Download MINISTRY OF HEALTH of REPUBLIC

Survey
yes no Was this document useful for you?
   Thank you for your participation!

* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project

Document related concepts

Mariko Aoki phenomenon wikipedia , lookup

Flatulence wikipedia , lookup

Colonoscopy wikipedia , lookup

Ulcerative colitis wikipedia , lookup

Schistosomiasis wikipedia , lookup

Bariatric surgery wikipedia , lookup

Surgical management of fecal incontinence wikipedia , lookup

Gastric bypass surgery wikipedia , lookup

Fecal incontinence wikipedia , lookup

Transcript
HEALTH CARE MINISTRY OF KAZAKHSTAN REPUBLIC
Karaganda State Medical University
R.D. Konakbaeva, Ye.M. Laryushina
CONSTIPATION
(Clinical aspects, diagnostics and treatment)
Karaganda 2011
1
УДК 616.34–008.15-07-08
ББК 54.133
К 64
REVIEWEPS:
Iskakov B.S. d.м.s., the professor,
Umbetalina N.S. d.м.s., the professor, the head of the transfusiology, pathological
anatomy, pharmacy with the course of increasing of pedagogic qualification DNIQ
of KSMU department.
Kosherova B.N. d.м.s., the professor, the head of the department of infectious
diseases
К 64 Konakbaeva R.D., Laryushina Ye.M. Constipation
(Clinical aspects, diagnostics and treatment).-Караганда.-2011.- 32p.
ББК 54.133
К 64
The presented educational-methodical manual is devoted to one of the most actual
sections of internal medicine - to diseases of intestines. The majority of diseases of
organs of the digestion is revealed by the general syndromes basis of which is in
the functional disturbances contributing to involving into the pathological process
motoric-evacuational function of organs of digestion, the significant place in its
clinical picture is paid to a syndrome of constipation. The educational-methodical
manual is for the students, interns and doctors.
It is confirmed and recommended to the edition by typographical way by МС of
KSMU
the protocol № 3 10.11.2010 y.
It is confirmed and recommended to the edition by typographical way by AC of
KSMU
the protocol № 4 25.11.2010 y.
© R.D.Konakbaeva, Ye.M.Larjushina 2011
2
CONTENTS
Introduction
4
1. Definition
5
2. Epidemiology
6
3. Etiology
6
4. Pathogenesis
9
5. Clinic and diagnostic
14
6. Treatment
18
Conclusion
25
Tests
26
Bibliography
31
3
INTRADUCTION
Despite of the significant achievements in the field of diagnostics and
treatment of constipation the effective solution of this problem is complicated, first
of all, because of bashfulness of patients to tell in details about the peculiarities of
their defecation, and also because of restraint of doctors which feel the certain
difficulties in making the solution of problems connected with constipattion. As a
result the patient often remains without the appropriate help that represents threat
not only to his health, but also disables the patient in social plan.
Simultaneously the problem becomes complicated with the increased
number of complaints with imaginary constipation. This condition is connected
with feeling of difficulty of the act of defecation and the disturbance of a regularity
of ejection, but not connected with constipation itself. By formalistic approach
such patients take in various medications for a long period of time, are followed-up
at specialists without the certain results. Therefore the purpose of this article is the
interpretation of basic questions connected with an origin, diagnostics and
treatment of constipation.
Constipation is a payment for a way of life. The constipation can be a
symptom of many diseases, including oncological ones. Therefore the chronic
constipation is a serious reason to get consultation of a gastroenterologist. It is with
a doctor that one should discuss the taking in of laxative drugs and the
administration of enema in constipation. Since uncontrolled taking in of laxative
drugs (about 200 preparations are registered in the Russian market) and
administration of enema can only aggravate chronic constipation, having formed a
syndrome of ’’lazy large intestine”.
4
1. DEFINITION
Constipation (from Latin: constipatio) is a syndrome characterising
disturbance of process of ejection (defecation): increase in intervals between acts
of defecation in comparison with individual physiological norm or regular
insufficient ejection. Normally, it is considered to be 3 times a day up to 3 times a
week. However the norm in every person is individual, and if stool begins to occur
in the patient 3 times a week and earlier it was a daily norm, only then it is
necessary to state the changing of function of intestines and development of
tendence to constipation.
To the constipation one may also refer daily, but a firm stool in a small
amount that can be accompanied with pains, additional expulsive efforts, finger
stimulation and as a result feeling of incomplete ejection.
It is necessary to consider constipation the difficulty of an act of defecation
(with the preservation of normal periodicity of stool). A clinical picture can be
complicated with difficult defecation, feeling of incomplete ejection and
discomfort in the abdomen. As concerning chronic constipation one may speak
about it in case if ejection of intestines occurs in 48 hours and more. The chronic
one is considered constipation at presence of two and more signs within 3 months.
Presence or absence of constipation is defined by the following characteristics:
frequency of stool, duration of expulsive efforts at an act of defecation, quality,
consistency and the form of stool, feeling of full or incomplete ejection of content
of intestines, presence or absence of anal or perianal pains (tenderness at an act of
defecation), abdominal pains, use of the finger help during an act of defecation.
The term "constipation" often used by patients and doctors, is interpreted by
them differently. In the majority of adults (70 %), following the European style of
diet, stool happens once a day. Frequency of acts of defecation is proved to be less
often in women. In men consistency of feces is softer, than in women.
For the description of the form and consistency of feces, it is purposefult to
use the Bristol’s scale. In healthy people the weight of feces a day on the average
makes 110 g, but fluctuations may be from 40 up to 260g. The consistency of feces
is determined by the quantity of water in it; in firm feces the quantity of it does not
exceed 40 %, in normal - 70 % and in liquid 95 %. Objective criterion of
constipation is considered the weight of feces less than 35g a day. In men and in
young people the weight of feces is more, than in women and in elderly people.
The quantity of feces is variable and depends on many reasons: peculiarities of
diet, social conditions, change of a usual daily regime, climate, volume of liquid
use, hormonal cycle (menses). All the specified characteristics of an act of
defecation depend on time of transit of intestinal content through the
gastrointestinal tract. Studying the time of transit with the use of contrast markers
or radioactive isotopes it was established, that in healthy people it takes about 60
hours: in women - 72 h, in men - 55 h.
5
2. EPIDEMIOLOGY
The wide spreadness of this disturbance has given the grounds to refer
constipation to illnesses of civilization. In different countries from 2 up to 27 % of
adult population and also 60-70-% of patients being for long time in a hospital on
a confinement to bed suffer from chronic constipation. In Great Britain up to 50 %
of adult population suffers from chronic constipation, that’s why this problem was
erected in a rank of the national one for this country; in Germany-30 %, in France
and the USA-20 %, in Russia - about 30-35 %. City dwellers suffer more often and
among them women (in 2 times) prevail. By available estimations, 10-25 % of
children suffer from chronic constipation, among of 60 years-old persons and older
the frequency of constipation increases up to 60 %. Unfortunately, women because
of biological features of an organism suffer from constipation in 3 times more
often than men.
In gastroenterological patients frequency of constipation comes nearer to
60-65 %, thus «the latent spreadness» is not taking into account because of false
bashfulness or underestimation of the importance of chronic constipation. In any
case it is not a harmless symptom, and it is the universal pathogenic factor
reducing quality of a life on 20 % and more.
3. ETIOLOGY
If not taken into account cases of development of constipation, connected
with peculiarities of way of life, then according to data by E.K.Hammad,
G.A.Grigorevoj (2000) among the reasons of chronic constipation in age group till
20 anatomic peculiarities of large intestine dominate; in age of 20-40 - a pathology
of anorectal zone dominate; after 40 - psychogenic, neurogenic and endocrine
reasons of constipation and the reasons connected with a pathology of anorectal
zone are often met equally.
Depending on the reasons constipations are divided into three big groups:
primary, secondary and idiopathic.
The reasons of primary constipation are anomalies, malformations of large
intestine development and its innervation.
The reasons of secondary constipation first of all are illnesses and injuries
of colon and rectum, also numerous illnesses of other organs and systems, and
metabolic disturbances developing along with them. Constipation may develop
due to unfavourable action of medicines (drugs).
Idiopathic constipation is caused by disturbances of motor function of
rectum and colon, the reason of the last is unknown (innert intestines, idiopathic
megacolon and etc.). But the most severe pathology contributing to the
constipation is cancerous and precancerous diseases of intestines. Indeed, the
cancer of intestines occurs rather seldom - in 3-5 % from all people (more often in
age of above 40, but there are also tragical exceptions). At early revealing the
cancer of intestines is quite curable, and it may be prevented!!! The truth is that if a
person reveals the malignant tumour of intestines, then, according to statistics it
may affect up to 10-15 % of his blood (genetically close) relatives.
6
Constipation may be situational, incidental and chronic. For example,
situational or incidental constipation occurs in various situations. For example, at
pregnancy, using some products or medicines, such constipations cannot be
reffered to the disease, this phenomenon is temporary and passing.
Constipation can be organic or functional by nature. According to the
Roman criteria II (1999), the diagnosis of functional constipation can be made only
in those cases when 2 or more of the following symptoms are present for the period
of 12 weeks, unessentially consecutive, during 12 months:
- frequency of an act of defecation less than 3 a week;
- expulsive efforts at an act of defecation, taking 25 % of its time;
- fragmented and (or) firm stool not less than at 1 from 4 of acts of
defecatoin;
- feeling of incomplete evacuation of intestinal content not less often than at
1 from 4 of acts of defecatoin;
- feeling of an obstacle at moovement of feces not less often than at 1 from
4 of acts of defecatoin;
- necessity of finger manipulations giving the relief to an act of defecation
more than at 1 from 4 of acts of defecatoin.
