Transcript Description

MALABSORPTION SYNDROME
• The term maldigestion refers to defective
hydrolysis
of
nutrients,
whereas
malabsorption refers to impaired mucosal
absorption.
• The major part of digestion occurs in the
duodenum and most proximal jejunum.
• The complete process of absorption consists of
a luminal phase, in which various nutrients
are hydrolyzed and solubilized; a mucosal
phase, in which further processing takes place
at the brush border of the epithelial cell with
subsequent transfer into the cell; and a
transport phase, in which nutrients are moved
from the epithelium to the portal venous or
lymphatic circulation.
LUMINAL PHASE
• pancreatic enzymes,
colipase, and trypsin;
• gastric digestive enzymes
particularly
lipase,
Mucosal Phase
• Extensive mucosal loss (resection or infarction)
• Diffuse
mucosal
disease
(celiac
sprue;
Crohn's disease; irradiation; infection; infiltrations;
drugs: alcohol, colchicine, neomycin, iron salts)
• Brush border hydrolase deficiency (lactase
deficiency)
• Transport defects (vitamin B12 and folate uptake)
TRANSPORT PHASE
• After absorption, nutrients leave the cells
through venous or lymphatic channels.
Consequently, malabsorption may occur after
mesenteric
venous
obstruction,
lymphangiectasia, or lymphatic obstruction
from malignancy or infiltrative processes (such
as Whipple's disease.)
Tests of absorption
These are required only in complicated cases.
 Fat malabsorption. The confirmation of the presence
of steatorrhoea is only occasionally necessary. Threeday faecal fat analysis, breath tests and serum β
carotene are now rarely performed. In the rare cases
when it is really necessary to confirm steatorrhoea,
Sudan III staining of a faecal sample can be used.
 Lactose
tolerance test. This involves the oral
ingestion of 50 g of lactose and the measurement of
blood glucose. The test is of little use in adults as
lactose intolerance is not a clinical problem since these
patients avoid milk by choice.
Other tests
 Hydrogen breath test. This is frequently
used as a screening test to detect bacterial
overgrowth. Oral lactulose or glucose is
metabolized by bacteria with the
production of hydrogen.
 An early rise in the breath hydrogen will
indicate bacterial breakdown in the small
intestine.


