Text Book Reading

GASTROENTEROLOGY
HEPATOLOGY DIVISION

Malabsorption
Read By :
Jimmi Diwindang Putra

Advisor :
DR. Dr. A. Muh. Lutfie Parewangi, SpPD, K-GEH

GASTROENTEROLOGY HEPATOLOGY DIVISION

INTERNAL MEDICINE DEPARTEMENT
MEDICAL FACULTY OF HASANUDDIN UNIVERSITY
MAKASSAR 2021
 Definition
 Malabsorption is the result of defective nutrient uptake or transport by
the intestinal mucosa
 Whereas maldigestion denotes the impaired breakdown of
macronutrients
 Malabsorption syndromes include disorders resulting from impaired
digestion and/or impaired absorption
 ETIOLOGY AND PATHOPHYSIOLOGY
 From a pathophysiologic point of view, mechanisms that
cause malabsorption can be divided into pre-mucosal
(luminal), mucosal, and postmucosal (vascular and
lymphatic) factors.
 Mucosal absorption can occur by active or passive carrier-
mediated transport or simple or facilitated diffusion (see
Chapter 101). Postmucosal transport of absorbed
substrates occurs in blood vessels and lymphatic vessels.
 ETIOLOGY AND PATHOPHYSIOLOGY
 Intestinal sensory and motor function permits detection
of the presence of nutrients, facilitates adequate mixing
of nutrients with intestinal secretions and delivery to
absorptive sites, and provides adequate time for nutrient
absorption.
 Neural and hormonal functions are required to stimulate
and coordinate digestive secretions, mucosal absorption,
and intestinal motility.
 Physiology of assimilation: the essentials
Absorption sites
 Absorption of macro and micronutrients occurs along a 3-meter length of small
intestine (duodenum, jejunum, ileum).
 Carbohydrates, proteins, and lipids are absorbed in the duodenum-jejunum, a
process completed at a point 100 cm distal to the duodenojejunal junction.
 Calcium, iron, zinc, folic acid, and the fat soluble vitamins A, D, E, and K are
absorbed in the proximal intestine.
 Physiology of assimilation: the essentials
 The ileum can assume the absorptive function of macronutrients if the proximal
intestinal structure or function is impaired.
 Vitamin B12 and bile salts are absorbed in the ileum; the duodenum-jejunum
cannot assume this function.
 Carbohydrates
 Ingested as polysaccharides (starch), disaccharides (lactose, sucrose), and
monosaccharides (glucose, fructose); absorbed only as monosaccharides.
 Polysaccharides digested primarily by salivary and pancreatic amylases to
disaccharides, trisaccharides and branched oligosaccharides.
 Brush border enzymes hydrolyze the products of amylase digestion to
monosaccharides.
 Carbohydrates
 Glucose (and galactose) absorption occurs primarily through secondary active
transport across the brush border membrane utilizing a sodium dependent co-
transporter (SGLT1), which couples two sodium ions with one monosaccharide
molecule
 Glucose (and galactose) accumulates intracellularly and enters the interstitial
space by facilitated diffusion utilizing a basolateral transport protein (GLUT2).
 The sodium ions that enter the enterocyte (absorbing epithelial cell) are
transported into the blood by a Na+/K+- pump in the basolateral membrane.
 Carbohydrates
 Fructose is absorbed by facilitated diffusion utilizing an apical fructose-specific
transport protein (GLUT5) as well as the basolateral transport protein (GLUT2).
The human small intestine does not have an unlimited capacity to absorb
fructose; its absorption is enhanced when ingested with glucose.
 • Unabsorbed disaccharides are metabolized by colonic bacteria to short chain
fatty acids that are absorbed by the colon (colonic salvage).
 Proteins
 Sources include ingested food, intestinal juices, sloughed epithelial cells.
 The chief cells in the stomach produce pepsin, which plays a minor role in
initiating digestion and yields amino acids and polypeptides.
 These products of hydrolysis stimulate release of cholecystokinin (CCK) from
the duodenum and jejunum.
 Proteins
 CCK stimulates the pancreas to secrete both endopeptidases (trypsin,
chymotrypsin, and elastase) and exopeptidases (carboxypeptidase A and B) as