The reason of constipation is more often the way of life. It is as a person eats
how much active he is, etc. In particular, constipations are caused by the refined
high-calorific food. But it is quite possible that the reason of constipation may be
the tumour of colon. In any case each person has different reasons. One shouldn’t
say that this phenomenon occurs only because of one type of reasons. But all the
same, the main causes must be pointed out.
1. "floating" schedule of work (day time - night changes).
2. nervous overstrain.
3. long sleep and as a consequence lack of time for morning defecation.
4. decrease in vegetative fibres in food. (Vegetative fibres increase volume of stool
masses and stimulate peristalsis).
5. the use in a plenty of the refined (cleared) products (such food does not contain
slags).
6. the use of fatty and protein food of animal origin.
7. fast food.
8. insufficient volume of liquid in diet.
9. abusing strong tea and coffee.
10. "sedentary" work, inactive way of life.
11. various drugs.
These are only a part of the reasons of constipation. But these are the reasons
which a person is able to regulate (to eat correctly, to be physically active, etc.).
Tthe reason of development of temporary constipation is changing of
conditions of a life and character of food, presence of unusual and not comfortable
conditions for defecation (so-called «constipation of travellers»). The emotional
stress is alco capable to provoke temporary disturbance in an act of defecation.
Besides, temporary constipations are quite often observed in pregnant women in
connection with natural physiological changes. In conditions of a hospital the
7
reason of disturbance of an adequate ejection of the large intestine may be
confinement to bed for a long period, use of various medications, administration of
barium sulfate in radiological contrast examinations. In some situations, when
expulsive efforts are especially harmful for the patient (in acute period of
myocardial infarction, the early period after operative interventions on organs of
the abdominal cavity), the prevention and treatment of constipation becomes
especially important. The temporary stool retention not in all cases should be
considered as a sign of any pathological condition. But there are many other
reasons. Constipation, as a signal or consequence of some diseases needs serious
treatment. Occurrence of constipation in the patient of an average or advanced age
must be of oncological alarm.
Traditionally most frequent reason of disturbance of intestinal transit is
considered irrational food (irregular diet, intake of small amounts of liquid and
food fibers). However the comparative analysis of character of food of persons
with constipation and those with normal stool testify to the absence of differences
in the use of ballasting substances. At the same time patients with constipation
revealed the weight of feces less, and time of intestinal transit is much more, than
in people with normal stool irrespective of whether they used food with cellulose
or not [6]. Quite often constipation occurs due to habitual suppression of desire to
defecate, caused by way of a life (morning hurry, peculiarities of work regime,
absence of conditions in a toilet).
Food plays an important role in regulation of motor function of intestines.
The long use of mechanically plain food, high-caloric, little volume of food, lack
in a diet of the products containing rough cellulose, or food fibers contribute to the
occurrence of constipation. There are products which possess consolidation action,
for example: strong coffee and tea, cocoa, cottage cheese, rice, pomegranates,
pears, quince, astringents, chocolate, starchy foods.
Painfullness during defecation (in thrombosis of external hemorrhoidal
nodules, anal fissure) acts as the additional factor contributing to stool retention.
Overdosage of many drugs or their unfavorable effects may also cause
constipation. Narcotic anaelgetics, anticholinergic substances, some hypotensive
remedies inhibit peristaltic activity of intestines, influencing its nervous regulation.
Aluminium containing antacids, ferum remedies also cause constipation. The
diseases of systems, accompanied with injuries of vessels and nerves of intestines
(diabetes mellitus, sclerodermatitis, and myopathy) form a picture of chronic
intestinal obstruction - a syndrome of intestines pseudo-obstruction. Constipation
is a rather characteristic symptom of such endocrine diseases, as hypothyroidism,
hyperparathyroidism. Deficiency of thyroid hormones and hypercalcemia are
accompanied with hypotonia of intestines. Terms of constipation occurrence in
patients with diabetes depend on severity of course of the disease.
The special group consists of patients with constipation which persists
despite of following of all recommendations: increase of vegetative cellulose in
food content; increase of liquid, leading an active way of life. In such situation we
speak about presence of refracter (resistent) constipation that is the indication for
the administration of laxatives remedies.
8
Constipations connected with disturbance of the anorectal transit are caused
by either primary disturbance of motility of rectum and muscles of pelvic floor or
their structural changes.
Quite often the reason of constipation may be pathological and viscerovisceral reflexes, occuring in ulcer disease, gastroduodenitis, cholecystitis and also
adhesive processes, in diseases of organs of small pelvis, etc. Constipation is also
caused by organic diseases of spinal cord and brain, cranial and spinal nerves and
nodules, horse tail where there is an injury of nervous regulation of intestines.
Quite often constipations develop in neurosis and mental diseases, especially in
depressions, schizophrenia, and nervous anorexia. Constipation may be one of the
manifestations of myxedema and diabetes complicated with neuropathy. Stool
retentions are often observed in pregnancy in connection with increased production
of progesterone, and in late terms - in connection with pressure of sigmoid colon
and enlarged uterus.
Patients with cardiac insufficiency, lungs emphysema, portal hypertensia
with ascitis, and also obese ones may have constipation due to weakening of
muscular tone of diaphragm and frontal abdominal wall, providing increase of
intraabdominal pressure during an act of defecation. The atrophy of muscles of
rectum may develop in sclerodermatitis.
The reason of senile constipation also can be hypotonia of the muscles
participating in the act of defecation. It was revealed that people of elderly and
senile age with constipation have slower moovement of intestine content than
young people do.
The difficulty of promotion of intestinal content due to tumour, usually of
the large intestine, stenosis of intestines, formation of impacted feces, and
compression of intestinal loops by tumoural formations of other organs of the
abdominal cavity often causes chronic reccurent diarrhea or contributes to the
alteration of diarrhea and constipation. However in these diseases persistent
constipation can be observed sometimes before the other symptoms.
Not always it is possible to find out the reason of constipations and their
connection with changes of the large intestine. These cases are defined as
idiopathic ones. Studying the duration of transit of radiocontrast marker along the
large intestine of similar patients it was established that in some of them markers
are placed along the whole large intestine, in other ones they accumulate either in
sigmoid colon or in rectum.Thus, constipations are caused by the different reasons
both of functional and organic character.
4. PATHOGENESIS
Mechanisms and the reasons of development of constipation. There are two
basic mechanisms of development of chronic constipation - dyskinesia of the large
intestine and disturbance of an act of defecation (disshezia).
In the first case constipation develops because of disturbance of coordination
of intestinal contractions and/or disturbance of tone of an intestinal wall in
disturbances of nervous regulation of large intestine, dyshormonal disturbances.
9
The second mechanism – decrease in sensitivity of the nervous endings of
large intestine and muscles of the pelvic floor in frequent psychogenic suppression
of an act of defecation or hypertone (the increased tone) of anal sphincter, and in
this connection for the excitation of an act of defecation the greater accumulation
of fecal masses in rectum is needed. These two kinds of constipation differ by
clinical pictures and by the results of instrumental methods of examination
(measuring the time of moovement of content along the large intestine and
defectography etc.).
From the pathogenetic positions constipation can be divided into three main types:
alimentary, mechanical and dyskinetic (tab. 1).
Table 1. Pathogenesis of constipation (Parfenov A.I., 1997)
Type of constipation
Alimentary
(decrease of
excrements volume)
Pathognetic mechanisms
Increased extra-intestinal loss of water (polyuria etc.)
Decreased use of wate. Decreased use of fibers
Decreased use of food. Decrease of alimentary fibers in diet
Mechanical
(disturbane of
moovement in the
intestine)
Small intestinal obstruction:
At suppression of the intestine externally (adhesions, tumour of the other
organs);
Intraparietal (diverticulitis); Intralumenal (cancer, polyp, invagination
etc.)
Large intestinal obstruction:
At suppression of the intestine externally (adhesions, tumour of the other
organs); Intrawall (diverticulitis, hematoma etc.);
Intralumenal (cancer, other tumours)
Anal obstruction:
At suppression externally (fibrosis, paraprocitis etc.);
Intralumenal (tumour, impacted feces etc.)
At anorectal malformations (atresia, stenosis)
Anomalies of development (drolichocolon, megacolon)
Anomalies of development of intramural nervous system of the large
intestine – Girshprung’s disease)
Diseases of periferal nervous Pseudoobstruction of the intestine
Sclerodermatitis Hypothyroidism and other endocrinopathies
Diseases of inner organs
Mental diseases Metabolic disturbances
Drugs’ action (opiates etc.)
Syndrome of irritated intestine
Disturbance of defecative reflex. Dischezia
Mechanism is unknown
Hypo- and dyskinetic
(reduced speed of
transit along the
intestine)
Idiopathic
To alimentary ones we refer constipations that caused by dehydration, i.e.
decrease of water in an organism, caused either by decrease of its use or increased
in evacuation by kidneys or with sweat. Due to dehydration, content of water in
feces decreases, its volume decreases and constipation occurs. Decrease of feces
volume is contributed by the decrease of volume of used food and content of
alimentary fibers in it.
10
The reasons of mechanical constipation are stenosis, tumours and other
obstacles of the organic nature, and hypo-and dyskinetic functional disturbances of
a motility of intestines. Disturbance of ejection of the large intestine at functional
constipation is connected with the changing of peristaltic activity of a wall of
intestines. Constipations are characterized as spastic when the tone of any site of
intestine is increased and fecal masses cannot pass through this place. Feces get a
kind of "sheep’s one".