Rapid transit of the lactulose to the large
intestine will also produce a rise in breath
hydrogen. As bacteria are present in the oral
cavity, the mouth should be rinsed out with an
antiseptic mouthwash prior to the test being
performed.
This test is simple to perform and it does not
involve radioisotopes. However, interpretation is
often difficult with a low sensitivity and
specificity.
 14C-glycocholic
acid breath test. This was
performed to look for bacterial overgrowth. Bacteria
deconjugate the bile salts, releasing [14C]-glycine,
which is metabolized and appears in the breath as
14CO2. It has largely been replaced by the hydrogen
breath test.
 Direct
intubation. Aspiration of intestinal juices is
another method by which bacterial contamination can
be detected, but is seldom used. Bacterial counts are
performed on aerobic and anaerobic cultures.
Chromatography of bile salts can also be performed
on the aspirate to detect evidence of deconjugation by
bacteria.
Pancreatic tests. these are used in the
differential diagnosis of steatorrhoea.
Other blood tests. Serum immunoglobulins
are measured to exclude immune deficiencies.
Gut peptides (e.g. vasoactive intestinal peptide
- VIP) are measured in high-volume secretory
diarrhoea, and chromogranins A and B are
raised in endocrine tumours.
MALABSORPTION
In many small bowel diseases, malabsorption
of specific substances occurs, but these
deficiencies do not dominate the clinical
picture.
An example is Crohn's disease, in which
malabsorption of vitamin B12 can be
demonstrated, but this is not usually a
problem and diarrhoea and general ill-health
are the major features.
Disorders of the small intestine
causing malabsorption
Coeliac disease
Dermatitis herpetiformis
Tropical sprue
Bacterial overgrowth
Intestinal resection
Whipple's disease
Radiation enteritis
Parasite infestation (e.g. Giardia intestinalis)
Coeliac disease (gluten-sensitive
enteropathy)
Coeliac disease is a condition in which there is an
inflammation of the jejunal mucosa that
improves when the patient is treated with a
gluten-free diet and relapses when gluten is
reintroduced. Gluten is contained in the cereals
wheat, rye and barley..
It is closely related to dermatitis herpetiformis, a
skin disorder that has an associated glutensensitive enteropathy (see below).
Incidence
 Coeliac disease is common in Northern Europe
and epidemiological studies have shown a
prevalence of 1 in 100 to 1 in 6500 in different
temperate countries. It occurs throughout the
world, but is rare in the black African.
 There is an increased incidence of coeliac disease
within families but the exact mode of inheritance
is unknown; 10-15% of first-degree relatives will
have the condition, although it may be
asymptomatic.
DQ2 (DQA*0501, DQB1*0201) and DQ8
(DQA1*0301, DQB1*0302) are associated with
coeliac disease. Over 90% of patients will have
DQ2, compared with 20-30% of the general
population.
Non-HLA regions linked to coeliac disease are
chromosome 5q31-33, possibly 11q, and others
are being identified. However, the fact that not all
patients have these haplotypes, and that as many
as 30% of identical twins are discordant for the
condition, suggests an additional factor, e.g.
environmental.
Aetiology
Gluten is a high - molecular - weight,
heterogeneous compound that can be
fractionated to produce α-, β-, γ- and ω-gliadin
peptides. α-Gliadin is the main damaging
peptide to the small intestinal mucosa although
the other smaller peptides are also 'toxic'.
T cells play a central role in the
aetiopathogenesis and react with the enzyme
tissue transglutaminase (the main antigen of the
endomysial antibody).
Pathology
 The mucosa of the proximal small bowel is
predominantly affected, the mucosal damage
decreasing in severity towards the ileum as the
gluten is digested into smaller 'non-toxic'
fragments.
 There is an absence of villi, making the mucosal
surface flat. Histological examination shows crypt
hyperplasia with chronic inflammatory cells in the
lamina propria and villous atrophy (Marsh type
III).
Clinical features
 Coeliac disease can present at any age. In infancy it
appears after weaning on to gluten-containing foods.
The peak incidence in adults is in the fifth decade,
with a female preponderance.
 The symptoms are very variable and often nonspecific with tiredness and malaise often associated
with an anaemia. Many patients are asymptomatic
(silent) and picked up on incidental findings, e.g. a
raised MCV.
 Common GI symptoms include diarrhoea or
steatorrhoea, abdominal discomfort, bloating or pain
and weight loss.
 Mouth ulcers and angular stomatitis are frequent and can
be intermittent. Infertility and neuropsychiatric symptoms
of anxiety and depression occur. Osteoporosis is common
and occurs even in patients on long-term gluten-free diets.
 Rare complications include tetany, osteomalacia, or gross
malnutrition with peripheral oedema. Neurological
symptoms such as paraesthesia, ataxia (due to cerebellar
calcification), muscle weakness or a polyneuropathy occur;
the prognosis for these symptoms is variable.
 There is an increased incidence of atopy and
autoimmune disease, including thyroid disease,
insulin-dependent diabetes, primary biliary cirrhosis
and Sjögren's syndrome.
 Other associated diseases include inflammatory
bowel disease, chronic liver disease, fibrosing
allergic alveolitis and epilepsy. IgA deficiency is
more common than in the general population.
 Physical signs are usually few and non-specific and
are related to anaemia and malnutrition.
Investigations
Endomysial (EMA) and tissue transglutaminase
(tTG) antibodies (IgA).
 These
antibodies have a high sensitivity and
specificity for the diagnosis of untreated coeliac
disease and can also be used as screening tests.
 They
are the investigation of first choice. An
immunofluorescent test for endomysial antibodies
(EMA) can be performed on umbilical cord tissue or
monkey oesophagus and the antigen for EMA is
tissue transglutaminase.

Anti-tissue transglutaminase antibodies are
measured using an ELISA. In the presence of a
typical clinical picture and the presence of these
antibodies, a confirmatory small bowel biopsy may
not always be required although most doctors
prefer to have one performed.

