MD; FRCP(London); FRCPEdin; FRCSEdin
Malabsorption Syndrome:
Failure to fully absorb nutrients
from the gastrointestinal tract.
There are many causes
including abnormalities of the
gut wall, failure to produce
digestive enzymes and
abnormalities of gut flora.
Clinical features
Malabsorption, from whatever
cause, may be accompanied by:
Changes in weight and
 Inadequate absorption of
calories will lead to loss of
weight in adults or stunting of
growth in children.
Adults will complain of
unintended weight loss and
perhaps tiredness, lethargy
and fatigue.
Children may have similar
symptoms accompanied
by failure to thrive with
growth failure (falling
through the centile charts for
height and weight).
Malabsorption Syndrome:
Diarrhea: Diarrhea frequently
is watery, reflecting the osmotic
load received by the intestine.
 Bacterial action producing
hydroxy fatty acids from
undigested fat further
worsening the diarrhea.
Steatorrhea: is the result of fat
 The hallmark of steatorrhea is
the passage of pale, bulky,
and malodorous stools.
 Such stools often float on top
of the toilet water and are
difficult to flush. Also,
patients find floating oil
droplets in the toilet
following defecation.
Weight loss and fatigue:
 Weight loss is common and
may be pronounced.
 Weight loss increases in
diseases involving the
intestine, such as celiac
disease and Whipple
Flatulence and abdominal
 Bacterial fermentation of
unabsorbed food releases
gaseous products, such as
hydrogen and methane,
causing flatulence.
 Flatulence often causes
uncomfortable abdominal
distention and cramps.
 Hypoalbuminemia from
chronic protein
malabsorption or from loss
of protein into the intestinal
lumen causes peripheral
 Extensive obstruction of the
lymphatics, can cause
protein loss.
 Severe protein depletion,
ascites may develop.
 Anemia can be either
microcytic or macrocytic
 Iron deficiency anemia
often is a manifestation of
celiac disease.
 Ileal involvement in Crohn
disease or ileal resection can
cause megaloblastic anemia
due to vitamin B-12
Bleeding disorders:
 Bleeding usually is a
consequence of vitamin K
malabsorption and
 Ecchymosis usually
manifests, although,
occasionally, melena and
hematuria occur.
Metabolic defects of bones:
 Vitamin D deficiency can
cause bone disorders, such
as osteopenia or
 Bone pain and pathologic
fractures may be observed.
 Malabsorption of calcium
can lead to secondary
Neurologic manifestations:
 Hypocalcemia &
hypomagnesemia, can lead
to tetany, manifesting as the
Trousseau sign and the
Chvostek sign.
Vitamin malabsorption can
 Generalized motor weakness
(pantothenic acid, vitamin
 Peripheral neuropathy
 Loss for vibration and
position (cobalamin),
 Night blindness (vitamin A)
 Seizures (biotin).
Signs and symptoms of malabsorption
Laboratory findings
Clinical features
Weight loss with normal appetite
Pale and voluminous stool, diarrhea
Stool fat >6 g/day
without flatulence, steatorrhea
Edema, muscle atrophy,
Watery diarrhea, flatulence, acidic
stool pH, milk intolerance, stool
osmotic gap
Increased breath
Vitamin B12
Anemia, subacute combined
degeneration of the spinal cord
(early symptoms are paresthesias
and ataxia associated with loss of
vibration and position sense)
Macrocytic anemia,
vitamin B12 decreased,
abnormal Schilling test,
serum methylmalonic
acid and homocysteine
Macrocytic anemia, serum
Signs and symptoms of malabsorption
Clinical features
Laboratory findings
Folic acid
Macrocytic anemia, serum
and RBC folate decreased,
serum homocysteine
Vitamin B, general
Cheilosis, painless glossitis,
acrodermatitis, angular stomatitis
Microcytic anemia, glossitis,
Serum iron and ferritin
decreased, total iron binding
capacity increased
Calcium and
vitamin D
Paresthesia, tetany, pathologic
fractures due to osteomalacia, positive
Chvostek and Trousseau signs
Hypocalcemia, serum
alkaline phosphatase
increased, abnormal bone
Vitamin A
Follicular hyperkeratosis, night
Serum retinol decreased
Hematoma, bleeding disorders
Prolonged prothrombin
time, vitamin K-dependent
coagulation factors
Vitamin K
Acrodermatitis enteropathica
Follicular Keratosis
Physical signs
General physical
 Patients may have
orthostatic hypotension.
 Patients may complain of
 Signs of weight loss, muscle
wasting, or both may be
 Patients may have signs of
loss of subcutaneous fat.
