[TOPICAL ISSUES IN NEUROLOGY AND NEPHROLOGY]
Includes bibliographies and index.
1. The Scientific Fundamentals of the Specific Interventions
for Enuresis by.
Prof.Dott.EmmanuelUdemezue Onyekwelu.
CSci,CSciTeach,BChir(Hons),BM,(Hons)MD,MRQA,FRSA,FCILED,FRGS,FRSH,FRCEM,FRSPH,FRSB,DSc/PhD(Hon)
This is the second edition of The Scientific Fundamentals of
the Specific Interventions for Enuresis published by
Prof.Dott.Emmanuel Udemezue Onyekwelu.
CSci,CSciTeach,BChir(Hons),BM,(Hons)MD,MRQA,FRSA,FCILED,FRGS,FRSH,FRCEM,FRSPH,FRSB,DSc/PhD(Hon)
AT C L A S S I C S A N D R E V I S I T S I N S C I E N T I F I C M E D I C I N E
Classics Revisits Sci.Med.
Preface to This Edition.
Enuresis is a defect of antiquity, with much historical remarks, the
emotional impact of enuresis on a child ,adolescence, adults and
their family could be considerable, however there is still some
ongoing struggle to comprehend and manage this defect more
effectively.
This textbook is one major step in the ongoing struggle to
antagonize this common defect.
Enuresis is still a very common health problem and its
pathophysiology, clinical manifestations and principles of
management interventions must be very well comprehended by both
the primary care clinician ,specialist clinician and other allied health
professionals.
This textbook covers all aspects of enuresis in a single volume.
It is divided into several sections covering respectively, the
historical aspects and cultural believes concerning enuresis, the
epidemiology, the pathophysiology, the associated pathologies, the
clinical features, the laboratory investigative aspects and the
management, in addition to the prospective plausible specific
interventions, the research directions and the preventive aspects of
enuresis.
The historical aspects of enuresis in childhood were reviewed in
details.
Recent concepts and the dynamism in the epidemiology of enuresis
were dilated on.
The pathogenesis and the pathophysiology of enuresis were then
discussed, with its clinico-pathological correlations.
In addition, its evidential therapeutic, prophylactic and integrative
interventions were espoused.
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Copyright © 2024 by Prof.Dott.Emmanuel Onyekwelu
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Prof.Dott.Emmanuel Onyekwelu.
CSci,CSciTeach,BChir(Hons),BM,(Hons)MD,MRQA,FRSA,FCILED,FRGS,FRSH,FRCEM,FRSPH,FRSB,DSc/PhD(Hon
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Foreword
A new review of the subject enuresis could be justified fairly in the
setting of proliferations of other monographs, texts, and periodicals
covering the other vast subjects in Neurology and Nephrology.
The goal of this volume is to provide an additional resource and
service to the affected family clinician, health professional and
clinician in the form of clinical information not usually assembled
conveniently in one text.
One type of textbook presented in this monograph form will cover
this specific topical issue in Neurology and Nephrology, expatiating
on pathogenesis, recent research, future research directions and
clinical aspects.
It is wished that such a compilation will be useful in its
thoroughness, range and breadth to the family clinician, health
professional, clinician or scientists interested in that particular
aspect in contest.
This type of book will present and stimulate discussions on clinical
topics encompassing many possible specific aetiologies.
Volumes like this will normally be comprehensive, focused and
related to the interests, expertise and experience of the author.
Regular revisions are planned so that this volume will remain as
current as it is complete. This is the second revision of this text
book.
We hope that these goals are met and that the present text
establishes its own identifiable and valuable niche in the growing
compendium of resource material available to the clinician on this
theme.
Preface to This Edition.
Enuresis is a defect of antiquity, with much historical remarks,
the emotional impact of enuresis on a child,adolescence,adults
and family, could be considerable, however there is still some
ongoing struggle to comprehend and manage this defect more
effectively.
This textbook is one major step in the ongoing struggle to
antagonize this common defect.
Enuresis is still a very common health problem and its
pathophysiology, clinical manifestations and principles of
management interventions must be very well comprehended by
both the primary care clinician and clinical specialist.
This textbook covers all aspects of enuresis in a single volume.
Like the previous edition, it has been divided into several
sections covering respectively, the historical aspects and
cultural believes concerning enuresis, the epidemiology, the
pathophysiology, the associated pathologies, the clinical
features, the laboratory investigative aspects and the
management, future possible interventions, the research
directions and preventive aspects of enuresis.
The historical aspects of enuresis in childhood,adolescence and
adults were reviewed in details.
This edition has been updated in the context of the current
evidential research directions and technical scientific research
reports.
Recent concepts and the dynamism in the epidemiology of
enuresis were dilated on.
The pathogenesis and the pathophysiology of enuresis were
then discussed, with clinico-pathological correlations, in
addition to its integrative interventions.
Preface to This Edition(Continued).
The plausible laboratory investigations and urodynamic studies
were further itemized and analyzed.
The role of environmental manipulations and pharmacotherapies
were outlined in the sections dealing with plausible management
and interventions.
The preventive and public health aspects of enuresis and their role
were mentioned and discussed.
Similarly from the scientific point of view, the potential for robust
data from the amalgamation of translational research from the bench
to bed employing multispecies derived experimental animal test
system models were well represented through the citation of
scientifically robust and rigorous data in the text, bibliography,
references and the suggestions and recommendations for further
reading sections.
Since enuresis is a common topical childhood ,adult and
adolescence issue, it is hoped that this volume will represent a
definitive resource for all basic and applied scientists, clinicians and
with guidance and direction to the very literate parents and
guardians, for their wards and relatives who are likely to deal with
enuresis.
Summarily, further research questions and directions were evoked.
Contents……………………………………………………………………Page
Series Preface…………………………………………………………………………..V
Preface to the Current Edition……………………………………………………….VI
1-Definitions and Nomenclature…………………………………………………….10
2-Historical Perspectives……………………………………………………………..24
3-EpidemiologicConsiderations…………………………………………………….32
4-Functional Anatomy,Physiology,and Pathophysiology----------------------------39
5-The Clinical Features and Associated Pathologies……………………………218
6-Generic&Specific Investigations and Urodynamic Studies………………….232
7-Plausible Non-Pharmacotherapeutic &Pharmacological Interventions …..238
8-Pharmacological Effectiveness of Interventions………………………………274
9-Comparisons of Interventions,other considerations&Research
Directions………………………………………………………………………………..364
10- Topics Index Metadata, and Subjects : Abbreviations Key Words. Medical
Science Headings(MeSH)…………………………………………………………….371
1-Definitions, Nomenclature and Systematic Classification Schemes:
The nomenclature enuresis was derived from the Greek phrase for the water
making process.
Over the years, various terms were used to describe enuresis in
childhood,adolsecence and adults.
This practice has created ambiguity and impeded standardization of definitions
and diagnosis.
Children are not considered enuretic until they have attained five years of age.
Mentally compromised children should have reached a mental age of four
years before they are considered enuretic.
Enuresis is defined as a repeated, spontaneous voiding of urine during sleep
in a child aged five years or more.
Enuresis was controversially discussed and pragmatically defined by several
authors because of the acceptable wide variation in the age range when
urinary control and regulation could be achieved.
Previously enuresis was specifically defined as the involuntary passage of
urine after the age of four years or more.
Almost always, continuing enuresis is usually perceived as a problem above
the age of four years.
More pragmatically, enuresis was defined as involuntary micturition occurring
in a child at an age when adequate bladder control should have been achieved.
It could occur during the day and or at night, and it is applicable to children
who are at least five years of age.
In enuresis, there is uncontrolled micturition at an age when a controlled
process is expected. It may be diurnal or nocturnal.
Anecdotally, it was generally agreed that there is no fixed age as such for
achieving urinary control, especially nocturnal urinary control which may be
almost optimal as early as twenty months or imperfect until the age of one
hundred and eight months or more in otherwise developmentally perfect
children.
These definitions although non-specific and pragmatic with regards to the age
limit appears to be more plausible and acceptable in different populations, and
cultural settings, given the wide variation in the expected age of achieving
nocturnal and diurnal urinary regulation.
Systematic Classification Schemes:
Evidence suggests that two distinct types of enuresis occur de novo and there are further
body of proof that these two subsets do not overlap commonly.
The first subset is known as the Primary or Persistent Enuresis, where as the second
subset is referred to as the Secondary or Regressive Enuresis:
A systematic standardized definition suggests that it must happen at least twice in a
fortnight but, in fact the frequency itself is not of diagnostic importance as such.
In the persistent or primary type of enuresis, nocturnal or diurnal urinary control has never
been previously achieved, where as in the regressive type, a previously micturition
continent child, adolescence or adult losses urinary regulation.
It is qualified as nocturnal enuresis if it occurs mostly at night.
In nocturnal enuresis there is intermittent incontinence while asleep or intermittent
nocturnal incontinence, whereas diurnal enuresis is applied to the predominantly daytime
phenomena.
The International Children's Continence Society has recommended the following
standardization of terminology: nocturnal enuresis is the involuntary loss of urine that
occurs only at night.
For the diagnosis of nocturnal enuresis to be established, a child five to six years old
should have had two or more bed-wetting episodes per month, and a child older than six
years of age should have had one or more wetting episodes per month.
A technical and encompassing definition of nocturnal enuresis is that of a child aged five
years or more, who has had at least one episode of micturition whilst asleep in bed at night,
the events do not necessarily have to be recurrent as such.
In nocturnal enuresis there is uncontrolled bedwetting or unintentional sleep wetting by a
healthy child above the age when normal continence should have been achieved.
Nocturnal enuresis is defined as primary if the child has never been dry for a period of more
than twenty four weeks, and secondary if such a period of dryness preceded the onset of
wetting.
Nocturnal enuresis could be primary or persistent when the child has never had a period of
night time continence or secondary or regressive (developing in a formerly dry child
following some emotional challenge or disruptive event.
Further quantitative categorization of nocturnal enuresis suggests that in type I (PEN I or
Primary nocturnal enuresis there is at least three nightly enuretic episodes in children aged
seven years and above, where the child has always been known to be enuretic and where
as in Type II (or Secondary Enuresis) enuresis has ocurred.in a child who has been dry for
at least six months.
The distinction between infrequent bedwetting and nocturnal enuresis is more of an
academic and technical thing.
Figures from the authors ongoing continual observational survey suggests that most cases
of enuresis were of the primary or persistent subset, whereas a few were of the secondary
or regressive form.
Monosymptomatic nocturnal enuresis is characterized by night time enuretic symptoms
only without other associated symptomatologies.
Diurnal Enuresis:
Diurnal enuresis which implies day time wetting is defined as a lack of bladder
regulation during waking, early morning or daytime hours in a child old
enough to be able to maintain urinary control.
In diurnal enuresis there is unexplained and unusually frequent day time
uncontrolled micturition.
Causative factors and associations for diurnal enuresis:
Daytime incontinence that is not associated with urinary infection or anatomic
abnormalities is less common than nighttime incontinence and tends to
disappear much earlier than the nighttime versions.
One possible cause of daytime enuresis is urinary incontinence due an
overactive bladder.
Diurnal enuresis could present as intermittent incontinence which is urine
leakage in discreet amounts.
Many children, adolescence and adults with daytime incontinence have
abnormal voiding habits, the most common being infrequent voiding.
This form of incontinence occurs more often in girls than in boys.
During the initial several years after urinary training, many children wet
themselves when they delay and defer micturition during the day, because they
are so engrossed in the ongoing extracurricular activities.
This could probably be classified as developmental, if it occurs less than twice
in a week.
Diurnal enuresis may be influenced and favoured by shyness about asking to
go to the lavatory fear of strange lavatories, negativistic tendencies, or chronic
anxiety leading to postponement of micturition.
In the older school age children, it is most often encountered in chronically
anxious children, those with personality disorders of the anxiety spectrum and
those with oppositional personality traits.
Since in most cases of childhood enuresis following an in-depth historical,
clinical, laboratory and specific urodynamic studies no clear cut cause of the
enuresis was established, so in otherwise normal children, diurnal enuresis is
not considered a problem until the age of thirty to thirty six months.
After this period, diurnal enuresis is a cause of concern.
Enuresis poses a major interventional challenge, because of its associated
symptomatologies.
Diurnal enuresis may cause social difficulties as the child commences
preschool care, or it may be inconsequential and relatively covert until the
early school years.
It is occasionally associated with nocturnal enuresis.
Relative to nocturnal enuresis, the incidence of encopresis in diurnal enuresis
Severity of Enuresis:
Severity of Enuresis:
Profound enuresis nocturna refers to more than one enuretic
event nightly.
Severe enuresis nocturna implies bedwetting on every night.
Marked enuresis nocturna suggests bedwetting at least once
weekly.
Occasionally, the word enuresis was adapted non
qualitatively with reference to urinary incontinence
associated with no organic or systemic pathology, however,
technically speaking, this should strictly and more precisely
be referred to as functional enuresis.
Functional Enuresis is the passage or discharge of urine at
night (nocturnal) or during the day (diurnal) in the absence of
congenital or acquired defects of the central nervous system
or the urinary tract in a child aged sixty months or more
without voluntary control, provided that historical notes
should have normally excluded polyuria or polydipsia or
other symptomatologies suggestive of other more common
or insidious pathological conditions such as diabetes
mellitus, diabetes insipidus, chronic renal insufficiency or
urinary frequency, urgency or urinary difficulty, consistent
with urinary tract infections or occasional age dependent
functional incontinence, extreme emotional outbursts, or
episodic deferment or delay of the urge for micturition.
Annotations and Summary for the Systematic Classification Schemes for Enuresis:
Systematic Classification Schemes for Enuresis, according to the
time of the day.
Nocturnal enuresis: passing of urine while asleep.
Diurnal enuresis or incontinence: leakage of urine during the day
Systematic Classification Schemes for Enuresis, according to the
presence of other symptomatologies:
Monosymptomatic or uncomplicated nocturnal enuresis: normal
voiding occurring at night in bed in the absence of other
symptomatologies referable to the urogenital or gastrointestinal
tract.
Subtyping of monosymptomatic nocturnal enuresis is more of an
academic activity, which may not necessarily have any useful
clinical impact and importance.
Polysymptomatic or complicated nocturnal enuresis:
Bedwetting associated with daytime symptomatologies such as
urgency, frequency, chronic constipation, or encopresis.
Although averaging available statistics suggests that, the
monosymptomatic forms of nocturnal enuresis accounts for about
one of eight of instances of nocturnal enuresis, however strictly and
technically speaking, in the author’s lengthy experience with a
representative sample, taking into consideration the impact of
associated urinary tract infections which were frequent, the ratio of
the polysymptomatic to the monosymptomatic pattern of nocturnal
enuresis was noted as two is to three.
Those children with the most severe forms of enuresis are likely to
persist with the problem and have more complex forms of enuresis
which is of the non-monosymptomatic form.
Systematic Classification Schemes for Enuresis, according to
previous periods of dryness
Primary enuresis is bed-wetting in a child who has never been
previously dry.
Whereas secondary enuresis is bed-wetting in a child who has had
at least six months of nighttime dryness.
Other synonymous defects having enuresis as a symptomatology
such as nocturnal incontinence could be excluded by an in-depth
historical and comprehensive physical evaluation, in addition to
selective laboratory investigations, such as urine examination at
the first instance.
In summary, enuresis is recurrent, spontaneous involuntary
micturition in children aged at least five years.
Classifications of enuresis include primary if there is a less than six
months of urinary continence) or secondary (enuresis if there is a
more than six months of continence), monosymptomatic
(uncomplicated) or nonmonosymptomatic (lower urinary tract
symptoms), and nocturnal [night time or diurnal daytime].
Factors associated with enuresis are nocturnal polyuria, decreased
bladder capacity, parental history, developmental delay, detrusor
instability, and sleep disorders.
Secondary enuresis is commonly linked with bladder dysfunction,
constipation, diabetes mellitus, hyperthyroidism, obstructive sleep
apnea, pinworm infection, psychological stress, urinary tract
infection, and rarely, chronic renal failure, diabetes insipidus,
seizure disorder, and sickle cell disease.
1-BIBLIOGRAPHY AND SUGGESTIONS FOR FURTHER READING.
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2-Historical Perspectives.
The defect enuresis and other common voiding abnormalities were one of the
most ancient of all human defects and is as old as life itself.
