2. Malabsorption
Maldigestion: refers to impaired hydrolysis of
luminal contents.
Malabsorptoin: refers to impaired transport
across the mucosa.
In clinical practice,malabsorption is used to d
escribe the end result of either defect.
Malabsorption may involve a broad range of
nutrients (Panmalabsorption) or only an indiv
udual nutrient or class of nutrients (specific
malabsorption).
3. • Each day, the average person consumes 2000 to 3000
kcal of food. Most of this caloric load is in the form
of polymers or other complex compounds that must b
e broken down into smaller molecules, to be transpor
ted across the small intestinal mucosa. Thus, proteins
are cleaved into dipeptides and amino acids, starches
are split into monosaccharides, and fats are broken d
own into fatty acids and monoglycerides.
4. • A typical Western diet ingested by an adult
includes approximately 100 g. of fat, 400 g
of carbohydrate, 100 g of protein, 2 L of flui
d, and the required sodium, potassium, chlor
ide, calcium, vitamins, and other elements.
Salivary, gastric, intestinal, hepatic, and pan
creatic secretions add an additional 7–8 L of
protein-, lipid-, and electrolyte-containing fl
uid to intestinal contents.
5. • This massive load is reduced by the small a
nd large intestines to less than 200 g of stool
that contains less than 8 g of fat, 1–2 g of ni
trogen, and less than 20 mM each of Na+, K
+, Cl–, HCO3–, Ca2+, or Mg2+.
• If there is impairment of any of the many st
eps involved in the complex process of nutri
ent digestion and absorption, intestinal mala
bsorption may ensue.
6. • Nearly 200 conditions are associated with d
efects in this process and can produce subst
antial disability.
7. Malabsorption can be
sorted pathophysiologically into conditions
that are associated with
1. Impaired luminal hydrolysis.
2. Impaired mucosal function (mucosal hydr
olysis, uptake and packaging).
3. Impaired removal of nutrients from the m
ucosa.
Pathophysiology
8. A.Imapired luminal hydrolysis or solubilization.
Pancreatic exocrine insufficiency.
Bile acid deficinecy.
Zollinger Ellison syndrome.
Post gastrectomy malabsorption.
Rapid intestinal trnasit.
Small bowel bacterial overgrowth.
Causes of malabsorption
14. • From a pathophysiologic point of view, mechanisms causing mal
absorption can be divided into premucosal (luminal) factors, muc
osal factors, and postmucosal factors (vascular and lymphatic)
FATS
• DEFECTIVE MIXING
• For sufficient digestion and absorption of lipids, dietary fat must
adequately mix with digestive secretions. Gastric resections or ga
strointestinal motility disorders that result in rapid gastric emptyi
ng or rapid intestinal transit, such as autonomic neuropathy result
ing from diabetes mellitus or amyloidosis, can cause fat malabsor
ption consequent to impaired gastrointestinal mixing of dietary fa
t.
15. REDUCED SOLUBILIZATION OF FAT
Fat malabsorption due to decreased formation of micelles occurs if
the luminal concentrations of conjugated bile acids are lower tha
n the critical concentration required for forming micelles.
DECREASED LIPOLYSIS
• If exocrine pancreatic function is severely reduced, impairment
of pancreatic lipase and colipase secretion results in decreased lu
minal hydrolysis of dietary fat. Even when pancreatic enzyme co
ncentrations are normal, reduced pancreatic lipase activity due to
a low luminal pH, excessive calcium ingestion, or ingestion of th
e specific lipase inhibitor orlistat can cause pancreatic steatorrhe
a.
16. • DECREASED MUCOSAL ABSORPTION AND CHY
LOMICRON FORMATION
• Generalized mucosal diseases, such as celiac disease or tropical sp
rue, often are associated with fat malabsorption. Defective uptake
of free fatty acids and monoglycerides results from reduced mucos
al surface area because of villus shortening, reduced enterocyte fu
nction, and mucosal inflammation.
• DEFECTIVE LYMPHATIC TRANSPORT OF CHYLOMICRO
NS
• Impairment of lymphatic transport of chylomicrons is a cause for
postmucosal malabsorption of dietary fat. Decreased lymphatic tra
nsport can result from congenital diseases such as primary intestin
al lymphangiectasia or from obstruction of lymphatic vessels due t
o metastatic solid tumors, lymphoma, Whipple's disease, retroperit
oneal fibrosis.
