Malabsorption syndrome due to various causes is associated with antroduodenal hypomotility

Original Article
Malabsorption syndrome due to various causes
is associated with antroduodenal hypomotility
Kshaunish Das, Sanjeev Sachdeva, Asha Misra, Uday C Ghoshal
Department of Gastroenterology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow 226 014
Background: Patients with celiac disease who present
with symptoms of gastrointestinal hypomotility have
abnormal antroduodenal manometry. There are no
data on antroduodenal manometry in malabsorption
syndrome (MAS) due to causes other than celiac
disease. Methods: Fasting, post-prandial and post
octreotide antroduodenal motility parameters were
compared in 18 untreated patients with MAS presenting
with chronic diarrhea (tropical sprue 10, small bowel
bacterial overgrowth 3, celiac disease 2, common
variable immunodeficiency 1, AIDS with isosporidiasis
and bacterial overgrowth 1, giardiasis 1) and 8 healthy
subjects. Results: Number of patients with MAS and
controls having spontaneous migratory motor
complexes (MMC) during fasting was comparable
(11/18 vs 7/8; p=ns). Fasting contraction amplitude
was weaker in MAS than in controls in the gastric
antrum (median 42 [range 17-90] vs 80 [31-120] mmHg;
p=0.001), proximal duodenum (50 [18-125] vs 72 [48
107]; p=0.013) and distal duodenum (45 [20-81] vs
76 [51-98]; p=0.001). In the fed state too, contraction
amplitudes were weaker in patients with MAS in the
antrum (32 [15-110] vs 76 [61-103] mmHg, p=0.002),
proximal duodenum (57 [20-177] vs 73 [56-113]; p=0.07)
and distal duodenum (45 [24-87] vs 75 [66-97];
p<0.0001). Patients with MAS had lower fasting and
post-prandial antral and duodenal motility indices
than healthy subjects. Intravenous octreotide induced
MMC in all patients and controls. Conclusions: MAS
due to various causes is associated with antroduodenal
hypomotility typical of myopathic disorders. [Indian
J Gastroenterol 2006;25:58-61]
T
he small bowel in patients with malabsorption
syndrome (MAS) is frequently dilated and has
excessive fluid in the lumen. This has clinical
significance as evidenced by reports of patients with
celiac disease presenting with intestinal pseudo
obstruction that improved with gluten-free diet, 1,2
and frequent finding of secondary small intestinal
bacterial overgrowth (SIBO) that may transiently
respond to antibiotics in patients with MAS due to
various causes. 3,4,5 SIBO in MAS due to another
cause may result in refractoriness to treatment directed
towards the primary cause. 5,6
Copyright © 2006 by Indian Society of Gastroenterology
Though a few reports from Western countries
have described multiple abnormalities in both fasting
and fed-state antroduodenal manometry (ADM) in
patients with MAS due to celiac disease,7,8 most of
them had symptoms of gastrointestinal hypomotility
instead of chronic small bowel diarrhea. Further, there
is no study on ADM in patients with MAS from the
tropics, where causes of MAS are heterogeneous.
We studied ADM in patients with MAS due to various
causes presenting with chronic small bowel diarrhea.
Methods
Eighteen consecutive patients with MAS due to vari
ous causes attending the Luminal Gastroenterology
Clinic at our tertiary center and agreeing to partici
pate in this study were included. Patients with un
controlled diabetes mellitus, chronic renal failure or
small intestinal stricture on barium small bowel se
ries were excluded. MAS was diagnosed based on
clinical presentation, absorption defect of two unre
lated substances such as abnormal 5-g D-xylose test
(normal <1 g/5 g/5 h) and increased fecal fat excre
tion (normal <7 g/d on 72-h estimation using van de
Kamer’s method [n=16] or <10/high power field on
Sudan III–stain on spot stool specimen [n=10]). The
cause of MAS was investigated using a standard
protocol described previously. 9 Eight healthy sub
jects were studied as controls.
Patients and controls underwent ADM after in
formed consent. Drugs that may influence gas
troduodenal motility and antibiotics were not used
within the previous four weeks; none of the patients
with MAS received specific treatment before ADM.
Our institution’s ethics committee approved the study.
Antroduodenal manometry
ADM was done after an overnight fast using a wa
ter-perfusion system and a low-compliance polyvi
nyl catheter (Redtech, Calabasas, CA, USA). The
catheter, with eight sideholes placed 3 cm apart from
each other, was passed through the nose without
any sedation or anesthesia, over a guidewire, and
was positioned under fluoroscopy such that at least
two proximal ports were in the antrum and the re
maining ports were in the duodenum.
Das, Sachdeva, Misra, Ghoshal
Antroduodenal manometry in malabsorption
Fasting motility was recorded for at least 120
min. A meal containing approximately 450 KCal (60%
carbohydrate, 15%-20% each of fat and protein)
was then given, followed by post-prandial motility
recording for at least 90 min. At this stage, 50 μg
octreotide (Octride; Sun Pharma, India) was given
intravenously over 2-3 min and antroduodenal motil
ity was recorded for at least 30 min.