Hypotonic or atonic functional constipations are connected with loss of a
tone of a site of the large intestine. In this case the retention of stool can reach 5-7
days; feces can be of great volume, leaky by a consistency.
Pathogenesis of constipation is connected with disturbance of regulation of
motor function of intestines. At constipation these disturbances usually associate
with increase of unproductive motor activity of intestines, especially of sigmoid
colon. If it regularly inhibits moovement of fecal masses constipation occurs. If
inhibition influence of sigmoid colon stops, there is diarrhea. Occurrence of
constpation speaks about disturbance of regulation of motor function of intestines.
Normally, a person’s rectum is empty. Feces accumulate in sigmoid intestine and
only its moving to an ampula of the rectum causes reflexly a desire to defecate. In
healthy people the desire occurs regularly in the morning under orthostatic
influence, after getting up from bed or soon after a breakfast under influence of
gastrocecal reflex. An act of defecation is controlled by the central nervous system,
and the healthy person can suppress a desire. The habit to suppress a desire to
defecate can lead to chronic overdistention of the rectum, to suppression of efferent
signals and to the development of so-called habitual constipation. Disturbance of
an afferent phase of defecative reflex leads to the development of atony of the
rectum and to the increase of its volume. This condition has received the name
"megarectum", or "inert" rectum. In patients, suffering from constipation, not only
inert rectum is revealed, but also inert sigmoid intestine.
Thus, pathophysiology of constipation finally is connected with the decrease
of volume of the fecal masses reaching an ampula of the rectum, or with
disturbance of an act of defecation, complicating evacuation of feces. The volume
of the fecal masses reaching the ampula of the rectum decreases at mechanical
obstruction, disturbance of motility or decrease of volume of intestinal content in
starvation.
In the basis of constipation development 3 basic pathogenetic mechanisms
occuring separately or in combination may be pointed out:
1) increased absorbtion of water in the large intestine;
2) inhibited transit of fecal masses along the large intestine;
3) inability of a patient to defecate.
Comparison of pathogenetic mechanisms with "functional units" of the large
intestine in some cases allows localizing the affected area of the large intestine. So,
formation of dense fragmented feces is characteristic for disturbance of propulsive
peristalsis of colon where the most intensive absorbtion of water occurs. If a
patient has no desire to defecate it points to the disturbance in sensitivity of
receptor apparatus of anorectal area which performs the function of accumulation
11
and evacuation of fecal masses. The basic mechanism of chymus moovement is
highly amplitude contractions of smooth muscles of a wall of intestines. Decrease
in amplitude of these contractions leads to the increase of time of transit of content
along the intestines and causes development of functional constipation. At the
retention of content in the lumen of intestines absorbtion of liquid increases, that
contributes to condensation of fecal masses, that else in a greater degree prevents
intestinal content from moovement and leads to the development of coprostasis.
Regulation of peristaltic contractions in large intestine is performed by sympathetic
and parasympathetic components of vegetative nervous system that in turn depend
on the central sections of nervous system. The any component of an act of
defecation is carried out with the participation of the cortex of big cerebral
hemispheres. In patients with constipation average time of transit takes from 67h
up to 120h. Normally, consequent moovement of content alont the large intestine is
provided by various types of its contraction. According to research of
myoelectrical activity the motility of large intestine is presented to activity as by
segmentary contractions (single or organized group phase contractions), so by
propulsive ones - special propulsive contractions. [3,4]. For large intestine are
usual circadian and day time rhythms of motor function. During a sleep its motor
activity is inhibited [5]. Within day segmentary and propulsive activity of large
intestine considerably increases, especially at morning awakening and after taking
meals. Excitation of motor activity occurs during 1-3 minutes after taking meals
and lasts up to 3 h. [6]. The motility of large intestine depends on structure of the
eaten food. Fats and carbohydrates stimulate, and amino acids and fibers suppress
motor activity of large intestine. In proxymal departments alimentary chymus mixs
up, accumulates and closely contacts with intestinal bacteria. Lactose bacteria
(bifid - and lactobacteria, Enterococcus faecalis) ferment cellulose and
hemicellulose, containing in a peel of vegetables and fruit and coat of grain, up to
end-products of disintegration - shortchain fat acids (lactic, propione acid, etc.) and
gases (metane, hydrogen, carbon dyoxide) which stimulate peristalsis of intestines.
Besides, indigestible cellulose retains water in the lumen of intestine, increasing
volume of intestinal content. Laxative action of food fibers is complex and is
connected with increase in volume of intestinal content due to retention of
molecules of water, increase in bacterial weight and irritation of receptors of large
intestine.
Protheolitical bacteria, in particular, representatives of sorts of Bacteroides,
Proteus, Clostridium, and also Escherichia coll separate fibers up to ammonium,
phenols, mercaptopurines and purines. Normally, at microbiocenosis protheo- and
diabetic bacteria work together, separating fibers and carbohydrates up to endproducts of disintegration. Changes of structure of intestinal microflora can lead to
disturbance of a metabolism (disbalance of vitamins, electrolits) and transit along a
large intestine. Distal parts of a large intestine moove faecal masses to a rectum. In
these parts electrolits and water (about 2 l/d) are finally absorbed. The defecation
begins at sufficient filling of sigmoid colon. Results of 24-hour manometry of a
large intestine showed, that defecation is preceded by increase in frequency of
highky amplitude and peristaltic contractions.
12
The reflex of defecation occurs at acute distension of rectum. If supraspinal
the centers contribute to this process, then during contraction of sigmoid colon and
rectum pressure in the ampule of rectum increases, smooths out rectosigmoid
corner. As a result of relaxation of internal and external anal sphincters excrement
masses are evacuated. The nervous centers of lumbar and sacral parts of a spinal
column participate in regulation of this function. The desire to defecate can be
strengthened due to increase in intraabdominal pressure by means of Valsalva’s
method (expulsive l efforts) or to suppress it by contraction of pelvic muscles of
diaphragm and external anal sphincter. Frequent suppression of desires to defecate
can lead to a chronic distension of rectum, decrease in tone and chronic
constipation.
The important reason contributing to the loss of motor-evacuational features
of intestines is the disturbance of sensitivity of bioreceptors of an intestinal wall.
At constipation disturbance of transferment of a nervous signal can be caused be
neuropathy of sacral part of spinal column after injury of afferent and efferent
parasympathetic nervous fibers in the lower hypogastral plexus. At loss of afferent
phase of defecative reflex of various genesis rectum increases in volume and atony
of its walls develops. In consequence of it, the desire to defecate occurs only after
the big accumulation of excrements in it (megarectum, or inert rectum). In patients
with chronic constipation at manometry of large intestine amount and duration
higly amplitude peristaltic contractions are considerably reduced, and also
«gastrocolitic» reply to taken food is suppressed or is absent in all segments of
large intestine. Thus, at constipation transit chymus mainly along large intestine or
in anorectal zone can be disturbed or there is a combination of these disturbances.
It is supposed the role of disbalance in the system gastrointestinal hormones
stimulating (gastrin, cholecystolinin, substance Р, enkefalines, and motilin) or
inhibiting a motility of intestines, in particular, glucagone, vasoactive intestinal
polipeptide (VIP), glucagone, serotonine, changes of sensitivity of receptor
apparatus of large intestine to various stimul. Significant attention is paid to the
disturbance of function of neuro-receptor apparatus of an intestinal wall
responsible for its motor activity. In practice of a doctor there are more often
constipations caused by secondary motor disturbances of intestines.
Motility of intestines, in particular the tone, propulsive movements and their
coordination, can be injured in the most various combinations at diseases of
abdominal cavity diseases, brain and spinal cord, endocrine system. So-called
dyskinetic constipations are one of the most often meeting forms of this symptom.
The term «dyskinetic constipation» reflects a true condition of intestines more
precisely, than the terms accepted in the past "spastic" and «atonic» constipation.
As radiological researches show, rarely it is possible to observe total atony of
intestines or prevalence of spastic contractions of its parts. In the majority of
patients the combination of spastically reduced and relaxed sites of intestines was
revealed, as a result barium moves unequally.
Disturbance of motor activity in anorectal zone testifies to constipations with
incomplete ejection of rectum even after strong expulsive efforts, with pains in the
lower part of the abdomen, in anal and perianal areas and fecal incontinence. In
13
spite of the fact that constipation and fecal incontinence, apparently, exclude each
other, quite often mechanisms causing them appear identical. So, repeated and long
expulsive efforts at constipation injure mucous membrane of rectum, sacral nerves
and muscles of pelvic floor. Finally these circumstances cause disturbance of
function of anal sphincters and fecal incontinence. Besides, with the formation of
fecal plugs at constipation liquefaction of fecal masses take place in the upper parts
of intestines, which flow dense fecal masses round and abundantly evacuate from
the anus – so called paradoxical diarrhea.
Thus, pathophysiology of constipation finally connects with the decrease in
volume of fecal masses, reaching an ampule of rectum or with the disturbance of
defecation, complicating ejection of excrements. The volume of fecal masses
reaching an ampule of rectum can be reduced as a result of mechanical obstruction,
disturbance of a motility or the general decrease in volume of intestinal content
(for example, at starvation).
5. CLINIC AND DIAGNOSTIC
Clinical features of constipation substantially depend on their reason,
duration, severity and features of injury of intestines.
Not only intestines suffer from constipation, people do not die because of
it, but suffer much. Constipation interfere duly ejection of intestines, poison one of
the main charms of a life – to eat well and tasty.
If only in the abdomen was not the order, but constipation because of
accumulation of intestinal toxins affects the inner sanctum - the brain.
