2. INTRODUCTION
• Maldigestion: Defective intraluminal hydrolysis of nutrients. There is
impaired breakdown of nutrients (carbohydrates, protein, fat) to
absorbable split-products (mono-, di-, or oligosaccharides;
aminoacids; oligopeptides; fatty acids; monoglycerides)
• Malabsorption: Defective mucosal uptake and transport of
adequately digested nutrients including vitamins and trace elements.
3. The integrated processes of digestion and absorption
can be described in three phases:
Luminal Phase
Mucosal phase
Postabsorbtive /Removal phase
Disturbances of the absorptive process can take place in any of these
three phases or defect in one or more than one can coexist
4. Normal physiology
• 3 major phases:
– Luminal phase
• dietary fats, proteins, and carbohydrates are hydrolyzed and solubilized depending largely on
pancreatic and biliary secretions.
– Mucosal phase
• During the mucosal phase, final hydrolysis and uptake of saccharides and peptides takes place
from lumen into cells and lipids taken up by epithelial cells are processed and packaged for
cellular export.
– Post-absorptive phase
• transported via lymphatics and portal circulation from epithelial cells to other parts of the
body.
5. Defects in luminal phase
A. Impaired nutrient hydrolysis
Digestive enzyme deficiency Chronic Pancreatitis, pancreatic cancer
Inactivation of digestive enzymes ZollingerEllison Syndrome
Inadequate mixing of nutrients, bile, and
pancreatic enzymes
rapid intestinal transit
Gastrojejunostomy
total and partial gastrectomy
Failure to convert a proenzyme to active
form
Enterokinase
trypsinogen deficiencies
B. Impaired micelle formation
bile salt synthesis Cirrhosis
Impaired bile secretion Chronic cholestasis
bile salt loss (impaired enterohepatic bile
circulation)
Ileal disease/resection
Bile salt de-conjugation Bacterial Overgrowth
C. Impaired luminal availability and processing
Bacterial consumption of nutrients Small intestinal bacterial overgrowth
intrinsic factor Pernicious anemia –B12Def
6.
7. Understanding of the normal absorptive process helps a great
deal to understand causes and consequences of malabsorption
and thus guide us in designing an appropriate differential
diagnostic strategy.
10. Within villus absorptive cells
• FA + MAG= TG
• Triglycerides, cholesterol esters, phospholipid, and apoproteins =
chylomicron
• Transported to the intestinal lymphatics
14. • Absorption- active transport (glucose and galactose) or passive transport
(fructose)
• Carbohydrates that are not digested and absorbed
• bacterial degradation in the colon
• formation of short-chain fatty acids (butyrate, propionate, acetate, lactate)
• additional energy source
• preferred energy source for colonic epithelial cells
• Production of hydrogen and methane
• basis of noninvasive breath tests
• to look for malabsorption of particular carbohydrates
17. Uptake into enterocytes of amino acids, di and tripeptides
takes place by secondary active transport intracytoplasmic
breakdown into amino acids then absorption of amino
acids across the brush border by facilitated diffusion.
18. VITAMIN, MINERAL, AND TRACE ELEMENT
ABSORPTION
• Fat-soluble vitamins (A, D, E, and K)
• require solubilization in a mixed micellar phase
• Most vitamins and minerals
• proximal half of the small intestine
• except vitamin B12 & magnesium
• Magnesium
• distal intestine (including the colon)
• Bariatric Sx - Roux-en-Y gastric bypass
• deficiency of Vitamin B12, iron, calcium, and vitamin D
19. CLINICAL FEATURES
• Global malabsorption
• Example -celiac disease
• Impaired absorption of almost all nutrients
• Diarrhea with pale, greasy, voluminous, foul-smelling stools and weight loss
despite adequate food intake
• Partial or isolated malabsorption
• Specific nutrient
• Symptoms attributable to the particular nutrient
20. History
• Diarrhea:
– Most common
– watery, reflecting the osmotic load received by the intestine.
– Bacterial action
• hydroxy fatty acids from undigested fat
• increase net fluid secretion
• furhter worsening the diarrhea.
21. • Steatorrhea :
– fat malabsorption
– pale, bulky, and malodorous stools
– float on top of the toilet water and are difficult to flush
– floating oil droplets in the toilet following defecation.
22. • Weight loss and fatigue:
– Weight loss common
– patients may compensate by increasing their caloric consumption, masking
weight loss
– Higher chances
• diffuse diseases
• such as celiac disease and Whipple disease.
