Gastrointestinal System

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GIT5: MALABSORPTION
SYNDROME
DR GAN SENG CHIEW
Associate Professor
FACULTY OF MEDICINE & HEALTH SCIENCES
UNIVERSITY TUNKU ABDUL RAHMAN

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Malabsorption
• The failure to absorb or digest normally one
or more dietary constituents.
• Patients normally complain of diarrhea.
• Most patients with malabsorption present
with a syndrome characterized by large,
loose, foul-smelling stools and loss of weight.
• A wide variety of dosorders of the organs of
digestion can cause malabsorption or
maldigestion.

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Malabsorption syndromes
encompass numerous clinical
entities that result in chronic
diarrhea, abdominal
distention, and failure to
thrive. Clinical malabsorption
can be broken down into
several distinct conditions,
both congenital and acquired,
that affect one or more of the
different steps in the intestinal
hydrolysis and subsequent
transport of nutrients.
The major site of absorption
is the small intestine,.

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Digestive Disorder Examples
Pancreatic exocrine
insufficiency
Chronic pancreatitis
Pancreatic carcinoma,
Bile acid insufficiency Small-bowel bacterial overgrowth
Crohn’s disease of the terminal ileum
Small-bowel disease:
a. Mucosal Disorder
b. Specific absorptive
defects
Celic spruce; Collagenous sprue;
Tropical Sprue; Whipple’s disease;
Radiation enteritis; Ischemic disease;
Intestinal lymphoma; Regional enteritis
(Crohn’s diisease); Amyloidosis.
Primary lactase deficiency
Abetalipoproteinemia
Lymphatic disorders Intestinal lymphangiectasia
Mixed defects in
absorption
Zollinger-Ellison syndrome
Postgastrectomy disorders

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Pathophysiology
• In general, the digestion and absorption of food
materials can be divided into 3 major phases: luminal,
mucosal, and postabsorptive.
• The luminal phase is the phase in which dietary fats,
proteins, and carbohydrates are hydrolyzed and
solubilized by secreted digestive enzymes and bile. The
mucosal phase relies on the integrity of the brush-border
membrane of intestinal epithelial cells to transport
digested products from the lumen into the cells. In the
postabsorptive phase, reassembled lipids and other key
nutrients are transported via lymphatics and portal
circulation from epithelial cells to other parts of the
body.
• Perturbation by disease processes in any of these phases
frequently results in malabsorption.

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Luminal phase: Impaired
nutrient hydrolysis
• The most common cause for impaired nutrient hydrolysis is
pancreatic insufficiency due to chronic pancreatitis,
pancreatic resection, pancreatic cancer, or cystic fibrosis. The
resultant deficiencies in lipase and proteases lead to lipid
and protein malabsorption, respectively.
• Inactivation of pancreatic enzymes by gastric hypersecretion,
as seen in Zollinger-Ellison syndrome, is another cause.
• Inadequate mixing of nutrients, bile, and pancreatic
enzymes, as seen in rapid intestinal transit,
gastrojejunostomy, total and partial gastrectomy, or
intestinal resection after mesenteric emboli or thrombosis,
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 malabsorption.

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Luminal phase: Impaired
micelle formation
• Impaired micelle formation causes a problem in fat
solubilization and subsequent fat malabsorption. This
impairment is due to different reasons, including (1)
decreased bile salt synthesis from severe parenchymal liver
disease (eg, cirrhosis); (2) impaired bile secretion from
biliary obstruction or cholestatic jaundice (eg, primary
biliary cirrhosis, primary sclerosing cholangitis); (3) impaired
enterohepatic bile circulation, as seen in small bowel
resection or regional enteritis; or (4) bile salt deconjugation
due to small bowel bacterial overgrowth.
• Stasis of intestinal content caused by a motor abnormality
(eg, scleroderma, diabetic neuropathy, intestinal
obstruction), an anatomic abnormality (eg, small bowel
diverticula, stricture, ischemia, blind loops), or small bowel
contamination from enterocolonic fistulas can cause
bacterial overgrowth.

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Luminal phase : 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 B-12 deficiency due to pernicious anemia is caused
by a lack of intrinsic factor and by pancreatic enzyme
deficiency.