Anti-reticulin antibodies (ARA) are also very
sensitive but not so specific, as they are seen in
other gastrointestinal conditions (e.g. Crohn's
disease). Anti-gliadin antibodies (AGA) are less
sensitive and are not used.
Duodenal/jejunal
biopsy. The mucosal
appearance of a small bowel biopsy specimen
is diagnostic and regarded as the 'gold
standard' although errors occur, particularly
with poorly orientated specimens. Other
causes of a flat mucosa in adults are rare and
are shown in.
At endoscopy, the duodenal folds look effaced
and a dye can be sprayed on to the duodenal
mucosa to accentuate the smoothness of the
mucosa (positive dye test) before the biopsy is
taken.
 Haematology.
A mild or moderate anaemia is
present in 50% of cases. Folate deficiency is
almost invariably present in coeliac disease, giving
rise in most instances to a high MCV. B12
deficiency is rare but iron deficiency due to
malabsorption of iron and increased loss of
desquamated cells is common.
 A blood film may therefore show microcytes and
macrocytes
as
well
as
hypersegmented
polymorphonuclear leucocytes and Howell-Jolly
bodies due to splenic atrophy found in most
patients.
 Absorption tests are often abnormal but are
seldom performed.
 Radiology.
A small bowel follow-through
may show dilatation of the small bowel with
a change in fold pattern. Folds become
thicker and in the severer forms total
effacement is seen. Radiology is now mainly
used when a complication, e.g. lymphoma, is
suspected.
 Wireless capsule endoscopy. is used to look for
gut abnormalities
suspected.
when a complication
is
 Bone densitometry. (DXA) should be performed
on all patients because of the risk of osteoporosis.
 Biochemistry.
In
the severely ill patient,
biochemical
abnormalities,
e.g.
hypoalbuminaemia, low calcium and high
phosphate (osteomalacia) are seen.
Treatment and management
 Treatment
with a gluten-free diet usually
produces a rapid clinical and morphological
improvement.
 Replacement
haematinics, e.g. iron, folic acid,
calcium, are given initially to replace body stores.
 The usual cause for failure to respond to the diet is
poor compliance. Dietary adherence can be
monitored by serial tests for EMA and tTG. If
clinical progress is suboptimal then a repeat
intestinal biopsy should be taken.
 If
the diagnosis is equivocal a gluten
challenge, i.e. reintroduction of gluten with
evidence of jejunal morphological change,
confirms the diagnosis, but is only
performed if the diagnosis is equivocal.
 A transient gluten intolerance can occur in
early childhood.
 Despite advice, many patients do not keep to a
strict diet but nevertheless maintain good health.
The long-term effects of this low gluten intake
are uncertain but osteoporosis is seen even in the
treated case.
 Patients
should
have
pneumococcal
vaccinations (because of splenic atrophy) once
every 5 years
Complications

A few patients do not improve on a strict diet
(unresponsive 'coeliac disease'). Often no cause for
this is found, but intestinal lymphoma, ulcerative
jejunitis or carcinoma are sometimes responsible. The
incidence of enteropathy-associated T-cell lymphoma
(EATCL) is increased in coeliac disease.

Ulcerative jejunitis may present with
abdominal pain, perforation and bleeding.
fever,
 Diagnosis for these conditions is with barium studies
but laparotomy with full-thickness biopsies is often
required.
 Steroids
and immunosuppressive
azathioprine, are used.
agents,
e.g.
 Carcinoma of the small bowel and oesophagus as well
as extragastrointestinal cancers are also seen.
Malignancy seems to be unrelated to the duration of the
disease but the incidence is reduced by a gluten-free
diet.
Dermatitis herpetiformis

This is an uncommon blistering subepidermal eruption
of the skin associated with a gluten-sensitive enteropathy.

Rarely there may be gross malabsorption, but usually
the jejunal morphological abnormalities are not as severe
as in coeliac disease.

