Download Free PDF

European Review for Medical and Pharmacological Sciences
2000; 4: 81-87
Diffuse gastrointestinal dysmotility by
ultrasonography, manometry and breath tests
in colonic inertia
P. PORTINCASA, A. MOSCHETTA, M. GIAMPAOLO, G. PALASCIANO
Istituto di Semeiotica Medica e Sezione di Medicina Interna, Dipartimento di Medicina Interna e
Medicina Pubblica (DIMIMP), University Hospital of Bari (Italy)
Abstract. – Patients with colonic inertia,
the most severe form of chronic functional constipation, may present with a more diffuse panenteric motility disorder. We describe a case of a
woman with severe longstanding colonic inertia
associated with chronic functional dyspepsia
and defective gastric, gallbladder and small intestinal motility, as confirmed by several diagnostic tests including two breath tests with the
13
C-stable isotope. A subclinical form of authonomic sympathetic neuropathy was diagnosed,
providing a possible pathophysiological explanation for the presence of simultaneous multiple
motility defects of the gastrointestinal tract.
Key Words:
13
C-breath test, Ultrasonography, Motility, Constipation.
Introduction
Constipation due to colonic inertia is a frequent condition in Western countries, particularly in the female sex1. The existence of a
pan-enteric motility disorder has been described in a subset of patients with colonic inertia2-4 and might be secondary to an otherwise subclinic idiopathic autonomic neuropathy involving several organs3,5-7.
Case history
A 42-year-old woman was referred to our
clinic for severe chronic and progressively
worsening constipation starting in the childhood. During the last four years she had been
treated with several agents, including bulk
laxatives, stool softeners, osmotic agents and
senna with poor benefit. She had stopped
such medications and using instead enemas
and suppositories with little effect.
Spontaneous bowel movements had a frequency of one in every 20-25 days. Dyspeptic
symptoms such as bloating and postprandial
fullness were reported several times during
each week.
At physical examination the nutritional
status was good; her last evacuation had been
20 days before and she felt very unconfortable. There was a mildly distended abdomen
with poor bowel sounds. Rectal examination
was normal. The blood count, serum electrolytes, calcium, thyroid hormones were all
normal and occult fecal blood was absent.
An upper abdominal ultrasound was normal with respect to liver, pancreas and kidneys. Although the gallbladder was normally
shaped with a thin wall (estimated fasting
volume of 25 mL8), there were small asymptomatic gallstones. A pancolonoscopy was
normal, apart from melanosis coli mainly in
the proximal colon and mild dilatation of the
sigmoid.
The relevance of dyspepsia was assessed by
ranking severity, frequency, and duration of
four separate symptoms: epigastric pain,
heartburn, belching, and bloating 9 . Total
symptom score indicated a high-grade condition and was 21 out of a maximum of 48 (upper cut-off value equal to 8.7 in a control
group of 100 healthy subjects from our series). An upper gastrointestinal endoscopy
was normal and Helicobacter pylori infection
was absent (negative rapid urease test).
Several functional tests were performed to
assess the motility of the gastrointestinal
tract: anorectal manometry, plain abdominal
X-ray films after ingestion of 60 radiopaque
markers for whole-gut (colonic) transit
time10, H2-breath test with 10 g lactulose as
81
P. Portincasa, A. Moschetta, M. Giampaolo, G. Palasciano
substrate for small intestinal transit (orocecal
transit time, OCTT) and functional ultrasonography for gallbladder and gastric emptying in response to liquid meal (200 ml
Nutridrink, Nutricia, NL)11,12.
Gastric emptying and small bowel transit
time were also measured using the 13C stable
isotope breath tests. These are noninvasive,
radiation-free tests; for the stomach 100 mL
13
C-octanoic acid is added to a the yolk of a
scrambled egg cooked with 5 g of margarine
and eaten together with 2 slices of white
bread and 150 mL of water; after passing the
pylorus, rapid disintegration of the meal
takes place in the duodenum, followed by
rapid trans-mucosal absorption of octanoic
acid into the portal vein system. For the intestine, 200 mg L-lactosyl-[ 13C]ureide 13 is
added to a liquid meal (250 mL Cecemel,
Nutricia, NL); this step is followed by substrate biotransformation by the bacterial intestinal flora (Clostridium innocuum and/or
Klebsiella). After a further liver mithocondrial oxidation of substrates, 13CO2 is rapidly
transferred into the plasma bicarbonate pool
and promptly excreted in exhaled air where it
can be reliably assessed by isotope-mass spectrometry. Samples of breath are collected at
fixed time points (e.g. every 15-30 min) for up
to 6 and 10 hours after ingestion of the substrate for gastric emptying and small bowel
transit, respectively14.
