2. Definition
Maldigestion: Impaired breakdown of nutrients (carbohydrates, protein,
fat) to absorbable split products (mono-, di-, or oligosaccharides; amino
acids; oligopeptides; fatty acids; monoglycerides)
Malabsorption: defective mucosal uptake and transport of adequately
digested nutrients including vitamins and trace elements.
Digestive and absorptive processes are so inextricably linked, that a third
term,
malassimilation has been
Malabsorption is still widely used as the global term for all aspects of
impairment of digestion and absorption
3. Mechanism of Absorption
The lengths of the small intestine and the colon are ~300 cm and
~80 cm, respectively.
However, the effective functional surface area is ~600-fold greater
Intestinal epithelial cells are continuously renewed
New proliferating epithelial cells at the base of the crypt migrate
over 48–72 h to the tip of the villus (or surface of the colon)
4. Carbhohydrate Digestion
Secondary lactase deficiency
is the most common clinical
condition associated with
lactose malabsorption
Damage to brush border and
reduced membrane enzyme
expression
Secondary lactase deficiency is
commonly associated with
inflammatory, infectious,
ischemic,toxic (e.g., cancer
chemotherapy), and radiation-
induced intestinal insults.
5. Protein Digestion
Humans require 0.65-1 g/kg
body weight per day of
protein to maintain nitrogen
balance and an adequate
supply of essential amino
acids
Digestive juices (35 g/day)
and desquamated intestinal
cells (30 g/day)
Protein absorption is
efficient, with 6–12 g of
nitrogen excreted daily.
7. Understanding site of Malabsorption
Luminal phase
Impaired nutrient hydrolysis
Impaired micelle formation
Luminal availability and processing
8. Impaired Nutrient Hydrolysis
MC cause pancreatic insufficiency
chronic pancreatitis, pancreatic resection, pancreatic cancer, or cystic
fibrosis
Resultant deficiencies in lipase and proteases lead to lipid and protein
malabsorption, respectively.
Inactivation of pancreatic enzymes by gastric hypersecretion-ZES
Inadequate mixing of nutrients, bile, and pancreatic enzymes -Rapid
intestinal transit
Thyrotoxicocsis, gastrojejunostomy, total and partial gastrectomy, or intestinal
resection
Failure to convert a proenzyme to its active form, such as enterokinase
and trypsinogen deficiencies
9. Impaired micelle formation- Fat
malabsorption
Decreased bile salt synthesis from severe parenchymal liver disease (eg,
cirrhosis)
Impaired bile secretion from biliary obstruction or cholestatic jaundice
(eg, primary biliary cirrhosis, primary sclerosing cholangitis)
Impaired enterohepatic bile circulation, as seen in small bowel resection
or regional enteritis, Bile salt malabsorption
Bile salt deconjugation due to small bowel bacterial overgrowth
Stasis by motor abnormality- scleroderma, diabetic neuropathy, intestinal
obstruction
an anatomic abnormality -small bowel diverticula, stricture, ischemia, blind
loops
small bowel contamination from entero colonic fistulas
10. Luminal availability and processing
Luminal bacterial overgrowth can cause a decrease in the
availability of substrates, including carbohydrates, proteins, and
vitamins (eg, vitamin B-12, folate).
Vitamin B12 (cobalamin) deficiency due to pernicious anemia is
caused by a lack of intrinsic factor and by pancreatic enzyme
deficiency.
11. Mucosal phase -Impaired brush-border hydrolase
activity
Disaccharidase deficiency
Lactase deficiency, either primary or secondary, is the most common form of
disaccharidase deficiency.
Genetic factors determine the primary form; C/T-13910 AND G/A-22018 mutations
Immunoglobulin A (IgA) deficiency (the most common immunodeficiency)
clinically similar to celiac disease and is unresponsive to a gluten-free diet.
Acrodermatitis enteropathica - selective inability to absorb zinc, leading to villous atrophy
and acral dermatitis.