Here only some consequences of constipation: a fog in a head, impossibility
to concentrate, gloomy mood. At constipation suffers both brainwork and vital
optimism, and high spirituality. Therefore the banal constipation often poisons
quality of a life more, than diseases much more serious and dangerous to a life.
Clinically the course of constipation can be divided into 3 stages:
The compensated stage: frequency of stool occurs in 2-3 days, feeling of
incomplete ejection of intestines. In half of patients meteorism is revealed. Pains in
the abdomen are available in half of cases, which disappear or strengthen after
defecation.
The subcompensated stage: stool retention takes place from 3 till 5 days. There is
no stool of its own and it can be received only with the help of laxatives or with the
use of cleansing enema. Quite often there are pains in the abdomen, meteorism,
painful defecation, extraintestinal manifestations of constipation appear.
Decompensated stage: stool retention takes place till 10 days and more. There is no
stool of its own. Stool can be received only after use of hypertonic or siphon
enema. At palpation of the abdomen it is possible to find out fecal bolus.
Encopresis develops, marked signs of fecal intoxication are revealed.
Symptoms:
1. Ejection of intestines less often, than 3 times a week.
2. Small amount of feces.
3. Defecation needs expulsive efforts.
14
4. A dry and firm consistency of feces.
5. Feeling after ejection, that the intestine is evacuated not up to the end.
If one of these signs is observed we may say about chronic constipation.
There are still symptoms from the category "unessential", i.e. these symptoms do
not occur in everybody, suffering from chronic constipation. One of such
symptoms – bloating of abdomen or meteorism, it occurs when fecal masses move
slowly along large intestine and increases gas formation (because of bacteria
activity in intestines). This symptom passes after defecation.
Symptoms which need the immediate manipulation of the doctor:
1. Cramp-like pains in an abdomen.
2. Body temperature elevation.
3. Blood from rectum during defecation or change of fecal color (black, tar-like).
4. Nausea, vomiting.
5. A pain in the field of anal orifice during defecation.
6. Change of fecal structure (ribbon stool).
For the establishment of diagnosis it is enough to register not less than 2 named
signs within last 3 months. The stool retention is quite often accompanied by
unpleasant subjective sensations, such as slackness, headache, insomnia
(sleeplessness), bad mood, reduction of appetite, nausea, unpleasant taste in a
mouth; discomfort, feeling of weight or overflow in abdominal cavity, bloating,
pains in abdomen of spastic character. For a significant part of the patients,
suffering from chronic constipation, characteristic features of psychological shape
are «leaving into illness», suspiciousness.
Examination of the patient with a syndrome of disturbance of ejection of
intestines must include thorough asking and examination of the patient, estimation
of a way of life, getting «drugs" anamnesis, digital examination «per rectum»,
examination of general and biochemical analysis of blood, coprogram. Obtained
data determine algorithm of the further examination.
Severe forms of constipation and coprostasis may cause the following
complications:
- loss of appetite, nausea, vomiting
- abdominal pains
- fecal incontinence, "paradoxical" diarrhea
- retention of urine (ischuria) and enuresis
- rectal bleeding
- mechanical intestinal obstruction
- peritonitis
In the majority of patients constipation develops gradually. The most
important anamnesis data are duration of constipation, presence or absence of a
painful syndrome and loss of weight. In process of deterioration of a motility
ejection of intestines of its own occurs less often and is carried out mainly after
taking of laxatives or enema. The patient may connect irregular ejection of
intestines with absence of desire to дефекации or with difficulty of excrements
evacuation. Absence of desires or their rare occurrence is the consequence of their
regular suppression. Some patients do not feel full ejection of intestines after stool.
15
It is caused either by retention of a part of fecal masses in the rectum that reveals
by digital examination, or by rectoscopy after defecation. More often the feeling of
incomplete ejection is caused by an insufficient relaxation of muscles of the rectum
and pelvis after finishing the defecation.
Intensive, spasmodic pains before defecation and during it especially in
patients with recently appeared constipation are characteristic for stenosis
processes in intestines. However they can be observed in patients with spastic large
intestine at a syndrome of irritating intestines. Pains in the rectum and anal orifice
during defecation testify to injury of distal parts of large intestine. Thus filling of
the rectum with fecal masses can be accompanied by pain. Often patients, suffering
from constipation, complain of bleeding from the rectum at defecation. Thus the
most frequent reasons of rectal bleedings are a hemorrhoids, sphincterites or anal
fissure. However even in case of revealing of these diseases it is necessary to
exclude other sources of bleeding by carrying out colonoscopy or irrigoscopy.
The long anamnesis of an obstructive syndrome, especially with diagnostic
laparatomy or laparoscopy in the past, should force the doctor to suspect intestinal
pseudo-obstruction. Anamnesis data about diseases of anal canal, such as chronic
anal fissures, long using of enemas at constipation and abdominal pains allow
assuming an opportunity of a syndrome of the irritating intestines. The sudden
beginning of constipation in more advanced age group always should suspect at the
doctor an idea of cancer of large intestine. During abdominal examination it is
possible to palpate a tumour of large intestine. Examination of rectum allows
revealing injuries of perianal and anal zones. The empty ampule of rectum may
serve as a symptom of Girshprung’s disease with injury of a short segment.
Presence of blood in excrements or at examination of rectum points to the injury of
mucous membrane of intestines, character of which should be found out during the
further examination.
The closest and authentic connection is traced between the development of
clinical manifestations and complications of diverticular disease and chronic
constipation which serve as one of the factors of pathogenesis of diverticulitis
development. In patients, suffering from long constipation, diverticular disease acts
as combined disease which frequency after 60 years reaches 50-70%, therefore
knowledge of features of clinics, course, and diagnostics of this disease is
extremely important from the practical point of view.
The following clinical forms of diverticular disease are distinguished:
asymptomatic diverticulosis, not complicated diverticulitis, complicated
diverticulitis and it is frequently recurrent diverticulitis of large intestine.
To the complications of diverticulitis one may refer such severe conditions,
as an abscess, perforation of a wall of intestine, formation of fistulas, fecal
peritonitis, bleeding and intestinal obstruction.
Diverticulosis of large intestine in 75 % of cases has asymptomatic course,
only 15 % of patients mark pains in the lower part of abdomen, meteorism,
diarrheas, constipations, blood admixture and mucus in stool.
In diverticulitis 95 % of patients have pains alonh the large intestine, in 50
% of patients may be the elevation of body temperature; 30 % of patients have
16
disturbance of stool (constipations or diarrheas), about 20 % of patients complain
of nausea and vomiting.
Methods of choice of diagnostics of diverticular disease are irrigoscopy and
computer tomography of large intestine. If the patient has clinical signs of
diverticulitis it is possible to carry out irrigoscopy only after relieving of symptoms
of an inflammation while the computer tomography has no contraindications to be
carried out. Colonoscopy serves as less sensitive method of diagnostics of
diverticular disease. Diverticulitis serves as contraindication for carrying out
colonoscopy because during examination the risk of perforation of the inflamed
wall of diverticula of large intestine increases.
The basic measure of prophylaxis of diverticulitis development and its
complications is the treatment of accompanying constipation.
Examination of patients with constipation includes two stages. At the first
stage diagnostic search is aimed to exclude organic pathology. The patients are
carried out with: general clinical examinations; digital examination of rectum;
rectoromanoscopy; irrigoscopy, if necessary - colonoscopy; examination by the
gynecologist (for women) the urologist (for men).
Especially thorough examination is needed by patients with constipation and
symptoms of "anxiety": unmotivated loss of body weight, night semiology (pains),
constant and intensive pains in the abdomen, the beginning of the "disease" in
advanced age, cancer of large intestines in relatives, fever, blood in stool,
leucocytosis, anemia, increased ESR (erythrocytes sedimentation rate), change of
the biochemical status, hepato-hypersplenism.
After organic pathology has been excluded, at the second stage of
examination the level of stasis of intestinal content is defined exactly, the type of
motor disturbances is determined ( hyper- or hypokinetic), the accompanying
pathology of gastrointestinal tract, endocrine and nervous systems are revealed.
Measurement of time of transit can be carried out by a radiological method with
barium passage or radioisotope markers along the large intestine. Thus not only a
level of stasis in intestines can be revealed, but also the type of motor disturbances
in this or that segment of intestines.
It is necessary to include into the protocol of research: ultrasound
examination of organs of abdominal cavity, laboratory tests for exclusion of
hypothyroidism, diabetes, dehydration, hypokaliemia and hypercalcemia;
examination of stool microflora; psychoneurological examination. At stasis of
content in the rectum the special examinations may be carried out in the
specialized medical centers (anometry defecography, electromyography of muscles
of pelvic floor, etc.).
In the basis of diagnostic concept must be said that constipation is not an
illness, but a symptom. The sequence of diagnostic process at constipation is
shown on the scheme 3 in the form of algorithm.
At absence of data for organic diseases of intestines and exclusion of other
reasons constipation is more often connected with a syndrome of irritating
intestines. The diagnosis is based on the objective anamnesis and laboratory
examinations. For more detailed definition of a degree of disturbance of motor
17
function time of large intestine transit is examinated, and if it is possible
physiological examination of anorectal area is carried out: sphincteromanometry is
appleid and biopsy of a wall of rectum by Svenson in order to exclude
aganglionosis.
To determine the time of transit along intestines various markers are used.
Tests for determining time of transit are of diagnostical value not only for
objectivisation of constipation, but also for strict selection of patients for surgical
treatment of constipation.