Before performing each test, the patient
was asked to fast overnight, avoiding fibers
and other fermentable products. The possible
influence of the physical presence of feces on
proximal gut motility was prevented by performing an enema the evening before studying the gallbladder, the stomach and the small
intestine.
Such tests yelded the following results:
presence of rectoanal inibitory reflex without
pelvic floor dysfunction (as confirmed by a
normal balloon expulsion test), grossly delayed colonic transit (i.e. 133 hours compared
with an upper normal limit of 68 hours in our
control healthy group of 15 subjects), delayed
gastric and gallbladder emptying to liquid
meal (half-emptying time of 48 min and 40
min, respectively; Figure 1 and 2), and delayed orocecal transit time (OCTT: 250 min.
compared with an upper normal limit of 139
min. in our control healthy group of 67 subjects). Also with 13C-breath tests, the patient
82
had delayed gastric emptying to solid meal
(half emptying time of 130 min) 15 and delayed small bowel transit time (460 min)16.
The integrity of the autonomic sympathetic
nervous system was studied with the acetylcholine sweat-spot-test on the dorsum of the
foot and resulted abnormal17.
A conservative treatment was started by
increasing the fiber content in the diet, cisapride (up to 20 mg t.i.d.) and subsequently
erythromycin (up to 200 mg b.i.d.). There was
no change in bowel movements and a mild
improvement of dyspepsia. The patient was
then offered surgical treatment (colectomy
with ileorectostomy)18,19 because of the severity and unresponsiveness of symptoms and a
progressive deterioration of the quality of
life; surgery was carried out 9 months later.
Immediately after operation the patient described 3-4 daily bowel movements with
emission of few loose stools each time, mainly postprandially. After few weeks bowel
movements could be fully controlled and she
resumed normal daily activities. So far, a follow-up of 30 months has been completed and
the patient is now stable describing one daily
evacuation. After operation the score of dyspepsia decreased to 9, almost a normal value.
A second study of combined gallbladder and
gastric emptying was performed 6 months
postoperatively and showed a persistent emptying delay of both organs (Figure 1 and 2).
Discussion
It has been suggested that functional constipation can be a symptom of a more generalized gastrointestinal motility disorder3. We
describe a patient with severe and longstanding constipation due to colonic inertia associated with a major delay of gallbladder and
gastric emptying, small intestinal transit and a
subclinical autonomic neuropathy of the sympathetic system. To achieve such a composite
diagnosis, several tests had to be carried out
to study separate segments and organs of the
gastrointestinal tract. This integrated approach requires a well standardized laboratory and experienced operators20.
In this woman the chief complaint – constipation – was associated with high-grade dyspeptic symptoms on a background of diffuse
Diffuse gastrointestinal dysmotility by ultrasonography, manometry and breath tests in colonic inertia
Figure 1. Ultrasonographic study of postprandial gastric emptying showing time-related changes of cross sections of
antral area at epigastrium expressed as cm2 (panel A) or normalized to fasting antral area (panel B) (small uppercase
20) in the patient with colonic inertia before and after colectomy and in a group of 60 healthy subjects (mean ± SE
shown). The test meal was ingested at time 0 and consisted of 200 mL drink (300 Kcal with 13 g fat, 10 g protein, 35 g
carbohydrate). The regression line is depicted for the control group (panel B) and is used for calculation of each half
emptying time (T/2). The patient had both delayed and incomplete gastric emptying which persisted after colectomy.
83
P. Portincasa, A. Moschetta, M. Giampaolo, G. Palasciano
Figure 2. Ultrasonographic study of postprandial gallbladder emptying showing time-related changes of gallbladder
volume expressed as mL (panel A) or normalized to fasting volume (panel B)20 in the patient with colonic inertia before and after colectomy and in a group of 60 healthy subjects (mean ± SE shown). Same test meal as for Figure 1.
The regression line is depicted for the control group (panel B) and is used for calculation of each half emptying time
(T/2). The patient had both delayed and incomplete gallbladder emptying which persisted after colectomy.
84
Diffuse gastrointestinal dysmotility by ultrasonography, manometry and breath tests in colonic inertia
impairement of gastrointestinal motility.
Indeed, in a subgroup of patients functional
dyspepsia can be related to either a delay of
gastric emptying 21 or H. pylori infection 22.