17. • PROTEINS AND AMINO ACIDS
Defective digestion or absorption of dietary proteins has to be differe
ntiated from excessive loss of serum proteins into the gastrointesti
nal tract, which is termed protein-losing enteropathy
DEFECTIVE INTRALUMINAL PROTEOLYSIS
• Protein digestion may be impaired in patients who have undergon
e partial or total gastric resection, presumably as a result of poor
mixing with digestive secretions, although gastric pepsin deficien
cy could be contributory. Defective proteolysis also occurs with e
xocrine pancreatic insufficiency.
DEFECTIVE MUCOSAL HYDROLYSIS OF PEPTIDES AND DE
CREASED ABSORPTION OF OLIGOPEPTIDES AND AMIN
O ACIDS
• Generalized mucosal diseases, such as celiac disease and tropical
sprue, result in global malabsorption
18. • CARBOHYDRATES
• DEFECTIVE INTRALUMINAL HYDROLYSIS OF CARBOHYDR
ATES
• Pancreatic α-amylase normally is secreted in excess into the intestinal
lumen. In mild forms of pancreatic insufficiency, carbohydrate digesti
on usually is at least partially preserved, but severe pancreatic insuffici
ency results in clinically apparent carbohydrate malabsorption and dia
rrhea due to decreased luminal hydrolysis of ingested starch.
• MUCOSAL DEFECTS OF CARBOHYDRATE DIGESTION AND
ABSORPTION
• The most common cause of carbohydrate malabsorption is late-onset l
actose malabsorption due to decreased levels of the intestinal brush bo
rder enzyme lactase . Acquired malabsorption of carbohydrates occurs
commonly after extensive intestinal resections, in diffuse mucosal dise
ases such as celiac disease or Crohn's disease, or temporarily after self
-limited gastrointestinal infections .
19. • VITAMINS
• FAT-SOLUBLE VITAMINS
• Diseases causing malabsorption of dietary fat commonly cause ma
labsorption of fat-soluble vitamins. Fat-soluble vitamins also are
malabsorbed in diffuse diseases of the mucosal surface area, in dis
eases affecting chylomicron formation and transport,[21] and in exo
crine pancreatic insufficiency.
• WATER-SOLUBLE VITAMINS
• Vitamin B12 (Cobalamin)
• Decreased release of dietary vitamin B12 from food sources becaus
e of impaired pepsin and acid secretion, as in atrophic gastritis[24]
or use of acid inhibitory drugs such as proton pump inhibitors,[25]
usually results in only mild cobalamin malabsorption without clini
cal consequences. By contrast, deficiency of gastric intrinsic factor
secretion, as occurs in pernicious anemia or after gastric resections
.
20. • Diseases and conditions affecting the ileal mucosa, such as Crohn'
s disease or ileal resection, lead to a reduction of specific absorpti
ve sites for the intrinsic factor-vitamin B12 complex.
• Folate
• Folate malabsorption occurs with mucosal diseases affecting the p
roximal small intestine, such as celiac disease, Whipple's disease,
and tropical sprue.
• MINERALS
• CALCIUM
• Severe calcium malabsorption can occur in diseases that affect the
small intestinal mucosa, such as celiac disease. In these disease st
ates, calcium absorption is impaired directly because of the reduct
ion of the intestinal surface area and indirectly because of formati
on of insoluble calcium soaps with malabsorbed long-chain fatty
acids.
21. • IRON
• Iron deficiency is common in patients with gastric resection or
with celiac disease. Reduction in the mucosal surface area of t
he small intestine as a result of diffuse mucosal disease, intesti
nal resection, or intestinal bypass also can result in impaired ir
on absorption.
22. MECHANISMS THAT COMPENSATE FOR MALABSORPTION.
ROLE OF THE COLON
• The colon has the capacity to absorb a limited number but a wide
variety of substances and nutrients including sodium, chloride, wat
er, oxalate, short chain fatty acids, calcium, and vitamin K.
• the nutritive role of the colon in patients with severe malabsorptio
n is clinically relevant. Colonic preservation of malabsorbed nutrie
nts also can result in symptoms and complications of malabsorptio
n, such as colonic hyperabsorption of oxalate, which contributes to
formation of renal stones.