Autoimmune enteropathy
diagnosed in children presenting with intractable secretory diarrhea and villous atrophy.
antibodies directed against intestinal epithelial and goblet cells
12. Impaired nutrient absorption
Inherited –
Defects include glucose-galactose malabsorption, abetalipoproteinemia,
cystinuria, and Hartnup disease.
Acquired disorders are far more common and are caused by the
following:
Decreased absorptive surface area, as seen in intestinal resection of
intestinal bypass
Damaged absorbing surface, as seen in celiac sprue, tropical sprue, Crohn
disease, AIDS enteropathy, chemotherapy, or radiation therapy
Infiltrating disease of the intestinal wall, such as lymphoma and amyloidosis
Infections, including bacterial overgrowth, giardiasis, Whipple disease,
cryptosporidiosis, and microsporidiosis
13. Post absorptive phase
Obstruction of the lymphatic system
Impairs the absorption of chylomicrons and lipoproteins and may
cause fat malabsorption or a protein-losing enteropathy
Both congenital (eg, intestinal lymphangiectasia, Milroy disease)
and acquired (eg, Whipple disease, neoplasm [including
lymphoma], tuberculosis), Amyloidosis ,CCF
19. Evaluation
Ultimate goal of the diagnostic approach is to find or to rule out a
disease or condition which causes malabsorption
It is less important to prove the presence of malabsorption per se
20. Approach
A good history is the cornerstone of diagnosis
Establish the presence of malabsorption through tests of
absorption: Global vs selective
Document the evidence of malnutrition of one or more nutrients
Systematically approach the diagnosis of malabsorption through
evaluation of small bowel morphology , by imaging and histology,
and the use of specific blood tests to diagnose specific disorders
27. Clinical Clues to the Presence of Specific
Diseases
Has the patient undergone previous surgery, such as gastric or
small bowel resection or a GI bypass operation?
Is there a family or childhood history of celiac disease?
Is there a history of travel to underdeveloped countries or endemic
areas of tropical sprue, giardiasis, or other GI infections?
Is there excessive alcohol consumption?
28. History …
Does the patient have a history of chronic pancreatitis or
symptoms suggesting a pancreatic tumour ?
Does the patient have clinical features of thyrotoxicosis, Addison’s
disease, Whipple’s disease, biliary or liver disease, or diabetic
neuropathy?
Does the patient eat a diet high in poorly absorbable
carbohydrates (sweeteners like sorbitol or fructose) or fat
substitutes or an unbalanced diet that could result in malnutrition?
29. Is there a likelihood of human immunodeficiency virus infection?
Is the patient receiving treatment with a drug that can cause
malabsorption?
Does the patient have a history of stem cell or organ
transplantation or abdominal radiation?
Does the patient have a history of extra intestinal manifestations of
inflammatory bowel disease, celiac disease, or Whipple’s disease?
30. Tests for a diagnosis
• The order of testing and choice of a particular test should be
individualized while considering the availability and expertise
needed for specialized testing.
• While many tests are established as gold standards for the
diagnosis of particular forms of malabsorption, new tests
continue to be developed and their diagnostic characteristics
remain uncertain
31. Order of testing
First Line Tests
Tests that detect the most common causes of malabsorption or are
noninvasive or inexpensive usually should be performed initially
Second Line tests
In some patients, testing for rarer causes of malabsorption and use of
more invasive or more expensive tests may be necessary to establish
the diagnosis
Third-line tests
For unusually difficult cases, additional tests may be required that may
be available only in specialized centers
41. Quantitative Tests
Not routinely available
Measurement of fecal fat might not influence the subsequent
evaluation
An elevated fecal fat level usually cannot differentiate among
biliary, pancreatic, and enteric causes
In severe steatorrhea, the stools have a very foul smell and a
characteristic porridge like appearance, and quantitative studies
are not necessary to establish fat malabsorption.
Normal fat balance does not imply normal absorptive function of the GI
tract.
