|
Marijana
Protic, Center for Gastroenterology and Hepatology, Zvezdara
University Clinical Center, Belgrade
Njegica Jojic, Daniela Bojic, Metabolic Department, Center
for Gastroenterology and Hepatology, Zvezdara University Clinical
Center, Belgrade
Svetlana Milutinovic, Institute for Pathology, Zvezdara
University Clinical Center, Belgrade
Dusanka Necic, Metabolic Laboratory, Center for
Gastroenterology and Hepatology, Zvezdara University Clinical
Center, Belgrade
Bozidar Bojic, Endoscopic Unit, Center for Gastroenterology
and Hepatology, Zvezdara University Clinical Center, Belgrade
Petar Svorcan, Center for Gastroenterology and Hepatology,
Zvezdara University Clinical Center, Belgrade
Miodrag Krstic, Center for Gastroenterology and Hepatology,
Clinical Center of Serbia, Belgrade
Obren Popovic, Center for Gastroenterology and Hepatology,
Zvezdara University Clinical Center, Belgrade
Correspondence to: Marijana Protic, MD, Assistant Professor,
Center for Gastroenterology and Hepatology, Zvezdara Clinical
Center, 161 Dimitrija Tucovica, Belgrade 11 000, Serbia and
Montenegro. marijanaprotic@beotel.yu
Telephone: +381-63-345985
Fax: +381-11-3806340
Received: 2005-01-19
Accepted: 2005-02-28
Abstract
AIM: To search the pathophysiological mechanism of diarrhea
based on daily stool weights, fecal electrolytes, osmotic gap and
pH.
METHODS: Seventy-six patients were included: 51 with
microscopic colitis (MC) [40 with lymphocytic colitis (LC); 11 with
collagenous colitis (CC); 7 with MC without diarrhea] and 18 as a
control group (CG). They collected stool for 3 d. Sodium and
potassium concentration were determined by flame photometry and
chloride concentration by titration method of Schales. Fecal osmotic
gap was calculated from the difference of osmolarity of fecal fluid
and double the sum of sodium and potassium concentration.
RESULTS: Fecal fluid sodium concentration was significantly
increased in LC 58.11±5.38 mmol/L (P<0.01)
and CC 54.14±8.42 mmol/L (P<0.05)
than in CG 34.28±2.98 mmol/L.
Potassium concentration in LC 74.65±5.29 mmol/L (P<0.01)
and CC 75.53±8.78 mmol/L (P<0.05)
was significantly less compared to CG 92.67±2.99 mmol/L.
Chloride concentration in CC 36.07±7.29 mmol/L was
significantly higher than in CG 24.11±2.05 mmol/L (P<0.05).
Forty-four (86.7%) patients had a secretory diarrhea compared to
fecal osmotic gap. Seven (13.3%) patients had osmotic diarrhea.
CONCLUSION: Diarrhea in MC mostly belongs to the secretory
type. The major pathophysiological mechanism in LC could be
explained by a decrease of active sodium absorption. In CC,
decreased Cl/HCO3
exchange rate and increased chloride secretion are coexistent
pathways.
ã 2005
The WJG Press and Elsevier Inc. All rights reserved.
Key words: Lymphocytic colitis; Collagenous colitis;
Secretory diarrhea
Protic M, Jojic N, Bojic D, Milutinovic S, Necic D, Bojic B, Svorcan
P, Krstic M, Popovic O. Mechanism of diarrhea in microscopic
colitis. World J Gastroenterol
2005; 11(35): 5535-5539
http://www.wjgnet.com/1007-9327/11/5535.asp
INTRODUCTION
Microscopic colitis is a new form of idiopathic inflammatory bowel
disease. First studies dealing with microscopic colitis appeared in
the late seventies[1-3].
Clinical manifestations are substantially milder than other forms of
idiopathic inflammatory bowel diseases. The main characteristics
include chronic watery diarrhea and abdominal cramps. Endoscopic[4-8]
and radiological examination of gastrointestinal tract are normal.
The major criteria for diagnosis are set on the basis of
histological findings of colonic mucosal biopsies[9]
and stool examinations. There are two basic types of microscopic
colitis: collagenous and lymphocytic colitis. They could be
differentiated on the basis of pathohistological findings.