inactive precursors (e.g., trypsinogen).
 The brush border enzyme, enterokinase, activates trypsinogen to trypsin, which
then autocatalyzes trypsinogen and all other peptidase precursors to their active
forms.
 The active peptidases digest the polypeptides to amino acids (AA) and 4–6 AA
residue peptides.
 Proteins
 Brush border peptidases digest the oligopeptides to tri- and dipeptides, some of
which are absorbed intact and further digested to AA by intracellular peptidases.
 AA are neutral, basic, acidic, and L-isomers, which are absorbed by active,
passive, and facilitated diffusion mechanisms.
 Lipids
 Long chain triglycerides
 Four distinct and interrelated stages characterize the assimilation of dietary
long-chain lipids: lipolytic, micellarization, cellular, and delivery.
 Lipolytic stage
 Lipids
 Lipases (lingual, gastric, pancreas) incompletely digest long-chain triglycerides
(TGs) to fatty acids (FAs), monoglycerides (MGs), diglycerides (DGs), and
glycerol.
 Lipolysis is enhanced by both bicarbonate (yielding an intestinal pH of 6.8), and
the detergent properties of conjugated bile salts.
 Pancreatic co-lipase facilitates binding of lipase to TG droplets, thus preventing
the inhibition of lipase by bile salts.
 Micellarization stage
 Defined as the solubilization of a complex mixture of the products of lipolysis
into a micelle.
 Requires conjugated bile acids (CBAs), reaching a critical micellar concentration
of >2–3 mol/m3.
 The resulting structure is a mixed micelle, consisting of CBAs, FAs, MGs, and
some DGs, capable of solubilizing other fat-soluble substances and facilitating
their absorption.
 The mixed micelle facilitates absorption of lipids through the epithelial cell
plasma membrane (unstirred water layer).
 Cellular stage
 Mixed micelles diffuse into the epithelial cell.
 Bile salts remain intraluminal, undergo absorption in the ileum via active
transport sodium-dependent mechanisms, return to the liver via the
enterohepatic (portal venous) circuit, and are recycled 4–6 times with each
meal.
 Cellular stage
 Absorbed FAs bind to cellular proteins, are transported to the smooth
endoplasmic reticulum where they undergo activation by acetyl CoA, and are
esterified with alphaglycerophosphate or 2-MGs to TG and phospholipid.
 Chylomicrons (TGs, phospholipids, cholesterol esters, apoprotein) undergo
synthesis in the Golgi apparatus.
 Delivery stage
 Apoprotein B synthesis is essential for the synthesis and transfer of synthesized
chylomicrons into the lymphatics.
 Lymphatics are intraintestinal (lamina propria lacteals) and extraintestinal
(cisterna chyli, thoracic duct).
 The process of transfer occurs via exocytosis.
 Medium chain triglycerides (MCTs)
 Include FAs of 6–10 carbons in length.
 TGs are hydrolyzed readily by intraluminal pancreatic lipases, but MCTs do not
require lipases for assimilation.
 Unhydrolyzed MCTs may be absorbed intact by the duodenojejunal epithelial
cell.
 Intracellular MCT lipases can hydrolyze TGs to FAs.
 FAs do not undergo esterification; they are absorbed into the portal circulation
bound to albumin.
 Vitamin B12 (cobalamin)
 Cleaved from dietary sources by gastric hydrochloric acid secreted by the
oxyntic (parietal) cell.
 At gastric pH < 3, gastric intrinsic factor (IF) secreted by the oxyntic cell has a
poor binding affinity for the vitamin.
 Salivary R-protein is bound to the free vitamin in the stomach and is cleaved
from the vitamin by pancreatic trypsin in the proximal small intestine.
 B12 then undergoes binding to IF in the duodenum.
 Vitamin B12 (cobalamin)
 The stable B12 –IF complex attaches to specific receptor sites on epithelial cells
of the terminal ileum.
 Once inside the epithelial cell, the complex is split, and the free vitamin is bound
to transcobalamin II and circulated via the enterohepatic circulation.
 Differential diagnosis
L  Luminal disorders
I  Infectious diseases
M  Mucosal disorders
P  Post-operative malabsorption
S  Systemic disorders
 Approaching the patient with suspected malabsorption