The inheritance and immunological abnormalities are
the same as for coeliac disease. The skin condition
responds to dapsone but both the gut and the skin will
improve on a gluten-free diet.
Tropical sprue
 This
is a condition presenting with
malabsorption that occurs in residents or
visitors to a tropical area where the disease is
endemic.
 Malabsorption of a mild degree, sometimes
following an enteric infection, is quite
common and is usually asymptomatic. This is
sometimes called tropical malabsorption.
 The
term tropical sprue is reserved for severe
malabsorption (of two or more substances) that is
usually accompanied by diarrhoea and
malnutrition. Tropical sprue is endemic in most of
Asia, some Caribbean islands, Puerto Rico and
parts of South America.
 Epidemics
occur, lasting up to 2 years, and in
some areas repeated epidemics occur at varying
intervals of up to 10 years.
Aetiology
The aetiology is unknown, but is likely to be
infective because the disease occurs in
epidemics and patients improve on
antibiotics.
A number of agents have been suggested but
none has been shown to be unequivocally
responsible. Different agents could be
involved in different parts of the world.
Clinical features
 These
vary in intensity and consist of diarrhoea,
anorexia, abdominal distension and weight loss. The onset
is sometimes acute and occurs either a few days or many
years after being in the tropics. Epidemics can break out
in villages, affecting thousands of people at the same time.
The onset can also be insidious, with chronic diarrhoea
and evidence of nutritional deficiency.
 The
clinical features of tropical sprue vary in different
parts of the world, particularly as different criteria are
used for diagnosis.
Diagnosis
Acute infective causes of diarrhoea must be excluded ,
particularly Giardia, which can produce a syndrome very
similar to tropical sprue.
Malabsorption should be demonstrated, particularly of fat
and B12.
The jejunal mucosa is abnormal, showing some villous
atrophy (partial villous atrophy). In most cases the lesion is
less severe than that found in coeliac disease, although it
affects the whole small bowel. Mild changes can be seen in
asymptomatic individuals in the tropics, so jejunal mucosal
changes must be interpreted carefully.
Treatment and prognosis
Many patients improve when they leave the sprue area and
take folic acid (5 mg daily). Most patients also require an
antibiotic (usually tetracycline 1 g daily) to ensure a
complete recovery; it may be necessary to give this for up to
6 months.
The severely ill patient requires resuscitation with fluids
and electrolytes for dehydration; any nutritional deficiencies
should be corrected. Vitamin B12 (1000 μg) is also given to
all acute cases.
The prognosis is excellent. Mortality is usually associated
with water and electrolyte depletion, particularly in
epidemics.
Bacterial overgrowth
 The gut contains many resident bacteria with
anaerobic bacteria, e.g. Bacteroides, bifidobacteria,
being 100-1000 times more abundant than aerobic
(facultative
anaerobes),
e.g.
Escherichia,
Enterobacter, Enterococcus.
 This gut microflora has major functions including
metabolic, e.g. fermentation of non-digestible
dietary residues into short chain fatty acids as an
energy source in the colon. Bacteria also initiate
vitamin K production.
 They control epithelial cell proliferation and are
involved in the development and maintenance of the
immune system. They protect the gut mucosa from
colonization by pathogenic bacteria.
 The upper part of the small intestine is almost
sterile, containing only a few organisms derived
fromthe mouth. Gastric acid kills most organisms and
intestinal motility keeps the jejunum empty. The
normal terminal ileum contains faecal-type organisms,
mainly Escherichia coli and anaerobes and the colon
has abundant bacteria.
 Bacterial overgrowth is normally only found associated
with a structural abnormality of the small intestine,
although it can occur occasionally in the elderly without
such abnormality. E. coli and/or Bacteroides, both in
concentrations greater than 106/mL are found as part of a
mixed flora.
 These bacteria are capable of deconjugating and
dehydroxylating bile salts, so that unconjugated and
dehydroxylated bile salts can be detected in aspirates by
chromatography. The clinical features are chiefly
diarrhoea and steatorrhoea. Steatorrhoea occurs as a result
of conjugated bile salt deficiency.
The bacteria are able to metabolize vitamin B12 and
interfere with its binding to intrinsic factor, thereby
leading to B12 deficiency. Conversely some bacteria
produce folic acid giving a high serum folate.
Bacterial overgrowth has only minimal effects on
other substances absorbed from the small intestine.
The vitamin B12 deficiency is not so severe as to
produce a neurological deficit. Confirmation of
bacterial overgrowth is with the hydrogen breath test ;
aspiration studies are not routinely performed.
Treatment
If possible, the underlying lesion should be
corrected (e.g. a stricture should be resected).
With multiple diverticula, grossly dilated
bowel, or in Crohn's disease, this may not be
possible and rotating courses of antibiotics are
necessary, such as metronidazole, a
tetracycline, or ciprofloxacin.
Intestinal resection
Intestinal resection is usually well tolerated, but
massive resection is followed by the short-bowel
syndrome.
The effects of resection depend on the extent and
the areas involved. Because the gut is long, a 3050% resection can usually be tolerated without
undue problems. Residual jejunum shows less
capacity for structural and functional adaptation
than residual ileum.
Ileal resection
The ileum has specific receptors for the
absorption of bile salts and vitamin B12, so that
relatively small resections will lead to
malabsorption of these substances. Removal of
the ileocaecal valve increases the incidence of
diarrhoea.
The following occur in ileal resection: Bile salts
and fatty acids enter the colon and cause
malabsorption of water and electrolytes leading
to diarrhoea .
 Increased
bile salt synthesis can
compensate for loss of approximately onethird of the bile salts in the faeces.
 Greater loss than this results in decreased
micellar formation and steatorrhoea, and
lithogenic bile and gallstone formation.
Increased oxalate absorption is caused by the
presence of bile salts in the colon. This gives rise
to renal oxalate stones.
There is a low serum B12 and macrocytosis.
Glucagon-like peptide 2 (GLP-2) is low following
ileal resection. GLP-2 is a specific growth
hormone for the enterocyte and this deficiency
may explain the lack of adaptation with an ileal
resection.
 Investigations include a small bowel followthrough, measurement of B12, bile salts and
occasionally fat absorption. A hydrogen breath
test will show rapid transit .
 Many patients require B12 replacement and
some need a low-fat diet if there is steatorrhoea.
 If diarrhoea is a problem, colestyramine,
which binds bile salts, often helps.
Jejunal resection
 The ileum can take over the jejunal
absorptive function. Jejunal resection may
lead to gastric hypersecretion with high
gastrin levels; the exact mechanism of this is
unclear.
 Structural
and
functional
intestinal
adaptation take place over the course of a
year, with an increase in the absorption per
unit length of bowel.
Shortened small intestine ending at a
terminal stoma
 The major problem is of sodium and fluid
depletion and the majority of patients with 100
cm or less of jejunum remaining will require
parenteral supplements of fluid and electrolytes,
often with nutrients. Sodium losses can be
minimized by increasing salt intake, restricting
clear fluids between meals and administering
oral glucose-electrolyte mixture with a sodium
concentration > 90 mmol/L.
Jejunal transit time can be increased and stomal
effluent loss of fluids and electrolytes reduced by
treatment with the somatostatin analogue
octreotide, and to a much lesser extent, with
loperamide, codeine phosphate or co-phenotrope.
There is no benefit of a low-fat diet, but fat
assimilation can be increased on treatment with
colestyramine and synthetic bile acids.
Shortened small intestine in continuity
with colon
 Only a small proportion of these patients require
parenteral supplementation of fluid, electrolytes and
nutrients because of the absorptive capacity of the
colon for fluid and electrolytes.
 Unabsorbed fat results in impairment of colonic
fluid and electrolyte absorption so patients should be
on a low-fat diet. A high carbohydrate intake is
advised as unabsorbed carbohydrate is metabolized
anaerobically to short-chain fatty acids (SCFAs).
Whipple's disease
 This is a rare disease usually affecting males. It
presents with steatorrhoea and abdominal pain
along with systemic symptoms of fever and weight
loss. Peripheral lymphadenopathy, arthritis and
involvement of the heart, lung and brain may
occur.
 Histologically, in the small bowel, the villi are
stunted and contain diagnostic periodic acid-Schiff
(PAS)-positive
macrophages.
On
electron
microscopy, bacilli can be seen 'within' the
macrophages.
 The organism was identified by the polymerase
chain reaction and can be cultured; it is
classified as an actinobacterium and has been
given the name Tropheryma whippeii.
A
dramatic improvement occurs with
antibiotic therapy, which should include an
antibiotic that crosses the blood-brain barrier
(e.g. co-trimoxazole) for 6 months.
Radiation enteritis