Disturbances of nervous-muscular coordination of an act of defecation,
occuring as a result of disturbance of fecal evacuation, are revealed with the help
of anal manometry. In normal people rectum filled with excrements or with air
stimulates relaxation of internal sphincter and contraction of external sphincter. At
Girshprung’s does not relax disease or at aganglionosis of segments of large
intestine internal sphincter at filling rectum with excrements. Therefore the use of
manometry allows establishing the diagnosis of this disease both in children and in
adults.
6. TREATMENT
If constipations have occured recently- it is not necessary to worry. This
phenomenon is probably episodic. In urgent case it is useful to take in laxatives
and then to overview the way of life. It is necessary to increase use of food fibers bran, vegetables, and fruit. Each person should accustom himself to certain time of
defecation (it is better in the morning, after sleep). Do any kind of gymnastics.
Better the special exercises, improving peristalsis. Do not get used to laxative
preparations. The case may be once, twice, but if more it is out of norm. Constant
use of laxative preparations may cause injury of mucous membrane of large
intestine. Drink more liquid - not less than 2 litres a day.
Main principle of treatment of constipation should be carrying out etiotropic
therapy, elimination of the reason contributing to the disturbance of ejection of
intestines. As it has been told above, it is rather frequent the only reason of
disturbance of normal peristaltic activity of intestines in inhabitants of the
developed countries is the lack of food fibers in food, and also decrease of motor
activity. In this connection a first step in treatment of constipation should be the
actions directed on following of a healthy way of life. Main principles of not
medicamentous correction of function of intestines include:
1) the use of food with the high content of food fibers. Indigestible food
fibers contribute to water retention, increase fecal volume and make its consistency
soft, that contributes to the restoration of peristalsis.
The use of crude vegetables, fruit, melon-growing cultures, sea kale, stoneberries, bananas, sour-milk products, friable porridges, bread from a flour of a
rough grinding, vegetable oil is recommended. It is expedient to reduce the use of
the products possessing action (cottage cheese, tea, coffee, cocoa, rice, chocolate,
farinaceous foods).
2) regular meals (to eat breakfast is especially important);
3) the sufficient use of liquid (it is desirable - up to 2 l a day);
18
4) to follow the rule of regular ejection of intestines. Activity of large intestine
increases after awakening and after meals so desires are observed mainly after
breakfast. Do not ignore desires to defecate as decrease in threshold of excitability
of receptors of rectum can be observed;
5) daily physical activity. It contributes to the increase of peristaltic activity of
intestines. At absence or insufficient efficiency of etiotropic therapy and not
medicamentous ways of stool restoration symptomatic therapy may be used. With
this purpose the preparations artificially increasing peristaltic activity of intestines
– laxatives are used.
The first stage of treatment includes the most important actions on training
the patient with constipation. Conversation with the patient concerning what is a
normal stool and the physiologic act of defecation, an explanation of connection of
function of intestines with character of food, a way of life. It is necessary to
explain, that the an act of defecation occures, as a rule, at one and the same time,
and training of "a gastroenteric reflex" is possible. For this purpose it is necessary
to recommend the patient visiting the toilet at one and the same time, it is better in
the morning as " the gastroenteric reflex " occures in 15-30 minutes after breakfast
more often. A glass of cold juice or water taking into an empty stomach before
breakfast may contribute to the defecation. It is necessary the use in food the
products rich in food fibers. Food fibers increase volume, weight and speed of
fecal transit, thus pressure in the lumen of intestines and contact of intestinal
content with mucous membrane decreases. To the products rich in food fibers
refer: bran, a seed of flax, beans, peas, a flour of rough grinding, soya, corn flakes,
dogrose, wood nuts, and raspberry. On the contrary, the products making the is of
diet of a odern person, such as butter, meat, fish, eggs, milk, tea, coffee, do not
contain at all food fibers. It is necessary to remind the importance of taking enough
liquid - not less than 1-1,5 l a day.
Treatment of constipation represents a difficult problem. It is complicated
with accustoming to the regular use of laxatives, often observed in these patients.
Especially often the doctors meet with this problem in patients of senile age. It is
necessary to convince the patient to refuse of bad habit to do regularly enemas and
to learn to regulate stool by means of food, correct chewing, and also to
recommend more mobile way of life. It is necessary to remember also, that the
uncontrolled regular use of laxatives can break absorbtion of various medicines, as
a result of fast transit and chemical linkage of some of them (for example,
tetracycline or digoxin packed into a cellulose matrix, etc.). At last, use of laxatives
is contraindicated because of abdomen, inflammatory diseases of intestines.
Diet. For improvement of intestinal transit and reduction of intraintestinal
pressure bran is used. Food fibers containing in bran absorb water and as they do
not undergo digestion increase fecal volume stool and make by it less firm.
At present, along with bran pleasant mixes containing food fibers of grain
cereals are used. They are for example, divizit and mukofalk.
Divizit is prepared of grains of oats, wheat and soya. In 100 g of the
preparation 25 g of food fibers are contained. The preparation is administrated for
50 g/a day. It is established that in patients with constipation divizit stimulates
19
motility of intestines, stool becomes softer and necessity for use of laxatives either
disappears, or decreases. Divizit reduces also the content of cholesterol in blood
serum in patients with hypercholesteronemia.
Mukofalk - a preparation containing seeds of plantain. Due to high
hydrofilling mukofalk eliminates constipation, bloating of abdomen and pain. It
stimulates motility of the left parts of colon and is administrated at chronic
constipation of functional origin. (Mihajlova T.L., 1997).
Medicamentous treatment. It is known, that the main regulator of intestinal
functions at action of various neuromediators is intestinal nervous system.
Enkephalines are produced by intestinal system and influence the specific
receptors of enkephalinergic type. The new direction of searching for the
preparations regulating motility of gastro-intestinal tract is in the field of
investigation of neuropeptides – endorphins and enkefalines. These substances
carry out a role of intercellular neuroregulators in an organism. Enkephalines are of
natural origin - opiate substances - play the important role in regulation of motor
function of stomach and intestines. The modulating effect on motility of intestines
makes synthetic enkephalinergic agonist (trimebutin). Debridat interacts with each
of three receptors of enkephalines: possess sttimulating and inhibiting effects on
motility of intestines. As well as natural enkephalines, trimebutin is capable to
stimulate or suppress peristaltic activity of intestines.
Debridat (trimebutin) is administered 0,1-0,2 g 3 times a day, before meals,
duration of treatment 2-4 weeks.
Medicamentous therapy is administered taking into account peculiarities of
disturbance of motility. At hypomotoric function prokinetics (mozaks) are
administered.
At markable dyskinesia of spastic type the certain effect can act as blocators
of m-cholinorecptors (atropine, aprophen, levzin, buskopane, metacine,
gastrocepine, pirencepine) and myotropic spasmolitic preparations (nospa,
papaverin, gnalidor). These preparations reduce spastic contractions of large
intestine and pain, but do not influence propulsive function, moreover, even reduce
it and, hence, do not influence constipation. Therefore at markable hypokinetic
constipation (inert large intestine, idiopatic constipation) it is purposeful to
administer prokinetics – preparations increasing tone and motility of
gastrointestinal tract. They are, besides listed above, inhibitors cholinesterase
ubretid, prozerin and kalymin.
Ubretid (distigimin bromide) is administered - 0,5 mg a day, in the morning.
Then if necessary and at good tolerance a doze is increased in 2 times.
Proserin is administered 10-15 mg 2-3 times a day.
Kalymin (pyridostigmini bromidum) - 0,06 g (1 dragee) from 1 up to 3 times
a day.
In complex therapy of constipation an important role have the preparations
possessing choleretic effect, especially containing bilious acids (allocholum,
liobilum), also including preparations containing chenodeoxycholic and
ursodeoxycholic acids (chenochol, chenofalk, ursofalk). The last, as is known,
have the expressed stimulating effect on motility of large intestine due to irritation
20
of its mucous membrane. This circumstance is one of the unfavourable effects
observed in patients who are administered with cheno -and ursofalk with the
purpose of dissolution of gallstones in bile duct.
Laxative medical preparations need to be administered as a rule, only at the
first stage of treatment of constipation with the purpose of more effective
restoration of lost defecative reflex.
By the mechanism of action laxatives are divided into four groups.
1. Osmotic or salt laxatives. They contain badly absorbed carbohydrates
(normaze) or the high-molecular polymers, capable to retain molecules of water
(forlax). Remaining in small intestine, they increase osmotic pressure of chymus
and contribute to secretion of water into the lumen of intestines. As a result the
large intestine is filled with a great amount of liquid fecal masses which stimulate
peristalsis and easily move along intestines. Purgating effect usually occurs in 6-8
h. Unlike the majority of laxatives these preparations do not influence irritatingly
the mucous membrane of large intestine and do not cause accustoming. Therefore
they may be administered for a long time. Normaze is administered - 1 dessert
spoon at night. Forlax is administered at night till 10-20 g (1-2 bags), preliminary
having dissolved in water.
2. Preparations inhibiting water absorption from intestines and stimulating
secretion. This effect is reached by irritation of chemoreceptors of mucous
membrane mainly of large intestine. They arev the preparations of a phytogenesis
containing antraglycosides (preparations of Folium Sennae, Radix Rhei, Fructus
Rhamni catharticae and Cortex Frangulae, Oleum Ricini), synthetic compounds
(bisakodil, dulkolaks, guttalaks, laxigal etc.) and salt laxatives (sodium sulfate,
magnesium sulfate, Sal carolinum factitium, etc.). Some of them are absorbed,
metabolized by liver and return to intestines with bile. The increase of peristalsis
and liquids in lumen of intestines reduces fecal moovement along the large
intestine up to 6-8 h. At continuous use of laxatives containing Sennae extract, in
mucous membrane of large intestine accumulates the pigment staining it in black
color, the degeneration of the nervous endings in large intestine develops. As a
result develops inert large intestine. Also can develop watery-electrolytes
disturbances connected with disturbance of sodium and water absorbtion in large
intestine.
