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Malabsorption
A clinical spectrum of symptoms and signs resulting from defective mucosal absorption
and excessive excretion of fat, carbohydrates, and proteins, with inadequate absorption
of vitamins, minerals, electrolytes, and water.
Although malabsorption generally denotes any defect in the absorptive process, the term
strictly refers to the defective mucosal absorption of nutrients. Maldigestion denotes
impaired nutrient hydrolysis.
Aging and Digestion
Although small-intestine mucosal surface area is reduced with age, the morphology of the
small bowel does not differ from that in younger persons. The digestive and absorptive
functions of the gastrointestinal (GI) system do not decline substantially with age. The
only age-related defect in intestinal absorption is that of calcium, which is probably due
to decreased renal production of 1,25-dihydroxycholecalciferol and reduced intestinal
response. Small-intestine motility appears to remain intact with age.
Aging does not significantly affect the structure and function of the exocrine pancreas.
The main pancreatic duct may become ectatic and is associated with ductal hyperplasia
and intralobular fibrosis. However, such morphologic changes are not known to cause
clinical dysfunction; malabsorption and maldigestion only occur when > 90% of
pancreatic exocrine function is lost. There are no age-related differences in the pancreatic
output of trypsin, chymotrypsin, and lipase after maximal doses of secretin and cerulein.
Etiology
Malabsorption has many causes (see Table 111-1). Pancreatic insufficiency, such as
occurs with chronic pancreatitis and pancreatic cancer, is the cause of malabsorption in
20 to 30% of cases in the elderly. A significant number of these patients have no history
of typical pain or predisposing factors (eg, alcoholism).
About 30% of malabsorption cases in elderly patients are due to anatomic abnormalities
(eg, small-intestine diverticulosis, strictures, partial obstruction), which promote stasis of
intestinal contents and predispose patients to the bacterial overgrowth syndrome.
Another 20% of patients with malabsorption have bacterial overgrowth syndrome in the
absence of anatomic abnormalities. This syndrome occurs when gastric acid secretion is
inadequate. Pernicious anemia and vitamin B12 deficiency are common, suggesting that
gastric atrophy and achlorhydria allow proliferation of gastric and small-intestine
bacteria. Intestinal motility disorders may also impair bacterial clearance, which can lead
to bacterial overgrowth.
Malabsorption of fat, proteins, minerals, and vitamins often occurs after gastrectomies
and small-intestine resections (enterectomy). A gastrectomy with vagotomy can result in
rapid gastric emptying and transit through the small intestine. Nutritional deficiencies
after a gastrectomy or small-intestine resection result from diminished absorption of iron,
calcium, fat, and protein and are related to the extent of the gastrectomy, rapidity of
intestinal transit, and the type of anastomosis. As a general rule, one third of the jejunum
and ileum may be excised without seriously impairing nutrient absorption. More radical
resection is tolerated poorly, and adults who have lost two thirds of the small intestine
usually develop severe metabolic problems. After resection of the terminal ileum,
absorption of vitamin B12 and bile acids is reduced. Resections of more than 100 cm of
small intestine result in marked steatorrhea and a depleted bile salt pool. Typically,
partial and total colectomy only temporarily diminish the absorption of water and some
electrolytes. Total proctocolectomy produces only temporary malabsorption.
Other causes of malabsorption include cirrhosis and biliary tract disease, which can result
in impaired micelle formation. Intestinal mucosal abnormalities arising from celiac sprue
(the cause in 30% of patients), tropical sprue, Whipple's disease, or Crohn's disease can
also cause malabsorption. Obstruction of the intestinal lymphatic system, such as occurs
in intestinal lymphangiectasia, results in lipoprotein malabsorption. Infestation with some
intestinal parasites (eg, giardiasis, cryptosporidiosis) can rarely lead to malabsorption.
Symptoms and Signs
Often, an elderly patient with a malabsorption syndrome may only have weight loss or
failure to maintain body weight, which leads to general debility. Often, symptoms may
include diarrhea, greasy stools, abdominal bloating, and gas. Although diarrhea is not
always present in persons with malabsorption, chronic diarrhea is the most common GI
symptom of malabsorption to prompt an evaluation.