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Mucosal phase : Impaired
brush-border hydrolase
activity
• Disaccharidase deficiency can lead to disaccharide
malabsorption.
• Lactase deficiency, either primary or secondary, is
the most common form of disaccharidase
deficiency. Genetic factors determine primary
lactase deficiency. Secondary lactase deficiency
can be due to acute gastroenteritis (rotavirus and
giardia infection), chronic alcoholism, celiac sprue,
radiation enteritis, regional enteritis, or AIDS
enteropathy.
• IgA deficiency (most common immunodeficiency)
is due to decreased or absent serum and intestinal
IgA, which clinically appears similar to celiac
disease and is unresponsive to a gluten-free diet.

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• 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. Additional cell
types affected by autoantibodies include islet and
parietal cells.
• Other carbohydrase deficiencies, such as sucrase-
isomaltase deficiency, may be the cause.

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Mucosal phase : 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: (1) decreased absorptive
surface area, as seen in intestinal resection of
intestinal bypass; (2) damaged absorbing surface,
as seen in celiac sprue, tropical sprue, Crohn's
disease, AIDS enteropathy, chemotherapy, or
radiation therapy; (3) infiltrating disease of the
intestinal wall, such as lymphoma and amyloidosis;
and (4) infections, including bacterial overgrowth,
giardiasis, Whipple's disease, cryptosporidiosis, and
microsporidiosis.

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Postabsorptive phase
Obstruction of the lymphatic system, both
congenital (eg, intestinal lymphangiectasia, Milroy
disease) and acquired (eg, Whipple disease,
neoplasm [including lymphoma], tuberculosis),
impairs the absorption of chylomicrons and
lipoproteins and may cause fat malabsorption or a
protein-losing enteropathy.

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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 malabsorption.
• Serum iron, vitamin B-12, and folate
concentrations may help establish a diagnosis.
• Prothrombin time may be prolonged because of
malabsorption of vitamin K, a fat-soluble vitamin.
Electrolytes and chemistries
• Malabsorption can involve electrolyte imbalances,
such as hypokalemia, hypocalcemia,
hypomagnesemia, and metabolic acidosis.

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• Protein malabsorption may cause
hypoproteinemia and hypoalbuminemia.
• Fat malabsorption can lead to low serum levels of
triglycerides, cholesterol, and alpha- and beta-
carotene.
• Westergren sedimentation rate is elevated in
Crohn disease and Whipple disease.
Serology
• No serologic tests are specific for malabsorption.
• 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.

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Imaging Studies
Small bowel barium studies
• An abnormal small bowel pattern obtained from
barium studies of the upper gastrointestinal tract
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.

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• 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.
• Plain abdominal x-ray film: Pancreatic
calcifications are indicative of chronic
pancreatitis.

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Upper endoscopy with small
bowel mucosal biopsy
• 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.
• Villous atrophy is seen in celiac sprue, giardiasis,
Crohn disease, Whipple disease, amyloidosis,
abetalipoproteinemia, and lymphoma.

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Treatment
Correction of nutritional deficiencies:
i. Supplementing various minerals, such as
calcium, magnesium, iron, and vitamins, which
may be deficient in malabsorption.
ii. Caloric and protein replacement.
iii. 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.
iv. In cases of massive resection and extensive
regional enteritis, parenteral nutrition may
become necessary.

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Treatment of causative diseases:
i. A gluten-free diet helps treat celiac disease.
ii. Similarly, a lactose-free diet helps correct
lactose intolerance; supplementing the first bite of
milk-containing food products with Lactaid also
helps.
iii. Protease and lipase supplements are the
therapy for pancreatic insufficiency.
iv. Antibiotics are the therapy for bacterial
overgrowth.
v. Corticosteroids, anti-inflammatory agents, such
as mesalamine, and other therapies are used to
treat regional enteritis.

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Diarrhea
Diarrhea (from the Greek, δι ρροια meaning "flowingὰ
through"), also spelled diarrhoea, is the condition of
having three or more loose or liquid bowel movements
per day. It is a common cause of death in developing
countries and the second most common cause of infant
deaths worldwide. The loss of fluids through diarrhea can
cause dehydration and electrolyte imbalances. In 2009
diarrhea was estimated to have caused 1.1 million deaths
in people aged 5 and over and 1.5 million deaths in
children under the age of 5. Oral rehydration salts and
zinc tablets are the treatment of choice and have been
estimated to have saved 50 million children in the past
25 years.

