Transcript Disorders of Absorption

DISORDERS
OF
ABSORPTION
Disorders
of absorption constitute a
broad spectrum of conditions with
multiple etiologies and varied
clinical manifestations.
Almost
all of these clinical problems
are associated with diminished
intestinal absorption of one or
more dietary nutrients and are
often referred to as the
malabsorption syndrome.
DIARRHEA
Diarrhea as a symptom (i.e., when used by patients to
describe their bowel movement pattern) may be
 a decrease in stool consistency,
 an increase in stool volume,
 an increase in number of bowel movements,
 or any combination of these three changes.
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
In contrast, diarrhea as a sign is a quantitative
increase in stool water or weight of>200-225 mL or
gram per 24 h, when a Western-type diet is consumed.
Individuals consuming a diet with higher fiber content
may normally have a stool weight of up to 400 g/24 h.
It
is also critical:
to establish whether a patient's
diarrhea is secondary to diminished
absorption of one or more dietary
nutrients,
 in contrast to diarrhea that is due to
small- and/or large-intestinal fluid
and electrolyte secretion.
 The former has often been termed
osmotic diarrhea, while the latter has
been referred to as secretory diarrhea.

a
substantial decrease in stool
output while fasting during a
quantitative stool collection of at
least 24 h is presumptive evidence that
the diarrhea is related to
malabsorption of a dietary nutrient.

The persistence of stool output while
fasting indicates that the diarrhea is
likely secretory and that the cause of
diarrhea is not a dietary nutrient.
NUTRIENT
DIGESTION AND
ABSORPTION
The
lengths of the small intestine
and colon are300 cm and 80 cm,
However,
the effective functional
surface area is approximately 600fold greater than that of a hollow
tube as a result of the presence of
folds, villi (in the smaIl intestine),
and microvilli.
 In
addition to nutrient digestion and
absorption, the intestinal epithelia have
several other functions:
 1. Barrier and immune defense.
 2. Fluid and electrolyte absorption
and secretion.
 3.Synthesis and secretion of several
proteins.
 4. Production of several bioactive
amines and peptides.
 Intestinal
epithelial cells are
continuously renewed, with new
proliferating epithelial cells at the base of
the crypt migrating over 48-72 h to the tip
of the villus (or surface of the colon),
where they are well-developed epithelial
cells with digestive and absorptive
function.
 This
high rate of cell turnover explains
the relatively rapid resolution of diarrhea
Nutrients,
minerals, and
vitamins are absorbed by one
or more active transport
mechanisms.
Active
transport mechanisms
are energy-dependent and
mediated by membrane
transport proteins.
The movement of these actively transported
nutrients against a concentration gradient is Na"
-dependent and is due to a Na" gradient across
the apical membrane.
 The Na" gradient is maintained by Na", Kt-adenosine
triphosphatase (A‘T'Pase)
 active glucose absorption and glucose-stimulated Na"
absorption require both the apical membrane
transport protein, SGLTl, and the basolateral Na", K+ATPase.
 In addition to glucose absorption being Na"dependent, glucose also stimulates Na" and fluid
absorption, which is the physiologic basis of oral
rehydration therapy for the treatment of
diarrhea

• ENTEROHEPATIC
CIRCULATION OF
BILE ACIDS
The
primary functions of bile
acids are:



(1) to promote bile flow,
(2) to solubilize cholesterol and
phospholipid in the gallbladder by mixed
micelle formation,
(3) to enhance dietary lipid digestion and
absorption by forming mixed micelles in
the proximal small intestine.
 Bile
acids are primarily absorbed by an
active, Na" –dependent process that is
located exclusively in the ileum,

though bile acids can also be absorbed to a
lesser extent by non-carrier-mediated
transport processes in the jejunum, ileum, and
colon.
 Conjugated
bile acids that enter the colon
are deconjugated by colonic bacterial
enzymes to unconjugated bile acids and are
rapidly absorbed by nonionic diffusion.
Patients
with limited ileal disease
or resection will often have
diarrhea but not steatorrhea.
The diarrhea, a result of bile acids
in the colon stimulating active Cl
secretion, has been called bile acid
diarrhea, or choleretic
enteropathy, and responds
promptly to cholestyramine, an
anion-binding resin.
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In contrast, patients with greater degrees of ileal
disease and/or resection will often have diarrhea and
steatorrhea that do not respond to cholestyrarnine.
hepatic synthesis can no longer increase sufficiently to
maintain the bile acid pool size. This second situation
is often called fatty acid diarrhea.
Cholestyramine may not be effective (and may even
increase the diarrhea by further depleting the
intraduodenal bile acid concentration);
however, a low-fat diet to reduce fatty acids entering
the colon can be effective.
LIPIDS
Three types of fatty acids compose fats:
 long-chain fatty acids (LCFAs),
 medium-chain fatty acids (MCFAs),
 short-chain fatty acids (SCFAs)