 (1) suspicion of malabsorption (based on signs, symptoms, and laboratory

abnormalities)
 (2) confirmation of the presence of malabsorption; and
 (3) defining the etiology of the malabsorption.
Suspecting Malabsorption “Bedside” Evaluation
 Chronic diarrhea is the most common symptom of malabsorption
 However most chronic diarrheal disorders are not the result of a malabsorption
syndrome
 Isolated carbohydrate malabsorption may result in increased gas production,
which leads to flatulence, bloating, and/or abdominal distension.
 Malabsorption syndromes
 Syndromes of fat malabsorption may result in deficiencies of the fat-soluble
vitamins A, D, E, and K
 Musculoskeletal symptoms such as tetany, muscle weakness, bone pain and
osteomalacia occur as a consequence of vitamin D deficiency and hypocalcemia.
 Ecchymoses and easy bleeding can result from the coagulopathy associated
with vitamin K deficiency.
 Vitamin A deficiency may lead to night blindness.
 Vitamin E deficiency, although rarely symptomatic, can lead to neuropathy and
retinopathy.
 Initial evaluation
 First-line laboratory studies should include a complete blood count and
differential, a complete chemistry profile, coagulation studies, and a lipid profile
 Some additional specific (e.g., thyroid-stimulating hormone) and nonspecific
(e.g., erythrocyte sedimentation rate (ESR) or C-reactive protein) tests can also
be considered in the first-line evaluation as screening tests
 Confirming malabsorption - Fat
 The initial step in evaluating a patient with suspected lipid malabsorption is
confirming the presence of steatorrhea, defined as the excretion of at least 7 g of
fat in a 24-hour stool collection
 A simple screening test is the qualitative Sudan III stain. The test has limited
value in patients with mild degrees of steatorrhea, i.e., 7–10 g/24 h
 False positive tests may occur in patients who are ingesting mineral oil,
excessive nut oils, or using suppositories containing oils
 Confirming malabsorption - Carbohydrates
 The most helpful screening test for isolated disaccharide malabsorption may simply
be a well-documented history of dietary intolerance to the implicated disaccharide
(i.e., lactose, sucrose)
 Stool examination for pH and osmotic gap are indirect tests that may indicate the
presence of carbohydrate malabsorption. An acidic fecal pH (under 5.5) results from
bacterial fermentation of malabsorbed carbohydrate
 Stool osmotic gap is measured in the fecal supernatant and is calculated as follows
based on the assumption that normal stool osmolarity is close to that of serum:
290mosm/L − 2 ([Na+ ]stool + [K+ ]stool )
 Confirming malabsorption –
Hydrogen breath tests
 Hydrogen breath tests can also demonstrate carbohydrate malabsorption
 In patients with carbohydrate malabsorption, an orally-administered disaccharide
such as lactose remains undigested and passes into the colon. There it is
fermented by the colonic bacteria, thus yielding a rise in breath hydrogen at 2–3
hours by 20 ppm from baseline
 Confirming malabsorption –
Vitamin B12 (Cobalamin)
 The Schilling test provides both a confirmation of vitamin B12 malabsorption as
well as a differential assessment of the etiology of the malabsorption.
 In part I of the Schilling test, 1 μg of radiolabeled vitamin B12 is administered
orally, and its excretion is measured in a 24-hour urine collection
 An injection of non-radiolabeled vitamin B12 is administered as well in order to
saturate the hepatic binding sites. At least 7% to 10% of the administered dose
should be recovered in the urine to be considered normal
 Endoscopic and histologic evaluation
 If celiac disease is suspected, confirmation is a simple matter of taking 4–6
biopsies from the second part of duodenum. With modern endoscopes, lack of
villi is obvious at the time of endoscopy
 Some diseases such as eosinophilic gastroenteritis, are patchy in nature, so
biopsies should be obtained from different portions of the intestine
 Wireless capsule endoscopy
 Wireless capsule endoscopy (WCE, see Chapter 128) was introduced in 2001 as a
method of directly imaging the small intestinal mucosa throughout the entire jejunum
and ileum. WCE has been found to be useful in confirming mucosal pathology in
patients with suspected non-stricturing small bowel Crohn’s disease and celiac disease
 It may also prove to be beneficial in uncovering other mucosal diseases, such as
Whipple’s disease and lymphangiectasia, in patients with malabsorption syndrome and
should be considered in selected cases, such as those with negative duodenal
biopsies
Radiologic examinations
 D-Xylose Testing
 As with radiology, testing D-xylose absorption is less routine than previously but
may be valuable in cryptic cases. After ingesting a 25 g dose of D-xylose, the 1-
or 2-hour serum value should be at least 25 mg/dL, and an adequate 5-hour
urine collection should yield at least 4 g of the compound. Failure to achieve
these levels suggests malabsorption as a result of proximal small bowel disease
 False positive tests can occur with renal impairment, delayed gastric emptying,
ascites (from third-spacing) and prokinetic or antimotility drug use
Steatorrhea: Problem-Solving
CITATION
Feldman M, Friedman L S, Brandt L J, et al. 2021.
Sleisenger and Fordtran’s Gastrointestinal and Liver
Disease, Eleventh Edition. Elsevier.

Hawkey C J, Bosch J, Richter J E, et al. 2012. Textbook

of Clinical Gastroenterology and Hepatology. 2nd ed.
Blackwell Publishing Ltd
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