Steatorrhea, which is due to the malabsorption of fat, is suggested by foul-smelling,
bulky stools that are difficult to flush. Steatorrhea occurs when > 6% of dietary fat is
excreted in the stool. Although physiologic steatorrhea can occur rarely in some
conditions, steatorrhea is considered to be the hallmark of malabsorption.
Abdominal bloating and excessive flatus suggest colonic fermentation of maldigested
carbohydrates. In advanced malabsorption, severe vitamin and mineral deficiencies
occur. Other clinical manifestations include anemia secondary to deficiencies in iron,
folate, vitamin B12, or any combination of these micronutrients; easy bruising and
bleeding secondary to vitamin K deficiency; muscular weakness and bone pain caused by
vitamin D deficiency; and cramps, numbness, and paresthesias suggesting hypocalcemia
and hypomagnesemia.
Diagnosis
The clinical features of the malabsorption syndromes are less obvious and more difficult
to recognize in the elderly than in younger persons. Occasionally, the syndrome is only
suspected when blood tests show deficiency states such as anemia, hypocalcemia, and
hypoalbuminemia. Therefore, the physician should maintain a high index of suspicion.
In many cases, the cause may be suggested by a history of lifelong symptoms of diarrhea
exacerbated by gluten products, stomach and intestinal operations, use of drugs, or
recurrent episodes of abdominal pain.
Steatorrhea should be identified and is usually confirmed by a quantitative 72-hour stool
collection. Severe fat malabsorption (fecal fat of >= 40 g) almost always indicates
pancreatic insufficiency or small-intestine mucosal disease. The d-xylose test is a good,
noninvasive way of differentiating pancreatitis (or another intraluminal etiology) from
mucosal disease, especially if the cause is not evident from the clinical data. If severe
steatorrhea is accompanied by a normal d-xylose test result, pancreatic disease should be
suspected. Often, the combination of history of alcoholism, pancreatic calcifications, and
recurrent abdominal pain can make the diagnosis of chronic pancreatitis apparent. If the
diagnosis is in doubt, pancreatic insufficiency can be confirmed with the secretin
stimulation test or with the bentiromide or pancreolauryl tests.
Other intraluminal causes of malabsorption include inadequate bile salt concentrations
from cirrhosis, severe parenchymal liver disease, and cholestasis. If severe steatorrhea is
accompanied by an abnormal d-xylose test result, mucosal disease is suggested and an
endoscopic biopsy should be performed. However, abnormal results of the d-xylose test
can also be caused by bacterial overgrowth. Therefore, an aspirate can be collected
during the biopsy to test for bacteria and parasites, particularly if bacterial overgrowth is
suspected. If bacterial overgrowth syndrome is documented by culture or breath tests, a
barium x-ray should be ordered to look for diverticula, blind loop syndrome, strictures,
fistulas, and other anatomic abnormalities.
If no anatomic abnormality that explains the malabsorption is found, pernicious anemia
or systemic diseases should be suspected, and a Schilling test is recommended to
differentiate between pernicious anemia, pancreatic insufficiency, and bacterial
overgrowth.
If pancreatic insufficiency needs to be further documented, pancreatic imaging studies are
a reasonable first step. If these are not diagnostic, the patient should be tested for
exocrine insufficiency.
Most tests assess malabsorption of fat, which is easier to measure than malabsorption of
other dietary components. Confirmation of carbohydrate malabsorption is not helpful
once steatorrhea is documented. Because fecal nitrogen is difficult to measure, tests for
protein absorption are rarely used.
Blood tests: Although neither sensitive nor specific, some blood tests may be
diagnostically helpful. Such tests include a complete blood cell count and peripheral
smear; serum levels of iron, ferritin, vitamin B12, calcium, and albumin; and red blood
cell (RBC) folate. Microcytic anemia without GI blood loss suggests iron malabsorption.
Macrocytic anemia strongly indicates folate or vitamin B12 malabsorption. A low RBC
folate level confirms folate malabsorption, which is common in mucosal disorders
involving the jejunum. A low serum vitamin B12 level suggests pernicious anemia,
bacterial overgrowth, or terminal ileal disease. A low serum albumin level may indicate
poor nutritional intake. Determination of carotene, a precursor of fat-soluble vitamin A, is
sometimes helpful. If dietary deficiency can be excluded in the elderly, serum carotene
levels of < 0.6 mg/dL indicate mucosal malabsorption.