The signal was visually scanned to remove ar
tifacts (e.g., those due to cough), filtered (9 and 24/
min for antral and duodenal frequency limits, re
spectively), and then analyzed (by UCG) using GiPC
motility software (Redtech). In the fasting record,
presence of spontaneous migratory motor complex
(MMC) and its duration was looked for. Post-pran
dial record was evaluated for conversion from fast
ing to fed pattern. Amplitude of contractions in the
antrum and proximal and distal duodenum was mea
sured using average of all ports in antrum, proximal
two and the remaining ports in duodenum, respec
tively. MMC in the duodenal ports after octreotide
injection were analyzed similarly.
Manometric patterns were defined using estab
lished criteria. 10 Motility index (MI) for every 15
minute period during fasting and post-prandial phase
was calculated as described previously using the GiPC
software. 11 MI in the antrum and proximal and dis
tal duodenum was calculated using average values
of all ports in antrum, proximal two and the remain
ing ports in duodenum, respectively. Average values
in the second 15-min period in fasting and post-meal
periods were compared between patients and con
trols.
Statistical analysis
Categorical and continuous variables were analyzed
using chi-squared test with Yates’ correction and
Mann-Whitney U test, respectively. Alpha value of
0.05 was considered as significant.
Results
Patients with MAS and controls were comparable in
age (42 [20-67] vs 33 [26-48] y) and gender distri
bution (13 vs 8 males). All patients presented with
chronic diarrhea. Causes of MAS included tropical
sprue (n=10), SIBO (3; systemic lupus erythemato
sus, peripheral vasculitis and jejunal diverticulae in
one each), celiac disease (2), common variable im
munodeficiency (1), acquired immunodeficiency
syndrome with isosporidiasis and SIBO (1), and
giardiasis (1). Median urinary D-xylose excretion,
number of fat droplets on Sudan III-stained spot
stool specimens and 24-h fecal fat excretion were
0.48 g/5 g/5 h (range: 0.16 to 0.79), 16 (6-35)
droplets per high power field, and 8.0 g/24 h (4.8
14.4), respectively. Of the 16 patients in whom fecal
fat excretion was estimated quantitatively, four had
normal value (<7.0 g/d); however, they had abnor
mal number of fat droplets on Sudan III staining.
Antroduodenal manometry (Table 1, Fig.)
The median duration of fasting record in patients
with MAS and controls was comparable (160 [range
120-186] vs 147 [120-180] min; p=0.94). Spontane
ous MMC was observed as frequently in patients as
in controls. The duration of spontaneous MMC in
the fasting state in patients with MAS and controls
was comparable. Fasting contraction amplitude was
weaker in MAS than in controls, in the antrum and
duodenum. In the fasting state, discrete clustered
contraction (DCC) was observed in one patient with
MAS (Fig. 1D) and none of the controls.
After meal ingestion, fed pattern was observed
in all study subjects except in one patient; this pa
tient showed DCC during the fed state (Fig. 1D). In
two other patients, the fed pattern was prematurely
interrupted after 25 min and 30 min by DCC and a
spontaneous MMC, respectively. In the fed state,
contraction amplitude in antrum and duodenum were
weaker in MAS.
Table 1: Manometry parameters in patients with malabsorp
tion syndrome (MAS) and controls
Parameters
MAS
(n =18)
Healthy subjects p
(n = 8)
value
Presence of spontaneous
MMC while fasting
11/18
7/8
ns
Duration of spontaneous
MMC (min)
6 (2-9)
8 (4 -12)
0.07
Fasting antral amplitude
(mmHg)
42 (17-90)
80 (31-120)
0.001
Fasting duodenal amplitude (mmHg)
Proximal
50 (18-125)
72 (48-107)
0.013
Distal
45 (20-81)
76 (51-98)
0.001
Conversion to fed pattern
after meal
17/18
8/8
ns
Post-prandial antral
amplitude (mmHg) 32 (15-110)
76 (61-103)
0.002
Post-prandial duodenal amplitude (mmHg)
Proximal
58 (21-177)
73 (56-113)
0.07
Distal
45 (25-87)
75 (66-97) <0.0001
Onset of MMC
with octreotide
18/18
8/8
ns
Duration of post-octreotide
MMC (min)
9 (2-21)
15 (6-17)
0.08
Amplitude of post-octreotide MMC (mmHg)
Proximal duodenum 30 (12-76)
63 (43-78)
0.003
Distal duodenum
27 (13-59)
64 (45-75) <0.0001
MMC: Migratory motor complex
Indian Journal of Gastroenterology 2006 Vol 25 March - April 59
Das, Sachdeva, Misra, Ghoshal
Antroduodenal manometry in malabsorption
Fig: Tracings of antroduodenal manometry: (A) Healthy subject. Later part of fasting record depicts spontaneous migratory
motor complex (MMC). Note that meal resulted in fed pattern and octreotide (oc) induced MMC. “sm” and “em” stand for
starting and ending of meal, respectively. (B) Patient with malabsorption syndrome (MAS). Note there is no spontaneous MMC
but intravenous octreotide (“oc”) induced MMC. Also note contractions are of lesser amplitude as compared with healthy
subject. (C) Patient with MAS (post-prandial record). Though meal resulted in post-prandial pattern, it was for short period
and was followed by MMC. (D) Patient with MAS (post-prandial record). Note discrete clustered contractions (DCC) instead
of normal post-prandial pattern. Values in X-axis denote time in minutes and in Y-axis denote highest limit of contraction
amplitude for respective port in mmHg
Octreotide led to induction of MMC in all patients
and controls. The amplitude of octreotide-induced
MMC was weaker in patients than in controls though
the duration of MMC and frequency of contractions
during MMC (median: 10 per min) were comparable.