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Mechanisms of Diarrhoea
1. Secretory
Secretory diarrhea means that there is an
increase in the active secretion, or there is an
inhibition of absorption. There is little to no
structural damage. The most common cause of
this type of diarrhea is a cholera toxin that
stimulates the secretion of anions, especially
chloride ions. Therefore, to maintain a charge
balance in the lumen, sodium is carried with it,
along with water. In this type of diarrhea
intestinal fluid secretion is isotonic with plasma
even during fasting. It continues even when
there is no oral food intake.

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2. Osmotic
Osmotic diarrhea occurs when too much water is drawn into
the bowels. This can be the result of maldigestion (e.g.,
pancreatic disease or celiac disease), in which the nutrients
are left in the lumen to pull in water. Osmotic diarrhea can
also be caused by osmotic laxatives (which work to alleviate
constipation by drawing water into the bowels). In healthy
individuals, too much magnesium or vitamin C or
undigested lactose can produce osmotic diarrhea and
distention of the bowel. A person who has lactose
intolerance can have difficulty absorbing lactose after an
extraordinarily high intake of dairy products. In persons
who have fructose malabsorption, excess fructose intake
can also cause diarrhea. High-fructose foods that also have a
high glucose content are more absorbable and less likely to
cause diarrhea. Sugar alcohols such as sorbitol (often found
in sugar-free foods) are difficult for the body to absorb and,
in large amounts, may lead to osmotic diarrhea. Diarrhea
stops when offending agent (e.g. milk, sorbitol) is stopped.

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3. Exudative
Exudative diarrhea occurs with the presence of blood and
pus in the stool. This occurs with inflammatory bowel
diseases, such as Crohn's disease or ulcerative colitis, and
other severe infections such as E. coli or other forms of
food poisoning.
4. Motility-related
Motility-related diarrhea is caused by the rapid movement
of food through the intestines (hypermotility). If the food
moves too quickly through the gastrointestinal tract, there
is not enough time for sufficient nutrients and water to be
absorbed. This can be due to a vagotomy or diabetic
neuropathy, or a complication of menstruation.
Hyperthyroidism can produce hypermotility and lead to
pseudodiarrhea and occasionally real diarrhea. Diarrhea
can be treated with antimotility agents (such as
loperamide). Hypermotility can be observed in people who
have had portions of their bowel removed, allowing less
total time for absorption of nutrients.

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5. Inflammatory
Inflammatory diarrhea occurs when there is damage to the
mucosal lining or brush border, which leads to a passive loss
of protein-rich fluids, and a decreased ability to absorb
these lost fluids. Features of all three of the other types of
diarrhea can be found in this type of diarrhea. It can be
caused by bacterial infections, viral infections, parasitic
infections, or autoimmune problems such as inflammatory
bowel diseases. It can also be caused by tuberculosis, colon
cancer, and enteritis.
6. Dysentery
Generally, if there is blood visible in the stools, it is not
diarrhea, but dysentery. The blood is trace of an invasion of
bowel tissue. Dysentery is a symptom of, among others,
Shigella, Entamoeba histolytica, and Salmonella.

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Differential diagnosis
Diarrhea is most commonly due to viral
gastroenteritis with rotavirus accounting for 40%
of cases in children under five. In travelers
however bacterial infections predominate.
It can also be the part of the presentations of a
number of medical conditions such as: Crohn's
disease or mushroom poisoning.
1. Infection
2. Malabsorption
3. Inflammatory Bowel Disease
4. Irritable Bowel Disease

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Other causes
• Diarrhea can be caused by chronic ethanol
ingestion.
• Ischemic bowel disease. This usually affects
older people and can be due to blocked
arteries.
• Hormone-secreting tumors: some hormones
(e.g., serotonin) can cause diarrhea if excreted
in excess (usually from a tumor).
• Chronic mild diarrhea in infants and toddlers
may occur with no obvious cause and with no
other ill effects; this condition is called
toddler's diarrhea.

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Evolution
According to two researchers, Nesse and
Williams, diarrhea may function as an evolved
expulsion defense mechanism. As a result, if it is
stopped, there might be a delay in recovery.
They cite in support of this argument research
published in 1973 which found that treating
Shigella with the anti-diarrhea drug (Co-
phenotrope, Lomotil) caused people to stay
feverish twice as long as those not so treated.
The researchers indeed themselves observed
that: "Lomotil may be contraindicated in
shigellosis. Diarrhea may represent a defense
mechanism".