Collagenous colitis is defined by the appearance of diffuse
thickening of subepithelial collagenous band (>10 mm)[10],
desquamation and degeneration of surface epithelium, increased
number of intraepithelial lymphocytes and mild or moderate
mononuclear infiltration of lamina propria[10,11-13].
Collagenous colitis shows striking predominance in women (F:M 7:1)
in their fifth and sixth decades[4,10,14].
They are often associated with other autoimmune diseases: rheumatoid
arthritis[15-17],
systemic and discoid lupus erythematosus[18,19],
juvenile sclerodermia[20],
CREST syndrome[21],
abnormal function of thyroid gland[14].
Lymphocytic colitis is defined by increased number of
intraepithelial lymphocyte of colonic mucosa (>20 IEL per 100
epithelial cells)[10].
Other histological features include flattened surface epithelium
with mucine depletion, mononuclear infiltration of lamina propria,
and minimal crypt distortion or cryptitis[10,11].
Lymphocytic colitis typically occurs in the sixth decade with
roughly equivalent female to male ratio[10,14,19-21].
According to data from the literature
there is an association between lymphocytic colitis and other
autoimmune diseases: sicca syndrome[15],
celiac disease[24-26]
idiopathic pulmonary fibrosis, uveitis, and idiopathic
thrombocytopenic purpura[12].
Ethiopathogenesis of microscopic colitis still remains unclear. The
long-term use of NSAID[27],
and other medication (cyclo3fort[28],
ranitidine[29],
ticlodipin) could be important. A good number of authors[19,20,30]
claim that autoimmune process is the cause of prime importance in
ethiopathogenetic mechanism.
Intraepithelial lymphocytes in lymphocytic and collagenous colitis
belong to T suppressor cells, CD8
group[19].
Stimulated by some luminal antigen they can cause cross reaction
with endogen antigen present in the epithelial cells, damage them or
reveal direct toxic action on the enterocytes[31].
The hypothesis of the infective etiology of microscopic colitis is
based on the results of success of antibiotic therapy[4].
Bile acids also may play a role as shown by malabsorption of bile
acids and proper therapeutic response to the cholestiramine[32],
which is also suggested by combined manifestation with primary ileal
villous atrophy[33].
Deregulation of a collagen synthesis[19,33]
has also been mentioned as a possible etiological factor. The
precise pathophysiological mechanism of secretory diarrhea typical
for microscopic colitis has not been clarified. Most of the authors[31,34,35]
believe that the following processes prevail in the development of
secretory diarrhea:
-
Reduced active sodium absorption
-
Inhibited chloride and bicarbonate exchange
-
Increased electrogenic chloride secretion followed by passive
sodium and water transport.
-
Decreased passive permeability of colonic mucosa.
Evidence
for each of these hypotheses is contained in a Bo-Linn perfusion
study[34].
Results of net and unidirectional electrolyte fluxes and electrical
potential difference suggested that colonic fluid absorption was
abnormal. The main reasons for these are: reduced active and passive
sodium and chloride absorption and reduced Cl/HCO3
exchange. Zeroogian and Chopra thought that mediators secreted by
inflammatory cells in lamina propria may play an important role in
disturbances of absorptive colonic capacity and reducing passive
transport[21].
Other authors consider that watery diarrhea is a consequence of
increased active chloride intraluminal secretion and accompanying
passive sodium and water transport[31,35].
Increased concentration of prostaglandin E2 secreted by pericryptal
fibroblasts may stimulate active chloride secretion. Pericryptal
fibroblasts compose pericryptal sheets which can cause functional
abnormalities. In some cases an increased concentration of
prostaglandin E2 is found in jejunal aspirate and feces[31].
The same group considers that injured surface epithelium and
collagen deposit band of colonic mucosa may prevent absorption of
luminal water and electrolytes. The most important
pathophysiological role could be played by inflammatory cells
infiltrated in the lamina propria, common characteristic for both
lymphocytic and collagenous colitis. Precise mechanism of diarrhea
remains unclear due to unknown etiological factors yet to be
discovered. It is possible that different mechanisms cause diarrhea
in the course of the disease, depending on whether pericryptal
absorption site are blocked by the collagen deposit or inflammatory
cells infiltrate.