The defect enuresis was mentioned in the writings of the great Greek
philosopher Aristotle.
Although enuresis has been considered a recognized problem for about four
thousand years now, it was sparsely discussed in the literature, and relatively
little investigation was carried out on the topic.
Although historically, enuresis has been a subject of speculation and study for
both the laymen and the scholars, however very few historical investigations
were carried out on this topic.
The most ancient medical literature describing the defect enuresis was
discovered in the Papyrus of Ebers, a form of ancient Egyptian records, dating
back to the fifteen thousand BC.
There were lots of superstitious beliefs surrounding the origin or cause of
enuresis and thus its historical interventions were weighted accordingly.
In ancient times, healers generally thought that its main cause was
witchcraftry.
Historical Medical notes reviews, revealed true proof of existence of this
phenomena already in the Persian and European medical texts by the 16th
century BC.
The topic enuresis and its interventions were documented in the ancient times,
several unusual folklore medications used in the management of enuresis
could be gleaned from the early medical writings.
Other historical therapeutics notes on the therapeutic and pharmacotherapies
of childhood enuresis mentioned the use of several non-orthodox modalities of
interventions at a point with differing degrees of benefits.
Archival notes dating as far back as seventh AD suggested several
interventions which were used in the management of enuresis, such as boiled
mice, infantile circumcision, at that point these regimens were thought to be
acceptable interventions for the management of enuresis.
Other folk regimens used through the ancient times were the eating of the
testicles of the hare and hedgehogs separately, licking of the hooves of a
newborn lamb or standing naked over a burning bird nest.
2-Historical Perspectives(Continued).
Reviews of other medical historiographic documents suggested that
when parents found bed wetting embarrassing and frustrating, they
visited the apothecaries who recommended a mixture of one juniper
berry and one leaf of cypress taken together in one glass of beer,
with the promise that bedwetting would cease a short while
thereafter, but disappointingly, although these regimens were far
from being reliable, they were followed for a long time.
Equisetums or horsetails were used since ancient times in Chinese
Medicine for the treatment of enuresis.
Further review of Chinese research on classical and ancient
remedies for enuresis suggests that in ancient times, parents would
look out for Wenguenguo trees, collect its seeds crush it and use it
to treat their children with enuresis.
The scientific management of enuresis revolutionized in 1938 when
the alarm system of management of nocturnal enuresis was
introduced.
Shortly thereafter followed the institution of behavioural,
responsibility training and environmental manipulations.
Having partly comprehended the putative defective pathologic
mechanisms in childhood enuresis further, a pragmatic search for
an appropriate pharmacological adjunct that could be used for the
management of children with enuresis was instituted.
Imipramine was the first drug that was introduced for the
pharmacological management of enuresis.
Drug History:
Imipramine was,in the late 1950s, the first tricyclic antidepressant to be
developed by Ciba,well before the introduction of other antidepressants.
It stood the test of time and was used in the most resistant and recalcitrant
depressions.
Therefore, it became extensively used as a standard antidepressant and later
served as a prototypical drug for the development of the other tricyclics
antidepressants.
It has also seen limited use in the treatment of migrainous
cephalgias,attention deficit hyperactivity disorders, and post concussive
syndromes.
Imipramine has additional therapeutic effects on panic attacks and recurrent
neuralgias.
It was relatively frequently used to treat nocturnal enuresis and nocturnal
frights and terrors.
Although to date the mechanism of its beneficial effects on enuresis has not
been completely elucidated and understood ,however its beneficial effects
were rather putatively thought to be due to an interplay of its effects on
several neurotransmitters ,hormonal and humoural factors.
However,Imipramine toxicities following overdoses were frequent and were
occasionally fatal,making a cautionary warning necessary for every
prescription.
Given this profile of unfavorable adverse effects and significant risk of death
with imipramine overdose, shortly after its introduction,the World Health
Organization (WHO) intimated that it does not recommend the application of
imipramine for the treatment of childhood enuresis. Given these shortcomings,
further attempts were made for the exploitation of anticholinergic drugs such
as oxybutynin and other allied agents etc.
DDAVP, vasopressin was introduced in the 1990s, and has response rates
similar to those of imipramine with fewer side effects, though with more
unfavourable financial implications.Also, following the introduction of
desmopressin in enuresis, there were postmarketing concerns especially with
regards to associated hyponatremic-related seizures.
Thereafter, the suggestions of these non-pharmacological and
pharmacological regimens and approach to the management of enuresis,
triggered off several anecdotal and scientific evidenced investigations with
different strengths and levels of evidence, although given its adverse
individual and familial impact compared to the magnitude of investigations
undertaken in other subjects of less importance,the extents of these
2-BIBLIOGRAPHY AND SUGGESTIONS FOR FURTHER READING:
REFERENCES FOR THE HISTORICAL ASPECTS OF ENURESIS
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Salmon MA (July 1975). An historical account of nocturnal enuresis
and its treatment. Proceedings of the Royal Society of Medicine. 68
(7): 443–5. doi:10.1177/003591577506800726. PMC 1863929. PMID
801839.
Rhus Aromatica in Enuresis. Eclectic Medical Journal 52, no. 4
(1892): 176.112
Allbutt T C (1870) Lancet ii, 733.
R. C. W. Enuresis. Eclectic Medical Journal 63, no. 10 (1903): 561563.An Operation for Incontinence of Urine in the Female. The
Eclectic Medical Journal56, no. 12 (1896).
Farquharson R (1879) Practitioner 23, 7
H. Incontinence of Urine. The Eclectic Medical Journal 50, no. 4
(April 1890).Incontinence of Urine Treated by Hydrate of Chloral.
The Eclectic Medical Journal 31,no. 6 (June 1871 ).
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Children. Saunders, Philadelphia.
Benjamin JA, Scott J: The history and development of urological
cinematography: The influence of John McIntyre of Glasgow. Read
in part at the Forum for the History of Urology, 68th Annual Meeting
of the American Urological Association, Inc., New York, May 14, 1973
Smith, George W. Incontinence of Urine. The Eclectic Medical
Journal 31, no. 8 (August 1871).
Ruddock H (1878) Diseases of Children and their Homeopathic and
General Treatment. London.
Incontinence of Urine in Children. The Eclectic Medical Journal 22,
no. 6 (June 1867).
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Adolphus, Joseph. Rhus Aromatica in Enuresis. Eclectic Medical
Journal 60, no. 7(1900): 411.
Adams F (1844) Sydenham Society, 1, 548.
Groenbech, Dr. Nocturnal Enuresis and Adenoid Vegetations.
Eclectic Medical Journal 56, no. 1 (1896).
Reed, M. L. Experience in Enuresis--Equisetum. Eclectic Medical
Journal39, no. 5(1879): 229-230.
Baruch S (1889) Archives of Pediatrics 6, 234
van Tienhoven, Dr. Nocturnal Incontinence in Children. The Eclectic
Medical Journal 51, no. 6 (June 1891).
Dickson T (1762) Medical Observations and Inquiries by a Society of
Physicians in London 2, 311
Herskovits M(1938) Dahomey, vol 1. New York
Corrigan, D. J. Treatment of lncontinence of Urine in Childhood and
Youth by M Collodion .The Eclectic Medical Journal 31, no. 2
(February 1871 ).
Mandel L (1931) British Journal of Children's Diseases 28, 1
Jacobi A (1891) In: Encyclopedia of the Diseases of Children.Ed. J M
Keating. Pentland, Edinburgh.
Nye S (1881) Medical and Surgical Reporter 45, 389
Incontinence of Urine Treated by Mechanical Distention of the
Bladder. The Eclectic Medical Journal 28, no. 12 (December
1868).
Rex 0 P (1893) International Clinics 1, 170
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REFERENCES FOR THE HISTORICAL ASPECTS OF ENURESIS
Onyekwelu E.U.(2014) The histriographic aspects of nephrology
Classics and Revisits in Scientific Medicine.2014.
Slade D D (1855) American Journal of the Medical Sciences 30, 71
Stalker H & Bland D (1946) Journal of Mental Science 92, 324
Torrey E F (1972) American Journal Of Orthopsychiatry 42, 69
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Onyekwelu E.U. (2011?)The challenges and lessons from the
historical scholarships from enuresis for the utmost interventions
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Backus PL, Mansell GS (October 1944). Enuresis in the Army. British
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Onyekwelu.E et al Discursive dissections and clarifications on the
salient histriographic aspects in the histological, functional and the
anatomical aspects of nephrology and a summary of the basic
principles of the application of renal dialysis and the other renal
replacement therapies.Classics and Revisits in Scientific Medicine.
(Nephrology Supp. 1 Issue 1 June 2014.)
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REFERENCES FOR THE HISTORICAL ASPECTS OF ENURESIS.
Coe, Henry C. The Electrical Treatment of Irritable Bladder.
The American Journal of the Medical Sciences (182 71924) 103/2: 8, February 1892. Journal online. Available
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26&RQT=309&VName=HNP. Internet, accessed 24 January
2005.
Simmons D B (1880) American Journal of Obstetrics and
Diseases of Women and Children 13, 431
Morand, M. Incontinence of Urine. The Eclectic Medical
Journal 23, no. 1 (January 1864): 94.
Vogel A(1885) Practical Treatise on Diseases of Children.
New York
King, John. Dr. King on Incontinence of Urine--(Enuresis).
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Incontinence of Urine. The Eclectic Medical Journal II, no. 1
(January 1858).
Simpson, F. C. Enuresis Diurna. In The Medico-Chirurgical
Society of Louisville held in Louisville 7 April I 893, edited
by Society Reports, 8. Philadelphia: Medical and Surgical
Reporter, 1893.
Harrison, R. A Case of lncontinence of Urine Successfully
Treated with Strychnia.Virgina Medical Surgical Journal4
(1855): 320.
Young, Hugh Hampton. The Renaissance of Urology. Johns
Hopkins Bulletin 309(November 1916): 327-331.
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Treatment of Enuresis. Medical and Surgical Reporter (I 858-I
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3-Epidemiologic Considerations:
Enuresis is much more wide spread than was previously supposed.
Thirty three of thirty four of the cases of enuresis is non-pathologic
and is usually a consequence of the peculiarities of the delay in its
maturational process.
The prevalence of childhood enuresis varies across several reviews,
due to a variety of sociodemographic and cultural dynamics of
various societies.
Childhood enuresis is common in highly developed and
industrialized regions.
The prevalence of enuresis were presumably similar globally,
however standardized setting specific figures may be incomplete,
because systematic evaluations of the incidence and prevalence of
bedwetting were not always undertaken or stood occasionally
undetermined.
Enuresis is one of the few pathologies that have no racial
predilection as such.
Overall, on the average, enuresis appears to be more common in
males.
At five years of age, one in seven to one in four children wet the bed.
With each year of maturity, the ratio of bed-wetters declines by about
one in seven.
Hence, two of twenty five and one of twenty five of early adolescent
girls are enuretic, only one of a hundred to one of thirty three of late
adolescents will still be wetting their bed.
From one of seven to one of four of bed-wetters have secondary
enuresis, but the treatment approach and anticipated response are
comparable.
It is estimated that at four years, one child of five wet more than
once a week, at five years, one in ten and at fourteen years one in
thirty five will do so.
3-Epidemiologic Considerations:
Of enuretic children, one of seven become dry between the ages of five and
nine, one of six between ten and fourteen and a further sixteen percent
between fifteen and nineteen years of age.
Despite the considerable incidence of enuresis, its frequency is probably
overestimated,because although enuresis could occur in as much as one in
ten children, only about one in fifteen cases, wet more than one or more
nights in a week.
Although averaged statistics suggests that between the ages of six and ten
year’s only one of four boys and one of five girls has enuresis.
In the author’s analysis of representative samples, there was no gender
preponderance as such despite the older ages of the cases.
Averaging the available statistics suggests that the overall prevalence of
enuresis in mid childhood is about one in ten in males compared to about one
in fifteen compared to about one in twenty to one in thirty three in aged
matched females.
The male female ratio of nocturnal enuresis is about three to one.
Almost always there is a family history of enuresis as buttressed by twin
studies which revealed a marked concordant familial pattern.
The reported incidence of nocturnal enuresis is one of seven if neither parent
has a history of enuresis, two of five if one parent has a history of enuresis,
and four of five if both parents have a history of enuresis.
However, in childhood, the prevalence of enuresis declines tardively with
advancing age.
Shortly after the expected age of urinary continence, one in four children will
be enuretic.
This figure tends to approximate the adult figures of about one in two hundred
to one in fifty towards adolescence.
The degree of parental concerns generally correlates with the frequency of
enuresis.
3-EPIDEMIOLOGIC CONSIDERATIONS:
Since most cases of enuresis are usually managed at
home, the true prevalence rate is usually
underestimated.
Enuresis is more common in boys in the earlier ages
but it evens out in the latter years.
Children in the boarding schools are more enuretic
compared to those attending the day care schools.
The point prevalence of nocturnal enuresis at the age
of five years is about one of fifteen for males and about
one of thirty three for females.
At the age of ten years it is three percent for males and
two percent for females.
 3-EPIDEMIOLOGIC CONSIDERATIONS:
3-EPIDEMIOLOGIC CONSIDERATIONS:
At the age eighteen it is one percent for males and extremely rare in
females.
Nocturnal enuresis is far more common than diurnal enuresis.
Nocturnal enuresis without overt daytime voiding symptoms affects
up to one in every fifth child at the age of about sixty months.
It ceases spontaneously in one in every sixth child thereafter.
Its frequency amongst adults is probably less than one of ninety
nine.
Nocturnal enuresis or nightly bedwetting in children more than
seven years of age affects about one in ten of early school aged
children, with a wide range of frequencies between populations.
From the age of seven years there is a spontaneous cure rate of
about one of seven per year, such that very few remain affected
towards later adolescence to early adulthood.
Enuresis is frequently associated to significant defective
psychosocial adaptations and it usually occupies an unduly lengthy
health care provider’s encounter time.
3-EPIDEMIOLOGIC CONSIDERATIONS:
BIBLIOGRAPHY AND SUGGESTIONS FOR FURTHER READING:
BIBLIOGRAPHY AND SUGGESTIONS FOR FURTHER READING:
Chung JM, Lee SD, Kang DI et al (2009). Prevalence and associated
factors of overactive bladder in Korean children 5-13 years old: a
nationwide multicentre study. Urology, 73:63-69.
Bower WF, Moore KH, Shepherd RB et al (1996). The epidemiology of
enuresis in Australia. British Journal of Urology, 78:602-606.
Baeyens D, Roeyers H, Demeyere I et al (2005). Attention
deficit/hyperactivity disorder (ADHD) as a risk factor for difficult to
cure nocturnal enuresis in children: A two-year follow-up study. Acta
Paediatrica, 94:1619.
Baeyens D, Roeyers H, D’Hase L et al (2006). The prevalence of
ADHD in children with enuresis: Comparison between samples of
primary care and pediatric clinic. Acta Paediatrica, 95: 347-352.
Butler RJ, Golding J, Northstone K et al (2005). Nocturnal enuresis at
7.5 years old: prevalence and analysis of clinical signs. BJU
International, 96:404-410.
von GontardA, Heron J, Joinson C (2011a). Family history of
nocturnal enuresis and urinary incontinence – results from a
large epidemiological study. Journal of Urology, 185:2303-2307.
Feehan M, Mc Gee R, Stanton W et al (1990). A 6 year follow up of
childhood enuresis: prevalence in adolescence and consequences
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nocturnal enuresis in Taiwanese children. BJU International, 87:678681.
BIBLIOGRAPHY AND SUGGESTIONS FOR FURTHER READING
von Gontard A, Baeyens D, Van Hoecke E et al (2011b).Psychological and
psychiatric issues in urinary and fecal incontinence. Journal of Urolog,
185:1432-1437.
von Gontard A, Moritz AM, Thome-Granz S et al (2011c). Association of
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Adolescent Psychiatric Disorders: The ICD-10 Classification of Mental and
Behavioural Disorders in Children and Adolescents. Cambridge, UK:
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FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE
RENAL AND URINARY TRACT SYSTEMS.
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE
RENAL AND URINARY TRACT SYSTEMS
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE
RENAL AND URINARY TRACT SYSTEMS .
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE RENAL AND URINARY TRACT SYSTEMS .