3. Preparations causing increase of volume fecal masses. They are
methylcellulose, psillium (fiberlak), calcium polycarbofil, bran, the linen seed, not
absorbed diglucosides (lactulose, sorbitol) Laminaria saccharina, methylcellulose,
psillium (fiberlak). Volumetric agents are the unique laxatives of long-term use.
They work slow, soft and safe for a regular support of normal stool. Causing
irritation of mechanic receptors due to increase in volume of fecal masses, they
stimulate motor-evacuative function of large intestine. To take these food additives
is better in the morning and at night with enough amount of liquid, adding 2-3
glasses a day of a liquid in addition.
Preparations softening stool and facilitating its moving along intestines by
greasing effect. They are Oleum vaselini, Oleum Amygdalarum and Oleum Olive,
norgalax, enimax. The majority of them possess as waterproof so hydrofilling
21
properties so that they increase the ability of small intestine to retain water, and
keep it in fecal masses increasing their volume. The increase of fecal volume
stimulates peristalsis, and softer consistency facilitates itsmoovement along
intestines. Mineral oils and other preparations of this group are purposeful to
administer to those patients being on a long confinement to bed, and those who
underwent surgical interventions on anorectal area. Norgalaks is produced in the
form of gel on 10 g in a tube with a tip, contains sodium dokusate,
carboximethylcellulose and glycerin, is administered in the form of microenema in
case of incidental constipation or for prepareness of patients to endoscopic
investigations of large intestine. Purgative action occurs in 5-20 minutes after
introduction of the preparation into rectum. Enimaks represents a hypertonic
solution of sodium phosphate, is issued on 120 ml in disposable plastic enema. It is
administered mainly to prepareness of patients for surgical operations, endoscopic
and to radiological investigations of large intestine.
The majority of preparations used nowadays act a level of large intestine
(the plants containing antraglycozides, bisakodil, dulkolax, guttalax, laxigal and
other synthetic preparations). Their action occurs in 5-12 h after taking. Stool is
more often porridge-like or liquid. At a level of small intestine вазелиновое and
vegetable oils act. Their effect occurs in 4-5 h after taking. Stool is often close to
normal. At introduction of laxative preparations directly into rectum in the form of
suppositories the purgative effect occurs in 10-20 minutes (suppositories
dulkolaks, etc.).
All the parts of intestines are influenced by all salt laxatives possessing, as is
known, most rough (drastic) effect in the form of abundant liquid stool, occuring in
4-6 h after taking in of the preparation. They are usually administered at acute
constipations and at food intoxications when it is necessary to empty intestines
quickly from toxic substances.
If laxatives are used incidentally at absence of contraindications their
administration is safe. Volumetric agents can reduce absorbtion of some substances
and medicines, but it usually has no clinical value.
The general contraindications for administration of laxatives are
inflammatory processes in abdominal cavity, intestinal obstruction and acute
feverish diseases, and also pregnancy in avoidance of complications. During the
period of lactation it is impossible to administer antraglykozides and synthetic
laxatives (dulkolaks, bisakodil) as they are absorbed and enter the milk.
The chronic use of stimulating laxatives causes irritation of intestines.
Besides, long uncontrolled taking of laxative preparations leads to fast enough
accustoming. Therefore patients have to to increase gradually a doze; leading up it
is frequently up to ultrahigh. Meanwhile at the long use of synthetic preparations
and preparations of antraglykozides greater dozes are capable to affect liver and
kidneys, nervous plexus in a wall of large intestine. As a result its motility is even
more injured. The inert large intestine develops. At the long use of сены melanois
of large intestine develops: its mucous membrane gets dark color due to deposit of
a pigment on the wall.
22
The least unfvourable effects at the long use cause modern osmotic laxative
preparations as forlax and normaze. Forlax and normaze. These laxatives are not
split, absorbed in the gastrointestinal tract and do not undergo metabolism.
Regular long use of laxative preparations is inadmissible. Therefore for
successful treatment of constipation it is necessary to establish first the reason of
their occurrence, i.e. the exact diagnosis, and only after that to develop a technique
of treatment.
At constipation with a spastic dyskinesia for prevention of strengthening of
spasms under the influence of food fibers the treatment begins with slagless diet
with an fat admixture, gradually adding to it boiled vegetables, and then crude
ones. As stimulators of an intestinal motility it is possible to use wheaten bran:
begin with 3 tea spoons a day and gradually increase a doze up to 3~6 table
spoons. Patients with constipation are administered mineral waters «Esentucki »,
«Batalinscaya », «Slovenic», «Djemruc ». More mineralized water, in particular, «
Esentucki №17 », is administered at constipation with hypomotor dyskinesia on
150-200 ml in a cold kind 2-3 times a day; less mineralized - in the same dozes in a
warm kind, for example, « Esentuki №4 » - at hypermotor dyskinesia. Patients
with constipation are recommended to increase physical activity (walking,
swimming, physical exercises, including ones for strengthening muscles of pelvic
floor and abdominal tension). In the morning the patient should provide time (1530 mines) for defecation after plentiful breakfast. The glass of water of a room
temperature or juice also can be sufficient for excitation gastrointestinal reflex. At
absence of defecation the first days laxative suppositories may be used. The diet
and physical exercises can be strengthened by physiotherapeutic procedures. For
electrostimulating therapy threshold and exponencial electroimpulses are used.
This method in a combination with a diet gives a positive effect on many patients
with hypokinetic constipation. Medicamentous therapy is administered taking into
account character of motor disturbances of large intestine. At hypomotor
dyskinesia of large intestine prokinetics are used, at spastic dyskinesia –
spasmolitics of myotrope action. For the last years significant progress has been
reached in specification of the mechanisms cntrolling motor function of digestive
tract, and creation of new medical preparations for correction of motor disturbance.
The motility of gastrointestinal tract is regulated by activity of the central and
vegetative nervous systems. In intestines the leading part belongs to the vegetative
innervation, presented by intramural (autonomous) and inserted neurons, united
into submucosal and muscular plexus. To intramural mediators refer: acetylcholin for cholinergic neurons; serotonin - for serotonine neurons; ATP - for purinergic
neurons (purinergic system inhibits the tone of smooth muscular fibers). To
intramural mediators refer also neuropeptides: VIP which can activate and inhibit
function of neurons muscles; somatostatin, inhibiting and stimulating intramural
neurons; the substance Р exciting intramural neurons; enkephalines, modulating
activity of intramural neurons. Strengthening of motility is observed at stimulation
of cholinoreceptors (through acetylcholine), of some opiate (ОР 1 and ОР 3) and
serotonin receptors, weakening at stimulation of adrenoreceptors, dophamine,
purine and other opiate (ОР 2) receptors. To prokinetics refer the following groups
23
of preparations: agonists 5-hydroxytriptamin (5НТ 4)-receptors (cysapride,
tegaserode, prukalopride, mossapride); agonists 5НТ-receptors (sumatriptane);
antagonists of dophamine D 2-receptors (methochlopromide, domperidone). From
the listed groups only agonists of 5НТ 4-receptors cause effective propulsive
action on large intestine.
If regularly following of all listed measures does not help to reach
occurrence of a regular stool then we speak of refracter constipation, and in such
situation the patient accepts long course of treatment by laxative medical products,
i.e. transition to the second stage of treatment.
Laxatives are the medicines accelerating evacuation of fecal masses from
intestines. "Ideal" laxative should promote occurrence of the shaped stool, should
not cause unfavourable effects, a diarrhea, to be well toleranted, to not possess
doze depending action and to have predicted time of effect after taking of a
standard doze.
Often patients select for themselves a laxative preparation by methods of
tests or according to friends or acquitances. There is a plenty of laxative medicines
and their various division into groups by the mechanism of action laxative
preparations are conditionally divided into four groups:
1) causing chemical irritation of receptors of mucous membrane of
intestines: антрахиноны (derivatives Sennae, Frangulae, rhubard, aloe), diphenolls
(bisacodil, sodium picosulfate), castor oil;
2) possessing osmotic properties: salt (sodium or magnesium sulfate,
Carlsbad’s saltsalt), DISAGHARAIDES (lactulose), multinuclear spirits (mannitol,
sorbitol), macrogol;
3) increasing volume of content of intestines - ballast substances (an agaragar, methylcellulose, bran, seed of flax);
4) promoting softening of stool (liquid paraffin, Oleum vaselini, macrogol).
The
acting
substance
of
vegetative
extracts
are
di-or
trihydroxilantrachinones in the form of antrachinone glicozides. From the extracts
of aloe, Sennae, Frangulae and rhubard in the large intestine active derivatives of
antrachinones which stimulate peristalsis of large intestine, inhibit the absorbtion
of water and electrolits. Action of preparations of this group depends on time of
evacuation of stomach, passage along large intestine and occures later in 6 hours
after taking them before meals. By the laxative effect the preparations are settled
down in following sequence: leaves of Sennae fruits > Cortex Frangulae> Radix
Rhei. Usage for a long period of time may cause melanosis of mucous membrane
of intestines. Often there is an accustoming to the given preparations, therefore at
the long use the increase in their doze is required. So, in 5 years of acception of the
same laxative medicine each 2-nd patient replies, and in 10 years - every 10-th.