MATERIALS AND METHODS
The study was performed in the Center for Gastroenterology and
Hepatology (Zvezdara, University Clinical Center, Belgrade) between
1993 and 2004. Seventy-six people were included in the study (58
with diagnoses of microscopic colitis and 18 healthy people
composing a control group).
The following diagnostic procedures were
performed in both groups: routine biochemical examinations with
electrolyte status, lactose tolerance test, thyroid status, presence
of antinuclear antibody (ANA), antimitochondrial antibody (AMA) and
antibodies to tyreoglobulin; standard and specific (Yersinia
enterocolitica and Campylobacter jejuni) stool
examinations for bacteria and parasites; duodenal tube with
quantitative and qualitative bacterial culture of aspirate; small
bowel barium enema, enteroscopy with small bowel biopsies;
colonoscopy with terminal ileoscopy and serial biopsies of colonic
and terminal ileum mucosa. Biopsy specimens were fixed with 40 g/L
formaldehyde and embedded in paraffin. Five micrometer sections were
stained with hematoxylin and eosin. Thickness of the subepithelial
collagen layer was measured with light microscopy using screw
micrometer by an experienced pathologist. Number of intraepithelial
lymphocytes was determined with regard to 100 epithelial cells of
colonic mucosa.
Functional examinations of stool
Stool samples All
patients collected stool for 3 d (72 h) in preweight plastic bucket
that held 3-5 L. Buckets with stools were kept cold under
refrigeration (+4 ℃)
during the collection period. During that time patients were on a
diet with 70-100 g fats per day.
Determination of sodium, potassium and chloride concentration in
fecal fluid Concentration
of sodium and potassium were determined by flame photometry (Corning
480 Flame Photometer)[36,37]
and chloride concentration by the titration method of Schales[38].
Data of sodium, potassium and chloride were multiplicities with
water dilution factor. Daily losses of electrolytes by stool were
calculated from the concentration of electrolytes in fecal fluid.
Fecal osmotic gap was calculated from the difference of measured
osmolality of fecal fluid and double sum of the sodium and potassium
concentration [290-(Na+K)2].
Estimation of pH of fecal fluid
For estimating fecal pH we used balanced Beckman Expandomatic
pH meter[37].
Determination of daily fecal fat
The amount of fat in daily stool was quantified by titration
method of Van de Kamer[39].
Normal values of fecal fat in our laboratory are less than 6 g/d.
Normal values by the data of Fine are 6.4 g/d[40,43].
Statistical analysis
For all tested parameters we calculated mean and standard error
(SE). For the statistical significant difference (P<0.05)
among different group of patients, unpaired Student’s t-test
was used.
RESULTS
There were 51 patients with complete conditions for diagnosis of
microscopic colitis [40 patients with lymphocytic colitis (LC) and
11 patients with collagenous colitis (CC)]. Seven patients had
histological diagnoses of MC (5 patients with LC and 2 with CC)
without diarrhea at that moment. Control group consisted of 18
healthy persons.
Based upon the status of the collagen plate and
the number of IEL of biopsy specimen of right colon, patients are
classified as a group with LC or CC or CG (Table 1). In the group of
patients with LC the median number of IEL/100 epithelial cells was
(32±12) and the
mean thickness of collagen plate was (8±2) mm with
moderate inflammation of lamina propria. Patients with CC had
average thickness of collagen band (25±9) mm and (14±4) IEL/100
epithelial cells with severe inflammation of lamina propria. Control
group of patients had (4±1) IEL/100
epithelial cells and mean thickness of collagen plate (8±3) mm.