23. • Flatulence and abdominal distention:
– Bacterial fermentation of unabsorbed food
– gaseous products
• Hydrogen
• methane
– flatulence
– abdominal distention and cramps.
24. • Edema :
– Hypoalbuminemia
• chronic protein malabsorption or loss of protein into the intestinal lumen
• peripheral edema.
– Extensive obstruction of the lymphatic system
• intestinal lymphangiectasia
• protein loss.
• severe protein depletion
– ascites
26. • Bleeding disorders :
– vitamin K malabsorption
– subsequent hypoprothrombinemia
– Ecchymosis usually is the manifesting symptom
– melena
– hematuria
27. • Metabolic defects of bones:
– Vitamin D deficiency
• osteopenia
• Osteomalacia
• Bone pain
• pathologic fractures
• Malabsorption of calcium
– secondary hyperparathyroidism.
28. • Neurologic manifestations :
– Electrolyte disturbances
• hypocalcemia and hypomagnesemia
• Tetany
• Trousseau sign and the Chvostek sign.
– Generalized motor weakness
• pantothenic acid
• vitamin D
– Peripheral neuropathy
• Thiamine
– Loss for vibration and position
• Cobalamin
– Night blindness
• vitamin A
– Seizures
• biotin
29. Examination
• General Physical Examination
orthostatic hypotension
weight loss,muscle wasting, or both
loss of subcutaneous fat
cheilosis, glossitis, or aphthous ulcers of the mouth
peripheral edema
30. • Abdominal examination:
– may be distended
– bowel sounds may be hyperactive
– Ascites
• severe hypoproteinemia.
35. DIAGNOSIS
• Malabsorption of fat
• Most commonly used indicator of global malabsorption
• Most complex absorption process among macronutrients
• Hence, most sensitive to interference from disease processes
• Most calorically dense macronutrient
• critical factor in the weight loss
36. TESTS FOR FAT MALABSORPTION
• Fecal fat determination
• In healthy people, daily fecal fat excretion is <6 g/d
• 72 hour sample is ideal because it reduces errors and variability
• 70 to 120 g/day of dietary fat
• Avoid nonabsorbable fat substitutes, such as olestra
• Sudan III stain
• Qualitative test
37. • Near infrared reflectance analysis
• Equally accurate but less time-consuming than a 72-hour fecal fat
• Simultaneous measurement of fecal fat, nitrogen, and carbohydrates in a
single sample
• Acid steatocrit
• Gravimetric assay
• Performed on a spot stool sample
38. TESTS FOR CARBOHYDRATE MALABSORPTION
• As a general rule, tests for carbohydrate malabsorption rely upon the
fermentation of undigested carbohydrates
• D-xylose test
• Measures the absorptive capacity of the proximal small intestine
• Pentose monosaccharide
• Active sodium transporter and by passive diffusion
• Measure of the permeability of the proximal small intestine, rather than a specific
defect in D-xylose absorption
• Overnight fast
• Ingests a 25 g dose of D-xylose
• Urine is collected for the next five hours
• Normal excretion of D-xylose is 6.0 +/- 1.5 g
• Serum D-xylose concentration less than 20 mg/dL suggests abnormal absorption
39.
40. • False positive:
• delayed gastric emptying
• impaired glomerular filtration
• Small intestinal bacterialovergrowth
• course of antibiotic (rifamixin) will improve d-xylose absorption
• Negative test: normal in pancreatic enzyme deficiency, Crohn disease
(due to involvement of distalsmall intestine), lactose intolerance
• Because no involvment of proximal intestine
41. • Lactose tolerance test
• Oral administration of a 50 g test dose
• Blood glucose levels are monitored at 0, 60, and 120 minutes
• Increase in blood glucose by <20 mg/dL + the development of symptoms is
Diagnostic
• Measurement of breath hydrogen following lactose challenge
• Increase in breath hydrogen by more than 20 ppm is diagnostic
42. TESTS FOR PROTEIN MALABSORPTION
• Generally not performed
• Technically difficult
• Plasma citrulline and arginine concentrations are highly correlated to
small bowel length
43. ADDITIONAL TESTS
• SeHCAT(Selenium homocholic acid taurine) test
• Bile acid malabsorption e.g terminal ileal disease, resection, primary bile salt
malabsorption.