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE
RENAL AND URINARY TRACT SYSTEMS: THE FUNCTIONAL
MICROSCOPIC ANATOMY OF THE URINARY SYSTEM
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE
RENAL AND URINARY TRACT SYSTEMS .
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE
RENAL AND URINARY TRACT SYSTEMS .
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE
RENAL AND URINARY TRACT SYSTEMS.
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE RENAL AND URINARY TRACT SYSTEMS.
THE FUNCTIONAL MICROSCOPIC ANATOMY OF THE URETERS
4-PHYSIOLOGY,PATHOPHYSIOLOGY, AETIO-PATHOPHYSIOLOGY AND PATHOGENESIS:
4-Physiology,Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE RENAL AND URINARY TRACT SYSTEMS.
Functional Anatomic Considerations:
The word enuresis is a Greek word which literally means the process of
making water and then urine, hence it will be worthwhile to appreciate the
rudiments of urine production.
The functional units of the kidneys is the nephrons. These are lengthy and
slender structures.
The dimensions of the kidneys are directly related to the number of nephrons
that they contain, children will normally have smaller kidneys compared to
adults and naturally have less nephrons.
The human kidneys, probably contains well over one million nephrons.
The glomerulus which is a small microscopic structure of about two hundred
micrometres is formed by an invagination of a tuft of capillaries into the dilated
blind end of the nephron called the Bowman’s capsule.
These capillaries are supplied by an afferent arteriole and drained by a slightly
smaller efferent arteriole.
There are two cellular layers separating the blood from the glomerular filtrate
in the Bowman’s capsule.
These are the capillary endothelium and the specialized epithelium that lies on
top of the glomerular capillaries.
These layers are separated by a basal lamina.Stellate cells called mesangial
cells are located between the basal lamina and the endothelium, these are
pericytes, which are usually localized in the capillaries walls.
Mesangial cells are especially common between two closely related and
adjacent capillaries and in these locations, the basal membrane forms a sheath
shared by both capillaries.
The mesangial cells are contractile and retractile and play a regulatory role in
the glomerular filtration process.
They also secrete various substances, take up immune complexes and are
involved in the mediation or propagation of deleterious glomerular
immunopathologies associated with various degrees of prolonged renal
insufficiencies.
The endothelium of the glomerular capillaries is closely interlaced and
fenestrated, with pores that are approximately between eighty five to one
hundred nanometers in its widest diameter.
The cells of the epithelium form foot like processes called the podocytes
which have numerous pseudopodia that interdigitate to form filtration slits
along the capillary walls.
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE
RENAL AND URINARY TRACT SYSTEMS.
A brief overview of the Basic Renal Physiology and the mechanisms
of urine production and elimination is pertinent.
4-PHYSIOLOGY,PATHOPHYSIOLOGY, AETIO-PATHOPHYSIOLOGY AND PATHOGENESIS:
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE RENAL AND URINARY TRACT SYSTEMS.
In their widest diameters, these ranges approximately from twenty to
thirty nanometres in its widest diameter and each is usually sealed
by a thin membrane.
Although microanatomically, the basal lamina does not contain
visible gaps or pores, however, physiologically, the glomerular
membrane permits the free passage of neutral substances up to five
nanometers in diameter, but it is unlikely to allow the passage of
neutral substances up to nine nanometres in diameter.
However, the charges on the molecules as well as their diameter
affects the permissiveness of their movements into the Bowman’s
capsules.
The average capillary area in each glomerulus is about half a
millimeter squared and the total area of glomerular endothelium
across which ultrtafiltration occurs in humans is about eight
millimeters squared.
The proximal convoluted tubule is about sixteen millimeters long
and sixty millimeters squared in diameter.
Its wall is made up of a single layer of cells that interdigitate with
one another and are united by apical tight junctions.
Between the bases of the cells there are extensions of the
extracellular space called the lateral intercellular spaces.
The luminal edges of the cells have a striate brush border due to the
presence of innumerable microvilli.
The convoluted portion of the proximal tubule also known as the
pars convoluta drains into the straight portion also called the pars
recta, which forms the initial part of the Loop of Henle.
The proximal tubule terminates in the thin segment of the
descending limb of the loop of Henle, which has an epithelium made
up of attenuated flat cells.
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE
RENAL AND URINARY TRACT SYSTEMS.
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE RENAL AND URINARY TRACT SYSTEMS.
4-PHYSIOLOGY,PATHOPHYSIOLOGY, AETIO-PATHOPHYSIOLOGY
AND PATHOGENESIS:FUNCTIONAL ANATOMY AND PHYSIOLOGY
FOR THE RENAL AND URINARY TRACT SYSTEMS.
A brief overview of the Basic Renal Physiology and the mechanisms
of urine production and elimination is pertinent.
The renal functional units or nephrons with their glomeruli in the
outer portions of the renal cortex have short Loops of Henle (cortical
nephrons) where as those with glomeruli in the juxtamedullary
region of the cortex(Juxtamedullary nephrons) have long loops
extending down into the medullary pyramids.
The ratio of the former to the latter is four is to one.
The total length of the thin segment of the loop of Henle varies
considerably, from about two and half millimeters to fifteen
millimeters in length.
It ends in the thick segment of the ascending limb which is about
thirteen millimeters in length.
They have numerous mitochondria, and the basilar portions of their
cell membranes are extensively invaginated.
The cells of the thick ascending limb are cuboidal.
The thick ascending limb of the loop of Henle reaches the
glomerulus of the nephron from which the tubule arose and passes
close to its afferent arteriole and efferent arteriole.
The walls of the afferent arterioles contain the rennin-secreting
juxtaglomerular cells.
At this point the tubular epithelium is modified histologically to form
the macula densa.
The juxtaglomerular cells, the macula densa and the lacis cells near
them are collectively known as the juxtaglomerular apparatus.
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE RENAL AND URINARY TRACT SYSTEMS.
4-PHYSIOLOGY,PATHOPHYSIOLOGY,AETIO-PATHOPHYSIOLOGY AND PATHOGENESIS
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE RENAL AND URINARY TRACT SYSTEMS.
The distal convoluted tubule is about five millimeters in length.
Its epithelium is lower than that of the proximal tubule, and although there are
few microvilli, there is no distinct brush border.
The distal tubules coalesce to form collecting ducts that are about twenty
millimeters in length, and passes through the renal cortex and medulla to
empty into the pelvis of the kidneys at the apexes of the medullary pyramids.
The epithelium of the collecting ducts is made up of principal cells (P cells),
which among other things respond to vasopressin with increased water
permeability and the Intercalated Cells (I cells), which secrete acid. In addition
there are I cells in the epithelium of the distal tubules.
The total length of the nephrons, including the collecting ducts, ranges from
forty five to sixty five millimeters.
Cells in the kidneys that appear to have a secretory function include not only
the juxtaglomerular cells, but also some of the cells in the interstitial cells of
the medulla.
These cells are called type I medullary interstitial cells.
They contain lipid droplets and probably secrete prostaglandins,
predominantly PGE2.
PGE2 is also secreted by the cells in the collecting ducts and prostacyclin
(PGI2),
as well as other prostaglandins is secreted by the arterioles and glomeruli.
The afferent arterioles are short, straight branches of the interlobular arteries.
Each divides into multiple capillaries branches to form the tuft of vessels in the
glomerulus.
The capillaries coalesce to form the efferent arteriole, which in turn
breaks up into capillaries that supply the tubules called the peritubular
capillaries.
Before draining into the interlobular veins.
The arterial segments between the glomeruli and tubules are thus technically a
portal system, and the glomerular capillaries are the only capillaries in the
body that drain into the arterioles.
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE RENAL AND URINARY TRACT SYSTEMS.
A brief overview of the Basic Renal Physiology and the mechanisms of urine production and elimination is pertinent.
4-Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
PHYSIOLOGY,PATHOPHYSIOLOGY,AETIO-PATHOPHYSIOLOGY AND PATHOGENESIS
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE RENAL AND URINARY TRACT SYSTEMS.
However, there is relatively little smooth muscle in the efferent arterioles.
The capillaries draining the tubules of the cortical nephrons form a peritubular
network, whereas the efferent arterioles from the juxtamedullary glomeruli
drain not only into a peritubular network but also into vessels that form hairpin
loops called the vasa recta.
These loops deep into the medullary pyramids alongside the loop of Henle.
Thus the tubule of each nephron does not necessarily receive blood supply
solely from the efferent arteriole of that nephron.
In humans, the total surface of the renal capillaries is approximately equal to
the surface area of the tubules, both being about thirteen millimeters squared.
The volume of blood in the renal capillaries at any given time is about thirty to
forty milliliters.
The kidneys have an abundant lymphatic supply that drains via the thoracic
duct into the venous circulation of the thorax.
The renal nerves travel alongside the renal blood vessels as they enter the
kidneys.
They contain many postganglionic sympathetic efferent fibers and a few
afferent fibres of unknown function.
There also appears to be a cholinergic innervation via the vagus nerve, but its
function is uncertain.
The sympathetic preganglionic innervation comes primarily from the lower
thoracic and upper lumbar segments of the spinal cord and the cell bodies of
the postganglionic neurons are in the sympathetic ganglion chain, in the
superior mesenteric ganglion and along the renal artery.
The sympathetic fibres are distributed primarily to the afferent and efferent
arterioles,
the proximal and distal tubules and the juxtaglomerular cells.
In addition, there is a dense noradrenergic innervation of the thick ascending
limb of the loop of Henle.
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4-PATHOPHYSIOLOGY, AETIO-PATHOPHYSIOLOGY AND PATHOGENESIS:
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An overview of the Basic Renal Physiology and the mechanisms of
urine production and elimination is pertinent.
In the nephrons which are the basic functional units of the kidneys, a
plasmacytoid fluid is filtered from the glomeruli capillaries into the renal
tubules.
This filtration process is an active process, therefore, glomerular filtration is an
energy dependent phenomenon.
The rate of this process of glomerular filtration is usually very rapid at about
two and half milliliters per kilogram per minute and is directly proportional to
an individuals body surface area.
Compared to the other tissue capillaries, the glomerular capillaries are usually
highly permeable, negatively charged with comparatively high pressure
gradients.
Relative to the afferent arterioles, the efferent arterioles have a much higher
resistivity.
It is the efferent arteriole from each glomerulus which breaks up into
capillaries that supply a number of different nephrons.
The glomerular filtration rate normo-equilibrium would normally be achieved
when, the glomerular efferent capillaries constrictive pressures is greater than
the afferent capillaries constrictive pressures.
The glomerular ultrafiltration is flow velocity rather than diffusability
dependent,therefore,like in most capillary meshworks, the filtration rate
through the glomerulus is dependent on the size of the glomerular capillary
stroma, its viscosity, conductivity and permeability coefficients, the
hydrostatic pressures, osmotic pressures, oncotic pressures gradients across
the glomerular capillary stroma and the net ultrafiltration surface area relative
to the osmotic pressure of the tubular filtrates.
The glomerular capillary hydrostatic pressure is usually in counterbalanced by
osmotic pressure gradient across the glomerular capillaries in addition to the
hydrostatic pressures in the Bowman’s Capsules this pressure equilibrations
will result in effective filtration.
Increased renal blood flow will invariably increase the glomerular filtration rate
by causing an increase in the exposed surface area of the capillaries along
which filtration of the blood will normally be taking place.
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE RENAL AND URINARY TRACT SYSTEMS.
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE RENAL AND URINARY TRACT SYSTEMS.
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A brief overview of the Basic Renal Physiology and the mechanisms of urine
production and elimination is pertinent
The size of the glomerular capillary stroma, available for glomerular
ultrafiltration is somewhat dependent on the relaxability,
retractability or contractibility of the mesangial capillary cells.
Dilatation and relaxations of the mesangial cells and glomerular
capillary points without trabeaculations or tortousities will enhance
the glomerular capillary surface areas available for ultrafiltration
with an increased renal filtration co-efficients.
The effective filtration fraction is the proportion of the glomerular
filtration rate to the Renal Plasma flow (RPF) which is usually about
one is to five.
However, the glomerular filtration rate is less dependent on the
systemic blood pressure compared to the RPF.
The filtration fraction is a function of the pressure changes due to
increased efferent arteriolar resistance when the renal plasma flow
RPF diminishes, the filtration fraction will invariably increase in
magnitude.
The Glomerular ultrafiltration rate and hence urine production rate
could be favoured by humoural mediators that cause relaxation of
the mesangial cells such as increased cyclic AMP, Prostaglandins
E,dopamine and atrial natriuretic peptide factors, some of these
factors such as dopamine and prostaglandins could also increase
the glomerular filtration rate through causing an increased renal
blood flow.
GFR could also be increased by increased systemic blood pressure
or afferent or afferent arteriolar constrictions.
Also in pathological conditions, the renal capsule is thin but tough.
If the kidneys becomes oedematous,the capsule limits the swelling
and the tissue pressure also called renal interstitial pressure then
rises.
This will decrease the glomerular filtration rate and it is postulated
that this will enhance and prolong the anuria in acute renal failure.
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A brief overview of the Basic Renal Physiology and the
mechanisms of urine production and elimination is pertinent
Tubular Function:
Three major processes namely, filtration, secretion and
absorption of substances take place in the tubules normally.
The quantity of any substance that undergoes filtration is
contingent on the glomerular filtration rate and the level of
that substance in the plasma, following filtration,
thereafter, the tubular cells may express more of a particular
substance into the filtrate in the tubules in a process called
tubular secretion or may take up some substances away
from the filtrate in a process called tubular absorption.
Almost always combinations of these processes are
involved.
The quantity of any substance excreted is equivalent to the
amount filtered and the net amount secreted or absorbed by
the renal tubules.
Small proteins and peptide hormones are reabsorbed in the
proximal tubules by a modified energy dependent diffusion
process otherwise referred to as endopinocytosis.
Whereas other substances are secreted or reabsorbed in the
tubules by passive or electrical gradients or actively
transported against such gradients.
Net motions of substances are by way of ion channels,
exchangers, cotransporters, ionic pumps and symports.
Therefore, the quantity of these solutes transported out of
the tubules is proportionate to the amount transiting the
tubules up to the Tm of the solute, but at higher
concentrations the transport systems could be overwhelmed
and there will be no significant increase in the amount
expelled out of the renal tubules.
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FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE RENAL AND URINARY TRACT SYSTEMS.
WATER FILTRATION AND REABSORPTION - URINARY
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mechanisms of urine production and elimination is pertinent
A wide range of anionic-cationic synports such as the
sodium-potassium-Hydrogen ions synports were
previously described and new mechanisms were
exponentially being described on daily basis.
The wide ranged differential distributions of these
ionic components between the proximal tubular
lumen and interstitium facilitates the net motion of
solutes across the epithelium to be achievable.
Sodium is mainly reabsorbed in the proximal tubules,
the thick portion of the ascending limb of the loop of
Henle, the distal tubules and the collecting ducts.
Sodium transport is coupled to the movement of
hydrogen ions, glucose, chloride, amino acids, lactate,
bicarbonates, citrates organic acids, phosphates, other
electrolytes, and other substances across the tubules.
These transport systems in the renal systems are like
active or passive transport systems elsewhere by
being energy dependent, or having a maximal rate or
transport maximum(Tm) at which they can transport
sodium, glucose or other solutes.
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A brief overview of the Basic Renal Physiology and the mechanisms
of urine production and elimination is pertinent.
Of relevance in the renal transport mechanisms is also the concept of the renal
threshold for particular substances such as glucose above which they cannot
be absorbed into the renal tubules and must move down the tubules to be
expressed in urine.
If an unduly copious amount of any solute is ingested, the solute will be
absorbed into the renal tubules, until the renal threshold or the transport
maximum of the solute is attained then the outstanding portion will then move
down the tubules to be expressed in the urine.
This outstanding solute will move on an obligatory volume of water with it.
This will manifest clinically as polyuria, nocturia and in children will favour
enuresis.
Other substances and drugs that are normally produced or metabolized in the
body and secreted into the tubular fluid such as steroids hormones,
conjugated substances such as sulfates, glucoronides ,and the principal
metabolite of several putative neurotransmitters or humoural factors on
excretion will usually carry on with it an osmotic load.
After glomerular ultrafiltrations, whilst in the distal tubules and the collecting
ducts most of the water is reabsorbed, however only a very small proportion of
water will be needed for the obligatory solute excretion.
