Transcript of DISORDERS OF MALABSORPTION E Rahimi, MD Assiatant Professor Department Of Internal Medicine MUK.
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- DISORDERS OF MALABSORPTION E Rahimi, MD Assiatant Professor
Department Of Internal Medicine MUK
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- 2007 Thomson - Wadsworth
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- Introduction 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
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- Steatorrhea Most, but not all, malabsorption syndromes are
associated with steatorrhea, an increase in stool fat excretion of
>6% of dietary fat intake
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- Malabsorption disorders are not associated with steatorrhea
primary lactase deficiency, a congenital absence of the small
intestinal brush border disaccharidase enzyme lactase, is
associated with lactose "malabsorption, pernicious anemia is
associated with a marked decrease in intestinal absorption of
cobalamin (vitamin B12) due to an absence of gastric parietal cell
intrinsic factor required for cobalamin absorption.
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- Nutrient Digestion and Absorption The lengths of the small
intestine and colon are ~300 cm and ~80 cm, respectively. The
effective functional surface area is approximately 600-fold greater
than that of a hollow tube as a result of the presence of folds,
villi (in the small intestine), and microvilli
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- Nutrient Digestion and Absorption
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- Intestinal epithelia several other functions: Barrier and
immune defense. The intestine is exposed to a large number of
potential antigens and enteric and invasive microorganisms, and it
is extremely effective preventing the entry of almost all these
agents. The intestinal mucosa also synthesizes and secretes
secretory IgA.
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- Intestinal epithelia several other functions Fluid and
electrolyte absorption and secretion. The intestine absorbs ~78 L
of fluid daily. dietary fluid intake (12 L/d) salivary, gastric,
pancreatic, biliary, and intestinal fluid (67 L/d). Several
stimuli, especially bacteria and bacterial enterotoxins, induce
fluid and electrolyte secretion that may lead to diarrhea
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- Intestinal epithelia several other functions Synthesis and
secretion of several proteins. The intestinal mucosa is a major
site for the production of proteins, including apolipoproteins
Production of several bioactive amines and peptides. The intestine
is one of the largest endocrine organs in the body and produces
several amines and peptides that serve as paracrine and hormonal
mediators of intestinal function
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- The small and large intestines are distinct anatomically (villi
are present in the small intestine but are absent in the colon) and
functionally (nutrient digestion and absorption take place in the
small intestine but not in the colon).
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- No precise anatomic characteristics separate duodenum, jejunum,
and ileum, although certain nutrients are absorbed exclusively in
specific areas of the small intestine
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- Defects in Enterohepatic Circulation of Bile Acids
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- Disease ExamplePathophysiologic DefectProcess
CirrhosisDecreased hepatic functionSynthesis Primary biliary
cirrhosisAltered canalicular functionBiliary secretion Jejunal
diverticulosis Crohn's disease Bacterial overgrowth Abnormal ileal
function Maintenance of conjugated bile acids Reabsorption
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- lipid Steatorrhea is caused by one or more defects in the
digestion and absorption of dietary fat. Average intake of dietary
fat in the United States is approximately 120150 g/d, and fat
absorption is linear to dietary fat intake. The total load of fat
presented to the small intestine is considerably greater, as
substantial amounts of lipid are secreted in bile each day
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- Defects in Lipid Digestion and Absorption in Steatorrhea
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- Disease ExamplePathophysiologic DefectPhase: Process Chronic
pancreatitis Decrease lipase secretion Decreased intraduodenal bile
acids Digestive Lipolysis formation Micelle formation Celiac
sprueMucosal dysfunction Absorptive Mucosal uptake and
resterification Abetalipoproteinemia Intestinal lymphangiectasia
Absent betalipoproteins Abnormal lymphatics Post-absorptive
Chylomicron formation Delivery from intestine
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- Lipolysis, micelle formation, and lipid uptake are all normal
in patients with abetalipoproteinemia, but the reesterified
triglyceride cannot exit from the epithelial cell because of the
failure to produce chylomicrons. Small-intestinal biopsies of these
rare patients in the postprandial state reveal lipid-laden
small-intestinal epithelial cells that become perfectly normal in
appearance following a 7296 h fast
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- Comparison of Different Types of Fatty Acids
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- Short cahinMedium chianLong chain Less than 128-12Moret han
12Carbon cahin length noSmall amountsLarge amountsPrsent in diet
Bacterial degradation in colon of nonabsorbed carbohydrate to fatty
acids Only in small amounts in diet as triglycerides In diet as
triglyceridesOrigin ColonSmall intestine Primary site of absorption
no yesRequires pancreatic lipolysis No Substantial No Yes minimal
Requires micelle formation Presence in stool
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- Medium cahin triglyceride Medium-chain triglycerides (MCTs),
composed of fatty acids with carbon chain lengths of 810, are
present in large amounts in coconut oil and are used as a
nutritional supplement. MCTs can be digested and absorbed by a
different pathway from LCTs and at one time held promise as an
important treatment of steatorrhea of almost all etiologies.
