Clinical features and diagnosis of malabsorption

1. Clinical features and diagnosis of
malabsorption
Presented by: Farshad Mirzavi
Ph.D candidate in Clinical Biochemistry

2. Introduction
oMalabsorption:
Impaired transport of nutrients from the intestine into the blood.
oMaldigestion:
Incomplete breakdown of nutrients in the gastrointestinal tract,
usually due to lack of digestive enzymes.
2

3. Introduction
o Three steps are required for normal nutrient absorption:
1. Luminal and brush border processing:
Dietary carbohydrates, proteins and fats are hydrolysed and solubilized.
2. Absorption into the intestinal mucosa:
Final hydrolysis and uptake of saccharides and peptides takes place and lipids taken
up by epithelial cells are processed and packaged for cellular export.
3. Transport into the circulation:
The absorbed nutrients enter the vascular or lymphatic circulation.
3

4. Causes
o Factors that may cause malabsorption syndrome include:
Damage to the intestine from infection, inflammation, trauma.
Prolonged use of antibiotics.
Lactase deficiency, or lactose intolerance.
Diseases of the gallbladder, liver, or pancreas.
Radiation therapy.
Some drugs, such as neomycin, colchicine, or cholestyramine.
Other conditions such as celiac disease, Crohn’s disease, chronic
pancreatitis, or cystic fibrosis.
4

5. laboratory manifestations of malabsorption
5

6. Mechanisms of Fat Malabsorption
• Pancreatic insufficiency
• Bile acid deficiency
• Small intestinal bacterial overgrowth
• Loss of absorptive surface area
• Defective enterocyte function
6

7. Mechanisms of Carbohydrate Malabsorption
• Selective disaccharidase deficiency
• Disruption of brush border/enterocyte function
• Loss of mucosal surface area
• Pancreatic insufficiency
7

8. Mechanisms of Protein Malabsorption
• Pancreatic insufficiency
• Disorders with impaired enterocyte function
• Disorders with decreased absorptive surface
• Protein-losing enteropathy
8

9. Diagnosis
oStool tests:
Stool tests can measure fat in samples of stool. These tests are the
most reliable because fat is usually present in the stool of someone
with malabsorption syndrome.
9

10. Diagnosis…
oBlood tests:
Such as vitamin B-12 , vitamin D , folate , iron , calcium , albumin
, phosphorus , and protein.
A lack of one of these nutrients may not necessarily mean you
have malabsorption syndrome. It can mean you are not choosing
foods with healthy levels of nutrients. Normal levels of these
nutrients suggest that malabsorption is not the problem.
10

11. Diagnosis…
oBreath tests:
Breath tests can be used to test for lactose intolerance. If lactose is
not being absorbed, it enters the colon. Bacteria in the colon break
down the lactose and produce hydrogen gas. The excess hydrogen
is absorbed from your intestine, into your bloodstream, and then
into your lungs. You will then exhale the gas.
If you have hydrogen gas in your breath after ingesting a product
containing lactose, you may have lactose intolerance.
11

12. Diagnosis…
oImaging tests:
Imaging tests, which take pictures of your digestive system, may be
done to look for structural problems. For instance, a CT scan may
be done to look for thickening of the wall of your small intestine,
which could be a sign of Crohn’s disease.
12

13. Diagnosis…
oBiopsy:
You may have a biopsy if your doctor suspects that you have
abnormal cells in the lining of your small intestine. This test will
likely be done using an endoscopy. A tube is inserted into your
mouth and sent through your esophagus and stomach and into
your small intestine, where it takes a small sample of cells.
13

14. Tests used in the evaluation of malabsorption
oCarbohydrate malabsorption
• D-xylose absorption test (decreased)
• Lactose Tolerance Test (decreased)
• Breath hydrogen test (increased)
oFat malabsorption
• Fecal fat determination (elevated)
• 14C-triolein breath test (decreased)
oSpecific disorders
• Celiac disease (Endomysial antibody present)
• Pernicious anemia (Schilling test)
• Cystic fibrosis (sweat test) 14

15. Carbohydrate malabsorption tests
D-xylose absorption test
Lactose tolerance test
Breath hydrogen test
15

16. D-xylose test
• The D-xylose test measures the absorptive capacity of the
proximal small intestine.
• Following an overnight fast, the patient ingests a 25 g dose of
D-xylose, and urine is collected for the next five hours.
Venous blood sample is also collected after one hour.
Normal excretion of D-xylose is 6.0 +/- 1.5 g.
Excretion of lesser amounts of D-xylose or a serum D-xylose
concentration less than 20 mg/dL suggests abnormal absorption.
• Low blood levels and urinary excretion suggests mucosal
disease such as celiac.
16