When a lot more water is retained in the body compared to solutes, the urine
will be concentrated with a high osmolality or specific gravity.
Where as when excess water is lost from the body much more than solutes,
the urine will be dilute with low osmolality or specific gravity.
The latter phenomena will favour polyuria, nocturia and enuresis in children.
Normally, more than one half of the filtered water and solutes especially
sodium, glucose, bicarbonate should have been reabsorbed by the time fluids
are leaving the proximal convoluted renal tubules.
The descending limb of the loop of Henle is permeable to water, but the
ascending limb is impermeable to water.
However an effective Sodium-Potassium-Chloride co-transport synport exists
for their reuptake at the ascending portion of the loop of Henle.
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A brief overview of the Basic Renal Physiology and the mechanisms of urine production and elimination
The fluid in the descending limb of the Loop of Henle becomes hypertonic as
water moves into the hypertonic interstitium.
In the ascending portion of the loop of Henle the fluid becomes more dilute, as
the fluid moves further on the ascending loop of Henle, it gets more hypotonic
relative to plasma because of the effective efflux of Sodium and Chloride out of
the ascending tubular lumen.
This Sodium-Chloride efflux is associated with further water absorption from
this portion of the renal tubules.
Though structurally distinct, but microanatomically, and physiologically, the
distal convoluted renal tubules are similar to the thick segment of the
ascending limb of loop of Henle,in its relative impermeablity to water and
further incessant removal of solutes relative to water further diluting the
tubular fluid more, the distinction is in the reabsorption of sodium which is
non-cotransported or symported but rather is regulated by aldosterone,
sodium influx encourages limited passive water re-absorption at this point.
Antidiuretic hormones or vasopressin from the posterior pituitary glands or
pars nervosa increases the permeability of the collecting ducts to water by
facilitating instantaneous cyclic AMP mediated insertions of water channels
into the luminal membranes of the luminal cells
The concentrating mechanisms depend upon the maintenance of a gradient of
increasing osmolality along the medullary pyramids.
This gradient is produced by the operation of the loops of Henle as
countercurrent multipliers and maintained by the operation of the vasa recta as
countercurrent exchangers.
A countercurrent fluid system is one in which the fluid inflow runs parallel to,
counter and in close proximity to the fluid outflow for some structural
length.This phenomenon is operational in the renal medulla where the loops of
Henle and also the vasa recta abuts into.
The operation of each Loop of Henle as a countercurrent multiplier depends on
the active transport of sodium and chloride out of the thick ascending limb, the
high permeability of its thin descending limb to water and the inflow of tubular
fluid from the proximal tubule, with continual inflow into the distal tubule.
The gradient against which sodium and chloride are pumped are reduced and
more enters into the interstitium, as hypotonic fluid flows into the distal tubule,
and also as the isotonic and subsequently hypertonic fluid flows into the
ascending thick limb, these processes are repeated through several cycles
until there is an osmotic gradient between the uppermost and the lowermost
portions of the Loop of Henle.
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In the Juxtaglomerular nephron with longer loops and thin ascending limbs,
the osmotic gradients is spread over a greater surface area and space and the
osmolality at the uppermost part is a lot steeper.
Given that the thin ascending limb of the loop of Henle
is relatively impermeable to water but permeable to sodium and chloride, so
these ions move down their concentration gradients into the renal interstitium
and supports an additional countercurrent multiplication.
The longer the Loop of Henle, the steeper the osmolality gradient achievable at
the uppermost part of the pyramid.
This osmotic gradient achieved in the medullary pyramids will not be
sustainable if the sodium and urea in the renal interstitial spaces were rapidly
eliminated by the circulating blood.
However, the vasa recta by acting as a countercurrent exchangers maintains
these solutes in the pyramids.
These solutes, diffuses out of the vessels conducting blood towards the renal
cortex and into the vessels descending into the pyramid.
The Sodium Potassium Pumps and symports facilitates these diffusion
processes.
Conversely, water diffuses out of the descending vessels and into the
ascending vessels.
Therefore the solute tends to recirculate in the medulla and water tends to
bypass it, so that hypertonicity is maintained.
The water removed from the collecting ducts in the pyramids is also removed
by the vasa recta and it enters the general circulation.
It should be noted that countercurrent exchange is a passive process which
depends on the diffusion of water and solutes in both directions across the
permeable walls of the vasa recta and could not maintain the osmotic gradient
along the pyramids if the process of countercurrent multiplication in the loops
of Henle were to stop.
There is a very large osmotic gradient in the loop of Henle and in the presence
of vasopressin in the collecting ducts, it is the countercurrent that makes this
gradient possible by spreading it along a system of tubules one centimeter or
more in length rather than across a single layer of cells that is only a few
micrometers thick.
Urea contributes to the initiation and sustainability of the osmotic gradient in
the medullary pyramids and to the ability to form a concentrated urine in the
collecting ducts, because urea moves passively out of the proximal tubules,
but except for the inner portion of the collecting duct, the rest of the tubular
epithelium is virtually impermeable to urea.
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A brief overview of the Basic Renal Physiology and the mechanisms of urine
production and elimination
A brief overview of the Basic Renal Physiology and the mechanisms of urine
production and elimination
Consequently, urea is increasingly concentrated in the fluid as water is removed in the loop
and distal tubule.
However when the inner medullary portions of the collecting duct is approached, urea
moves into the interstitium of the pyramids, adding to the hyperosmolality.
The movement of urea in this portion of the collecting duct is facilitated by vasopressin.
Conversely, when the tubular fluid reaching this region is dilute in the absence of
vasopressin, urea moves from the interstitium into the tubular lumen and the osmotic
gradient in the pyramids is reduced.
The amount of urea in the medullary interstitium and consequently in the urine varies with
the amount of urea filtered, and this in turn varies with the dietary intake of proteins.
Therefore, a high protein diet increases the ability of the kidneys to concentrate urine,
where as a low dietary protein intake will favour a dilute urine, polyuria and in children
enuresis.
Of a growing interest to the postulated renal phenomena that could favour enuresis in
childhood is the phenomena of Osmotic diuresis and water diuresis, in which the presence
of large quantities of unreabsorbed solutes in the renal tubules could cause an increase in
the urine volume.
Solutes that are not reabsorbed in the proximal tubules exert an appreciable osmotic effect
as the volume of tubular fluids decreases and the concentrations of those solutes
increases.
Therefore they retain water in the tubules.
In addition, there is a limit to the concentration gradient against which sodium could be
pumped out of the proximal tubules.
Normally, the movement of water out of the proximal tubules prevents any appreciable
gradient from developing, but the sodium concentrations in the fluid falls when water
reabsorption is decreased because of the presence in the tubular fluid of increased
amounts of unabsorbable solutes.
The limiting concentration gradient is approached, and further proximal reabsorption of
sodium is prevented, therefore more sodium remains in the tubules and an obligatory
quantity of water will be kept with the sodium.
The result is that the Loop of Henle is presented with a greatly increased volume of isotonic
fluid.
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE RENAL AND URINARY TRACT SYSTEMS.
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE RENAL AND URINARY TRACT SYSTEMS.
A brief overview of the Basic Renal Physiology and the mechanisms of urine production and elimination
This fluid has a decreased sodium concentration, but the total amount of
sodium reaching the loop per unit time is increased.
In the loop, reabsorption of water and sodium is decreased, because the
medullary hypertonicity is decreased.
The decrease is due primarily to decreased reabsorption of sodium,
potassium, and chloride in the ascending limb of the loop of Henle because the
limiting concentration gradient for sodium reabsorption is reached.
More fluid passes through the distal tubules and because of the decrease in
the osmotic gradient, along the medullary pyramids, less water is reabsorbed
in the collecting ducts.
The result is a marked increase in urine volume and excretion of sodium and
electrolytes and this will favour polyuria and enuresis.
Osmotic diuresis is usually produced by the presence of large amounts of
starchy polysaccharides and other naturally occurring substances which are
usually filtered into but not reabsorbed by the tubules at all, partly absorbed or
completely absorbed by the kidneys.
However, occasionally as demonstrated from the author’s lengthy research
experience from a representative sample in this topic, the contribution of this
aspect of osmotic diuresis to enuresis in childhood could have been
overemphasized, because, from his series, historical notes inferring nonexcessive or compulsive, non-nocturnally weighted fluid or food intake
undermined the contributory aetio-pathogenic roles of osmotic diuresis in his
studies subsets.
Large amounts of glucose, sodium chloride and urea if present in the tubules
after filtrations in amounts exceeding their transport maxima TmG could cause
polyuria, nocturia and in childhood favour enuresis.
In water diuresis, a binge of an acute water imbibition produces an
infinitesimal diminution in vasopressin secretion before the water is absorbed,
although most of the inhibition of vasopressin expression is produced by the
decrease in plasma osmolality after the water is re-absorbed.
Water diuresis usually occurs less than an hour after the ingestion of copious
amounts of hypotonic fluids, so excessive compulsive late night fluid
ingestion just before reclining to bed will favour nocturia and in childhood
nocturnal enuresis.
With increasing load of the excreted solute, the concentration of the urine
approaches that of the plasma, despite an optimal vasopressin expression,
because an increasingly huge fraction of the excreted urine is isotonic
proximal tubular fluid in transit.
Hence osmotic diuresis could still occur in the presence of vasopressin when
the solute intake is considerably bouty and copious.
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Although exacerbations of these two phenomena could favour polyuria and
childhood enuresis, their driving mechanisms differ in that, in water diuresis,
the amount of water reabsorbed from the proximal tubules and the maximal
urine flow rates are fairly constant, whereas in osmotic diuresis, increased
urine flow rates follows decreased water absorption at the proximal tubules
and loops of Henle and this favours polyuria and nocturnal enuresis.
Humoural mediators and mechanisms influencing urine production
in the renal tubules:
The Renin-Angiotensin-Aldosterone mechanisms ,Atrial Natriuretic Factor, Anti
diuretic hormones [vasopressin],prostaglandins and other putative humoural
factors were some of the mediators of fluid, electrolyte balance regulations
and could influence the diurnal variation in urine production and hence
enuresis.
Renin is an acidic aspartyl protease secreted by the kidneys after production
at the Juxtaglomerular apparatus comprising of the lacis cells, the JG cells and
the macula densa into the blood stream.
There appears to be some rennin produced from the mesangial cells.
Its preprohormone are preprorenin and prorenin respectively.
They are physiologically inactive, and their conversion to the active form
usually takes place in the kidneys.
The details of this conversion process are complex and still somewhat
controversial.
The half life of rennin in circulation is about an hour.
The up regulation of its secretion is probably humoural especially
prostaglandins, prostacyclin and natriemia mediated.
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While in the liver, Rennin normally acts on its substrate angiotensinogen an
alpha 2 globulin which is a glycopeptide produced in the hepatic endoplasmic
reticulum and splits off angiotensin I.
Whilst circulating through the endothelium of the lungs parenchyma
especially and other systemic endothelium also, an Angiotensin converting
enzyme (ACE) a dipeptidyl-carboxypeptidase cleaves off histydyl-leucine from
the physiologically inactive angiotensin I synthesizing an octapeptide
angiotensin II. Angiotensin II acts directly on the adrenal cortex, especially, the
zona glomerulosa to increase the secretion of aldosterone, the renninangiotensin system is a principal modulator of adosterone secretion.
Angiotensin II stimulates increased secretion of vasopressin and ACTH there
by increasing water ingestion, and the arterial blood pressure.
This effects are unlikely to be due to its direct effect on the cerebral neurons
since it does not cross the blood brain barrier, but it is likely related its cytohumoural effect on the circumventricular organs, which are four small organs
outside the blood-brain barrier.Of utmost relevance of these organs are the
subfornical organs [SFO] and the organun vasculosum of the lamina terminalis
[OVLT], which are concerned mainly with increase in water intake
(poylydipsogenic) effects, where as the area postrema is concerned mainly
with vasopressor effects.
All these organs are probably responsible collectively for the contributions to
increases in vasopressin and ACTH secretion.
Vasopressin has antidiuretic effect by causing permeability changes at the
collecting ducts so that water enters the hypertonic interstitium of the renal
pyramids.
With diminution in the levels of vasopressin urine volume increases.
Of interest in the Renin-Angiotensin-aldosterone-vasopressin mechanisms is
the role of angiotensin III a bye product of angiotensin II metabolism by a
catabolic aminopeptidase enzyme found principally in the red blood cells and
other tissues called angiotensinase by the cleavage of the Aspartate residue
from the N terminal end of the peptide.Unlike most peptide fragments, this
resulting heptapeptide has a considerable physiologic activity.
The angiotensinase could also convert angiotensin I through isomerisation to
des-Aspartate angiotensin I which could then be converted directly to
angiotensin III by the action of the angiotensin converting enzyme.
Pulmonary and other extrapulmomary tissues entrapment appears to be other
mechanisms involved in the elimination of angiotensin II from the circulation.
The physiological activities of both angiotensin II and angiotensin III are quite
comparable with regards to its aldosterone stimulating effect, where as the
pressor effect, of the latter is probably less than one-half of that of the former.
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Also of further relevance in the pathophysiology of enuresis are the natriuretic
hormones, especially with those secreted by the heart muscles mostly in
response to stretch.
The myocytes in the atria contain secretory granules that undergoes
hyperplasia in response to increases in distension and stretch related to
increased body sodium, chloride,
Increased blood, plasma or extra cellular fluid volumes by causing some
natriuresis.
The initial and most significant of these hormones include the atria natriuretic
peptide
(ANP), a cyclic polypeptide hormone with a twenty eight amino acid residues
formed by a cysteine derived disulfide bond.
Its preprohormones are considerably larger polypeptides with about six times
its amino acid composition.
The other natriuretic hormones found principally in the brain, such as Brain
Natruretic peptide (BNP) and the CNP are probably of less import to the
pathophysiology of enuresis and their genomic determinations considerably
differs.
There are several postulated mechanisms through which, Atrial Natriuretic
Factor could cause natruresis such as by leading to an increase in the
glomerular filtration rate (GFR)
There are ANF receptors on the mesangial cells in the glomeruli and the
relaxation of these cells produced by ANP presumably increases the effective
surface area available for glomerular filtration.
Also it is possible that ANP could act directly on the tubules to promote
natruresis.
However, the exact mechanisms are largely undetermined and the ongoing
postulations are largely speculative. ANF decreases the responsiveness of the
zona glomerulosa to stimuli that normally increase aldosterone secretion, it
also inhibits the secretion of vasopressin or antidiuretic hormone.
Infact,the actions of ANF are actually opposite to that of the angiotensin II.
The magnitude of ANF secreted is directly related to the degree to which the
atria are stretched following increases in central venous pressures.However,
circulating ANF has a considerably short half life.
Other circulating natriuretic factors of less significance include putative
steroids compounds with their productions principally localized to the
suprarenal glands.They have Sodium-potassium ATPase-Inhibiting activities
and there by causes natriuresis.
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Impulsation of the urinary system and The Regulation of urinary continence:
Parasympathetic nerve fibres relayed through the pelvic splanchnic nerves.
support the principal motor impulsation of the bladder Sympathetic fibres
emanate from
L1 and L2 segments of the cord via the superior hypogastric and pelvic
plexuses.
For most of the bladder the sympathetic fibres are vasomotor and probably
inhibitory to the detrusor muscle, but as noted above they supply the
superficial trigonal muscle and (in the male) the internal urethral sphincters.
The sensation of normal bladder distension travels with parasympathetic
fibres, and it appears that painful stimuli to the bladder will be relayed to the
spinal cord through both the parasympathetic and sympathetic pathways.
The detrusor or smooth muscles of the bladder like that of the ureters are
arranged in spiral, longitudinal and circular fascicles.
Contraction of the bladder detrusor muscle is mainly responsible for its
emptying during micturition.
Muscle bundles pass on either side of the urethra and these fibers are
sometimes called the internal urethral sphincter, although anatomically, they
do not encircle the urethra completely normally, but functionally they are very
competent
Further along the urethra there is a sphincter of skeletal muscle, the sphincter
of the membranous urethra referred to as the external urethral sphincter.
The bladder epithelium is made up of a superficial layer of flat cells and a deep
layer of cuboidal cells.