Derivative of diphenylmethane - bisakodil - by frequency of administration takes
the 1st place among preparations of this group. It is issued in two medical forms: in
a form of a dragee and supposititory. Unlike the preparations
containingantrachynions, bisakodil is active at intake already in the stomach.
Therefore its taking, especially at increase in a doze, is often accompanied by
spastic pains in the upper part of the abdomen.
24
CONCLUSION
Syndrome of chronic constipation is an actual problem of gastroenterology
in connection with negative influence on quality of a life of patients. At the same
time, in daily clinical practice the constipation remains to one of least effectively
diagnosed and corrigated syndromes. Wide diapason of reasons causing a
constipation, later the reference of patients behind medical aid, because of
bashfulness in details to tell about features defecation increases probability of
occurrence of the patient with constipation in practice of doctors - therapists,
doctors general practice and other specialities.
In the educational-methodical grant questions etiology, epidemiology,
pathogenesis are submitted, clinics, diagnostics and treatment of a constipation,
and also are analyzed results of numerous researches. The wide circulation of a
syndrome of a chronic constipation and influence on quality of a life of patients
dictates necessity of early diagnostics and therapy.
25
TESTS
1. In pathophisiology of asyndrome maldigesty and malabsorbtion everything
matters, except for:
A) Reduction in production of pancreatic enzymes
B) Fast transit of intestinal contents
C) Reduction in concentration of enzymes as a result of cultivation
D) Deficiency of bilious acids in thin intestines
E) Infringement absorbtion products of hydrolysis of carbohydrates, fats, proteins
2. At the woman of 45 years alternation of constipations and diarrheas, a swelling
of a stomach, sensation of inflow, pains in a stomach at the certificate defication,
absence menstruation. Stool with an impurity of slime. It is closed, depressive. A
stomach soft, sensitive on a course of thick intestines. Full clinico-laboratory
research has not revealed pathological changes. The presumable diagnosis:
A) A chronic pancreatitis
B) Nonspecific ulcer colitis
C) Crone 's disease the
D) amebiasis
E) A syndrome of the irritated intestines
3. The syndrome of the irritated intestines is characterized by frustration motor and
secretion functions of intestines at absence of an organic pathology. The given
definition:
A) True
B) Not true
C) True, only frustration of motor function
D) True, only frustration secretion functions
E) Not true, the organic pathology should be
4. That is incorrect concerning a syndrome of the irritated intestines:
A) Disease is known as well as spastic colitis, membranous colitis
B) Propensity to constipations or diarrheas or their alternation
C) Frequently there is a feeling of alarm, excitation
D) More often at women than 40 years are more senior
E) There can be an allocation of slime with stool
5. What from statements concerning a syndrome of the irritated intestines
incorrectly:
A) The direct gut is usually filled feaces with weights
B) rectoromanoscopy it is necessary for exception of organic disease distal a
department of a small gut
C) Characteristic radiological attributes are not present
D) constipations with allocation of slime
E) constipations with allocation of blood
6. What from the subsequent positions truly for a syndrome of the irritated thick
gut:
A) The most preferable definition - deficiency of lactose
B) Presence of nervous - muscular or hormonal defect is probable
C) Presence of the defect developed on the immune mechanism is probable
D) The syndrome can be a precancer condition
E) A usual clinical attribute - non holding of stool
7. The young woman has acted with complaints to a swelling of a stomach, his
feeling , pains in a stomach, an often liquid aqueous chair. rectoromanoscopy a
mucous membrane of a gut without features. The prospective diagnosis:
A) Nonspecific ulcer colitis
B) A syndrome of the irritated gut
C) lambliosis
D) A chronic pancreatitis
E) disease the Crone
26
8. For a hypermotor dyskinesia of a thick gut are characteristic:
A) The diarrheas, varying constipations (a unstable chair, "sheep" Stool)
B) Blood and slime in stool
C) Phobias, depressions
D) sphyncteritis
E) Persistent headaches
9. Everything concern to symptoms excluding a syndrome of the irritated gut,
except for:
A) Loss of weight of a body
B) The beginning of disease in advanced age
C) Imperative desires on the certificate defication
D) Constant intensive pains in a stomach, as a unique and conducting symptom
E) A fever
10. Contra-indication for assignment mesalasine at patients with a syndrome of the
irritated gut is his ability to cause:
A) diarrhea
B) A constipation
C) meteorism
D) maldigestion
E) malabsorbtion
11. On the mechanism of action laxative share on all listed, except for:
A) Causing chemical irritation receptor's the device of a thick gut
B) Possessing osmotic properties
C) Increasing volume of contents of intestines
D) Promoting a softening feaces weights
E) Walls of intestines causing mechanical irritation
12. At the patient 21 years, disturb constipations, a swelling of a stomach,
periodically changed diarrheas. Persistent constipations marks since the childhood.
Periodically comes to light Stool as "fuse". At radiological research narrowing in
rectosigmoid a department of a thick gut sharply contrasting with suprastenotic
expansion of colon guts is revealed. The most probable preliminary diagnosis is:
A) Nonspecific ulcer colitis
B) A syndrome of the irritated gut
C) Yersiniose enteritis
D) Girshprung'sdisease
E) дисахаридазная insufficiency
13. The difficulty of the certificate defication refers to:
A) meteorism
B) A constipation
C) disshezia
D) flatulention
E) apstipation
14. What statement concerning a syndrome of the irritated intestines incorrectly:
A) The basic symptom - alternation of diarrheas and constipations
B) The diagnosis proves to be true characteristic changes at irrigoscopy
C) Symptoms are connected to infringement motor and secretion functions of
intestines
D) In stool there can be an impurity of slime
E) Pains in a stomach changeable and varying localization
15. The patient of 46 years disturb alternation of a liquid chair and constipations,
occurrence of blood in stool, change of the form feaces (lentiforms), pains in a
bottom of a stomach. Objectively: the common condition satisfactory, the stomach
is moderately inflated, in the rest palpation a stomach without features.
Periodically there is a sensation incomplete palpation intestines after the certificate
defication. Pick up the most probable reason of disease:
A) Nonspecific ulcer colitis
27
B) cologenic colitis
C) pseudomembranose colitis
D) A syndrome of the irritated gut
E) An infection campilobacter
16. What from below listed symptoms is not characteristic for a syndrome of the
irritated intestines:
A) The most often symptom - pains in illiac or hypogastial areas
B) Pains in a stomach always intensive
C) Pains in a stomach of varying localization
D) There are constipations, changed diarrheas
E) Frequently there is a rumbling and transfusion in a stomach
17. For the patient of 46 years it is diagnosed SII with prevalence of constipations,
with pains in a stomach, occurrence of blood in stool, change of the form feaces .
A condition satisfactory, the stomach is moderately inflated, in the rest palpation a
stomach without features. Treatment includes everything, except for:
A) A diet with addition of food fibres
B) dicetile
C) forlacs
D) smecta
E) dicicloverinum
18. The man of 42 years has addressed with complaints on pains in a stomach,
amplifying after reception of food; constipations till 2-3 days, feeling of a swelling
of a stomach, and also character of a chair on type « sheep feaces ». Carrying out
of colonoscopy was painful; on a mucous membrane of a thick gut a plenty of
slime was defined. What from the listed diagnoses IS MOST PROBABLE?
A) Crone's disease
B) A cancer of thick intestines
C) SII with prevalence of constipations
D) SII with prevalence of diarrheas
E) A syndrome superfluous microbic contamination
19. To out intestinal to displays of a syndrome of the irritated gut most probably
concerns:
A) A constipation
B) A pain in a stomach
C) An often, liquid chair
D) A constipation alternating to diarrheas
E) A disturbing - depressive syndrome
20. At the patient with complaints to the constipations described by presence
feaces of weights as balls with an impurity of slime of a pain in left iliac of the
area, disappearing after the certificate defication, at rectoromanoscopy are revealed
multilayered.
The most probable diagnosis:
A) diverticulesis
B) diverticulitis
C) A cancer of a thick gut
D) pararectal an abscess
E) adenomatous polyp
21. To the patient with diverticulesis initial medical action should be:
A) Food rich tissue
B) Food poor tissue
C) lactulose
D) Laxative means
E) colomyotomy
22. Patient Н., 76 years has addressed with complaints to whining stupid pains in
the bottom part of the stomach, disappearing after the certificate defication;
constipations. Objectively: a stomach soft, painful on a course of thick intestines,
28
spasmed. Coprology: the microscopy without a pathology is a lot of slime, "sheep"
Stool. Colonoscopy: catharal proctosigmoiditis. The diet with inclusion of bran,
mineral waters is appointed. The MOST EXPEDIENT tactics:
A) No-spa+ cerucal
B) forlacs + motilium
C) fortrans + motilium
D) regulacs + cholestiramine
E) An extract senum + maalocks
23. Patient Р., 86 years has acted with complaints to pains in a stomach, irradiated
in lumbar area; a swelling of a stomach, propensity to constipations, "sheep" Stool
with slime and blood on surfaces, weakness, losing of weight. In the anamnesis
polyps of a thick department of intestines. At survey of the lowered feed, a leather
pale. Language is impose. A stomach soft, painful in the bottom departments. In
blood: leukocytes of-10 thousand, ESR-52 mm / h. Irrigoscopy: in area sigmoid
during 20 sm circular the gleam, in the center of narrowing proof depot of barium
is narrowed. What from the listed methods of inspection is MOST
INFORMATIVE:
A) FGDS
B) Duodenography
C) Roengenoscopy a stomach
D) Colonoscopy with aim biopsy
E) Fractional research of gastric juice
24. The patient of 56 years has addressed with complaints to constipations,
occurrence of blood in stool, change of the form feaces (lentiforms), pains in the
bottom of a stomach. Objectively: the common condition satisfactory, integuments
and mucous pale, the stomach is moderately inflated, in the rest palpation a
stomach without features. First of all it is necessary for patient to carry out research
A) irrigoscopy
B) coprogramm
C) Manual research of a direct gut
D) rectoromanoscopy
E) fibrocolonoscopy
25. At the woman who one year ago have transferred cholecystectomy concerning
cholelithiasis, pains in left hypohondrium, a nausea, constipations have appeared.