In two patients with MAS and none of the controls
the duration of post-octreotide MMC was shorter
than 5 min. One patient and no control had retrograde
contractions with vomiting during the study.
Both fasting and fed-state motility indices were
Table 2: Motility indices (MI) in patients with malabsorption
syndrome and healthy controls
Parameters
MAS
Healthy subjects p
(n =18)
(n = 8)
value
138 (52-268) 191 (153-284)
0.01
Fasting antral MI
Fasting duodenal MI
Proximal
148 (48-351)
Distal
133 (84-340)
Post-prandial antral MI
150 (23-408)
Post-prandial duodenal MI
Proximal
152 (82-285)
Distal
142 (81-261)
199 (176-287)
205 (184-274)
0.01
0.002
284 (178-368)
0.001
290 (196-393)
269 (236-398)
<0.0001
<0.0001
lower in patients than in controls (Table 2).
Discussion
This study shows that patients with MAS due to
various causes often have abnormalities of ADM in
the form of reduced amplitude of contractions in
fasting and post-prandial states both in the antrum
and duodenum, and reduced motility index.
Similar observations have been reported previ
ously in two studies, one each in children 7 and in
adults. 8 However, all these patients had celiac dis
ease. Moreover, most of these patients presented
with symptoms of gastrointestinal dysmotility rather
than chronic diarrhea. Ours is perhaps the first study
from the tropics on ADM in patients with MAS due
to other causes, particularly tropical sprue; further,
all our patients presented with chronic diarrhea and
not symptoms of gastrointestinal dysmotility.
The motility abnormalities found in this study
are quite expected. The small bowel in patients with
MAS is usually atonic with dilatation and increase in
luminal fluid. 12 Reduced amplitude of contractions
60 Indian Journal of Gastroenterology 2006 Vol 25 March - April
Das, Sachdeva, Misra, Ghoshal
Antroduodenal manometry in malabsorption
and reduced MI found in the present study are as
sociated with myopathic conditions of the gut. 13 Since
myopathy is associated with reduced propulsive
movement, these results may explain the dilatation
of the gut in patients with MAS. We presume that
abnormal ADM is associated with diffuse motility
abnormality of the whole small bowel.12 This may
also explain the prolonged oro-cecal transit time
(OCTT) that is known to be associated with sec
ondary bacterial overgrowth, in patients with MAS
due to tropical sprue 4 and celiac disease. 14 Since
previous reports documented that this prolonged OCTT
may normalize after specific treatment directed to
wards these diseases, 4,14 further work is needed to
evaluate whether such normalization is associated
with correction of ADM abnormalities.
The pathogenesis of this altered antroduodenal
motility in patients with MAS is unclear. It may be
related to chronic inflammation, immune-mediated
changes, alteration in mast cells, or changes in enteric
neuropeptides, all of which have been proposed to
explain intestinal hypomotility observed in a few
patients with celiac disease. 7,8
Induction of MMC in most patients with MAS
by intravenous injection of octreotide is another
interesting finding in this study. Absence of MMC
may be associated with SIBO, 1 5 which often
complicates MAS due to various causes 3 and poses
special problems in diagnosis and management of
these patients. 5,6 In fact, octreotide has been used in
the treatment of refractory diarrhea and SIBO. 16,17
Our study documents that even in the presence of
marked antroduodenal hypomotility, the gut responds
to intravenous octreotide by generating MMC, though
somewhat weaker and shorter than in healthy subjects.
In conclusion, we have shown that patients with
MAS exhibit fasting and fed-state antroduodenal
hypomotility; such manometric abnormalities in
patients with tropical sprue have not been reported
previously. Antroduodenal hypomotility may have
pathophysiological significance as prolonged OCTT
is common in these patients, which might result in
SIBO.
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Correspondence to: Dr Ghoshal, Associate Professor. Fax:
(522) 266 8017, 266 8078. E-mail: ghoshal@sgpgi.ac.in
Received July 15, 2005. Received in final revised form October
22, 2005. Accepted November 8, 2005
Indian Journal of Gastroenterology 2006 Vol 25 March - April 61