The bladder detrusor muscle receives parasympathetic motor innervation from
the pelvic nerves derived from the S2, S3 and S4 spinal segments, where as its
sensory innervation is derived mainly from the S2 component of the pelvic
nerves, whereas its sympathetic motor innervation is derived from the
descending roots of the hypogastric nerves with contributions from the L1, L2,
L3 segments forming the inferior mesenteric ganglion which innervates both
the descending colon and the bladder detrusor muscle.
The somatic innervation to the external urethral sphincter is through the
pudendal nerves which are derived from the S1, S2, S3 spinal segments, where
as its sensory supply is mainly from the S2 segment.
Although the neuronal impulsation of the bladder is rather anatomically basic,
however several complexities could arise if its basic physiology is disturbed.
The physiology of micturition and its disorders are subjects about which there
is much controversy.
Micturition is fundamentally a spinal reflex facilitated and inhibited by higher
neuronal centers and like defecation, subject to voluntary control, facilitation
and inhibition.
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Impulsation of the urinary system and The Regulation of urinary continence:
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE RENAL AND URINARY TRACT SYSTEMS
THE FUNCTIONAL MICROSCOPIC ANATOMY OF THE URINARY BLADDER
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE RENAL AND URINARY TRACT SYSTEMS
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE RENAL AND URINARY TRACT SYSTEMS
THE NEUROPHYSIOLOGY AND THE NEURAL REGULATION OF MICTURITION
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE RENAL AND URINARY TRACT SYSTEMS
NEURAL REGULATION OF MICTURITION
4-PATHOPHYSIOLOGY, AETIO-PATHOPHYSIOLOGY AND PATHOGENESIS:
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE RENAL AND URINARY TRACT SYSTEMS
A brief overview of the Basic Renal Physiology and the mechanisms of urine production and elimination
Urine enters the bladder without producing much increase in intravesical
pressure until the viscus is well filled.
In addition, like the other subsets of smooth muscles, the bladder muscle has
the property of plasticity, during stretch, because the initially produced tension
is not sustained.
The relationship between the intravesical pressure and volume could be
studied in a procedure known as cystometry, in which following the insertion
of a transducer-catheter and bladder emptying, the intravesical pressure
changes as the bladder is being filled with graded increments of water or air
could be recorded.
Following this procedure a cystometrogram could be derived, which is a plot
of intravesical pressure against the volume of fluid in the bladder.
Ideally, for a non-pathological cystometrographic curve at the first instance, a
slight rise in pressure with initial increases in the volumes are produced, a
long nearly flat segment as further increments in volume are produced, and a
sudden sharp rise in pressures as the micturition reflex is triggered.
he pattern of the second flat and lengthy component of the curve is consistent
with the law of Laplace, which suggests that the pressure in a spherical viscus
is equal to twice its wall tension divided by its radius.
Attainments of these three components are physiologically important and are
quite relevant for the attainment of a normal urinary regulation and during
regular and remedial urinary regulation training.
The initial voiding urge is felt at a bladder volume of about three milliliters per
kilogram body weight and a marked sense of fullness with considerable
urgency at a volume of about eight milliliters per kilogram body weight.In the
case of the bladder, the tension increases as the organ fills, but so does the
radius.
Therefore, initially, the intravesical pressure increase is inconsequential until
the bladder is relatively full.
Normal bladder emptying occurs by detrusor muscle contractions and
reciprocal external sphincter and pelvic floor muscles especially the levator
ani muscles relaxabilties.
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE RENAL AND URINARY TRACT SYSTEMS
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE RENAL AND URINARY TRACT SYSTEMS
URINARY BLADDER CONTRACTION AND RELAXATION: PHYSIOLOGY AND PATHOPHYSIOLOGY
4-PHYSIOLOGY, AETIO-PATHOPHYSIOLOGY AND PATHOGENESIS:
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE RENAL AND URINARY TRACT SYSTEMS
A brief overview of the Basic Renal Physiology and the mechanisms of urine production and elimination
Initially, following bladder filling, intravesical tension does not increase as
such, due to relaxability of the bladder detrusor muscle leading to relative
bladder muscle hypotonicity and accommodation of the influxing urine,
however with a progressive collection of urine, the bladder muscle walls are
distended with time causing an augmented hypertonicity which induces the
stretch receptors responsible for afferent impulses relay, traveling along the
pelvic splanchnic nerves to the sacral segments of the cord.
The parasympathetic cell bodies are in turn stimulated and efferent impulses
travel to the pelvic splanchnic nerves synapsed to the postganglionic cells
within the bladder wall where contractions could be initiated.
The autonomic stretch reflex giving bladder control at the spinal level is typical
of the infant with urinary regulatory training, with time and further
sophisticated neuronal development, urinary regulation by higher more
encephalised cortico-cerebral neuronal centres becomes dominant compared
to the influence exerted by their spinal counterparts and then bladder
evacuation is triggered off and is usually assisted and sustained by voluntary
contractions of the abdominal muscles.
There is a cerebral cortical micturition facilitatory centre on the medial surface
of the cerebral hemisphere, in the middle frontal gyrus in close proximity to the
anterior aspect of the motor area impulsating the perineal region with fibres
passing to a detrusor motor centre in the medial part of the pontine reticular
formation which corresponds to the Pontine Micturating Centre. (PMC)
From there, reticulospinal fibres run down the spinal cord along with those of
the lateral corticospinal tract to the sacral spinal segments.
The smooth muscles from the bladder are usually continual with the
longitudinal smooth muscle of the urethra.
The external sphincter of skeletal muscle is controlled by the perineal branch
of the pudendal nerves which is derived from the anterior horn cells of
approximately the same cord segments that gave origin to the pelvic
splanchnic nerves.
The sphincter will normally relax as the bladder detrusor muscle contracts.
Towards the cessation of micturition, the pubovaginalis part of the levator ani
muscle will complement the contractility of the external urethral sphincter.
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE RENAL AND URINARY TRACT SYSTEMS
THE PHYSIOLOGY OF MICTURITION
4-PHYSIOLOGY,PATHOPHYSIOLOGY, AETIO-PATHOPHYSIOLOGY AND PATHOGENESIS:
A brief overview of the Basic Renal Physiology and the mechanisms of urine production and elimination.
The smooth muscle of the bladder wall the detrusor is composed of an
interlacing network of fibres running in different directions.
Both externally and internally (beneath the mucous membrane) they produce a
trabaculated appearance.
They are well supplied by parasympathetic (cholinergic) nerves fibres.
However, the trigone possesses a superficial triangular layer of muscle (the
superficial trigonal muscles) that is histological and histochemically different
from the rest of the bladder musculature (including the deep part of the
trigone) and extends into the proximal urethra in both genders.
In further contrast to the detrusor muscles, the superficial trigonal muscle
receives predominantly sympathetic (adrenergic) fibres.
The significance of this distinctive patch of muscle is not clear but it is
postulated that it may assist in the closure of the urethral orifices.
At the internal urethral orifice in the male, circular smooth muscle fibres
provide an internal urethral sphincter.
In the male child, the circular smooth muscles are continuous with the smooth
muscle of the prostate and the seminal vesicles, and like the superficial
trigonal muscles are profusely supplied with sympathetic (adrenergic nerves)
In the female child, muscles in this region are arranged longitudinally so there
is no internal sphincter of muscles as such, suggesting that the sphincter has
no role to play in incontinence as such.
In summary, arousal to the sensation of a full or contracting bladder involves
interconnected anatomic areas, including the cerebral cortex, the reticular
activating system (RAS), the locus ceruelus (LC), the hypothalamus, the
pontine micturating centre (PMC), the spinal cord and the bladder.
Following lesions of the brain stem just above the pons, the threshold for
micturition is lowered less bladder filling is required to trigger the micturition
act, whereas with neuropathologies above the midbrain, the threshold for the
micturition reflex is essentially normal.
The RAS controls depth of sleep, the LC controls arousal, and the PMC
initiates the command for a detrusor contraction. Various neurotransmitters
are involved, including noradrenaline, serotonin, and antidiuretic hormone
(ADH)
4-PHYSIOLOGY,PATHOPHYSIOLOGY, AETIO-PATHOPHYSIOLOGY AND PATHOGENESIS:
A brief overview of the Basic Renal Physiology and the mechanisms of urine production and elimination.
4-PHYSIOLOGY,PATHOPHYSIOLOGY, AETIO-PATHOPHYSIOLOGY AND PATHOGENESIS:
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE RENAL AND URINARY TRACT SYSTEMS
A brief overview of the Basic Renal Physiology and the mechanisms of urine production and elimination.
The mechanism by which voluntary urination is initiated remains unsettled.
During micturition, the perineal muscles and the external urethral sphincters
are relaxed, the detrusor muscles contracts, and urine effluxes through the
urethra.
These bands of smooth muscles on either sides of the urethra apparently play
no role in micturition.
One of the initial events during the onset of micturition is relaxation of the
muscles of the pelvic floor, and this may cause a sufficient down ward tug on
the detrusor muscles to initiate its contractions.
The perineal muscles and external sphincters could be contracted voluntarily,
preventing urine from passing down the urethra or interrupting the flow once
micturition has begun.
It is through this adaptive ability to maintain the external sphincter in a
tonically contracted state that adults are able to delay micturition until the
opportunity to void presents itself.
After micturition,the female urethra empties by gravity,whereas urine
remaining in the urethra of the male is expelled by several contractions of the
bulbocavernosus muscle.
The Involuntary Regulation of Micturition:
The bladder smooth muscle has an inherent contractile activity, however when
its nerve supply is intact, stretch receptors in the bladder wall initiate a reflex
contraction that has a lower threshold than the inherent contractile response
of the muscle.
Fibers in the pelvic nerves are the afferent limb of the micturition reflex, and
the parasympathetic fibers to the bladder that constitute the efferent limb also
relayed in these nerves.
The reflex is integrated in the sacral portion of the spinal cord.
The volume of urine in the bladder that normally initiates a reflex contraction is
about 6-8mls/kg.
In childhhod, the sympathetic nerves to the bladder play no part as such in
micturition.
but they do mediate the contraction of the bladder muscle.
There is no small motor nerve system to the stretch receptors in the bladder
wall, but the threshold for the voiding reflex, like the stretch reflexes, is
adjusted by the activity of the facilitatory and inhibitory centres in the brain
stem.
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE RENAL AND URINARY TRACT SYSTEMS
4-PHYSIOLOGY,PATHOPHYSIOLOGY, AETIO-PATHOPHYSIOLOGY AND PATHOGENESIS:
FUNCTIONAL ANATOMY AND PHYSIOLOGY FOR THE RENAL AND URINARY TRACT SYSTEMS
A brief overview of the Basic Renal Physiology and the mechanisms of urine production and elimination
There is a facilitatory area in the pontine region and an inhibitory
centre in the midbrain.
There is another facilitatory area in the posterior hypothalamus.
With lesions of the superior frontal gyrus, there appears to be inertia
in the desire to micturate, but there also appears to be some
difficulty in cessation of micturition once it was initiated.
However, several neurophysiological studies suggest that other
cortical areas also affect the micturition process.
The bladder can be made to contract by voluntary facilitation of the
spinal voiding reflexes when it contains only a few milliliters of
urine.
Voluntary contraction of the abdominal muscles aids the expulsion
of urine by increasing the intra-abdominal pressure, but micturition
could be initiated without straining even when the bladder is nearly
empty.
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4-Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
The Physiology of Normal Micturition Control:
Nocturnal continence is usually achieved following the achievement
of diurnal continence.
By the age of two, children start to develop the ability to voluntarily
relax the external sphincter and initiate voiding, even in the absence
of the desire to void.
On the average by the age of four years, all children with normal
bladder function should have achieved continence.
Several psychosocial factors without obvious organic lesions could
determine the age of attainment of nocturnal bladder regulation.
Physiology of Attainment of Normal Urinary Continence:
For Day Time Continence conservative figures suggest that:
One out of every other two children will achieve day time continence
by the age of thirty months, whereas nineteen out of every twenty
children will achieve day time continence by the age of forty eight
months.
For Night Time Incontinence:
Two out of every three children will achieve night time continence by
the age of thirty six months where as three in every fourth child will
achieve night time continence by the age of forty eight months.
Nine of every tenth child will achieve night time continence by the
age of ninety six months.
Forty nine out of every fifty children will achieve night time
continence by the age of one hundred and forty four to one hundred
and eighty months respectively.
4-Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
The Aetiology of Enuresis:
To date, the current status of research into the pathophysiology of nocturnal enuresis is
still quite enigmatic and a unified model for the aetiopathogenesis of nocturnal enuresis
has been unachievable.
The current belief is that the aetiopathogenic factors for this condition is multifactorial.
Numerous etiologic factors were investigated, and various theories were proposed.
In trying to achieve the pathophysiological basis for enuresis patho-biological,
psychogenic, philosophical, anthrpological and traditional concepts were occasionally
implicated.
However, putatively, of all these aetiological phenomena in enuresis, Idiopathy, genetic
considerations and maturational delays, were the most frequently suggested putative
aetiopathogenic mechanisms.
Most types of enuresis are usually associated with an inappropriate or inadequate infantile
urinary bladder training in a developmentally normal child or a suboptimal micturition
training in a child with a comparatively developmental lag in bladder control mechanisms,
without other urinary or neuropsychological disturbances and unduly more doting parents.
Return of enuresis in a child who was previously stable always suggests either the
occurrence of urinary tract infections either overtly or asymptomatically or else
psychological stress at home, at school or at play.
Primary nocturnal enuresis is caused by a disparity between bladder capacity and
nocturnal urine production and failure of the child to awaken in response to a full bladder.
Less commonly, enuresis is secondary to a medical, psychological or behavioural problem.
The prevalence of nocturnal enuresis is three times that of daytime wetting, with rates of
one in fifteen in younger children and one in thirty three in older children.Three times as
many boys are affected compared to girls.
The main classifications of enuresis are primary or secondary and monosymptomatic
(uncomplicated) or nonmonosymptomatic (e.g., accompanied by lower urinary tract
symptoms).
Children with primary nocturnal enuresis are monosymptomatic, with no history of bladder
dysfunction and no lower urinary tract symptoms other than nocturia.
Secondary causes of enuresis, which account for less than one in four of the cases, include
urinary tract infection, bladder dysfunction, chronic renal failure, constipation, pinworm
infection, diabetes insipidus or diabetes mellitus, hyperthyroidism, sickle cell disease,
obstructive sleep apnea, psychological stress, or seizure disorder.
When enuresis develops during a period of stress in a child with no history of the
condition, underlying psychological stressors should be suspected.
4-Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
Physiologic Causes of Diurnal Enuresis includes:
Functional Enuresis:
Only a very small proportion of bedwetters are also wet by the day.
Children with both day and night wetting are more difficult to treat and often
have other symptoms such as urinary urgency or faecal soiling which
distinguish them from both those with nocturnal enuresis alone.
It is often assumed by parents that if there is no underlying physical disorder,
enuresis are due to laziness, a deliberate avoidance of the effort needed to
achieve bladder control by the child and gain continence, however, bladder
control is usually achieved without much effort.
However nocturnal enuresis cannot be due lack of effort because the children
are otherwise asleep.
Developmentally, children become dry during the day before they achieve
dryness at night.
Functional nocturnal enuresis is more common in males, than females, males
become dry latter, are more likely to relapse after a period of continence and
are slower in achieving a spontaneous cure.
Other studies suggested that in nine of twenty instances of twenty four to
thirty six months old girls to be dry at night compared with one in three of the
boys.
By their middle teens, twice as many boys as girls are enuretic.
These subsets could also respond to Indomethacin and other selective
NSAIDS intimating that defective humoural factors maturations and
regulations, especially prostaglandins rather that neurogenic maturational lag
may be other putative aetiopathogenic mechanisms.
4-Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
Nocturnal enuresis is akin to developmental disorders in general such as
language, motor or visuo-spatial skills in several respects:
[1]-The prevalence falls with age
[2]-Boys are more often affected than girls.
[3]-It is much more represented in intellectually retarded children.
[4]-The condition is familial and has a genetic constituent.
Seven of Ten children with enuresis have a first degree relative who previously
had the disorder and the concordance for enuresis is greater in uniovular
compared to binovular twins.
Children with developmental delays especially boys may fail to acquire urinary
regulation or break down in response to stressful life events.
This may prove disappointing and frustrating to his effortful and
overenthusiastic parents who may then use a coercive child rearing and
bladder training techniques.
This adds to the anxiety surrounding urinary training and may further delay in
the acquisition of urinary regulation.