Neither conditions, however, might have
been relevant in this case since H. pylori infection was absent and gastric emptying was
still delayed despite improved dyspepsia
postoperatively. Clinical symptoms or gastric
half emptying times are poor predictors of
gastrointestinal dysmotility in patients with
functional dyspepsia23 and dyspepsia could also originate from altered small intestinal
motility and sensory thresholds24. Indeed, we
found severe delay of small intestinal transit
as confirmed by two indipendent breath tests.
Both ultrasonography and 13C-octanoic
breath test confirmed that in colonic inertia
gastric emptying can be delayed to both a liquid and a solid meal. Gastric emptying of
solids has been studied using stable isotopes
substrates like 13C-octanoic acid and 13CSpirulina platensis compared with radionuclide scintigraphy25-28; preliminary results are
encouraging29,30 and further validation studies
are being performed at our laboratory
(Portincasa P. et al., personal data)14,31.
In the small intestine, whereas the correlation between 13C-lactose-ureide breath test
and scintigraphy was fairly good31, OCTT appears much shorter with H2-breath test than
with 13C-lactose-ureide breath test; this might
be due to the osmotic effect of lactulose itself
which is missing for the lactose-ureide molecule32; such a difference was also noticed in
this study and further information are required to widely extend the stable isotope
breath test to a variety of conditions in health
and disease.
The presence of gallstones, although small
and asymptomatic, points to an early defect of
gallbladder motility causing stasis and cholesterol crystallization from a supersaturated,
concentrated bile33. An additional pathogenic
factor is the sluggish intestinal transit which
has been associated with increased colonic
bacterial dehydroxylation of primary bile salts
and increased intestinal input of the lithogenic
secondary bile salt deoxycholate, an additional
risk of cholesterol gallstone formation34,35. An
abnormal colonic motility per se, at least in the
present condition, may play a minor role with
respect to the gallbladder, as gallbladder hypomotility persisted after colectomy.
Few items must be discussed when considering the diffuse impairment of gastrointestinal motility in colonic inertia. Firstly, a delay
of the most proximal gut might be secondary
to “mechanical” obstruction for longstanding
retention of fecal material; however this condition is unlikely to play a major role since the
motility defect was found when the colon had
been properly cleaned. Secondly, a colonic inertia per se might negatively affect proximal
transit even without luminal obstruction. This
might not be completely true since in the present report neither gallbladder or gastric emptying improved after colectomy. By contrast,
abnormal sweat-spot test points to an early
defect of the autonomic sympathetic system
leading to loss of fine regulation of gastrointestinal motility; we recently described this
finding in a larger study3.
From a practical point of view, we believe
that patients with severe slow transit constipation deserve an extensive diagnostic
workup to detect and to quantitate motility
disturbances of the gastrointestinal tract. It is
suggested that the prognosis might be poorer
in the presence of severe and multiple gastrointestinal motility defects36.
Lastly, although patient’s compliance is
fairly good for noninvasive tests, breath tests
with stable isotope require longer observation times; this, together with high costs for
substrates might decrease their diagnostic
power for routine clinical workups.
Nevertheless, stable isotope breath tests
might represent major research tools for wide
epidemiological and simultaneous field studies for detecting gastrointestinal motility disturbances28,31,37,38.
References
1) Gastrointestinal Disease: pathophysiology, diagnosis, management. 5th ed. Philadelphia: W.B.
Saunders, 1993.
2) WATIER A, DEVROEDE G, DURANCEAU A, ABDEL-RAHMAN
M, DUGUAY C, FORAND MD et al. Constipation with
colonic inertia. A manifestation of systemic disease? Dig Dis Sci 1983; 28: 1025-1033.
3) ALTOMARE DF, PORTINCASA P, RINALDI M, DI CIAULA A,
MARTINELLI E, AMORUSO AC et al. Slow-transit constipation: a solitary symptom of a systemic gastrointestinal disease. Dis Colon Rectum 1999; 42:
231-240.
85
P. Portincasa, A. Moschetta, M. Giampaolo, G. Palasciano
4) BASSOTTI G, STANGHELLINI V, CHIARIONI G, GERMANI U,
DE GIORGIO R, VANTINI I et al. Upper gastrointestinal motor activity in patients with slow-transit constipation. Further evidence for an enteric neuropathy. Dig Dis Sci 1996; 41: 1999-2005.
