
Agamaglobulinemia
Abetalipoprotinemia
Endocrine/Metabolic disorders
DM
Hyperthyroidism
adrenal insufficiency
carcinoid syndrome

5. 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)

6. 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

7. Specific nutrient malabsorptive disorder
Carbohydrate malabsorption
- lactase deficiency (congenital,
secondary)
- Congenital sucrase-isomaltase
deficiency
- 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

8. 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

9. Mechanisms
1. 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

10. 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

11. Symptom or Sign Mechanism
Weight loss/malnutrition Anorexia, malabsorption of nutrients
Diarrhea 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, pancreatitis
Bone pain Calcium, vitamin D malabsorption, protein deficiency, osteoporosis
Tetany, paresthesia Calcium and magnesium malabsorption
Weakness Anemia, electrolyte depletion (particularly K+)
Azotemia, hypotension Fluid and electrolyte depletion
Amenorrhea, 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 malabsorption
Peripheral neuropathy Vitamin B12 and thiamine deficiency
Dermatitis Deficiency of vitamin A, zinc, and essential fatty acid

12. Signs, symptoms
Caloric 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

13. Malasportion syndrome
Diagnosis

15. 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 enteroscopy
wireless capsule endoscopy

16. 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

17. Wireless video-capsule

18. 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

19. Functional tests for malabsorption
(excluding pancreatic causes)
• Steatorrhea
• Shilling test
• Lactose test
• Xylose test
• Hydrogen breath test

20. 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

21. Schilling test
– To determine the cause of cobalamine(B12) malabsorbtion
– Helps to asses the integrity of gastric, pancreatic and ileal
functions.
• 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 hepatic
binding sites
• Collecting urine for 24 hr
(dependant on normal renal & bladder function)
• Abnormal - <10% excretion in 24 hrs

22. 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 excretion
show duodenal / jejunal mucosal D.
– False +ve results:
Renal dysfunction
 Inadequate urine sample
 Impaired gastric empyting,
 Ascites
 Drugs(ASA, indometacin, Neomycin)

23. Steatorrhea and D-Xylose Test Discriminate Maldigestion
from Malabsorption
MALDIGESTION
(pancreatic insufficiency)
MALABSORPTION
(celiac sprue)
Fecal Fat
D-Xylose
Excretion Normal
Jejunal Biopsy
Normal Abnormal “flat”

24. • 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