• Primary bile salt malabsorption may reflect impaired fibroblast growth factor
19 feedback inhibition causing excessive bile acid synthesis
• Administration of a selenium75 labeled synthetic bile acid
• Followed by measurement of retention of the bile acid by whole body scan or
gamma camera at seven days (abnormal is less than 5 percent)
44. •Tests for bacterial overgrowth
• Direct quantitative measurement of bacterial counts from aspirated intestinal
fluid.
• Normal counts < 10(4)/mL in the jejunum and 10(5)/mL in the ileum
• Requires intubation of the intestine
• Hydrogen breath tests with lactulose
45. • Schilling test
• Identifies the cause of vitamin B12 malabsorption
• Rarely performed
• availability of serum B12 and methylmalonic acid to diagnose B12 deficiency
• easy use of oral crystalline or parenteral injection of B12.
• Nevertheless, there may be occasional patients in whom it can be
informative.
46. Stage 1
• Administer a small oral dose 1ug of radiolabeled vitamin B12
• within one or two hours, a large intramuscular flushing dose of nonradiolabeled
vitamin B12
• Unlabeled B12 saturates vitamin B12 carriers
• radioactive vitamin B12 absorbed by the intestine is excreted in the urine
• If less than 7% to 10% of the administered dose is recovered in urine within
24 hours
• vitamin B12 malabsorption is confirmed
47. Stage 2
• oral administration of intrinsic factor done.
• pernicious anemia
• normalize after oral administration of intrinsic factor
Stage 3- In small bowel bacterial overgrowth(SIBO
improve after antibiotic therapy
Stage 4-Patients with pancreatic exocrine insufficiency
normalize with addition of pancreatic enzymes
48. • Tests for pancreatic insufficiency
• Direct tests
• administration of a meal or hormonal secretagogues
• stimulation of the pancreas
• duodenal fluid is collected and analyzed
• quantify normal pancreatic secretory content (ie, enzymes, and bicarbonate).
• A normal person should release a large volume of bicarbonate-rich
pancreatic fluid in response to the intravenous injection of secretin.
• Indirect tests measure the consequences of pancreatic insufficiency
and are more widely available
• declined by more than 90 percent
• insensitive to early pancreatic insufficiency
49.
50. • Serology :
– Serum anti-TTG, Serum antigliadin ,antiendomysial antibodies
– many pts with biopsy confirmed celiac have negative IgA antibodies screen due to
concurrent selective IgA deficiency which is common in celiac disease
– If IgA serology is negative and suspicion is high
– Serum IgA -IgA deficiency.
– Determination of fecal elastase and chymotrypsin
• 2 proteases produced by the pancreas
• distinguish between pancreatic causes and intestinal causes of malabsorption.
51. • Small bowel barium studies:
• mucosa pattern associated with celiac disease
• obliterated or coarsened.
• Small bowel dilatation and diverticulosis
– scleroderma.
• Regional enteritis of the small intestine
– Stricture
– Ulceration
– fistula formation.
• Other anatomic abnormalities, such as surgical changes or enterocolonic fistula.
52. • Plain abdominal x-ray film:
– Pancreatic calcifications are indicative of chronic pancreatitis.
53. • CT scan of the abdomen:
– evidence of chronic pancreatitis, such as pancreatic calcification or atrophy
– Enlarged lymph nodes
• Whipple disease
• lymphoma.
54. • Endoscopic retrograde cholangiopancreatogram (ERCP):
– pancreatic or biliary-related disorders
Severe pancreatic duct
changes with dilation of
the main pancreatic duct
and of the primary and
secondary branches.
55. • Upper endoscopy with small bowel mucosal biopsy :
– Examples of conditions that can be diagnosed this way include
• celiac sprue, giardiasis, Crohn disease, Whipple disease, amyloidosis,
abetalipoproteinemia, and lymphoma.
Scalloped duodenal folds
seen on endoscopy in a
patient with celiac disease.
57. • Histologic Findings:
– Depending on the cause
– A frequently encountered histologic finding
• villous atrophy
– celiac disease,
– tropical sprue,
– viral gastroenteritis,
– bacterial overgrowth,
– inflammatory bowel disease,
– immunodeficiency syndromes,
– lymphoma, and
– radiation enteritis.
58. ASPIRATION
• Fluid aspirated- Descending part of duodenum/jejunum.
• Examined microscopically for Giardia
• Cultured to detect SIBO- Gold standard for diagnosis. Normal counts
rarely exceed 10(4)/mL in the jejunum and 10(5)/mL in the ileum.