It creates a setting in which a developmental symptom becomes perpetuated
and transformed into an emotional disorder with mutually reinforcing patterns
of maladaptive behaviour between the child and his parents.
While coercive child rearing practices have often been incriminated as a cause
for enuresis, its negative impact has been considerably reduced where
parental counseling were carried out by a paediatrician during early infancy
and childhood with the aim of allaying parental anxiety about possible delays
in achieving bladder regulation and the avoidance of coercive training
techniques.
Vaginal reflux of urine.
Reflux of urine into the vagina during micturition occurs frequently after
normal voiding, when girls stand up and walk, the urine seeps out of the
vagina, wetting their under wears.
4-Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
Giggle Incontinence.
Children may also be affected by giggle incontinence, an involuntary response
to laughter.
In giggle incontinence, there is a sudden, involuntary, uncontrollable, and
complete emptying of the bladder when giggling or laughing.
It could also be caused by tickling or by excitement.
Urgency Incontinence.
This could be defined as an attack of intense bladder spasms that leads to
abrupt voiding and wetting.
In about one in thirty three instances, enuresis could be pathological.
Organic causes of diurnal enuresis account for less than one in twenty cases
of diurnal enuresis, the other factors are rather idiopathic.
Idiopathic factors:
[A]-Tardively developing neurological system signals.
When nocturnal enuresis occurs between the ages of sixty months and one
hundred and twenty months,factors such as a limited bladder
capacity,prolonged sleep periods,and pertubartions of the micturition alarms
signals relative to the filling or emptying state of the urinary bladder due to
immaturity or delayed maturity were implicated most frequently.
Invaiably, most children wet because their bladders have not matured.
This form of incontinence will fade away as the bladder capacity incases with
age and the natural alarms becomes well tuned and operational.
In these idiopathic cases, the cause is uncertain and probably represents an
inconsistency in the processes of impulsation, relay and execution of the
cerebral cortical, sub-cortical signals to the somatic, vegetative and automatic
innervations of bladder.
Although the cause of enuresis is not precisely or perfectly known, in these
instances,
it appears to involve delayed maturation of the cortical mechanisms that allow
the voluntary control of the micturition reflex.
4-Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
Therefore, enuresis in some children may just represent a constitutional
delayed chronologically dependent micturition regulatory maturational
sequence ladders have no warning signals that indicate
In functional enuresis, a neurophysiological maturational lag was the most
plausible putative defect in the acquisition of continence, this maturational
delay is implicated most in the primary type and in the secondary form of
enuresis, it is considered an important, predisposing and contributing factor in
the development of enuresis or the relapse of urine control in response to
stress or a urinary tract infection.
Furthermore, both primary and secondary enuresis were associated with
delays in early speech development.
Although, neurogenic maturational processes are basic to the acquisition of
urinary control and are an essential requisite for learning day time urinary
control and for spontaneously acquiring urinary continence at night, however,
the aetiology of enuresis is almost certainly multifactorial.
Children with enuresis, have their urinary bladders still functioning like an
infant’s urinary bladder, which basically contracts unregulated, these
contractions are known as uninhibited contractions.
More often than not the real problem is that their that their bladder is filling or
is already full.
Imbalance of humoural factors such as prostaglandins could also be probably
be implicated.
Only a few fractions of these cases are caused by specific medical situations.
In other cases enuresis could be a consequence of a defect in any of the
factors outlined below.
Bibliography and Suggestions for Further Reading:
Fergusson DM, Horwood LJ, Shannon FT (1986). Factors related to
the age of attainment of nocturnal bladder control. Pediatrics,
78:884-890.
Franco I (2007). Overactive bladder in children. Part
1:pathophysiology. Journal or Urology, 178:761-768.
Gill D (1995). Enuresis through the ages. Paediatric Nephrology,
9:120-122, DOI: 10.1007/BF00858991.
4-Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
Genetics Considerations and Familial Trends
Genetic Determinants:
Some familial tendencies towards enuresis are commonly seen.
Certain inherited genes appear to contribute to defective micturition regulation
and enuresis.
Genetic predisposition appears to be the most frequently proposed etiologic
variable.
Putatively, enuresis is thought to be usually transmitted in an autosomal
dominant pattern.
Inheritance patterns appear to be polygenic.
Several chromosome genetic loci particularly those localized to the lengthy
fragments of chromosomes five, eight, twelve, thirteen, sixteen and twenty two
were implicated determinants in nocturnal enuresis at a point in time
respectively.
Strong linkage with Deoxyribonucleic acids polymorphisms were described for
enuretic genetic chromosomes on multipoint analysis with clustering of the
defective pathogenic
locus at the long arm of chromosome thirteen.
The localisation of the genomic determinant of enuresis on human
chromosome thirteen especially for nocturnal enuresis were
contemperonously suggested by several investigations ,in addition, to several
other, undetermined genetic chromosomal loci which may equally be
implicated determinants of enuresis.
Some familial tendencies are common in most cases of childhood enuresis.
When both parents were enuretic as children, their offspring had a four in five
risk of having nocturnal enuresis.
The risk declined to two of five when one parent was enuretic as a child, and to
one of seven when neither parents were enuretic.
In two of three to four of five of children with nocturnal enuresis, there is a
positive family history of enuresis in his first degree relatives.
If the father was enuretic as a child, the relative risk for the child being enuretic
was somewhat higher, compared to when the mother was enuretic.
Several investigations report varying but a high prevalence of enuresis in other
family members with enuresis.
4-Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
Genetics Considerations and Familial Trends
Genetic Determinants
Putatively, several deranged mechanisms postulated to drive enuresis such as
sleep arousability, nocturnal circadian variability in the nadir of arginine
vasopressin and urodynamics irregularities were thought to be cytogenetically
determined and genomically driven.
As much as my investigative experience suggests applying an analysis from a
mature data from a representative sample from a lengthy experience there is a
familial pattern to the inheritance and transmission of bedwetting and the
evidence for genetic inheritance for enuresis appears to be convincing.
The autosomal dominantly inherited subset of nocturnal enuresis (ENUR-1)
has been assigned to the long arm of chromosome thirteen.
The inheritance pattern in nocturnal enuresis appears to have followed an
autosomal dominant mode of inheritance with penetrance well above ninety
percent.
The discovery of further genetic loci in enuresis will assist in both its
diagnosis and interventions.
Whereas genetic familial factors offer predictable and consistent determinants
associations for the inheritance of enuresis, but conversely, the
representations for other familial psychosocial factors, social economic
circumstances, unexpected adverse life events, and fluctuations in family
structures ,constitutions, place of domicile or abode, in the achievement of
urinary control were some what inconsistent.
Disorders of sleep arousal.
In principles and practice, somnologic medical studies in the enuretic child
suggest that the depth of sleep and sleep habits among enuretic and
incontinent children appears to be somewhat disturbed in pattern and depth.
For a long time, whether enuresis is a sleep disorder related disease spectrum
was contentiously discussed.
Children with enuresis do not wake up normally in response to an auditory
stimuli and signals such as alarm clocks or bells suggesting a preponderance
of arousal defects in these subsets.
Nocturnal enuresis usually occurs during slow wave sleep or more specifically
during arousal from slow wave sleeps and not during the rapid eye movement
sleep.
With progressive bladder distension, the arousal centre will be activated to
signal a switch over from deep sleep to a less profuse sleep profile facilitating
urinary control and the urge for voluntary.micturation.
These switch over signals and sequences were disturbed in enuretic children.
4-Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
Genetics Considerations and Familial Trends
Genetic Determinants
Sleep Related Respiratory Difficulties:
Sleep Related Respiratory Difficulties are pathological conditions associated
with respiratory distress of some sort, diminished arousabilities and enuresis
during sleep.
The most common cause of Sleep Related Respiratory Difficulties in childhood
is adenotonsillar hypertrophy, which has a peak incidence in children aged
twenty months to seventy two months.
The possible explanation for this could be related to the negative impact of
anoxia on the arousal state.
There is a trend towards greater spontaneous arousals in the children who wet
less frequently.
Sleep Related Obstructive Apneic events probably through a hypoxia driven
neurogenic, cardiogenic or nephrogenic mechanisms could cause a polyuria.
It is possible that these perturbations were associated with a decreased
nocturnal secretion of Anti Diuretic Hormone and increased secretion of Atrial
Natriuretic Peptides.
Arousabilities difficulties rather than nocturnal polyuria or diminished
functional bladder capacity could probably adduce a better and adequate
explanation and reasons for the inability of children with nocturnal enuresis to
wake up to void.
On the average, sleep electroencephalograms in nocturnal enuresis depicted
normative features or subtle non-specific differences which were not clinically
or statistically significant or superior relative to those of their non-enuretic
controls.
On the basis of the author’s practice and research experience on this topic,
parents consistently maintain that their children with nocturnal enuresis are on
the average comparatively deep sleepers relative to their non-enuretic siblings.
Children with nocturnal enuresis are more likely to encounter traumatic
awakenings, such as nocturnal terrors, nightmares, frightful dreams or
somnambulism, compared to their non-enuretic sibs or counterparts.
BIBLIOGRAPHY AND SUGGESTIONS FOR FURTHER READING
Eiberg H, Schaumburg HL, von Gontard A et al (2001).Linkage study in a
large Danish four generation family with urge incontinence and nocturnal
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Wolfish NM, Pivik RT, Busby KA (1997). Elevated sleep arousal thresholds
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Bakwin H (1973). The Genetics of Enuresis. In Kolvin I, MacKeith RCI,
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4-Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
[C]-Nocturnal Polyuria.
An unduly copious amount of urine output during sleep could favour enuresis.
Normally, the physiological circidian rhythm and trend is for the production of
ADH to be more during sleep so that urinary production and micturation urge
is less.
Irregularities in this circidian rhythm leading to less production of nocturnal
ADH will lead to profuse urine production , leading to bladder overfilling ,tilting
the child with an enueritic diathesis into bedwetting.
A diminution in the nadir of nocturnal secretion of antidiuretic hormones could
be associated with enuresis because, diuresis is influenced by several
humoural factors especially the antidiuretic hormone (ADH), which controls
the absorption of water from the distal tubules and collecting ducts.
Optimal neuroendocrine development includes the establishment of a
circadian rhythm in the secretion of arginine vasopressin, the antidiuretic
hormone.
A nocturnal rise in this hormone would decrease the amount of urine produced
at night.
In children with nocturnal enuresis maturational irregularities and delay in
achieving this circadian rise in arginine vasopressin will favour the
propagation of nocturnal polyuria,overwhelming the bladder's capacity for
urinary retention, making voluntary urinary regulation unachievable.
On the other hand, however, since, bladder distension influences the nocturnal
secretion of ADH positively, whereas the level of ADH is noted to diminish with
bladder emptying, it is possible that the low levels of ADH derived for children
with enuresis could be the consequence rather than the cause of the enuresis.
There are several other controversially discussed factors which could cause
nocturnal polyuria and lead to nocturnal enuresis in children such as:
Excessive fluid ingestion before bedtime will certainly tilt a child with an
enuretic diathesis to a frank enuretic profile.
Excessive food consumption before going to bed especially high starchy
carbohydrate foods and excessive caffeine and tea intake will also lead to an
enuretic tendency, given the obligate liquid content of the excreted solute and
their diuretic effect.
In the other subsets of children with enuresis, perturbations were observed in
the levels of atrial natriuretic peptide (ANP), aldosterone, prostaglandins and
other humoural factors which control solute and therefore indirectly influence
diuresis.
4-Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
For some unclear reasons, increased nocturnal solute secretions, especially
sodium and potassium in the setting of an intact rennin-angiotensin
aldosterone mechanisms with normative ANP were observed in some children
with enuresis.
It is possible that in these subsets perturbations of the prostaglandins and
other putative humoural factors may be implicated in the initiation, sustenance
and drive of enuresis.
The notable response of functional nocturnal enuresis to NSAIDS especially
indomethacin which is a prostaglandin synthesis inhibitor and causes salt and
water retention lends support to this aetiopathophysiological basis.
Although nocturnal polyuria is an important factor in the pathophysiology of
enuresis, overproduction of urine as such cannot be implicated in all instances
of enuresis.
The relative refractoriness to arousals by enuretic children despite a full
bladder or contracting bladder or diurnal enuresis remains unaccounted for by
these postulations.
Reset osmostat:
A cryptogenic diminution in the nadir or levels of antidiuretic hormones
associated with a markedly diminished plasma osmolality from secondary
systemic pathology such as Tuberculosis could predispose a child to enuresis.
Restricted nocturnal bladder capacity.
Restricted nocturnal bladder capacity as a plausible aetiopathogenic factor in
nocturnal enuresis was controversially discussed.
Nocturnal circadian rhythms of the humoral factors could explain the reasons
for the putative diminutive nocturnal profiles in the bladder capacities seen in
children with nocturnal enuresis, who have diurnal bladder capacities within
the normative profile, on urodynamic studies, given that small bladder capacity
is usually associated with a lower nocturnal bladder urine volume production,
so these group of enuretics might be making less nocturnal urines, such that
their detrussor muscles are now conditioned to respond to lower urine
volumes.
Although on neurosomnologic studies the depth of sleep in children with
nocturnal enuresis is not immense, and their bladder capacity is not strikingly
diminished.
However, children with nocturnal enuresis seem to experience greater than
normal urgency in response to bladder distension during sleep, external
sphincter regulatory defects were implicated most in these instances.
Overall urodynamic evaluations have revealed normative micturition bladder
functions and apparent anatomical bladder capacity in children with nocturnal
enuresis, functional bladder evacuation capacity could be somewhat limited in
4-Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
[E]-Overactive bladder and dysfunctional voiding.
This is early to mid childhood feminine phenomena, usually nonprogressive, transient time limiting phenomena co-existing in a
vicious complex of urinary difficulty, frequency, urgency, frequent
squatting, diurnal and nocturnal enuresis.
The squatting posture is an adaptive conditioned response having
both a central and peripheral suppressive effect on unanticipated
and unwanted detrusor muscle contractions and a bulbar detrusor
inhibitory reflex effect.
In these subsets, secondary enuresis following an overactive
bladder with dysfunctional voiding associated with a low nocturnal
bladder capacity, and defective arousal mechanisms, various
degrees of vesicoureteral reflux defects are more commonly
associated phenomena to the enuresis, in addition to cystitis,
constipation and obstipation.
Urodynamic studies especially with a videocystourethrography will
normally reveal an unstable detrusor contraction in the early filling
phase.
In keeping with the deranged pathophysiology, these subsets
appears to be fairly responsive to membrane stabilizing neurogenic
mediated anti cerebral dysarrythmic drugs especially
carbamazepine.
The most common organic disease associated with enuresis is
urinary tract infection.
Both enuresis and urinary tract infection are common.
In one of fifteen cases of enuresis in girls, urinary tract infections
were implicated, compared to a one is sixty for their non-enuretic
controls.
Among the most frequent female daily bedwetters, one in ten of
them will have a culture proven, monomicrobial or polymicrobial
urinary tract infections.
Whereas amongst enuretic boys urinary tract infections were
seldom present.
In collorary, among children above the age of three in general, who
have a microbial urinary tract infection, one in six cases will be
enuretic.
Urinary tract infections could precipitate or prolong enuresis in
children with enuretic diathesis.
Cystitis by causing uninterrupted detrusor muscle instabilities could
cause frequent detrusor muscle contractions leading to frequent
bouts of both diurnal and nocturnal enuresis.
BIBLIOGRAPHY AND SUGGESTIONS FOR FURTHER READING
Suggestions for further readings:
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4-Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
A cause and effect vicious cycle may make it difficult to determine
the preceding aetiological factor on presentation, because it may be
that both conditions are related to underlying structural or functional
abnormalities of the genitourinary tract, bedwetting,may predispose
a child to ascending urinary tract infection or alternatively may
predispose the frequency of micturition and irritability of the bladder
associated with cystitis may precipitate the enuresis.
While no specific type of enuresis characterizes children who also
have urinary tract infection, the latter tends to show an association
with secondary enuresis (enuresis after a period of continence)
wetting by day as well as by night, abdominal pains, frequency of
micturition, dysuria or other pattern of urinary difficulties.
Cystitis is a fairly common cause of enuresis, other symptoms of
infection may occasionally be present, the episodes of enuresis will
naturally improve as the cystitis responds to specific antimicrobials
if it is the only implicated factor in the aetiopathogenesis of the
enuresis.