Physical examination, all biochemical tests, radiological and
endoscopic findings were normal in all patients. Diagnoses of
microscopic colitis was established based on the data of verified
diarrhea [daily stool weight (DSW)> 200 g/24 h] and
histopathology analysis of biopsy specimens of colonic mucosa. Mean
values of DSW (mean±SE)
in the group of patients with LC and CC were statistically
significantly higher than in the other two groups: CG and group of 7
patients with histological signs of microscopic colitis without
diarrhea (P<0.01, Table 2). The average values of sodium
concentration in the patients with LC (P<0.01) and CC (P<0.05)
were statistically significantly different than in the CG. Daily
fecal loss of this electrolyte patient with LC and CC was
statistically significantly different than among the healthy people
(P<0.05, Figure 1) The mean values of potassium
concentration in patients with LC (P<0.01) and CC (P<0.05)
were statistically significantly different than CG. Daily fecal loss
of potassium in patients with LC and CC was statistically
significantly different with regard to CG (P<0.05).
The average value of chloride concentration in patients with CC was
statistically significantly different with regard to CG (P<0.05).
Daily fecal loss of this electrolyte in patients with LC and CC was
statistically significantly different than among the healthy people
(P<0.05). We tried to clarify the mechanism of diarrhea by
calculation of the fecal osmotic gap (FOG). Secretory diarrhea (FOG
<50 memo/kg) was found in 44 (86.7%) of patients with microscopic
colitis. Osmotic diarrhea was present in 7 (13.3%) of patients. The
reason in determining the concentration of fecal fat in patients
with LC and CC was to establish possible impact of some other
disease (small bowel or pancreatic) on pathophysiological mechanism
of diarrhea. Six (11.7%) patients with LC had slightly increased
daily fecal fat (9-11 g/24 h). DSW in the group of patients [9
(17.46%)] with LC and accompanying disease (mean: 315.10 g/24 h) was
not statistically significantly different than in the group of
patients with LC (mean: 372.64 g/24 h). The average values of fecal
pH in the patients with LC (6.31±0.14) and CC
(6.36±0.11) were not
statistically significantly different compared to CG.
Table 1 Mean±SD
of number of IEL/100 EC and thickness of collagen plate in patients
with LC and CC
| |
n |
No.
of IEL/100 EC
(mean±SD) |
Thickness
of collagen band
(mean±SD) |
Inflammation
of propria |
| Lymphocytic
colitis |
46 |
32±12 |
8±2 |
Moderate |
| Collagenous
colitis |
13 |
14±4 |
25±9 |
Severe |
| Control
group |
18 |
4±1 |
8±3 |
Mild/none |
Figure
1 (PDF) Average
values of fecal daily loss of Na+,
K+,
Cl-
(mean±SE).
DISCUSSION
Precise mechanism of diarrhea in patients with microscopic colitis
still remains unclear. Most of the authors[31,34,35]
believe that dominant processes in the development of diarrhea are:
1. Reduced active sodium absorption 2. Inhibited chloride and
bicarbonate exchange 3. Increased electrogenic chloride secretion
followed by passive sodium and water transport. 4. Decreased passive
permeability of colonic mucosa. First data about mechanism of
secretory diarrhea were established by Bo-Linn perfusion study[34].
The average values of DSW in this and other similar studies[21,33,34]
were higher than values from our study (LC: 200, 2-1 400 g/24 h; CC:
206-350 g/24 h). Using "steady-state"
perfusion method, the authors have proved that electrolyte and fluid
absorption in colon were seriously disturbed in patients with
microscopic colitis. The reasons for reduced electrolyte and fluid
absorption are microscopic changes of colonic mucosa. Degenerative
injuries of surface epithelium, subepithelial collagen deposit and
persistence of inflammatory cells (prostaglandin E2)[31,34,35]
infiltrate in lamina propria play the most important role in
decreased absorption of luminal water and electrolyte.
Pathohistological findings of colonic biopsy specimen in our
patients are in accordance with the results of previous studies[8-10].
Decreased active sodium absorption is visible by a reduction of the
flux lumen/plasma of sodium and chloride. Inhibited chloride and
bicarbonate exchange is shown by the reduced bicarbonate secretion
rate and lowered chloride absorption[34].
In our study, sodium concentration of the fecal fluid in patients
with LC and CC was highly increased in relation to control group.