Accuracy depends on quantitative stool collections for 48 to 72 hours,
adherence to a diet that contains 80 to 100 g of fat daily, and a diet
diary to determine fat intake
42. Fat Malabsorption
Qualitative
Stool sample + glacial acetic acid + Sudan 3 stain examine for
orange globules after heating
Up to globules per HPF <4mm
Semi Quantitative- Acid Steatocrit test
AS <31% is normal
Breath Tests : C14/13 Triolein tests
Serum Tests – Beta Carotene <100mg/100ml suggests and
<47/100 strongly indicates
43.
44. Carbhohydrate Malabsorption
In diarrhea – Stool pH <5.5 qualitative marker of carbhohydrate
malabsorption
Hydrogen Breath Tests
Lactose : >20 ppm inc after 20-50gm, Measured at 30,60,90,180,240
min
Fructose
Lactulose- oro cecal transit time
Glucose-SIBO
Lactose Tolerance Test <20mg/dl rise with in 30min of 50gm lactose
In research setting:
Individual SCFAs can be determined by gas chromatography
45. Tests of Protein Malabsorption
Fecal nitrogen - normal- 2-2.5 gm/day .
azotorrhoea- more than 3gm/day
radioisotopic methods
51cr-labeled albumin
99mtc-labeled transferrin
125i-labeled albumin
Indirect methods
Fecal -1 antitrypsin clearance (> 25 mg/d)
46. Protein Malabsorption
Combined 14C-octanoic acid–13C-egg white breath test
accompanied by measurement of the urinary output of phenol and p-cresol,
to assess the effect of gastric acid on protein digestion.
labelling of the 13C-egg protein test meal with 14C-octanoic acid allows
simultaneous measurement of protein assimilation and gastric emptying rate.
Phenol and p-cresol are the quantitatively most important phenolic
compounds in feces and urine and are specific metabolites of tyrosine,
produced by bacterial fermentation in the colon.
Recovery of higher amounts of urinary phenols observed after omeprazole
treatment in the study of this test indicated an increased availability of protein
in the colon
47. Protein-Losing Enteropathy
Characterized by excessive loss of serum proteins into the gut
Hypoproteinemia, hypoalbuminemia, edema, muscle atrophy
May occur as isolated phenomenon or part of global malabsorption
Need to r/o malnutrition, nephrosis, liver disease
48. Tests For Protein Losing Enteropathy
Alpha 1 Antitrypsin Clearance
72 hour stool collection
Stool /serum (alpha 1 AT)* volume
>24ml/day
>56ml/day in patients with diarrhea
Tc 99 Dextran
Tc 99 labelled HSA
50. Vitamin B12 malabsorption- The Schilling test
Phase I
Administer a small oral dose of radiolabeled vitamin B12 and,
simultaneously or within 1 or 2 hours, a large intramuscular “flushing
dose” of nonradiolabeled vitamin B12.
If less than 7% to 10% of the administered dose is recovered in urine
within 24 hours, vitamin B12 malabsorption is confirmed.
False-positive results on the Schilling test may be due to renal
dysfunction or inadequate urine collection.
Phase 2
Additives
51. Interpretation of Schilling Test
Condition Phase 1
(B12)
With IF With Enzymes With Antibiotic
Any cause of B12
Malabsorption
Decreased
Pernicious anemia Decreased Normal
Chronic pancreatitis Decreased Decreased Normal
SIBO Decreased Decreased Decreased Normal
Ileal resection Decreased Decreased Decreased Decreased
Phase II
52. SIBO
Quantitative culture of a small intestinal aspirate
Measurement of deconjugated bile acids or vitamin B12 analogs in
intestinal aspirates
Measurement of serum folate, b12
Breath tests
14C-glycocholate breath test
14C-d xylose breath test
lactulose hydrogen breath test
the glucose hydrogen breath test
53. Small Bowel Culture
Gold Standard” test for SIBO
Abnormal > 105 cfu/ml
Many limitations
Invasive
Expensive
Contamination
Many bacterial uncultivatable
Difficulty culturing anaerobes
57. D Xylose test
Intestinal vs Pancreatic
Passive diffusion
25gm xylose , 50% metabolized and rest excreted n urine
Collect Urine over 5 hours/ Venous sample after 1 hour
<4gm (16% excretion)/ <20mg/dl
False-positive
if the duration of urine collection is too short
dehydrated or has renal dysfunction, significant ascites, delayed gastric
emptying, or portal hypertension.