5) ALTOMARE D, PILOT MA, SCOTT M, WILLIAMS N, RUBINO
M, ILINCIC L et al. Detection of subclinical autonomic neuropathy in constipated patients using a
sweat test. Gut 1992; 33: 1539-1543.
6) CAMILLERI M, FEALEY RD. Idiopathic autonomic denervation in eight patients presenting with functional gastrointestinal disease. A causal association?
Dig Dis Sci 1990; 35: 609-616.
7) KERRIGAN DD, LUCAS MG, SUN WM, DONNELLY TC,
READ NW. Idiopathic constipation associated with
impaired urethrovesical and sacral reflex function.
Br J Surg 1989; 76: 748-751.
8) K ISHK SMA, D AR WEESH RMA, D ODDS WJ, et al.
Sonographic evaluation of resting gallbladder volume and postprandial emptying in patients with
gallstones. A J R 1987; 148: 875-879.
9) BUCKLEY MJ, SCANLON C, MCGURGAN P, O’MORAIN C.
A validated dyspepsia symptom score. Ital J
Gastroenterol Hepatol 1997; 29: 495-500.
10) METCALF A, PHILLIPS SF, ZINSMEISTER AR, MACCARTY RL,
BEART RW, WOLFF BG. Simplified assessment of
segmental colonic transit. Gastroenterology 1987;
92: 40-47.
11) PORTINCASA P, DI CIAULA A, PALMIERI V, VELARDI A,
VANBERGE-HENEGOUWEN GP, PALASCIANO G. Impaired
gallbladder and gastric motility and pathological
gastro-esophageal reflux in gallstone patients.
Eur J Clin Invest 1997; 8: 653-661.
18) PICCIRILLO MF, REISSMAN P, WEXNER SD. Colectomy as
treatment for constipation in selected patients. Br
J Surg 1995; 82: 898-901.
19) WEXNER SD, DANIEL N, JAGELMAN DG. Colectomy for
constipation. Physiologic investigation is the key
to success. Dis Colon Rectum 1991; 34: 851-856.
20) PORTINCASA P, COLECCHIA A, DI CIAULA A, LAROCCA A,
PALASCIANO G, RODA E et al. Standards for diagnosis of gastrointestinal motility disorders.
Ultrasonography. Dig Liver Dis 2000; 32: 160172.
21) STANGHELLINI V, TOSETTI C, PATERNICÒ A, BARBARA G,
MORSELLI LABATE AM, MONETTI N et al. Risk indicators of delayed gastric emptying of solids in patients with functional dyspepsia. Gastroenterology
1996; 110(4):1036-1042.
22) T ESTONI PA, B AGNOLO F, B OLOGNA P, C OLOMBO E,
B ONASSI U, L ELLA F et al. Higher prevalence of
Helicobacter pylori infection in dyspeptic patients
who do not have gastric phase III of the migrating
motor complex. Scand J Gastroenterol 1996; 31:
1063-1068.
23) W ILMER A, V AN C UTSEM E, A NDRIOLI A, T ACK J,
COREMANS G, JANSSENS J. Ambulatory gastrojejunal
manometry in severe motility-like dyspepsia: lack
of correlation between dysmotility, symptoms, and
gastric emptying. Gut 1998; 42: 235-242.
24) HOLTMANN G, TALLEY NJ, GOEBELL H. Association
between H. pylori, duodenal mechanosensory
thresholds, and small intestinal motility in chronic
unexplained dyspepsia. Dig Dis Sci 1996; 41:
1285-1291.
12) L A B ROOY SJ, M ALE PJ, B EAVIS AK, M ISIEWICZ JJ.
Assessment of the reproducibility of the lactulose
H2 breath test as a measure of mouth to caecum
transit time. Gut 1983; 24: 893-896.
25) CHOI MG, CAMILLERI M, BURTON DD, ZINSMEISTER AR,
FORSTROM LA, NAIR KS. [13C]octanoic acid breath
test for gastric emptying of solids: accuracy, reproducibility, and comparison with scintigraphy.
Gastroenterology 1997; 112: 1155-1162.
13) WUTZKE KD, HEINE WE, PLATH C, LEITZMANN P, RADKE
M, MOHR C et al. Evaluation of oro-coecal transit
time: a comparison of the lactose- [13C, 15N]ureide 13CO2- and the lactulose H2-breath test in humans. Eur J Clin Nutr 1997; 51: 11-19.
26) CHOI MG, CAMILLERI M, BURTON DD, ZINSMEISTER AR,
FORSTROM LA, NAIR KS. Reproducibility and simplification of 13C-octanoic acid breath test for gastric
emptying of solids. Am J Gastroenterol 1998; 93:
92-98.