Abdominal examination
 The abdomen may be
distended, and bowel
sounds may be
 Ascites may be present in
severe hypoproteinemia.
Physical signs
 Pale skin may reveal anemia.
 Ecchymoses due to vitamin K
deficiency may be present.
 Dermatitis herpetiformis,
erythema nodosum, and
pyoderma gangrenosum may
be present.
 Pellagra, alopecia, or
seborrheic dermatitis may be
Neurologic examination
 Motor weakness, peripheral
neuropathy, or ataxia may be
 The Chvostek sign or the
Trousseau sign may be
 Cheilosis, glossitis, or
aphthous ulcers of the mouth
Causes: The best way to classify the numerous causes of malabsorption is to consider
the 3 phases of digestion and absorption.
Luminal phase
Impaired nutrient hydrolysis
 The most common cause for
impaired nutrient hydrolysis
is pancreatic insufficiency.
The resultant deficiencies in
lipase and proteases lead to
lipid and protein
malabsorption, respectively.
 Inactivation of pancreatic
enzymes by gastric
hypersecretion, as seen in ZEllison syndrome, is another
Inadequate mixing of
nutrients, bile, and
pancreatic enzymes, as seen
in rapid intestinal transit,
gastrojejunostomy also causes
impaired hydrolysis.
Rarely, a failure to convert a
proenzyme to active form,
such as enterokinase and
trypsinogen deficiencies, also
can cause protein
maldigestion and
Impaired micelle formation :
Inadequate fat solubilization
leading to fat malabsorption.
This impairment is due to
 Decreased bile salt synthesis
from severe parenchymal liver
 Impaired bile secretion from
biliary obstruction or
cholestatic jaundice
 Impaired enterohepatic bile
circulation, as seen in small
bowel resection or regional
Stasis of intestinal content
caused by:
Motor abnormality (e.g.,
Diabetic neuropathy
Intestinal obstruction
Anatomic abnormality (e.g.,
small bowel diverticula,
stricture, ischemia, blind
Small bowel contamination
from enterocolonic fistulas
can cause bacterial
Luminal availability and
 Luminal bacterial overgrowth
can cause a decrease in the
availability of substrates,
including carbohydrates,
proteins, and vitamins (eg,
vitamin B-12, folate).
 Vitamin B-12 deficiency due
to pernicious anemia is
caused by a lack of intrinsic
factor and by pancreatic
enzyme deficiency.
Mucosal phase:
Impaired brush-border hydrolase
Disaccharidase deficiency can
lead to disaccharide
Lactase deficiency, either
primary or secondary, is the
most common form of
disaccharidase deficiency.
Immunoglobulin A (IgA)
deficiency is due to decreased
or absent serum & intestinal
IgA, which clinically appears
similar to celiac disease and is
unresponsive to a gluten-free
Mucosal phase: (Continued)
 Acrodermatitis
enteropathica is an
autosomal recessive disease
with selective inability to
absorb zinc, leading to villous
atrophy and acral dermatitis.
 Autoimmune enteropathy
primarily diagnosed in
children presenting with
intractable secretory diarrhea
and villous atrophy.
Autoimmune enteropathy is
due to antibodies directed
against intestinal epithelial
and goblet cells.
Impaired nutrient
Nutrient malabsorption is due
to inherited or acquired defects.
 Inherited defects include
cystinuria, and Hartnup
 Other carbohydrase
deficiencies, such as sucraseisomaltase deficiency, may be
the cause.
Impaired nutrient
Acquired disorders are far more
common and are caused by:
1. Intestinal resection of
intestinal bypass;
2. Damaged absorbing surface,
as seen in celiac sprue,
tropical sprue, Crohn's
3. Infiltrating disease of the
intestinal wall: lymphoma
and amyloidosis;
4. Infections bacterial
overgrowth giardiasis,
Whipple's disease,
cryptosporidiosis, and
Postabsorptive phase:
 Congenital: intestinal
lymphangiectasia, Milroy
 Acquired: Whipple disease,
neoplasm including
lymphoma, tuberculosis
impairs the absorption of
chylomicrons & lipoproteins
and may cause fat
malabsorption or a proteinlosing enteropathy.