Radiation of more than 40 Gy will damage the
intestine. The ileum and rectum are the areas most
often involved, as pelvic irradiation is frequently
used for gynaecological and urinary tract
malignancies.

There may be nausea, vomiting, diarrhoea and
abdominal pain at the time of the irradiation.
These symptoms usually improve within 6 weeks
after completion of therapy.

Chronic radiation enteritis is diagnosed if
symptoms persist for 3 months or more. The
prevalence is more than 15%. Many patients
suffer from an increased bowel frequency.

Radiation produces muscle fibre atrophy,
ulcerative changes due to ischaemia, and
obstruction due to strictures produced by
radiation-induced fibrosis.

Abdominal pain is the main symptom due to the
obstruction, which is usually partial but eventually
may be complete. Malabsorption due to mucosal
damage as well as bacterial overgrowth in dilated
segments can occur.

Treatment is symptomatic, although often
unsuccessful in chronic enteritis. Surgery should be
avoided if at all possible, being reserved for lifethreatening situations such as complete obstruction or
occasionally perforation.

Radiation damage to the rectum produces a
radiation proctitis with diarrhoea, with or without
blood and tenesmus. Local steroids sometimes
help initially.

The telangiectasia that form and cause persistent
bleeding can be treated with argon plasma
coagulation or by placing a formalin-soaked swab
in the rectum (for 2 min), both of which heal the
lesions.
Parasite infestation

Giardia intestinalis not only produces
diarrhoea but can produce malabsorption with
steatorrhoea. Minor changes are seen in the
jejunal mucosa and the organism can be found
in the jejunal fluid or mucosa.

Cryptosporidiosis
malabsorption.

Patients with HIV infection are particularly
prone to parasitic infestation.
can
also
produce