Dietary fat is exclusively composed of long-chain
triglycerides (LCTs),
While the majority of dietary LCFAs have carbon
chain lengths of 16 or 18, fatty acids of carbon chain
length >12 are metabolized in the same manner;
saturated and unsaturated fatty acids are handled
identically.
 Assimilation
of dietary lipid requires
three integrated processes:
 (I) an intraluminal, or digestive,
phase;
 (2) a mucosal, or absorptive, phase;
 (3) a delivery, or postabsorptive,
phase.

An abnormality at any site
of this process can cause
steatorrhea
The SCFAs present in stool are primarily:
 acetate,
 propionate,
 butyrate,
 Butyrate is the primary nutrient for colonic epithelial
cells
 SCFAs conserve calories and carbohydrate, because
carbohydrates not completely absorbed in the small
intestine will not be absorbed in the large intestine
due to the absence of both disaccharidases and SGLT1
 In contrast, SCFAs are rapidly absorbed and
stimulate colonic Na-Cl and fluid absorption

 Steatorrhea
can be responsible for diarrhea;
 if
the primary cause of the steatorrhea has not
been identified, a low-fat diet can often
ameliorate the diarrhea by decreasing fecal fat
excretion.
 Steatorrhea
is often associated with fatsoluble vitamin deficiency, which will
require replacement with water-soluble
preparations of these vitamins.
CARBOHYDRATES
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Carbohydrates in the diet are present in the form
of starch, disaccharides (sucrose and lactose), and
glucose.
Carbohydrates are absorbed only in the
small intestine and only in the form of
monosaccharides.
Therefore, before their absorption, starch and
disaccharides must first be digested by
pancreatic amylase and intestinal brush border
Monosaccharide absorption occurs by a Nadependent process mediated by the brush
border transport protein SGLT1.
Lactose
malabsorption is the
only clinically important
disorder of carbohydrate
absorption.
Lactose,
the disaccharide
present in milk, requires
digestion by brush border
lactase to its two constituent
monosaccharides, glucose and
galactose.
 Development
of symptoms of
lactose intolerance is related to
several factors:
 1.
Amount of lactose in the diet.
 2. Rate of gastric emptying.
 3. Small-intestinal transit time.
 4. Colonic compensation by
production of SCFAs from
nonabsorbed lactose.
PROTEINS
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Protein is present in food almost exclusively as
polypeptides and requires extensive hydrolysis to
di- and tripeptides and amino acids before
absorption.
Proteolysis occurs in both the stomach and
small intestine; it is mediated by pepsin
secreted as pepsinogen by gastric chief cells
and trypsinogen and other peptidases from
pancreatic acinar cells.
These proenzymes, pepsinogen and trypsinogen,
must be activated to pepsin (by pepsin in the
presence of a pH <5) and to trypsin (by the
intestinal brush border enzyme enterokinase and
subsequently by trypsin), respectively.
 Proteins
are absorbed by separate
transport systems for di- and
tripeptides and for different types of
amino acids, e.g., neutral and
dibasic.
 Alterations
in either protein or
amino acid digestion and
absorption are rarely observed
clinically, even in the presence
of extensive small-intestinal
mucosal inflammation.
APPROACH TO
THE PATIENT
WITH
MALABSORPTION
The
clues provided by:
the history,
symptoms,
 initial preliminary observations
will serve to limit extensive, illfocused, and expensive
laboratory and imaging studies.
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For example, a clinician evaluating a patient with
symptoms suggestive of malabsorption, who
recently had extensive small-intestinal resection
for mesenteric ischemia, should direct the initial
assessment almost exclusively to define whether a
short bowel syndrome might explain the entire
clinical picture.
Similarly, the development of a pattern of bowel
movements suggestive of steatorrhea in a
patient with long-standing alcohol abuse and
chronic pancreatitis should lead toward
assessing pancreatic exocrine function.
 Although
diarrhea can be caused by
changes in fluid and electrolyte
movement in either the small or the
large intestine, dietary nutrients
are absorbed almost exclusively
in the small intestine.
 Therefore,
the demonstration of
diminished absorption of a dietary
nutrient provides unequivocal
evidence of small-intestinal disease,
calcium,
iron, and folic acid