Whipple’s Disease
Malabsorption: Examples of conditions causing malabsorption,
categorized by the phase of absorption that is impaired
Phase and nature of malabsorptive defect
Luminal phase
A. Substrate hydrolysis
1. Digestive enzyme deficiency
Chronic pancreatitis
2. Digestive enzyme inactivation
Zollinger-Ellison syndrome
3. Dysynchrony of enzyme release, inadequate mixing
Post Billroth II procedure
B. Fat Solubilization
1. Diminished bile salt synthesis
2. Impaired bile secretion
Chronic cholestasis
3. Bile salt de-conjugation
Bacterial overgrowth
4. Increased bile salt loss
Ileal disease or resection
C. Luminal availability of specific nutrients
1. Diminished gastric acid
Atrophic gastritis - vitamin B12
2. Diminished intrinsic factor
Pernicious anemia - vitamin B12
3. Bacterial consumption of nutrients
Bacterial overgrowth - vitamin
Malabsorption: Examples of conditions causing malabsorption,
categorized by the phase of absorption that is impaired
Phase and nature of malabsorptive defect
Mucosal (absorptive) phase
A. Brush border hydrolysis*
1. Congenital disaccharidase defect
Sucrase-isomaltase deficiency
2. Acquired disaccharidase defect
Lactase deficiency
B. Epithelial transport
1. Nutrient-specific defects in transport
Hartnup's disease
2. Global defects in transport
Celiac sprue
Postabsorptive, processing phase
A. Enterocyte processing
B. Lymphatic
Intestinal lymphangiectasia
* This process is sometimes considered as part of the luminal phase.
Malabsorption syndrome: Causes
Mucosal causes
 Coeliac disease usually
presents in childhood but
can present later. It is due to
allergy to gluten in the diet
that results in subtotal
villous atrophy.
 Cows' milk intolerance.
 Soya milk intolerance.
Fructose intolerance and
simultaneous consumption
of glucose reduces fructose
Malabsorption syndrome: Causes
 Giardiasis
 Whipple's
 Intestinal tuberculosis
 Tropical sprue
 Traveller's diarrhoea
 Diphyllobothriasis
(tapeworm can cause
vitaminB12 malabsorptio)
 Ancylostomiasis
 Strongyloidiasis
In patients with an
inflammatory bowel
disorder and malabsorption,
an immune deficiency,
including HIV enteropathy,
should be considered.
Intestinal lymphangiectasia
and other causes of
lymphatic obstruction
include lymphoma,
tuberculosis and cardiac
Malabsorption syndrome: Causes
Intraluminal causes
 Pancreatic insufficiency:
 Cystic fibrosis
 Chronic pancreatitis
 Carcinoma of pancreas
 Zollinger-Ellison syndrome
 Defective secretions of bile
salts, due to cholestatic
jaundice or disease of the
terminal ileum.
 Drugs.
Structural causes
 Intestinal hurry:
 Post-gastrectomy
 Post-vagotomy
 Gastrojejunostomy
 The blind loop syndrome
involves disturbance of normal
gut flora with malabsorption.
 Fistulae.
 Diverticulae and strictures.
 Crohn's disease.
 Amyloidosis.
 Short bowel syndrome.
 Eosinophilic gastroenteropathy.
 Mesenteric arterial insufficiency.
 Radiation enteritis.
Differential diagnosis:
Cystic Fibrosis
Hartnup Disease
Intestinal Lymphangiectasia
Whipple Disease
Zollinger-Ellison Syndrome
Laboratory studies:
Hematologic tests:
 A CBC count may reveal
microcytic anemia due to
iron deficiency or
macrocytic anemia due to
vitamin B-12 or folate
 Serum iron, vitamin B-12,
and folate concentrations
may help establish a
 Prothrombin time may be
prolonged because of
malabsorption of vitamin K,
a fat-soluble vitamin.
Laboratory Studies:
Electrolytes and chemistries:
Malabsorption can involve electrolyte
imbalances, such as hypokalemia,
hypocalcemia, hypomagnesemia, and
metabolic acidosis.
 Protein malabsorption may cause
hypoproteinemia and
 Fat malabsorption can lead to low
serum levels of triglycerides,
cholesterol, and alpha- and betacarotene.
 ESR is elevated in Crohn’s disease
and Whipple disease.
 No serologic tests are specific for
 Serum antigliadin and
antiendomysial antibodies can be
used to help diagnose celiac sprue.
 Serum IgA can be used to rule out
IgA deficiency.
 Determination of fecal elastase and
chymotrypsin (2 proteases
produced by the pancreas) can be
used to try to distinguish between
pancreatic causes and intestinal
causes of malabsorption.
Laboratory Studies:
Imaging Studies:
Small bowel barium studies
 An abnormal small bowel pattern
from barium studies may reveal the
nature of malabsorption.
 The mucosa pattern associated
with celiac disease often becomes
obliterated or coarsened.
 Flocculation of the barium occurs
in the gut lumen.
 Small bowel dilatation and
diverticulosis are frequently
identified in scleroderma.
 Regional enteritis of the small
intestine can lead to stricture,
ulceration, and fistula formation.