Enuresis may make urinary tract infections more difficult to manage,
enuretic girls tends to have more persist bacteruria compared to
their age matched controls.
Cystitis could predispose to enuresis at any age although its effects
tend to be more pronounced in the younger age groups.
Factors predisposing to recurrent cystitis in childhood include,
overactive bladder, dysfunctional voiding, various forms of
neurogenic bladders, such as in Cerebral Palsies, urethral
obstructions, anatomical and structural urogenital tract
abnormalities such as ectopic ureters and metabolic disorders such
as Diabetes Mellitus, HbSS, Congenital adrenal hyperplasias
Congenital and other urinary tract abnormalities should be
considered especially in intractable, persistent or recurrent cases of
enuresis.
4-Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
Equally, children with enuresis are prone to urinary tract infections
because strong contractions of the proximal urethra and pelvic floor
muscles might cause urinary tract infections by leading to
vesicourethral reflux of bacteria in the proximal urethra.
Constipation and Obstipation could be associated with both primary
and secondary enuresis.
Constipation aggravates the progression of enuresis when it coexists with the predisposing factors.
Although the mechanism by which constipation aggravates enuresis
has not been completely elucidated, it is likely that the pressure of
the stool in the adjacent descending and sigmoid colon on the
bladder could trigger off uninhibited detrusor contractions.
Also children with enuresis are prone to constipation because pelvic
floor overactivity and bladder dysfunction are thought to
simultaneously cause over constriction of the anal sphincter
resulting in constipation. In this way a viscous cycle might be set
up.
Neurological Factors:
Neurogenic bladder: In this pathological state, there is a
retrogression to the infantile or senile pattern of unregulated
micturition, where the bladder will empty automatically following
filling.
A neurogenic bladder could develop following an idiopathic,
congenital, neoplastic, cerebrovascular or degenerative neuropathological lesion at any level of the nervous system, including the
cerebral cortex, the spinal cord, or the peripheral nerves.
In spinal cord pathologies superior to S2 spinal segment, afferent
impulses indicating bladder distension cannot be relayed to the
pontine micturation regulatory centre, therefore, cortical control of
the sacral micturition reflex is lost, and relaxation of the external
sphincter goes unregulated.
Because the sacral spinal centre itself is intact, the bladder
automatically empties when distended, as in an infant.
If the sacral segments themselves are destroyed, the detrusor
muscle is paralyzed and the bladder becomes abnormally distended
4-Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
Nocturnal enuresis is more common in children with neurogenic bladder and
neuropsychopathologies, spina bifida manifesta or occulta.
Patients with myelomeningocele almost always have enuresis.
Other spinal cord abnormalities such as caudal regression syndrome, tethered
cord, tumours, anterior spinal artery syndrome, and spinal cord trauma could
cause enuresis.
Sacral agenesis could be associated with a neurogenic bladder.
As many as one in twenty cases of imperforate anus have a neurogenic
bladder, and most patients also have a lumbosacral anomaly.
Specific dysfunction in the external urethral sphincter can develop after pelvic
extirpative surgery, radiation therapy for pelvic malignancy, pelvic fracture and
incontinence surgery.
Anecdotally and evidentially,cerebral dysarrythmias were implicated in some
cases of enuresis :
Compraratively, on the average, neurologic defects related to true incontinence
or structural abnormalities of the bladder, the proximal urethra or the urinary
tract as a whole were not over represented in those subsets of children with
enuresis.
No correlation has been found between urethral or meatal stenosis and bedwetting.
Furthermore, congenital, structural, or anatomic abnormalities rarely present
solely as enuresis.
Psychogenic and Socio-Cultural factors.
Early childhoods exposure to recurrent neurotic precipitating events:
Suggestions that anxiety-provoking events occurring in the lives of children
aged twenty four months to forty eight months might lead to incontinence
before the child achieves total bladder control seems unfounded.
Anxiety experienced after the age of forty eight months might lead to wetting
after the child has been dry for a period of six months or more.
Such events include non compassionate parental figures,unfamiliar social
circumstances and overwhelming familial events such as the birth of a new
sibling.
4-Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
A vicious cycle is propagated and sustained since, enuresis itself is an
anxiety-provoking phenomena.
Diurnal enuresis could cause humuliation loss of confidence and self esteem
and apprehensions which could tilt overnight and cause nocturnal enuresis.
Although, nocturnal enuresis was once thought to be a psychologic condition,
however on the average, children with nocturnal enuresis have not been found
to have an increased incidence of emotional problems.
It is possible that psychologic problems may be the result of the enuresis and
not the cause of the enuresis.
Psychosocially, the putative aetiology of childhood enuresis is diverse which
may account for the contentions and controversial discussions with regards to
the responsible psycopathies and the perturbations in the socio-cultural
interactions between the child and his parental figures.
Psychological factors such as fears, nightmares, worries, anxiety,
humiliations, stress, feelings of insecurity are some of the factors which could
predispose a child to enuresis.
The regressive type of bedwetting is precipitated by stressful environmental
events, such as a move to a new home, familial and parental marital or
domestic discord, birth of a new sibling, or familial demise. Overall, persistent
nocturnal enuresis is usually the result of inadequate or inappropriate
micturition training and on the average for most children is not a of revengeful
act.
Although, occasionally parents who demand that the child become micturition
trained promptly in a coercive manner may generate a rebellious or
oppositional response in the child who will subconsciously wet his bed with a
revengeful demeanor.
On the other hand parents who are not sufficiently close to the needs of the
child to support urinary training may undermine his or her endevours at
aiming to achieve expertise at micturition regulation.
Chronic psychological stress, unrelated to urinary training experiences but
reoccurring during the toddler period could also hinder the child’s ability to
achieve urinary regulation.
Such enuresis is usually transient, periodic and the prognosis and
management less difficult than in the child with primary persistent enuresis.
These psychosocial factors could be considerably modified by a cordial and
standardized child doctor relationships.
Several unexpected and unusual adverse life events such as birth of a new
sibling, parental discord, child abuse, loss of a family member, or any other
social dysfunction at school or home could predispose a child to having
4-Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
Children with enuresis are significantly more likely to have higher rates of
behavioural disorders compared to their aged matched peers.
Children with enuresis are usually in more psychological difficulties compared
to their age matched peers
Occasionally, some children with nocturnal enuresis shows somewhat a
developmental delay in somatic, vegetative or executive regulatory
mechanisms which is unwelcomed to their parental figures, although on the
average they are not usually imbeciles or they may not have defective self
regulatory behaviours as such, although they may lack self confidence,
somewhat irritable and their self comportment may be compromised.
Nocturnal enuresis may be a single symptomatic manifestation of an overall
inability to achieve a programmed nighttime control of vegetative functions.
A few disturbed children with much resentment underlying passive-aggressive
behaviour demonstrate a revengeful type of enuresis that is bedwetting
represents a conscious volitional act, usually carried out secretly.
Psychotic children may have enuresis frequently, because of negativism or
due to an inability to comprehend the significance of micturition training.
Children usually of the male gender with tension discharge disorders
frequently of the impulse ridden type show problems in the control of certain
executive and non-executive neurological functions.
They may not have manifest cerebral dysarrthmias but they often exhibit
dysarhythmic electroencephalographic patterns which may invariably be
related to defective neuronal maturation sequence rather than from other
aetiological factors.
Most types of enuresis are often associated with coercive urinary training in
infancy, or occasionally with a compromised permissive urinary training, grave
inattentiveness or with an apparent developmental lag in bladder regulatory
mechanisms without other obvious disturbances as such.
In some children with previously repressed neurotic conflicts, these enuretic
events were accompanied by nightmares and frightful dreams.
In most of these cases the paternal figure could have been unduly corrective
and strict and the maternal figure unprotective and non compassionate.
4-Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
Familial domestic discords were frequent historical features, lack of affection
were also common.
Male children with nocturnal enuresis are usually passive, somewhat inhibited
and often overly dependent or manifest phobic tendencies.
The parental figures were usually non-symbolic, the symptomatologies could
occasionally be a keen to a hysteric conversion disorder, involving relaxations
of the external sphincters in relation to unconscious sexual conflicts often
demonstrated in terrifying nightmares during which loss of control occurs.
Also enuretic females seem to be more active, sometimes overly independent
and competitive towards their male counterparts, with a tendency toward more
masculine identification in an attempt to handle psychological concerns.
This might imply unconscious symptomatologies ranging from hostilities
towards the maternal figure to that towards male gender, which could
occasionally have deleterious consequences.
Anxiety provoking life events in the first four years particularly in the third and
fourth years when bladder regulation is normally acquired have been found to
significantly associated with subsequent enuresis especially in female
children.
Proportionately, several psycho-social life events which could be implicated in
the causation of enuresis through the induction of asynchrony of native
familial structure includes demise, divorce or separation, separation of the
child from his mother, stay in a strange environment, the birth of a sibling,
change of abode, prolonged hospitalizations, accidents and operations, of all
these adverse psycho-social phenomena, early separation from the maternal
figure appears to be the most implicated factor.
The number of disturbing events correlated with the percentage of the children
latter determined to be enuretic, and at each age the highest prevalence of
enuresis was found in children who lost their mothers.
These facts are consistent with the observation that enuresis is particularly
common in institutionalized children.
Enuresis is also common in socio-economically deprived families probably for
obvious multiple reasons.
Children, especially younger girls, exposed to emotionally or physically
challenging life events may depict enuretic tendencies later on.
4-Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
Secondary enuresis often follows most anxiety inducing life events.
Once enuretic, the secondary anxieties associated with loss of self esteem and
guilt as a result of shame and stigma at school and domestic parental
disapproval, militate against spontaneous cure and often give rise to secondary
emotional and or conduct disorders in a vicious cycle.
This may be stress related, enuresis could occur in any child who is
significantly frightened.
Chronic stress, such as the loss of a close relative, marital discord, or
hospitalization could lead to this kind of diurnal enuresis.
The resistant child is one who is about thirty months of age and refuses to be
bladder trained.
About seven in ten of these children are males who are predominantly or totally
wet.
Often, this recalcitrant situation followed high pressured attempts at urinary
training.
Most children with diurnal enuresis, but nighttime continence have some
behavioural basis for this pattern of enuresis.
An organic pathological basis for diurnal enuresis, accounts for less than one
of twenty instances of diurnal enuresis
Psychiatric Disorder:
The relationship between nocturnal enuresis and psychiatric disorder is
complex.
Only minorities of children with enuresis were psychiatrically disturbed, but
about twice as many children especially girls who are enuretic have a
psychiatric disorder in mid childhood compared to non-enuretic children.
Disturbed children are more likely to become enuretic and relapse of bladder
regulation often follow stressful experiences.
Conversely, disturbed enuretic children are more likely to improve
psychiatrically,if they become continent compared to if the enuresis is allowed
to persist.
A wide range of psychiatric disorders are associated with enuresis, emotional
disturbances as well as conduct disorders were equally implicated.
Other common precipitating factors for enuresis are the arrival of a sibling with
the attending threat that the child will be displaced in his parent’s affection,
admissions to hospital by the arrival of a sibling, separation from one or other
parents or educational failure at school or even the arrival of a new teacher.
Post Infective Autoimmune Phenomena. PANS is an acronym for [Paediatric
Acute Onset Neuropsychiatric Syndrome].
4-Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
The putative condition [PANDAS](pediatric autoimmune neuropsychiatric
disorders associated with streptococcal infections) applies to a set of children
who have a rapid onset of [Obsessive Compulsive Spectrum Disorder] and/or
tic disorders following a streptococcal infection, with an association to other
symptoms such as gustatory defects in association to other multiple
neuropsychiatric symptomatologies such as enuresis.
A more comprehensive classification of this hypothesis, PANS, has been
proposed which states that some patients suffer these symptoms in response
to other non-streptococcal infections such as mycoplasma ,chlamydia
,ureoplasma urealyticum or Borrelia burgdorferi or other putative multiple
viraemias.
Putatively,these children experience a rise in dopaminergic receptor
hypersensitivity levels as a result of a post infective autoimmune antineuronal antibodies with host organisms shared epitopes.
These parainfectious or post infectious dopaminergic receptor hypersensitivity
could precipitate sympathetically driven neuropsychopathologies such as
enuresis, bed-wetting, and urinary urgency.
Attention Deficit Hyperactivity Spectrum Disorders:
Invariably, bedwetting is a very strong clue to the diagnosis of ADD/ADHD
spectrum disorders.
Transmission of primary nocturnal enuresis and attention deficit hyperactivity
disorder appears to be linked or overlapped.
Experientially, enuresis could be a link to the diagnosis of ADD/ADHD
spectrum disorders.
It is its characteristics or associated co-morbidity, in about one half of the
cases with the diagnosis of ADD/ADHD
Infact, one of the medications used in the management of ADHD imipramine, is
equally effective for the management of nocturnal enuresis, where it gives a
rapid response rate in those cases that would be amenable to this intervention.
While enuresis is a significant linkage to achieving the diagnosis of ADHD, the
converse that most children with enuresis have ADHD like defect is untrue.
Hence it will be very unwary to imply that all children with enuresis should be
treated with medications for ADHD or be recommended for psychotherapy or
placed in a school. for children with special needs.
However, for children with enuresis, who suffer from temper tantrums, or have
learning difficulties or unexplained defects of social integration which are not
time or self limiting, ADHD should be suspected and studied.
4-Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
Perturbations associated with deranged ADHD neurobiochemistry appears to
make children less receptive to adaptive social conditioning or acquisition of
specialized skills despite good parenting.
In such cases, timely institution of treatment should be encouraged to
circumvent adverse future psychological consequences.
Technically, ADD/ADHD should be suspected ,evaluated and intervened for in
any child with enuresis who have school related attentiveness difficulties, or
academic concentrations difficulties, exhibitions of impulsive demeanor
,consistently fidgety, having continual temper tantrums, or having some
conduct or oppositional behaviour or dyslexia.
Children with ADHD/ADD could have primary nocturnal enuresis because of
the compromised ability to wake up when the urinary bladder is completely
filled or lacks the focused drive and direction to micturate with the emergence
of the appropriate urinary urge.
Infact almost always children with ADD/ADHD will have significant difficulties
with night time and early morning wakenings.
Occasionally like other children, they could also have enuresis due to other
secondary factors.
It is disheartening that enuresis is still a very under-represented pathology in
the considerations of co-morbidities associated with ADD/ADHD
neuropathology by health care professionals.
In the author’s experience, with a considerable number of putative or
presumptive ADD/ADHD children one half of the cases also had enuresis
In secondary enuresis, anatomical problems could account for about one of
twenty cases.
Urethral Obstruction in children could be congenital such as with posterior
urethral valves, a congenital stricture, or urethral diverticula, or acquired
because of a traumatic or infectious stricture.
Traumatic strictures may follow a traumatic urethral catheterization, or a
foreign body in the urethra or a pelvic trauma.
Infectious strictures are a complication of purulent urethritis due to bacteria
such as Neisseria gonorrhoeae.
Meatal strictures could follow male circumcisions, and could cause distal
urethral obstructions.
Other structural defects to be considered in cases of enuresis include ectopic
urethras and vagino-urethral fistulas.
4-Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
Ectopic Ureters:
This rare congenital abnormality is due to the insertion of the ureter in a
location further down the urethra rather than the lateral angle of the bladder
trigone.
Enuresis results when the insertion is distal to the external urethral sphincter
in females.
In males, the most common site of insertion of the ectopic ureter is adjacent to
the external urethral meatus, where as in females it is below the external
sphincters.
Ectopic ureters are frequently three to four times more common in girls than in
boys and this usually causes incontinence only in females.
Seizure disorders.
Secondary enuresis may be a symptom of an overnight unobserved major
motor convulsive event in a child with a known seizure disorder.
New onset seizures rarely occur only at night, and bed wetting is therefore a
rare manifestation.
Individual or familial seizural diathesis were no more preponderant in enuretic
children
as a group.
Diabetes Insipidus is an uncommon cause of enuresis.
Although nocturnal polyuria is often presumed to be the cause of bedwetting,
a disorder of arousal may also be present.
Diabetes Insipidus could be central or nephrogenic.
Central diabetes insipidus, could result from an intracranial tumour, head
trauma, encephalitis, or meningitis especially those related to Tuberculous
Encephalitis:
Actinomycosis and lymphoproliferative disorders.