Pains carry spastic character, arise after infringement of a diet. At inspection: a
stomach soft, painful in the left half epigastrium. In blood: moderate leukocytosis,
acceleration ESR, in coprogramm amylorrhea, crearorrhea, steatorrhea.
What plan of medical actions is most expedient:
A) spasmolitics, enzymes
B) analgetics, spasmolitics
C) inhibitors of prothease, starvation
D) analgetics, inhibitors prothease
E) desintoxication means, analgetics
26. The woman of 63 years complains on spastic pains in epigastrium and left
hypohondrium, connected with errors in a diet, a nausea, propensity to
constipations. 6 months ago has transferred cholecystectomy. Objectively: a
stomach soft, painful in points of a projection of a pancreas. In the common
analysis of blood: leukocytes - 9,8 thousand, ESR - 22 mm / ю, in coprogramm
neutral fat, vegetative tissue.
What from the listed diagnoses IS MOST PROBABLE:
A) A chronic hepatites
B) A cancer of a pancreas
C) An aggravation chronic cholangitis
D) The painful form of a chronic pancreatitis
E) PCES, a chronic pancreatitis in a phase of an aggravation
29
27. The man of 43 years after stress complains of pains in a stomach, decreasing
the ambassador passage a chair and gases; alternation of constipations and
diarrheas; bad dream, irritability. Objectively: the stomach is inflated, morbidity on
a course of a descending department of a thick gut is defined. At radiological
research attributes of a dyskinesia of a thick gut are revealed; at colonoscopy propensity to spasms.
What from the listed variants of a syndrome of the irritated intestines IS MOST
PROBABLE:
A) With prevalence of constipations
B) With prevalence diarrhea
C) With prevalence meteorism
D) With prevalence of pains in a stomach
E) With prevalence of pains in a stomach and метеоризмом
28. Patient E., 34 years has acted with complaints to whining pains in the bottom
and lateral departments of the stomach, amplifying through 7-8 hours after meal; a
unstable chair: the diarrheas alternating to constipations. Diarrheas arise after
reception of milk, at constipations Stool fragmented. Objectively: morbidity,
rumbling of thick intestines. On irrigoscopy narrowing of a gleam of a thick gut,
presence plural gaustration, supporting an intestinal contour. What from the listed
diagnoses is MOST PROBABLE:
A) shygelesis
B) disease the Crone
C) Ischemic colitis
D) pseudomembranose colitis
E) Nonspecific ulcer colitis
29. The woman of 52 years who is taking place in the period menopause, within
2th years pains around umbiliccus a various degree of the intensity, disappearing
the ambassador passage a chair disturb; periodically an indulgence of a chair; a
swelling of a stomach. Objectively: morbidity of all thick gut. Coprological: a
plenty of slime. At radiological research of thick intestines: attributes of a
dyskinesia; at colonoscopy: propensity to spasms.
What from the listed diagnoses is most probable:
A) Ulcer colitis
B) Chronic colitis
C) lymhpocytic colitis
D) pseudomembranose colitis
E) A syndrome of the irritated intestines
30. Expressed sensitivity of all stomach, a pain at easy palpation at absence of an
organic pathology of intestines is most probable for:
A) Ulcer colitis
B) Collagenic colitis
C) Post infectious colitis
List of answers:
1
2
3
4
5
-
A
E
A
D
A
16
17
18
19
20
-
B
D
C
E
A
6
7
8
9
10
-
B
B
A
C
A
21
22
23
24
25
30
-
A
D
D
C
A
11
12
13
14
15
-
E
D
C
B
D
26
27
28
29
30
-
C
E
E
E
E
BIBLIOGRAPHY
1. Шульпекова Ю.О. Запор и методы его лечения / Ю.О. Шульпекова // Русский
медицинский журнал.- 2007.- №15.- С. 25-32.3.
2. Attar A. Comparison of a low dose polyethylene glycol electrolyte solution with lactulose for
the treatment of chronic constipation / A.Attar [et al.] // Gut.-2008.-Vol.44.-P.226–230.
3.Самсонов А.А. Синдром хронического запора / А.А. Самсонов // Русский медицинский
журнал.- 2009.- №4.- C. 25-31.
4. Bernier J.J. Effect of low dose polyethylene glycol 4000 on fecal consistency and dilution
water in normal subjects / J.J. Bernier, Y.Donazollo // Gastroenterol.Clin.Biol.-2007.-Vol.21.P.7–11.
5. Brandt L.J. Systematic rewiew on the management of chronic constipation in North America /
L.J. Brandt [et al.] // Am. J. Gastroenterology.- 2005.- Vol. 100.-P.-5–21.
6. Higgins P.D. Epidemiology of constipation in North America: a systematic rewiew / P.D.
Higgins, J.F.Johanson // Am. J. Gastroenterology.- 2006.- Vol. 99.-P.750–759.
7. Минушкин О.Н. Осмотические слабительные в лечении функциональных запоров /
О.Н.Минушкин [и др.] // Русский медицинский журнал.- 2010.- №6.- С.12-17.
8. Щербаков П.Л. Метеоризм у детей / П.Л. Щербаков // Трудный пациент.-2006.-№9.С.19–21.
9. Кузьменко Л.Г. Расстройства пищеварения / Л.Г. Кузьменко //Фармацевтический
вестник.- 2005.- №25.- С. 5-9.
10. Savino F. Lactobacillus reuteri (American type culture collection strain 55730) versus
simethicone in the treatment of infantile colic: a prospective randomized study / Savino F. [et al.]
//
Pediatrics.2007.Vol.119.-P.
124–130.
11. Higgins P.D. Epidemiology of constipation in North America: a systematic review //
P.D.Higgins, J.F. Johanson // Am. J. Gastroenterol. -2008. – Vol. 99.- P.750–759.
12. Bosshard W. The treatment of chronic constipation in elderly people: an update /
W.Bosshard, R.Dreher, J.F.Schnegg Bula // Drugs Aging. -2004. Vol.21.-P.911–930.
13. Bassotti G. Italian Constipation Study Group. An extended assessment of bowel habits in a
general population / G. Bassotti [et al.] // J. Gastroenterol. – 2009.–Vol.10.-P.713–716.
14. Тимофеева А.В. Дюфалак в лечении запора у пожилых пациентов, страдающих
сердечно–сосудистыми заболеваниями/А.В.Тимофеева, Ю.Н.Моисеева, И.А.Либов //
Русский медицинский журнал.- 2007.- № 6.- С. 17–21.
15. Koch A. Symptoms in chronic constipation. Dis. Colon Rectum / A.Koch [et al].-2006.Vol.40.-P.902–906.
16. Garrigues V., Galvez C., Ortiz V., Ponce M., Nos P., Ponce J. Prevalence of constipation:
agreement among several criteria and evaluation of the diagnostic accuracy of qualifying
symptoms and self–reported definition in a population–based survey in Spain. Am. J. Epidemiol.
2004;
159:
520–526.
17. Tramonte S.M. Is constipation associated with decreased physical activity in normally active
subjects? / Tramonte S.M. [et al.] // Am. J. Gastroenterol. – 2005.-Vol.100.-P.124–129.
18. Барановский А.Ю., Кондрашина Э.А. Дисбактериоз кишечника. M.: Питер,2007.–240с.
19. Talley N.J.3rd. Constipation in an elderly community: a study of prevalence and potential
risk factors / N.J.Talley [et al] // Am. J. Gastroenterol. – 2005.-Vol.91.-P.19–25.
20. Dukas L. Association between physical activity, fiber intake, and other lifestyle variables and
constipation in a study of women / L.Dukas, W.C.Willett, E.L.Giovannucci // Am. J.
Gastroenterol.
–
2003.Vol.
98.
P.
1790–1796.
21. Tramonte S.M. Is constipation associated with decreased physical activity in normally active
subjects? / S.M.Tramonte [et al] // Am. J. Gastroenterol. – 2005.-Vol.100.P.124–129.
22. Chassagne P.Does treatment of constipation improve faecal incontinence in institutionalized
elderly patients? / P.Chassagne [et al] // Age Ageing. – 2009. -Vol. 29. –P.159–164.
23. Gibson G.R. Dietary modulation of the human gut microflora using the prebiotics
oligofwtose and inulin / G.R. Gibson // J. Nutr.-2008.- Vol. 129. –P.1438–1441.
24. Roberfroid M.B. Prebiotics and probiotics: are they functional foods / M.B.
Roberfroid//Am.J.Clin.Nutr.-2007.-Vol.71.-P.1682–1687.
25. Пейлли Ф. Открытое полугодовое исследование безопасности применения Транзипега
для лечения запора в рамках медицинского обслуживания / Ф.Пейлли, Н.Коломбей,
Б.Аллоуми [и др.] // Русский медицинский журнал.- 2006.- № 11.- С.11–15.
31
Подписано в печать 13.12.2010 г.
Объем 2 уч.печ.л.
Формат 60х84 1/16. Тираж 100 экз.
Отпечатано в типографии КГМУ
г. Караганда, ул, Гоголя, 40
32