These facts are in accordance with data of other authors. Potassium
concentration in fecal fluid of patients with LC and CC was
significantly less compared to CG. But the average values of
potassium concentration were higher with regard to data from other
studies. The mean values of chloride concentrations in patients with
CC were statistically significantly higher with regard to CG. These
results in our study were less than the data of other authors[34,35].
Daily fecal loss of electrolyte in patients with LC and CC were
significantly higher compared to a group of healthy persons. These
results were expected for sodium and chloride, due to great
concentration of these electrolytes in fecal fluid. Despite smaller
potassium fecal concentration, great potassium fecal loss appeared,
due to daily stool weight. This fact could have clinical
significance and could explain uncommon severe hypokalemia in some
patients with microscopic colitis. Finally, our results of fecal
electrolytes concentration and their daily fecal loss also confirm
the hypothesis of disturbed active sodium absorption and
absorption/secretion of chloride[31,34,35,41].
The dominant process in electrolyte malabsorption in patients with
LC could be reduced by active sodium absorption. In the group of
patients with CC prevailing mechanisms are decreasing the rate of Cl/HCO3
exchange and increased electrogenic Cl secretion, in addition to,
reduced active sodium absorption. There were no significant
differences between main values of fecal pH of examined patients
with LC and CC with regard to healthy persons. Still it is
interesting to note that all patients with proper therapeutic
response to cholestyramine had slightly increased fecal pH
(>6.8). This data could suggest possible co-factorial influence
of bile acid malabsorption[17,33]
on the mechanism of diarrhea in microscopic colitis. Only 6 (11.7%)
patients had slightly increased daily fecal fat (9-11 g/24 h). All
of them had lymphocytic colitis. In the group of patients with
microscopic colitis and associated disease there were no differences
in average values of daily stool weight compared to patients with
microscopic colitis without accompanied disease. On the basis of our
results it could be concluded that influence of accompanied disease
on the mechanism of diarrhea is of secondary importance. Most of the
authors[31,34,41-43,45]
claim that secretory diarrhea is characteristic of microscopic
colitis. By Erer’s criteria, the border value of fecal osmotic gap
(FOG) for distinction between secretory and osmotic diarrhea is 50
mOsmol/kg[43,44].
In our study 86.7% of patients had secretory diarrhea and 13.3%
osmotic diarrhea. All patients with secretory diarrhea belong to the
group of patients with lymphocytic colitis. There was a group of 7
patients with histological diagnosis of microscopic colitis and
without approved diarrhea. All of them had intermittent diarrhea. We
recommended them to collect stool during the period of diarrhea. The
schedule for future examination of these patients remains imprecise.
In conclusion, on the basis of our results it
could be stated that diarrhea in microscopic colitis (LC, CC)
belongs to the secretory type. The major pathophysiological
mechanism in patients with LC may be a decrease of active sodium
absorption. In collagenous colitis decreased Cl/HCO3
exchange rate and increased electrogenic chloride secretion is
coexistent pathway in the genesis of diarrhea.
Table 2 mean±SE
values of daily stool weight, electrolyte concentration in fecal
fluid and fecal pH in examined group of patients
| |
DSW
(g/24 h) |
Conc
Na+
(mmol/L) |
Conc
K+
(mmol/L ) |
Conc
Cl–
(mmol/L) |
pH |
| Lympocytic
colitis |
386.25±5.39b |
58.11±5.38b |
74.65±5.29b |
28.85±2.55 |
6.31±0.14 |
| Collagenous
colitis |
245.66±18.43b |
54.14±8.42a |
75.53±8.78a |
36.07±7.29a |
6.36±0.11 |
| Control
group |
118.34±8.79 |
34.28±2.98 |
92.67±2.99 |
24.11±2.05 |
6.36±0.15 |
| MC
without diarrhea |
139.19±15.92 |
|
|
|
|
aP<0.05
vs Control group; bP<0.01
vs control group.