are exclusively absorbed by
active transport processes in the
proximal small intestine,
especially the duodenum;
in
contrast, the active transport
mechanisms for both cobalamin
and bile acids are present only
in the ileum.
 Some
nutrients, e.g., glucose,
amino acids, and lipids, are
absorbed throughout the small
intestine, though their rate of
absorption is greater in the proximal
than in the distal segments.
 However,
following segmental
resection of the small intestine, the
remaining segments undergo both
morphologic and functional
"adaptation" to enhance
absorption..
 Establishing
the presence of steatorrhea
and identifying its specific cause are
often quite difficult.
 The
"gold standard" still remains a timed,
quantitative stool fat determination.
A
qualitative test-Sudan III stain-has
long been available to establish the presence
of an increase in stool fat.
 This
test is rapid and inexpensive but, as a
qualitative test, does not establish the degree
of fat malabsorption and is best used as a
preliminary screening study.
 Despite
this situation, the use of routine
laboratory studies:
 (i.e., complete blood count, prothrombin
time, serum protein determination,
alkaline phosphatase) may suggest the
presence of dietary nutrient depletion,
especially iron, folate, cobalamin, and
vitamins D and K.
 Additional studies include measurement of
serum carotene, cholesterol, albumin,
iron, folate, and cobalamin levels.
 The serum carotene level can also be reduced
if the patient has poor dietary intake of leafy
vegetables.
If
steatorrhea and/or altered
absorption of other nutrients are
suspected:
 the history,
clinical observations,
laboratory testing
can help detect deficiency of a
nutrient, especially:
 the fat-soluble vitamins A, D,
E, or K.
Thus,
evidence of
metabolic bone disease
with :
elevated
alkaline phosphatase
and/or
reduced serum calcium levels
would
suggest vitamin D
malabsorption.
A
deficiency of vitamin K
would be suggested by :
an elevated
prothrombin time
in an individual without
liver disease who was not
taking anticoagulants
 The
presence of iron-deficiency
anemia
 in the absence of occult bleeding
from the gastrointestinal tract in
either a male or a nonmenstruating
female would require :
 evaluation of iron
malabsorption and the
exclusion of celiac disease, as
iron is absorbed exclusively in the
proximal small intestine
Macrocytic
anemia
would lead to
evaluation of
whether cobalamin
or folic acid
malabsorption was
present..
a
timed (72 h) quantitative stool
collection, preferably on a defined
diet, must be obtained to determine
stool fat content and establish the
presence of steatorrhea.
 The
presence of steatorrhea then
requires further assessment to
establish the pathophysiologic
process(es) responsible for the defect
in dietary lipid digestion-absorption
other
the
studies include :
Schilling test,
 D-xylose test,
duodenal mucosal biopsy,
small-intestinal radiologic
examination,
tests of pancreatic
exocrine function.
URINARY
D-XYLOSE TEST
The
urinary D-xylose test for
carbohydrate absorption
provides
an assessment of
proximal small intestinal
mucosal function.


D-Xylose, a pentose, is absorbed almost
exclusively in the proximal small intestine.
The D-xylose test is usually performed by giving
25 g D-xylose and collecting urine for 5 h.
An
abnormal test (<4.5 g
excretion) primarily
reflects the presence of
duodenal/jejunal mucosal
disease.
RADIOLOGIC EXAMINATION
Radiologic
examination of
the small intestine using
barium contrast (smallbowel series or study)
 can provide important information
in the evaluation of the patient with
presumed or suspected
malabsorption.
 Other
imaging studies to assess the
integrity of small intestinal
morphology are :
CT
enteroclysis
magnetic resonance (MR)
enteroclysis
capsule endoscopy
 double-barrel
enteroscopy
BIOPSY OF SMALL-INTESTINAL MUCOSA
 is
essential in the evaluation of a
patient with documented
steatorrhea or chronic diarrhea
(lasting >3 weeks)
 The ready availability of endoscopic
equipment to examine the stomach
and duodenum has led to its almost
uniform use as the preferred method
to obtain histologic material of
proximal small-intestinal
mucosa..
The
primary indications for
a small-intestinal biopsy are :
(1) evaluation of a patient either
with documented or
suspected steatorrhea or
with chronic diarrhea
(2) diffuse or focal
abnormalities of the small
intestine defined on a smallintestinal series