Other anatomic abnormalities,
such as surgical changes or
enterocolonic fistula, also can
be detected on x-ray films.
Imaging Studies:
 CT scan of the abdomen:
Performing this study may help
detect evidence of chronic
pancreatitis, such as pancreatic
calcification or atrophy. Enlarged
lymph nodes are seen in Whipple
disease and lymphoma.
 Endoscopic retrograde
cholangiopancreatogram (ERCP):
This study helps document
malabsorption due to pancreatic or
biliary-related disorders.
Imaging Studies
Plain abdominal x-ray film:
Pancreatic calcifications are
indicative of chronic
Other Tests
Tests of fat malabsorption
 This usually is the first test
because many disease
processes result in fat
 Quantitative measurement of
fat absorption, a 72-hour
fecal fat collection is often
performed and is considered
the criterion standard.
Qualitative tests include the
acid steatocrit test and
Sudan III stain of stool, but
these tests are less reliable.
Serum retinyl palmitate to
identify severe cases of fat
malabsorption may be useful
relative to the 72-hour fecal
fat test.
Instruct patients to consume
a normal amount (80-100
g/d) of fat before and during
the collection. Based on this
intake, fecal fat excretion in
healthy individuals should be
less than 7 g/d.
Laboratory Studies
D-xylose test
 If the 72-hour fecal fat
collection results
demonstrate fat
malabsorption, the D-xylose
test is used to document the
integrity of the intestinal
 Facilitated diffusion in the
proximal intestine primarily
absorbs D-xylose.
 Approximately half of the
absorbed D-xylose is
excreted in urine,
If the absorption of D-xylose
is impaired due to either a
luminal factor (e.g., bacterial
overgrowth) or a reduced or
damaged mucosal surface area
(e.g., surgical resection, celiac
disease), urinary excretion is
lower than normal.
Cases of pancreatic
insufficiency usually result in
normal urinary excretion
because the absorption of Dxylose is still intact.
Other tests:
Tests of carbohydrate
A simple sensitive test for
carbohydrate malabsorption
is the hydrogen breath test,
in which patients are given an
oral solution of lactose.
 In cases of lactase deficiency,
colonic flora digest the
unabsorbed lactose, resulting
in an elevated hydrogen
content in the expired air.
Bacterial overgrowth or rapid
transit also can cause an early
rise in breath hydrogen,
necessitating the use of
glucose instead of lactose to
make a diagnosis. However,
18% of patients are hydrogen
nonexcretors, causing a falsenegative test result.
Other tests:
Test of bile salt absorption:
Bile salt breath test can
determine the integrity of bile
salt metabolism.
 The patient is given oral
conjugated bile salt, such as
glycine cholic acid with the
glycine radiolabeled in the
carbon position.
The bile salt is deconjugated
and subsequently
metabolized by bacteria,
leading to a radioactively
labeled elevated breath
carbon dioxide level if
interrupted enterohepatic
circulation, such as bacterial
overgrowth, ileal resection, or
disease, is present.
Other tests:
Wireless capsule
endoscopy :
 Wireless capsule endoscopy
allows for visualization of
the entire small bowel and
allows for much more
detailed evaluation of small
bowel mucosal disease than
barium studies. Thus, it may
have a role in evaluating
suspected small bowel
disease (such as Crohn's
disease) associated with
Because of the risk of
retention, wireless capsule
endoscopy should generally
be avoided in patients with
known or suspected small
bowel strictures
Other tests:
Upper endoscopy with
small bowel mucosal
 Establishing a definitive
diagnosis of malabsorption
of the mucosal phase often
can be achieved by
histologic examination of
biopsied mucosal
specimens obtained during
routine upper endoscopy
Examples of conditions
that can be diagnosed this
way include celiac sprue,
giardiasis, Crohn disease,
Whipple disease,
abetalipoproteinemia, and
Principles of management:
There are three major
principles underlying the
management of patients
with malabsorption and
maldigestion, and
appropriate care of such
patients in the majority of
cases necessitates that each
of these three are
Identification and
treatment of the
underlying disease
Treatment of the diarrhea
that often accompanies
these disorders
Identification and
correction of nutritional
Principles of management:
Summary and
 Malabsorption depend
upon the cause and severity
of the disease
 The etiology can often be
obtained from a detailed
patient history, which can
also exclude other causes of
 Deficiencies of specific
nutrients and vitamins may
also identify the underlying
cause and its duration
Because symptoms may be
absent or mimic other
diseases, a routine battery
of blood tests is often
helpful as an initial step
Several invasive and
noninvasive tests are
available to establish the
cause of malabsorption.
Further testing may not be
necessary in patients who
have gross steatorrhea.