59. Video capsule endoscopy(VCE)
• Used to diagnose a wider range of disease such as crohn’s ds, celiac
disease and other malabsorptive disease.
• In refractory celiac disease, VCE can detect changes such as
ulcerations and strictures that suggest T- cell lymphoma.
60. Balloon Enteroscopy
• In some case of malabsorption, balloon enteroscopy with biopsies of the jejunum
and ileum can be helpful to establish the diagnosis.
• Comparison of VCE and BE
• Advantage-biopsy from altered mucosa area
• Disadvantage- time consuming and uncomfortable for the patients
61. • Tropical sprue (37%)
• CD (19%)
• Small intestinal bacterial overgrowth (10%)
• AIDS (5.4%)
• Giardiasis (5%)
• Hypogammaglobulinemia (4%)
• Intestinal tuberculosis (2.5%)
• Strongyloidiasis (2%)
• Immunoproliferative small intestinal disease (2%)
• Crohn’s disease 6 (2%), amyloidosis (1.5%)
• Intestinal lymphangiectasia (1%)
• Unknown (8%)
• Spectrum of malabsorption syndrome among adults & factors differentiating celiac disease &
tropical malabsorption Uday C. Ghoshal, Mansi Mehrotra, Sunil Kumar, Ujjala Ghoshal*, Narendra
Krishnani**,Asha Misra, Rakesh Aggarwal & Gourdas Choudhuri:Indian J Med Res 136, September
2012, pp 451-459
62. • Tropical sprue (29%)
• Celiac and Crohn's disease (15.3% each)
• Parasitic infestations (9.7%)
• Immune deficiency disorders (5.6%)
• Intestinal tuberculosis ( 2.4%)
• Spectrum of malabsorption in India--tropical sprue is still the leader.Dutta AK , Balekuduru A,
Chacko A. J Assoc Physicians India. 2011 Jul;59:420-2.
63. Management
• Two basic principles
– correction of nutritional deficiencies
– treatment of causative diseases.
64. • Nutritional support :
– Supplementing various minerals, such as calcium, magnesium, iron, and
vitamins, which may be deficient in malabsorption, is important.
– Caloric and protein replacement also is essential.
– Medium-chain triglycerides can be used as fat substitutes because they do not
require micelle formation for absorption and their route of transport is portal
rather than lymphatic.
– In severe intestinal disease, such as massive resection and extensive regional
enteritis, parenteral nutrition may become necessary.
65. • Treatment of causative diseases :
– lactose-free diet helps correct lactose intolerance; supplementing the first
bite of milk-containing food products with Lactaid also helps.
– Protease and lipase supplements are the therapy for pancreatic insufficiency.
– Antibiotics are the therapy for bacterial overgrowth.
– Corticosteroids, anti-inflammatory agents, such as mesalamine, and other
therapies are used to treat regional enteritis
66. Treatment of tropical sprue
• Treat deficiencies of Ca, Mg,K,vitamins A ,B, D.
• Parenteral vitamin B12, oral folate and iron replacement result in prompt
resolution of symptoms of anaemia, glossitis and anorexia, and result in weight
gain even before improvement in intestinal absorption.
• Folate supplementation improves villous atrophy.
• Antimicrobial agents :Tetracycline 250 mg four times daily (or doxycycline 100
mg once daily) for 3–6 months.
• Complete recovery is the rule in the returned traveller.
• In endemic sprue, relapses are common, occurring in 50% of affected people.
67. Management of celiac sprue
• Gluten-free diet helps treat celiac disease
Eliminate wheat, oats, rye, and barley from the diet
Beer, whiskey, and most vodkas are derived from wheat
WINE IS OKAY
• Pneumococcal vaccination as celiac ds is associated with hyposplenism
• Treatment with sulfones (dapsone) for dermatitis herpetiformis
• Screening of family members
• Steroids
• Refractory sprue
• Acute celiac crisis/ Celiac shock after gluten challenge
• Associated autoimmune hepatitis
68. Conclusion
• Etiology of malabsorption in tropical areas differs from that in
temperate countries
• Tropical sprue ,tuberculosis - a common cause of malabsorption in
India
• Celiac disease and inflammatory bowel disorders are emerging as
important causes
• Detailed history ,physical examination is mandatory
• The order of testing and choice of a particular test should be
individualized while considering the availability and expertise needed
for specialized testing.
• Emphasis should be put on defining an underlying disease entity
which then provides the basis for appropriate treatment.