Tests for steatorrhea: The qualitative Sudan stain is specific for dietary triglycerides
and lipolytic metabolites. A stool specimen is examined microscopically after being
heated in glacial acetic acid in the presence of Sudan III stain. Multiple orange-red
globules indicate steatorrhea. When steatorrhea is < 10 g/24 hours, the estimated falsenegative rate is 25%. The correlation between this qualitative test and the quantitative
fecal fat test is poor.
The most accurate test for determining steatorrhea is a quantitative fecal fat test, which
measures fatty acids from exogenous and endogenous sources. After the patient
consumes a daily diet of 100 g of fat for at least 3 days, the total amount of fat in the stool
collected during a 72-hour period is measured. Fecal fat > 6 g daily is abnormal. Fecal fat
> 40 g daily suggests defective lipolysis (eg, due to pancreatic insufficiency) or massive
ileal resection.
The 14C-triolein breath test can confirm fat malabsorption. The patient ingests 60 g of
labeled 14C-triolein, a triglyceride that undergoes lipid hydrolysis and is subsequently
absorbed and metabolized, releasing CO2. Breath samples are then analyzed for
radioactivity. The results may be erroneous in patients with diabetes mellitus, obesity,
hyperlipidemia, thyroid disorders, chronic liver disease, or lung disease, because altered
metabolism of triolein or impaired excretion of CO2 occurs in these conditions.
Tests for mucosal diseases: The d-xylose absorption test is the best noninvasive
method for assessing intestinal mucosal integrity. Xylose is a pentose that does not
require pancreatic enzymes for digestion. Thus, this test helps differentiate maldigestion
from malabsorption. A normal d-xylose test in the presence of steatorrhea indicates
pancreatic exocrine insufficiency rather than small-intestine mucosal disease. This test
has a reported 98% specificity and 91% sensitivity.
The patient is given an oral dose of 25 g of d-xylose. A venous blood sample is taken 1
hour after ingestion, and urine is collected over 5 hours. A serum level of < 20 mg/dL and
a d-xylose level of < 4 g in the urine collection indicate abnormal absorption of the
pentose. Falsely low levels can occur in patients with renal diseases, bacterial
overgrowth, ascites, portal hypertension, or delayed gastric emptying time.
The Schilling test assesses malabsorption of vitamin B12 and can determine whether the
deficiency is due to pernicious anemia, pancreatic exocrine insufficiency, bacterial
overgrowth, or ileal disease. Controversy exists about the usefulness of this test. In this
test, if there is normalization with the addition of pancreatic enzymes, cobalamin
malabsorption is secondary to pancreatic insufficiency. Correction after antimicrobial
therapy suggests bacterial overgrowth, whereas cobalamin deficiency secondary to ileal
disease or ileal resection indicates abnormalities at all stages of absorption.
Endoscopic small-bowel biopsy allows visual assessment of the small-intestine mucosa
and can allow directed biopsies if there are areas of patchy involvement. Histologic
features may establish a diagnosis of parasitic infection (eg, Giardia lamblia,
Coccidiodes immitis, Cryptosporidia), amyloidosis, Whipple's disease, mastocytosis,
lymphangiectasia, or collagenous sprue. In amyloidosis, deposits of amyloid are seen
within the walls of the arterioles in the submucosa. In Whipple's disease, the lamina
propria becomes infiltrated with periodic acid-Schiff-positive macrophages. In
lymphangiectasia, markedly dilated lamina propria lymphatics are found together with
edema and villous distortion. Villous atrophy is characteristic of celiac sprue but may be
seen in tropical sprue, Crohn's disease, lymphoma, Whipple's disease, and bacterial
overgrowth.
Contrast small-intestine x-rays are not adequately sensitive for evaluating mucosal
disease; their usefulness lies in the detection of anatomic abnormalities that predispose to
bacterial overgrowth (eg, diverticula, surgically created stagnant loops, strictures, fistulas,
ulcerations, dilated small-bowel loops). These x-rays can also demonstrate patchy or
distal mucosal disease (eg, Crohn's disease).