58. Bile Salt Malabsorption
Compensated vs Decompensated : depending on length of ileum
Measurement of Fecal Bile Acid Output
14Carbon-Taurocholate Bile Acid Absorption Test
Therapeutic Trial of Bile Acid-Binding Resins (Cholestyramine)
Selenium-75-Labeled Homotaurocholic Acid Test (SeHCAT)
radioactive taurocholic acid analog used for this test is resistant to bacterial
deconjugation
59. Malabsorption in Diabetes
Mild steatorrhea is often present in patients with diabetic diarrhea
and also in diabetic patients who do not complain of diarrhea.
Autonomic neuropathy: Rapid intestinal transit
Infections
Pancreatic insufficiency
SIBO
Celiac
Drugs
60. Giardia lamblia infestation
Very frequent
Diagnosis:
Stool analysis
Duodenal tubing, vegetatíve forms can be found only
here
Therapy:
Metronidazole
This treatment can be begun without diagnosis
64. Conclusion
Take careful history including drug intake, travelling and special
foods, drinks or sweets
Consider family history
Notice hints for malabsorption from physical examination
Look at stool for volume, appearance, admixtures of mucus, blood,
parasites
Draw blood for screening laboratory examination to find additional
hints
65. Abdominal ultrasound (gallbladder; liver; pancreas; intestinal wall
aspects; adenopathy; etc.)
H2-breath tests for carbohydrate malabsorption (lactose, fructose)
endomysial-, antigliadin- and/or tissue transglutaminase-antibodies
(celiac disease) search for giardia lamblia, enteropathogenic
bacteria, parasites and ova
Oesophago-Gastro-Duodenoscopy including biopsies from
stomach (autoimmunegastritis? H. pylori?) and duodenum (celiac
disease?, inflammatory bowel diseases? Especially duodenojejunal
involvement is associated with malabsorption ;
66. Ileocolonoscopy including biopsies of colon and ileum (ileal
disease? bile salts ? , vit. B12 ?)
If pancreatic disease with secretory insufficiency is suspected,
Consider:
tests for secretory function e.g. elastase or chymotrypsin in stool
computer tomography; magnetic resonance imaging of pancreatic
duct-systems or ERCP
67. If small bowel disease is still within the differential diagnostic scope,
Consider
Glucose-H2-test (bacterial overgrowth)
Small bowel X-ray (fistulae, diverticula, blind loops, short bowel, etc.)
Angiography of celiac and mesenteric arteries (ischemic bowel
damage
a1-antitrypsin clearance (intestinal protein loss
68. Thank You
It is not recommended to apply a multitude of tests in every patient with
suspected malabsorptive disorder.
Instead the diagnostic approach should aim primarily to establish a
diagnosis of underlying diseases rather than to prove or exclude a
"malabsorption syndrome".
Editor's Notes
sample of stool is diluted
1 : 3 with distilled water in a test tube. The diluted stool is
homogenized, and a 500-μL aliquot is pipetted into a tube.
Then 100 mL of 5M HClO4 is added to allow better fat extraction
and separation of the lipid layer. An aliquot of the diluted
stool-HClO4 mixture is put into a non-heparinized microcapillary
tube and sealed on one end. After centrifugation of this
aliquot at 13,000 rpm for 15 minutes, the fatty layer (FL) and the solid layer (SL) are measured, and the AS is determined
according to the following equation