17. D-xylose test…
• Several conditions may lead to false positive results:
Renal dysfunction or an inadequate urine sample is associated
with falsely depressed urinary values of D-xylose. This may
occur in some older patients (>65) due to a decrease in the GFR.
False positive results can also be seen with urinary retention, or
fermentation of D-xylose by intestinal bacteria in patients with
bacterial overgrowth.
17

18. Lactose Tolerance Test
• Following oral administration of a 50 gr test dose, blood glucose
levels are monitored at 0, 60, and 120 minutes.
• Increase in blood glucose by less than 20 mg/dL is diagnostic.
• False negative results:
 Diabetes
 Bacterial overgrowth
 Abnormal gastric emptying may also lead to false results as
blood glucose may be relatively higher with rapid and
artificially depressed with delayed gastric emptying.
18

19. Breath tests
• Breath tests using H2 or CO2 can be used to diagnose specific
forms of carbohydrate malabsorption (e.g, lactose, fructose,
sucrose and others).
• E.g. raised hydrogen breath levels indicate the improper digestion
of lactose, which could lead to a diagnosis of lactose
intolerance or the presence of abnormal bacteria in the colon.
• Breath tests rely on bacterial fermentation of non-absorbed
carbohydrate and therefore concurrent antibiotic administration
often alters the results.
19

20. Fat malabsorption tests
Fecal fat test
14C-triolein breath test
20

21. Fecal fat test
• Preparing for fecal fat testing:
• Everyone who undergoes fecal fat testing is required to follow a
high-fat diet for three days prior to the test.
• You will be asked to eat 100 grams of fat each day for 3 days
before taking the fecal fat test.
• After following the high-fat diet for three days, you’ll return to a
normal diet and begin the stool collection process.
21

22. Fecal fat test…
• The normal range for fecal fat testing is 2 to 7 gr over a 24-hour.
• Normal results for a 72-hour test period would be 21 grams.
• However, fecal fat excretion can be moderately increased in
diarrheal diseases even without fat malabsorption.
• Thus, a modest increase in fecal fat excretion in a patient with
diarrhea does not necessarily indicate malabsorption as the
primary cause and other tests should be performed to identify the
cause of the diarrhea.
22

23. 14C-triolein breath test
• In principle, a 14C-labelled triglyceride is ingested, digested,
absorbed and metabolised, releasing 14C-labelled carbon dioxide.
• The test is unreliable in the following circumstances:
Diabetes mellitus
Gross obesity
Thyroid disease
Chronic respiratory insufficiency
23

24. 14C-triolein breath test
• The protocol is as follows:
The patient is fasted overnight
Collect a basal sample of expired air
Administer 10 microci of 14c-triolein in a 60 g fat meal
Collect samples of expired air each hour for 7 hours
Measure the 14C in the expired air
• Interpretation:
• The 14C activity in expired air is significantly reduced in patients
with fat malabsorption
24

25. Specific disorders tests
Celiac disease (Endomysial antibody present)
Pernicious anemia (Schilling test)
25

26. Celiac Disease Antibody Test
• Accurate diagnosis of celiac disease requires gluten in the patient’s
diet at the time of testing.
• Anti-tissue transglutaminase antibody (anti-tTG):
 IgA: detects antibodies to tissue transglutaminase.
The sensitivity of this test is close to 100% and specificity is around 95%.
• Anti-endomysial antibodies (EMA):
 IgA class: detects antibodies to endomysium (endomysium, the thin
connective tissue layer that covers individual muscle fibers).
• If this test is positive, the patient should have multiple small bowel
biopsies from the second part of the duodenum and beyond to
establish the diagnosis. 26

27. Schilling test
• Vitamin B12 (cobalamin) is an essential cofactor for DNA synthesis.
• B12 deficiency can be due to decreased intrinsic factor or decreased
absorption due to pancreatic or ileal disease.
• The Schilling test is performed by orally administering
57Co-radiolabeled B12 and quantitating its appearance in the serum,
feces or in the urine.
• A reference population excretes > 8% of the ingested dose in a 24
hour urine collection, while < 7% is excreted in pernicious anemia.
 If the abnormality corrects with the co-administration of intrinsic
factor with B12, the defect is due to deficiency of intrinsic factor
rather than malabsorption due to pancreatic or ileal causes. 27

28. Thanks for your attention
28

29. 29

30. 30

31. Sweat test
• Most cystic fibrosis (CF) patients malabsorb dietary fats because
of pancreatic insufficiency, which leads to impaired lipolysis.
• The sweat test is the most reliable laboratory test for the diagnosis
of cystic fibrosis.
• Collection of sample
0.3% solution of pilocarpine (a cholinergic drug) is introduced
into the skin by iontophoresis to induce sweating.
Sweat is collected with a gauze pad, weighed, eluted, and
analyzed for Cl- and less often Na+.
• In cystic fibrosis, sweat chloride values are 60-120 mmol/L;
normal values are < 60 mmol/L. 31

32. Sweat test…
32