REFERENCES
1
Lindstrom CG. "Collagenous
colitis" with watery diarrhea - a new entity? Pathol Eur 1976;
11: 87-89
2
Read NW, Krejs GJ, Read MG. Chronic diarrhea of
unknown origin. Gastroenterology 1980; 78: 264-271
3
Kingham JG, Levison DA, Ball JA. Microscopic colitis-a
cause of chronic watery diarrhea. Br Med J 1982; 285:
1601-1604
4
Bohr J, Tysk C, Eriksson S. Collagenous colitis: A
retrospective study of clinical presentation and treatment in
163 patients. Gut 1996; 39:
846-851
5
Olesen M, Eriksson S, Bohr J, Jarnerot G, Tysk C.
Lymphocytic colitis: a retrospective clinical study of 199
Swedish patients. Gut 2004; 53:
536-541
6
Barta Z, Mekkel G, Csipo I, Toth L, Szakall S, Szabo
GG, Bako G, Szegedi G, Zeher M. Microscopic colitis: A
retrospective study of clinical
presentation in 53 patients. World J Gastroenterol 2005; 11:
1351-1355
7
Baert F, Wouters K, D'Haens
G. Lymphocytic colitis: a distinct clinical entity? A
clinicopathological confrontation
of lymphocytic and collagenous
colitis. Gut 1999; 45: 375381
8
Veress B, Loffberg R, Bergman L. Microscopic colitis
syndrome. Gut 1995; 36: 880-886
9
Lazenby AJ, Yardley JH, Giardiello FM. Lymphocytic ("microscopic")
colitis: a comparative histopathologic study
with particular reference to
collagenous colitis. Hum Pathol 1989; 20: 1828
10
Bogomoletz WV, Flejou JF.
Newly recognized forms of colitis: Collagenous, microscopic (lymphocytic)
colitis
and lymphoid follicular
proctitis. Semin Diagh Pathol 1991; 8: 178-189
11
Fernandez-Banares F, Salas A, Esteve M, Espinos J,
Forne M, Viver JM. Collagenous and lymphocytic colitis.
Evaluation of clinical and
histological features, response to treatment, and long-term
follow-up. Am J Gastroenterol
2003; 98: 340-347
12
Robert ME. Microscopic colitis: pathologic
considerations, changing dogma. J Clin Gastroenterol 2004; 38:
18-26
13
Olesen M, Eriksson S, Bohr J, Jarnerot
G, Tysk C. Microscopic colitis: a common diarrhoeal disease.
An
epidemiological study in Orebro,
Sweden 19931998. Gut 2004; 53: 346-350
14
Zins BJ, Sandborn WJ, Tremaine WJ.
Collagenous and lymphocytic colitis: Subject review and
therapeutic
alternatives. Am J
Gastroenterol 1995; 90: 1394-1399
15
Castanet J, Lacour JP, Ortonne JP. Arthritis,
collagenous colitis, and discoid lupus. Ann Intern Med 1994; 120:
89-90
16
Sowa JM. Arthritis and collagenous colitis. Ann
Intern Med 1994; 121: 237
17
Bowling TE, Price AB, Al-Adnani M. Interchange between
collagenous and lymphocytic colitis in severs disease
with autoimmune associations
requiring colectomy: a case report. Gut 1996; 38:
788-791
18
Heckerling P, Urtubey A, Te J. Collagenous colitis and
Systemic Lupus Erythematosus. Ann Intern Med 1995;
122: 71-72
19
Schiller LR. Diagnosis and management of microscopic
colitis syndrome. J Clin Gastroenterol 2004; 38:
27
20
Bohr J, Tysk C, Yang P. Autoantibodies and
immunoglobulins in collagenous colitis. Gut 1996; 69:
73-76
21
Zeroogian JM, Chopra S. Colagenous colitis and
Lymphocytic colitis. Annu Rev Med 1994; 45: 105 -123
22
Tagkalidis P, Bhathal P, Gibson P. Microscopic
colitis. J Gastroenterol Hepatol 2002; 17: 236-248
23
Pardi DS, Ramnath VR, Loftus EV Jr, Tremaine WJ,
Sandborn WJ. Lymphocytic colitis: clinical features,
treatment,
and outcomes. Am J
Gastroenterol 2002; 97: 2829-2833
24
Freeman HJ. Collagenous colitis as the presenting
feature of biopsy defined celiac disease. J Clin Gastroenterol
2004; 38: 664-668
25
Matteoni CA, Goldblum JR, Wang N, Brzezinski A, Achkar
E, Soffer EE. Celiac disease is highly prevalent in
lymphocytic colitis. J Clin
Gastroenterol 2001; 32: 193-195
26
Abdulkarim AS, Burgart LJ, See J, Murray JA. Etiology
of nonresponsive celiac disease: results of a
systematic approach. Am J
Gastroenterol 2002; 97: 2016-2021
27
Mulder CJ, Harkemar IM, Meijer JW, De Boer NK.