14) PORTINCASA P, PALASCIANO G. Breath testing for gastric emptying and intestinal transit evaluation.
Gastroenterology International 1999; 12 (Suppl
2): 46-48.
27) M A E S BD, G E Y P E N S BJ, G H O O S YF, H I E L E MI,
R UTGEERTS PJ. 13C-Octanoic acid breath test for
gastric emptying rate of solids. Gastroenterology
1998; 114: 856-859.
15) GHOOS YF, MAES BD, GEYPENS BJ, MYS G, HIELE MI,
RUTGEERTS PJ et al. Measurement of gastric emptying rate of solids by means of a carbon- labeled
octanoic acid breath test. Gastroenterology 1993;
104: 1640-1647.
28) LEE JS, CAMILLERI M, ZINSMEISTER A, BURTON D, KOST
LJ, KLEIN PD. A valid, accurate, office based, nonradioactive test for gastric emptying of solids. Gut
2000; 46:768-773.
16) G EYPENS B, B ENNINK R, P EETERS M, E VENEPOEL P,
MORTELMANS L, MAES B et al. Validation of the lactose-[13C]ureide breath test for determination of
orocecal transit time by scintigraphy. J Nucl Med
1999; 40: 1451-1455.
17) RYDER RE, MARSHALL R, JOHNSON K, RYDER AP, OWENS
DR, HAYES TM. Acetylcholine sweatspot test for
autonomic denervation. Lancet 1988; 1(8598):
1303-1305.
86
29) PERRI F, CLEMENTE R, FESTA V, QUITADAMO M, NIRO G,
ANDRIULLI A. 13C-octanoic acid breath test: a reliable tool for measuring gastric emptying. Ital J
Gastroenterol Hepatol 1998; 30: 211-217.
30) MAES BD, SPITZ B, GHOOS YF, HIELE MI, EVENEPOEL P,
RUTGEERTS PJ. Gastric emptying in hyperemesis
gravidarum and non-dyspeptic pregnancy.
Aliment Pharmacol Ther 1999; 13: 237-243.
31) PORTINCASA P, MOSCHETTA A, PALASCIANO G. Nuovi
breath test per lo studio dello svuotamento gastri-
Diffuse gastrointestinal dysmotility by ultrasonography, manometry and breath tests in colonic inertia
co e del transito intestinale. Rilevanza in pazienti
con stipsi funzionale. UCP News 2001; in press.
32) M ILLER MA, PARKMAN HP, U RBAIN JL, B ROWN KL,
DONAHUE DJ, KNIGHT LC et al. Comparison of scintigraphy and lactulose breath hydrogen test for assessment of orocecal transit: lactulose accelerates
small bowel transit. Dig Dis Sci 1997; 42: 10-18.
33) PORTINCASA P, DI CIAULA A, BALDASSARRE G, PALMIERI V,
G ENTILE A, C IMMINO A et al. Gallbladder motor
function in gallstone patients: sonographic and in
vitro studies on the role of gallstones, smooth
muscle function and gallbladder wall inflammation. J Hepatol 1994; 21: 430-440.
34) THOMAS LA, VEYSEY MJ, BATHGATE T, KING A, FRENCH
G, SMEETON NC et al. Mechanism for the transit-induced increase in colonic deoxycholic acid formation in cholesterol cholelithiasis. Gastroenterology
2000; 119: 806-815.
35) HEATON KW, EMMETT PM, SYMES CL, BRADDON FEM.
An explanation for gallstones in normal-weight
woman: slow intestinal transit. Lancet 1993; 341:
8-10.
36) R EDMOND JM, S MITH GW, B AROFSKY I, R ATYCH RE,
GOLDSBOROUGH DC, SCHUSTER MM. Physiological
tests to predict long-term outcome of total abdominal colectomy for intractable constipation.
Am J Gastroenterol 1995; 90(5):748-753.
37) LEE JS, CAMILLERI M, ZINSMEISTER A, BURTON D, CHOI
MG, NAIR KS. Accurate, simple measurement of
gastric emptying by 13C-octanoic acid breath test
(OBT) in diabetics. Gastroenterology 116, A3055
1999.
38) CAMILLERI M, HASLER WL, PARKMAN HP, QUIGLEY EM,
SOFFER E. Measurement of gastrointestinal motility
in the GI laboratory. Gastroenterology 1998; 115:
747-762.
87