Tests for pancreatic insufficiency: The secretin test is the most sensitive test for
demonstrating pancreatic exocrine insufficiency. A tube with distal aspiration holes is
placed via fluoroscopy in the duodenum at the entrance of the pancreatic duct. Collection
of the duodenal aspirate is performed after stimulation of pancreatic secretions by IV
administration of secretin alone or with cholecystokinin or cerulein. If cholecystokinin or
cerulein is given, the aspirate is measured for trypsin, amylase, or lipase. If secretin alone
is given, the aspirate is measured for bicarbonate. Bicarbonate secretion is probably the
single most useful measure of exocrine function. Most investigators consider a
bicarbonate concentration < 70 mEq/L and a secretion volume < 2 mL/kg of body weight
as abnormal. However, this test is invasive, time-consuming, expensive, and unavailable
in most hospitals.
Other tests for pancreatic function include the bentiromide test, which measures
pancreatic chymotrypsin activity, and the pancreolauryl test, in which oral fluorescein
dilaurate is hydrolyzed by pancreatic esterase. Para-aminobenzoic acid and fluorescein
are measured in the urine, respectively. Both tests are sensitive for moderate to severe
pancreatic insufficiency but are of limited value in mild pancreatic impairment.
The serum trypsinogen test is a simple noninvasive radioimmunoassay blood test that
may help diagnose chronic pancreatitis. A serum trypsinogen level of < 20 ng/mL
(normal is 20 to 80 ng/mL) is characteristic of pancreatic insufficiency.
Pancreatic calcifications on plain abdominal x-rays suggest chronic pancreatitis.
However, calcifications are seen only when severe pancreatic damage has already
occurred and are found in only 20 to 30% of patients with pancreatic insufficiency.
Ultrasound and CT are useful in imaging the pancreas to exclude pancreatic cancer.
Endoscopic retrograde cannulation of the pancreatic duct can demonstrate obstruction,
irregularities, and narrowing of the main duct and side branches, which suggest chronic
pancreatitis. However, this procedure is invasive and causes pancreatitis in 4% of
patients.
Tests for bacterial overgrowth: The diagnosis of bacterial overgrowth is best made
with a direct quantitative bacterial count and/or positive aspirate culture. An aspirate is
collected from the proximal small intestine, which is normally free of bacteria. An
aspirate that contains > 105 organisms/mL suggests bacterial overgrowth syndrome.
Bacteria commonly implicated are coliforms and other aerobic bacteria as well as
anaerobic organisms (eg, bacteroides, lactobacilli, clostridia). The same aspirate can also
be examined for giardiasis.
Breath tests are sensitive, inexpensive, and generally acceptable to most patients. These
tests measure the production of volatile metabolites produced by bacteria after the
ingestion of fermentable substrates in a timed breath excretion collection. The acid breath
test identifies abnormal bacterial deconjugation of previously administered 14Cglycocholic acid. The glycine residue is metabolized and results in 14CO2 in the breath.
An early rise of 14CO2 within 6 hours indicates small-intestine bacterial overgrowth.
However, this test has only a 65% sensitivity. The 14C d-xylose breath test depends on the
ability of gram-negative aerobic bacteria to metabolize d-xylose, resulting in 14CO2 in the
expired air after 60 minutes. This test has an overall sensitivity of 65 to 95%.
Treatment
The main objectives are correcting deficiencies of nutrients, vitamins, and trace minerals
and identifying and treating the underlying causes.
Patients with iron deficiency are given supplemental ferrous sulfate or gluconate tablets.
Oral folic acid can be given to patients with folate deficiency, and intramuscular vitamin
B12 injections can be given monthly to persons with cobalamin deficiency. Patients with
marked steatorrhea require fat-soluble vitamin and calcium supplementation. A highprotein, low-fat diet and high-calorie dietary supplementation are recommended for
patients with severe weight loss. A low-fat diet reduces steatorrhea and bile salt
excretion, especially in patients with small-intestine resections. Medium-chain
triglycerides, given as a dietary supplement, are preferred because they are hydrolyzed
more readily by pancreatic lipase, and micelle formation is not necessary for their
absorption. Parenteral nutrition may be considered in patients with severe malnutrition
who are unresponsive to oral feeding. However, parenteral nutrition is reserved as the
sole source of primary nutrients for persons with conditions in which the temporary
avoidance of enteral feeding is necessary. In only rare conditions is long-term parenteral
feeding appropriate.