Microscopic colitis. Rom J Gastroenterol 2004; 13:
113-117
28
Beaugerie L, Luboinski J, Brousse N. Drug induced
lymphocyitic colitis. Gut 1994; 35: 426-428
29
Beaugerie L, Patey N, Brosse N. Ranitidine, diarrhoea,
and lymphocytic colitis. Gut 1995; 37: 708-711
30
Jarenot G, Bohr J, Tysk C. Fecal stream diversion in
patients with collagenous colitis. Gut 1996; 38:
154-155
31
Stampfl DA, Freidman LS. Collagenos colitis -
Pathophysiologic Considerations. Dig Dis Sci l991; 36:
705-711
32
Baert D, Coppens M, Burvenich P, De Cock G, Lagae J,
Rasquin K, Vanderstraeten E. Chronic diarrhoea in
non collagenous microscopic
colitis: therapeutic effect of cholestyramine. Acta Clin Belg 2004;
59: 258-262
33
Marteau P, Lavergne-Slove A, Lemann M. Primary ileal
villous atrophy is often associated with microscopic colitis.
Gut 1997; 41:
561-564
34
Bo-Linn GW, Vendrell DD, Lee E, Fordtran JS. An
evaluation of the significance of microscopic colitis in
patients
with chronic diarrhea. J
Clin Invest 1985; 75: 1559-1569
35 Ernest
DL, Hixon LJ. Collagenous and lymphocytic colitis. In Sleisenger
MN, Fordtran JS (Eds): Gastrointestinal
disease. 5th
ed. WB Saunders Co. Philadelphia 1993: 1563-1570
36 Jesenovac
N. Determination of sodium in fecal fluid. Special methods of
biochemical laboratory analysis.
Yugoslav society of medical
biochemistries. Karlovac 1988; 1: 192-193
37 Jesenovac
N. Determination of potassium in fecal fluid. Special methods of
biochemical laboratory analysis.
Yugoslav society of medical
biochemistries. Karlovac 1988: 1: 182-183
38 Jesenovac
N. Determination of chloride in fecal fluid. Special methods of
biochemical laboratory analysis.
Yugoslav society of medical
biochemistries. Karlovac 1988: 1: 257-258
39
Van de Kamer JH. Quantitative determination of the
saturated and unsaturated higher fatty acids in fecal fat.
Scand J Clin Lab Invest
1953; 5: 30-36
40
Fine K, Fordtran JS. The effect of diarrhea on fecal
fat excretion. Gastroenterology 1992; 102: 1936-1939
41
Delgado J, Delgado B, Fich A, Odes S. Microscopic
colitis. Isr Med Assoc J 2004; 6: 482-484
42
Koskela RM, Niemela SE, Karttunen TJ, Lehtola JK.
Clinical characteristics of collagenous and lymphocytic
colitis.
Scand J Gastroenterol
2004; 39: 837-845
43 Fine
KD, Krejs GJ, Fordtran JS. Diarrhea. In Sleisenger MH, Fordtran
JS (eds.): Gastrointestinal disease. 5th
ed.
WB
Saunders Co. Philadelphia 1993: 1043-1072
44
Eherer AJ, Fordtran JS. Fecal Osmotic gap and pH in
experimental diarrhea of various causes. Gastroenterology
1992; 103: 545-551
45
Menduina Guillen MJ, Alaminos Garcia P, Valenzuela
Barranco M. Microscopic colitis. A possible diagnosis in
secretory diarrhea. An Med
Intern 2004; 21: 387-390
Science
Editor Guo SY Language
Editor Elsevier HK
| |
PubMed