23. • Colonic Salvage of Incompletely Absorbed Carbohydrates
• Carbohydrates that reach the colon cannot be absorbed by the col
onic mucosa, but they can be metabolized by the colonic bacterial
flora. Metabolism by anaerobic bacteria results in the breakdown
of oligosaccharides and polysaccharides to mono- and disaccharid
es, which are metabolized further to lactic acid; short-chain (C2 to
C4) fatty acids (SCFAs) such as acetate, propionate, and butyrate;
and to odorless gases, including hydrogen, methane, and carbon d
ioxide. Because SCFAs have caloric values between 3.4 and 5.9
5 kcal/g, their colonic absorption can contribute positively to over
all calorie balance. In patients with short bowel syndrome, coloni
c salvage of malabsorbed carbohydrates can save up to 700 to 95
0 kcal/day,
24. • Not all SCFAs are absorbed by the colon, and those that are not a
bsorbed contribute to osmotic diarrhea.
• The beneficial effects of colonic bacterial carbohydrate metabolis
m may be accompanied by side effects due to gas production.
25. • Role of the Colon in Fat Malabsorption
• Long-chain triglycerides or fatty acids, which constitute most
dietary fat, cannot be absorbed by the human colon. Long-cha
in fatty acids bind calcium in the colon, thereby increasing the
amount of sodium oxalate that is absorbed. Fatty acids with ch
ain lengths longer than 12 carbons can cause diarrhea, because
they increase mucosal permeability and inhibit colonic absorp
tion of fluid and electrolytes. An increase in colonic permeabil
ity due to long-chain fatty acids also may be a contributing fac
tor for the increased colonic oxalate absorption seen in patient
s with steatorrhea and hyperoxaluria.
26. • CALCIUM OXALATE KIDNEY STONES
• Fat malabsorption secondary to bile acid deficiency in patients
with extensive ileal resection is associated with an increased ris
k of oxalate kidney stones if the colon is preserved. Oxalate in f
ood usually precipitates as calcium oxalate in the intestinal lum
en and is lost in the stool. Lipolysis in patients with SBS and fa
t malabsorption is normal, and unabsorbed long-chain fatty aci
ds compete with oxalate for available luminal calcium. Conseq
uently, a larger amount of free oxalate is lost to the colon, wher
e it is absorbed and ultimately excreted by the kidney.
28. Clinical findings in intestinal malabsorption.
Organ System Clinical Feature Cause
Gastrointestinal tract Diarrhea Nutrient malabsorption; small
intestinal secretion of fluid and
electrolytes; action of unabsorbed
bile acids and hydroxy-fatty acids on
colonic mucosa
Weight loss Nutrient malabsorption; decreased
dietary intake
Flatus Bacterial fermentation of unabsorbed
dietary carbohydrates
Abdominal pain Distention of bowel, muscle spasm,
serosal and peritoneal
Glossitis, stomatitis, Iron, riboflavin, niacin deficiency
cheilosis
29. Musculoskeletal system
Osteopenic bone disease Calcium, vitamin D
malabsorption
Osteoarthropathy Not known
Tetany Calcium, magnesium, and
vitamin D deficiency
Endocrine system
Amenorrhea, impotence, infertility Generalized malabsorption and
malnutrition
Secondary hyperparathyroidism Protracted calcium and vitamin
D deficiency
30. Skin
Purpura Vitamin K deficiency
Follicular hyperkeratosis Vitamin A, zinc, essential fatty acids,
and dermatitis niacin deficiency
Edema Protein-losing enteropathy,
malabsorption of dietary protein
Hyperpigmentation Secondary hypopituitarism and adrenal
insufficiency
Nervous system
Xerophthalmia, night blindness Vitamin A deficiency
Peripheral neuropathy Vitamin B12, thiamine
deficiency
31. Night Blindness
(Vitamin A)
Anaemiairon, Folate,B12
Angular stomatits,glossitis
(iron,folate,B12)
Bleeding gums
(vitamin C)
Acrodermatitis enteropathica
(Zinc)
Koilonychia
(iron)
Parasthesia,tetany
(calcium,Magnesium)
clubbing
Osteomalacia,rickets
(Calcium,Vitamin D)
Muscle wasting
(Protein)
Proximal myopathy
(vitamin D)
Peripheral neuropathy
(B12)
Peripheral edema
(hypoalbuminaemia)
Folicular hyperkeratosis
(Vitamin A)
Possible Physical consequences of Malabsorption
33. Immunologic Markers
Immunoglobulins IgA deficiency, immunodeficiency syndromes
Autoantibodies (e.g., ANA) Connective tissue diseases
Antimitochondrial autoantibodies Primary biliary cirrhosis
ACTH, cortisol Abnormal values in Addison's disease
5-Hydroxyindoleacetic acid in urine Elevated in carcinoid syndrome
Gastrin* Elevated in Zollinger-Ellison syndrome
Glucagon* Elevated in glucagonoma
Serum TSH
Decreased in hyperthyroidism; increased in h
ypothyroidism
Somatostatin*
Elevated in somatostatinoma (normal in duo
denal somatostatinoma)
Tissue transglutaminase antibodies, EMA Celiac disease
34. `1. Stool studies— Careful inspection of the stool by the physician is
an important component of the malabsorption evaluation. Steatorrh
eic. The simplest approach to detect the presence of fat malabsorpti
on is a qualititative examination of stool. A spot specimen is smeare
d on a microscope slide and is gently heated with a drop of glacial a
cetic acid for a few seconds to allow fat droplets to form. A fat-solu
ble stain, such as Sudan III, is then applied and the slide is examine
d under the microscope. Stained fat droplets are sought and the num
ber of droplets is assessed semiquantitatively.