Unfortunately, their therapeutic effects have been less than
expected because their use is often not associated with an increase
in body weight for reasons that are not completely understood.
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- Medium cahin triglyceride MCTs are absorbed more efficiently
than LCTs for the following reasons: (1) the rate of MCT absorption
is greater than that of long- chain fatty acids; (2) following
absorption are not reesterified; (3) following absorption, MCTs are
hydrolyzed to medium- chain fatty acids; (4) MCTs do not require
chylomicron formation for their exit from the intestinal epithelial
cells; (5) their route of exit is via the portal vein and not via
lymphatics.
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- Short chain fatty acid SCFAs are not dietary lipids but are
synthesized by colonic bacterial enzymes from nonabsorbed
carbohydrate and are the anions in highest concentration in stool
(between 80 and 130 mM). The SCFAs present in stool are primarily
acetate, propionate, and butyrate, whose carbon chain lengths are
2, 3, and 4, respectively. Butyrate is the primary nutrient for
colonic epithelial cells, and its deficiency may be associated with
one or more colitides.
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- Short chain fatty acid 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, the transport
protein that mediates monosaccharide absorption. In contrast, SCFAs
are rapidly absorbed and stimulate colonic Na-Cl and fluid
absorption.
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- Most nonClostridium difficile antibiotic-associated diarrhea is
due to antibiotic suppression of colonic microflora, with a
resulting decrease in SCFA production. As C. difficile accounts for
about 1015% of all antibiotic-associated diarrhea, a relative
decrease in colonic production of SCFAs is likely the cause of most
antibiotic-associated diarrhea.
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- Carbohydrates 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.
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- Carbohydrates Before their absorption, starch and disaccharides
must first be digested by pancreatic amylase and intestinal brush
border disaccharidases to monosaccharides. Monosaccharide
absorption occurs by a Na- dependent process mediated by the brush
border transport protein SGLT1.
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- Lactose malabsorption 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. In primary lactase deficiency, a genetically determined
decrease or absence of lactase is noted, while all other aspects of
both intestinal absorption and brush border enzymes are normal
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- Lactose malabsorption secondary lactase deficiency occurs in
association with small-intestinal mucosal disease with
abnormalities in both structure and function of other brush border
enzymes and transport processes. Secondary lactase deficiency is
often seen in celiac sprue
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- lactose malabsorption Some individuals with lactose
malabsorption develop symptoms such as diarrhea, abdominal pain,
cramps, and/or flatus. Most individuals with primary lactase
deficiency do not have symptoms. Since lactose intolerance may be
associated with symptoms suggestive of irritable bowel syndrome,
persistence of such symptoms in an individual with lactose
intolerance while on a strict lactose-free diet would suggest that
the individual's symptoms were related to irritable bowel
syndrome.
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- Proteins 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. Proteins are
absorbed by separate transport systems for di- and tripeptides and
for different types of amino acids, e.g., neutral and dibasic
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- Approach to the Patient with Malabsorption
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- Disease with malabsorption must be suspected in individuals
with less severe symptoms and signs and with subtle evidence of the
altered absorption of only a single nutrient rather than obvious
evidence of the malabsorption of multiple nutrients.
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- Dietary nutrient absorption may be segmental or diffuse along
the small intestine and is site- specific. Calcium, iron, and folic
acid are exclusively absorbed by active transport processes in the
proximal small intestine, especially the duodenum
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- Active transport mechanisms for both cobalamin and bile acids
are present only in the ileum. 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
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- Differential Results of Schilling Test in Several Diseases
Associated with Cobalamin (CBL) Malabsorption
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- After 5 Days of Antibiotics With Pancreatic Enzymes With
Intrinsic Factor 58Co-Cbl Reduced NormalReduced Pernicious anemia
ReducedNormalReduced Chronic pancreatitis Normal Reduced Bacterial
overgrowth Ileal disease
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- 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 (