• This test is regularly positive (more than five droplets per high pow
er field) when substantial steatorrhea is present.
35. Sudan stain of stool for fat. The positive stain (left) shows larger globules of unabsorbed fat (arrows).
36. • Quantitative determination of fat in a pooled 48- or 72-hour st
ool collection, although cumbersome, remains the definitive te
st for steatorrhea. The van de Kamer method .
• Ideally the patient should be placed on an 80–100-g fat diet for
a day or two before the stool collection is begun and maintain t
hat intake throughout the collection period. a stool fat concent
ration over 9.5% suggests intraluminal maldigestion whereas a
stool fat concentration less than 9.5% suggests mucosal diseas
e as intestinal fluid secretion and malabsorptions of other nutri
ents dilute stool fat in the latter situation.
37. • Measurements of the pancreatic enzyme, elastase, in the stool ass
ayed is useful for detecting severe pancreatic exocrine deficiency.
• Stool samples should be evaluated for ova and parasites and for s
pecific parasitic antigens in patients with suspected malabsorption
, especially if diarrhea is present. Several protozoal
diseases, including giardiasis, cryptosporidiosis, microsporidiosis,
and Isospora belli infection, can produce significant malabsorptio
n.
38. Test of fat absorption
Qualitative fecal fat (>5 fat droplets/HP
F)
Quantitaive fecal fat (>7gm/24 hrs)
May be normal with mild or moderate st
eatorrhoea
Useful for follow up, affected by stool we
ight
Rest for protein absorption
Fecal nitrogen excretion
Alpha antitrypsine clearance
Adds little to assessment.
Useful to identify protein losing enterop
athy.
Laboratory tests for malabsorption
39. Tests of carbohydrate absorption
Quantitative excretion tests(anthrone)
Stool PH<5.5
Osmotic gap in stool water
Stool reducing substance
D- Xylose absorption test
Oral glucose, sucrose, lactose tolerance t
ests
Breath hydrogen tests
Does not account for colonic salvage
Charecteristics for carbohydrate malabso
rption
Not specific
May be positive with reducing substance
s other than carbohydrate
Measure urine and blood concentration,
low results suggestsproximal intestinal d
ysfunction
May be misleading in patients with diabe
tes mellitus, bacterial overgrowth.
Simple and inexpensive test for malabso
rption of specific of a specific substance
40. • Specific oral absorption tests and breath tests—The
• D-xylose absorption test may help to differentiate malabsorption c
aused by small intestinal mucosal disease from malabsorption due
to impaired intraluminal digestion or lymphatic obstruction. This p
entose sugar requires no intraluminal processing and is absorbed b
y facilitated diffusion. After administration of a 25-g dose orally to
a well-hydrated patient, 5 g or more are normally excreted in the u
rine over 5 hours and blood levels should reach 25 mg/dL 2 hours
after the test dose. Low urine excretion and blood levels suggest di
sease of the mucosa of the proximal small intestine such as celiac
sprue.
41. Hydrogen Breath Test
• To screen for intestinal lactase or, less commonly, sucrase def
iciency, either breath hydrogen excretion or blood glucose ca
n be measured following an orally administered test dose of l
actose or sucrose. If lactose is malabsorbed, it travels to the di
stal small intestine where the bacterial flora metabolize the su
gar releasing hydrogen, which is excreted by the lungs and ca
n be readily measured in the breath. After a test dose of 2 g/k
g (25 g maximum) a rise of less than 10 parts per million (PP
M) is normal whereas a rise to 20 PPM suggests lactase defic
iency.
42. Schilling test with intrinsic factor
Low urinary recovery
Dual lebeled study
Suggests ileal dysfunction, may be abno
rmal with pancreatic exocrine insufficie
ncy and bacterial overgrowth.
Corrects for pancreatic exocrine insuffici
ency
Tests for bile acid malabsorption
Fecal bile acid excretion
Radiolebeled bile acid excretion
75SeHCAT retention
selenium-75-homotaurocholic aci
d test
[14C]Glycocolic acid breath test
Gold standard but difficult to assay
Correlates with fecal bile acid excretion
Sensitive indicator of ileal bile acid mala
bsorption
Abnormal with small bowel overgrowth
or bile acid malabsorption.
43. Tests for small bowel bacterial overgrowth
[14C]Xylose breath test
Glucose breath hydrogen test
Quantitative culture of jejunal asp
irate (>10 x 10000/ml)
Sensitivity may be low
Inexpensive some false negative
Gold standard for this diagnosis.
Tests for exocrine pancreatic insufficiency
Stool chymotrypsin concentration
Dual lebeled schilling test
Low concentration in presence of steato
rrhoea highly suggestive in pancreatic in
suficinecy.
Complex test
Secretin/CCK test Involve intubation,complex analysis.
44. • The Schilling Test
• The Schilling test can be used clinically to distinguish between gast
ric and ileal causes of vitamin B12 deficiency.
• The Schilling test is performed by administering a small oral dose
of radiolabeled vitamin B12 and, simultaneously or within one or t
wo hours, a large intramuscular flushing dose of nonradiolabeled v
itamin B12. The unlabeled B12 saturates vitamin B12 carriers; thus, a
ny radioactive vitamin B12 absorbed by the intestine is excreted in t
he urine. If less than 7% to 10% of the administered dose is recove
red in urine within 24 hours, vitamin B12 malabsorption is confirme
d. To specify the site of vitamin B12 malabsorption, a second phase
of the Schilling test is performed subsequently with oral administra
tion of intrinsic factor. In patients with pernicious anemia, the resul
ts of the Schilling test normalize after oral administration of intrinsi
c factor.
45. • Patients with pancreatic exocrine insufficiency might have an abn
ormal result on the Schilling test, with or without added intrinsic f
actor, but results normalize with addition of pancreatic enzymes .
In small bowel bacterial overgrowth the results of the Schilling te
st can improve after antibiotic therapy . In ileal disease or followi
ng ileal resection, abnormal results of the Schilling test persist des
pite intrinsic factor.
46. Imaging for diaqgnosis of malabsorption
1. Plain X- ray abdomen: Pancreatic calcifications.
2. USG : Biliary obstruction, and chronic pancreatits
3. Small Bowel Follow-through and Small Bowel Enteroclysis: The
principal role of small bowel radiologic series in evaluating mala
bsorption is to identify focal or diffuse abnormalities and alterati
ons that predispose to bacterial overgrowth, including diverticula,
stagnant loops of intestine, generalized intestinal hypomotility or
dilatation, intestinal fistulas, and tumor.
4. Abdominal Computed Tomography: CT scanning is useful to det
ect focal intestinal lesions, such as thickening of the small bowel
wall in Crohn's disease or small intestinal lymphoma, intestinal fi
stula, and dilated bowel loops.
48. • Endoscopy:
1. Upper GI endoscopy with duodenal biopsy
2. VCE: Videocapsule endoscopy: Can see the m
ucosal abnormality but has limitation of taking
biopsy.
3. Balloon enteroscopy: Single or double bvaloon
.
49. • Endoscopy
• Endoscopic inspection of the duodenal mucosa can provide clue
s to some causes of malabsorption. Aphthae suggest Crohn's dis
ease, and small, diffuse, white, punctate lesions can be seen in p
rimary or secondary lymphangiectasia. Mosaic-like scalloping o
f duodenal folds and reduction in the number of duodenal folds
are highly suggestive of villus atrophy in celiac disease.