Nephrogenic diabetes insipidus may result from any cause of renal failure,
diffuse renal cortical or medullary damage, hypokalemia, hypercalcaemia, or
nephrotoxic drugs.
Other systemic pathologies associated with Diabetes Insipidus includes:
Langerhans Cells Histiocytosis X:
Enuresis in erythrophygocytic histiocytosis-X would be most related to the
associated Diabetes Insipidus following pituitary dysfunction especially the
pars nervosa and hypothalamic dysfunctions in these subsets especially in the
Hand Shuller Christian form.
Children with Wolframs syndrome, septo-optic dysplasias could have Diabetes
mellitus, Diabetes Insipidus as an association and hence more tendency to
enuresis.
4-Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
Sarcoidosis:
Of some pathological interest is the increased incidence of enuresis noted in
children with
Systemic or pulmonary Sarcoidosis, this could be related to the perturbations
in the elaboration of angiotensin converting enzymes by the pulmonary tissues
implicated by the Boecks Sarcoids.
A secondary factor in the aetiopathogenesis of enuresis in Sarcoidosis could
be related to the extensive renal calcinosis resulting in renal insufficiencies
following the marked dystrophic and metastatic calcifications secondary to
prolonged hypercalcaemia especially in those children with advanced
Sarcoidosis.
Diabetes Mellitus:
Enuresis is usually not the presenting complaint in a child with a new onset
diabetes mellitus.
Other symptomatologies of insulin deficiency may overwhelm the presence of
bedwetting.
Secondary enuresis, in a child with established diabetes mellitus may be a
symptom of suboptimal control with nocturnal polyuria due to hyperglycaemia.
Although nocturnal polyuria is presumed to be a cause of bedwetting, a
disorder of arousal is also likely to be contributory because most school aged
patients develop nocturia but maintain a dry bed.
Diabetes mellitus is also associated with abnormalities in the afferent sensory
pathways to the bladder which may initiate a neurogenic bladder which may
contribute to enuresis.
4-Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
Heart Block:
Very rarely, secondary enuresis may be consequential to a severe
artrioventricular heart block, usually of the Mobitz type II or III with
Wackenbach’s phenomena.
It is possible that hypoxia and nocturnal bradycardia could cause a problem
with the arousal mechanisms which could lead to nocturnal enuresis.
Almost always most of these heart blocks driven nocturnal enuresis resolve
following the implantation of ventricular demand pacemakers.
Hypothyroidism could predispose a child to enuresis, however resolutions of
enuresis will almost always follows the attainment of the eurothyroid states.
Renal Disease:
With significant renal disease, the urine becomes less concentrated and urine
volume is increased producing the symptoms of polyuria, nocturia and
enuresis.
In early renal disease, the diluting ability of the kidneys is retained, but the
concentrating ability is lost, due to a defective countercurrent mechanism,
which will invariably result in polyuria.
With a more advanced renal disease, both the concentrating and the diluting
abilities of the kidneys will be lost, so that the osmolality of the urine
approximates to that of the plasma.
4-Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
Irritable bladder diathesis:
The principal function of the sphicteric muscles surrounding the
urethra which is the cylindrical like urine conduit moving urine away
from the bladder is to keep the condiut closed, thereby
circumventing the unregulated efflux of urine from the urethras.
However, in some instances especially following cystitis associated
to a urinary tract infection in older girls,the fine bladder regulation
could be lost and the bladder could contract abruptly without premicturition signals,in such instances the sphincteric muscles
surrounding the urethra may become partly or totally incompetent
resulting in unguarded efflux of urine out of the urethra.
Delayed Micturition:
Infrequent voiding refers to a child holding urine voluntarily for
prolonged intervals because of overwhelming circumstances or
engagements in captivating activities leading to the negligence of
the micturation urge from a full bladder.
Compromised lavatory facilities at school may also lead to
postponement of micturition until enuresis occurs.
In the author’s research with enuretic children, although the daytime
micturition pattern was not unusually delayed or postponed,
however occasionally, inferred responses intimates that the enuretic
children’s involvement in captivating extracurricular activities or
engagements could have deterred timely micturition.
In such instances, the bladder could get overfilled and leak urine
invpluntarily and unconsciously.
Additionally, these children often develop urinary tract infections
(UTIs), leading to an irritable or overactive bladder.
Drugs and Diuretics:
Some drugs especially the high ceiling loop diuretics and the
thiazides diuretics could precipitate enuresis in a predisposed child.
4-Pathophysiology, Aetio-Pathophysiology and Pathogenesis:
Dietary and Micronutrient Factors:
Diets poor in micronutrients,such as those with low calcium and magnesium
contents, and food substances, causing allergies like dairy products, citrus
fruits, chocolates and food containing high levels of artificial colors and
flavors could predispose an individual child to enuresis.
Some of the same factors that contribute to nocturnal enuresis may act
together with infrequent voiding to produce diurnal incontinence.
These factors include a restricted bladder capacity, constipation and food
containing caffeine, chocolate or artificial coloring.
Occasionally,an overenthusiastic micturition training may make a child unable
to relax the sphincters and the pelvic floor for the bladder to be emptied
completely,undue micturition postponement, urinary retention or incomplete
bladder emptying predisposes a child to urinary tract infections and
popagates and sets up a viscious cycle enueisis and cystitis.
Worms invasion:
Bladder helminthic infestation such as schistosomiasis following
Schistosoma haematobium infestations could cause enuresis directly by
causing detrusor muscle irritability or indirectly through causing the
commonly associated salmonella species related urinary tract infections seen
in bladder bilharziasis.
Whereas intestinal or colonic helminthic invasion or intestinal parasitosis will
cause intraluminal irritability, bowel motion changes which could be
transmitted to the juxta uretero- cystic apparatus leading to bladder irritability,
urinary difficulties, urgencies and frequencies.
Haemoglobinopathies:
Enuresis in haemoglobinopathic children is related most to the associated
hyposthenurias linked to the complication of renal interstitial nephritis.
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4-THE NATURAL HISTORY OF ENURESIS:
THE NATURAL HISTORY OF ENURESIS:
Chronologically, most cases of enuresis will fade away naturally, because of
improved psychosocial and neurohumoural maturation with advancing age.
These chronological maturational sequence could be partly or wholely due to
the acquisition of the ability to respond to the physiological micturition
signals by the growing child,increasing bladder capacity and activation of the
natural body alarms ,or stabilisation of an overactive bladder optimisation of
the production of antidiuretic hormones, attenuation of psychological and
emotionally challenging stessors.
Overall, many children will outgrow their enuretic tendencies with
chronological advancements.
The number of cases of incontinence goes down by one in seven instances for
each year after the age of sixty months.
It will be unscientific to think that in all instances of bedwetting or enuresis is
almost always due to a developmental delay that subsides with time, in some
instances it may not improve completely or at all, in other instances, it persists
into adulthood.
Even in those instances when the frequency of enuresis attenuates with
increasing age, reminiscence of the circumstances surrounding the childhood
enuretic event could be considerably traumatic emotionally, especially to the
socially conscious teenagers.
Children with enuresis almost always are overwhelmed by concerns of being
socially exposed ridiculed, punished or humiliated especially if they are in a
boarding school or have to go on short or long vacation to a relatives or friend
house.
They will normally be taunted by their peers.
The immense psychosocial traumas experienced by these groups of children
should be taken into consideration by the attending paediatricians, while
planning the appropriate interventions for them, group or individual
psychotherapy may occasionally be indicated for some cases.
Nocturnal enuresis has widely differing outcomes, from spontaneous
resolution to complete resistance to all current treatments.
The overall outlook appears reassuring because on the average, only about
one in a hundred adults is enuretic where as, about one of every seventh child
becomes continent in a year.
In idiopathic enuresis, an unduly invasive evaluations or investigations
intensive pharmacotherapy or invasive interventions could not be indicated as
such, because from observations in the author’s lengthy and representative
BIBLIOGRAPHY AND SUGGESTED READING
Fergusson DM, Horwood LJ, Shannon FT. Factors related to the age
of attainment of nocturnal bladder control: an eight-year longitudinal
study. Pediatrics 1986;78:884–90.
Forsythe WI, Redmond A. Enuresis and spontaneous cure rate.
Study of 1129 enuresis. Arch Dis Child 1974;49:259–63.
von Gontard A, Heron J, Joinson C. Family history of nocturnal
enuresis and urinary incontinence: results from a large
epidemiological study. J Urol 2011;185:2303–6 .
5-The Clinical Features and the Associated Pathologies of Enuresis:
5-The Clinical Features and the Associated Pathologies of Enuresis:
The involuntary discharge of urine after the age at which bladder control
should have been established is one of the most common and perplexing
problems brought to the attention of the paediatrician.
Although, functional enuresis is the most common type, however in every case
of enuresis the possibility of organic pathology needs to be considered,
excluded or studied.
Evaluation of a child with enuresis will include a thorough historical, physical
and laboratory evaluations.
The clinical features associated with both primary and secondary enuresis are
frequency, urgency, nocturia, constipation, and daytime wetting.
Behavioral problems, including depression, anxiety, social phobias, conduct
disorders, and attention-deficit-hyperactivity disorder, are more common with
daytime wetting and secondary enuresis.
When undertaking the historical notes from an enuretic child some questions
are pertinent.
Parents and the child should be asked about the time of the enuresis onset, its
duration, and severity, and if there is associated daytime wetting,
constipation, genitourinary tract symptoms, neurologic symptoms, family
history of enuresis, and a methodologic enquiry into the child’s medical
history, psychosocial history and previous medical or surgical interventions.
Dysuria, genital or rectal pain or discharge, straining during micturition or
combined diurnal and nocturnal frequency with enuresis would suggest a
nonmonosymptomatic enuresis.
The minimum physical examination that should be undertaken in an enuretic
child includes an assessment of the ears, nose, throat, abdomen, spine,
genitalia, rectum, neurologic system, and a watch out for signs of abuse.
The relevance of undertaking these physical examination focused at the ears,
nose, and throat would be to evaluate for adenotonsillar hypertrophy; the
abdominal examination would be aimed to verify if the bladder or kidneys were
enlarged or if there are fecal masses indicative of encopresis,the genital
examinations would be targeted to verify for hypospadias, epispadias, meatal
stenosis, ectopic ureter, or labial adhesions, and rectal examination would be
aimed to check for perianal and perineal sensation and rectal sphincter tone
and for the detection of perianal excoriations or vulvovaginitis.
A focused neurologic evaluation would include an examination of the gait,
muscle tone, strength, and perineal sensation as well as a search for spinal
pathologic process, deformity, or sacral dimple or hair tuft suggesting
underlying spinal dysraphism.
To achieve a distinction between primary persistent enuresis from secondary
5-The Clinical Features and the Associated Pathologies of Enuresis:
To distinguish uncomplicated from complicated enuresis, it would be good to
establish if the child wets his or her pants during the day, if the child wets her
pants during the day, this will suggest a complicated nocturnal enuresis.
If the child appears to have pain during micturition, a urinary tract infection
would be suggested.
If the child’s bowel motions were not frequent, but rather hard some degree of
constipation would be implied.
Whereas encopresis would be suggested if the child soils his or her
underwears.
The historical enquiry should do well enough to establish a distinction
between a possible functional bladder dysfunction disorders from nocturnal
polyuria.
A functional bladder dysfunction rather than nocturnal polyuria would be
suggested if the child had at least eight instances of micturition in a day.
If the child has to run to the lavatory each time he wishes to micturate, a
functional bladder dysfunction disorder rather than nocturnal polyuria should
be considered.
If the child defers micturition unduly, then a functional bladder capacity
disorder would be more likely implicated.
If the child wets the bed most nights in a week rather than every one or two
other nights in a week, a functional bladder disorder rather than a nocturnal
polyuria should be studied.
If the nocturnal enuretic episodes are of relatively large volumes, then a
nocturnal polyuria rather than a functional bladder capacity would be
suggested, whereas relatively smaller volumes would more likely suggest a
functional bladder disorder.
Given the negative view on enuresis, family history of enuresis may be not
always be exact, be unreliable or difficult to obtain, evaluate or determine.
The information given by parents on the frequency of enuresis, bowel habits
and arousabilities are most likely to be either overestimates or underestimates.
If the child has more than one enuretic episode in a night, a functional bladder
disorder rather than a nocturnal polyuria would be implied.
5-The Clinical Features and the Associated Pathologies of Enuresis:
On information pertaining to the previous, ongoing and future
interventions, it would be worthwhile to watch out for information
suggesting that the child has been humiliated or severely punished
for his enuretic events.
Parents become distressed the longer their child remains enuretic
since problems will emerge with diurnal enuresis at school, or
nocturnal enuresis at boarding school or when staying away from
home.
A full assessment including the child’s history, personality,
development, and his mother’s condition during pregnancy should
be undertaken.
Historical comments of unrelieved dampness in the upright position
should raise the possibility of an ectopic ureter opening into the
vagina.
Evidence of neurological damage should be sought and the
intelligence quotient of the child approximately assessed.
It is worthwhile to remember that a history of bedwetting (Primary
Nocturnal Enuresis) is a very strong clue to the diagnosis of
ADD/ADHD neuropsychopathology.
Any emotional or psychogenic problems should be probed.
Since enuresis is thought to be failure to transit to the normal state
during the first year,it is postulated that delayed micturition
maturational sequence is involved in its pathophysiology, this will
imply historical inquiries directed at other aspects of executive
functions especially vocal and auditory functions.
5-The Clinical Features and the Associated Pathologies of Enuresis:
Since sleeping habits clearly plays a part and very deep sleeping
pattern is a common finding in such patients, an enquiry into this
pattern of sleep should be derived from the child’s parents, but
occasionally most parents would have already suggested that on the
average their enuretic children are relatively deep sleepers
compared to their other non enuretic siblings.
The minimum investigations that should be undertaken in every
case of enuresis will include a full biochemical, microscopic and
bacteriological evaluations and a complete urine examination.
The blood pressure should be recorded and the genitalia examined.
The child with nocturnal enuresis should be examined carefully for
neurological and spinal abnormalities.
Any evidence of neurological anomaly or abnormality of the skull,
optic fundi or spine should be sought.
Radiological investigation is best reserved for those with
concomitant urinary tract infections, persistent and profound
enuresis especially for those aged ninety six months and above.
A careful history should be obtained especially with respect to fluid
intake and urinary output.
Children with diabetes insipidus, diabetes mellitus and chronic renal
diseases may have high obligatory urinary output and a
compensatory polydipsia.
A complete examination should include palpation of the abdomen
and rectal examination after voiding, to assess for the possibility of
a chronically distended bladder.
If possible, the child should be watched during micturition to
observe the force and quality of the urinary stream.
The history of parental bedwetting in childhood could be indirectly
derived from the child’s parents.
Since there is a familial tendency to enuresis, the parent’s history
should be sought from the grand parents and as much as possible
about the family pattern.
In the authors practice and research experience with a
representative series, although there were no parental histories of
childhood or juvenile enuresis, however this could have been
underestimated given its associated negative motivational aspect
5-The Clinical Features and the Associated Pathologies of Enuresis:
Interestingly, dry periods were noted improved during vacations
and with parental rewards.
There were no serious individual/familial neuro-psychopathologies,
although in one in four instances, there were occasional
taunted/teased by peers, and in one in eight instances the children
were orphans, in about one in fourteen instances, at least a parent
was already dead.
Parental consanguinity was demonstrated in one of four
instances.Monomicrobial Urinary Tract Infections occurred in one in
four instances,
In one of forty instances, recurrent otitis media in sibs, where as
recurrent Respiratory Tract Infections occurred in one of eight
instances.
Associated encopresis at one of eight instances were confined to
the regressional subsets.
In occasional instances, enuresis could have been part of the
automaticities associated with psychomotor seizures, with dystonic
axial-rhizo-appendicular motions associated with unusual cries
quite distinct from nocturnal snoring.
Most parents inferred that their enuretic children were
comparatively deeper sleeper.
Perineal dermatitis, were some of the complications of enuresis.
Historical enquiry will attempt to elucidate the following points from
the parents of the child.
However, the optimal time for treating enuresis should be based on
the motivation of the child.
The most important aspect of the investigation is a very detailed
and meticulous history, which could establish the diagnosis, lead to
more precise treatment and recommendations
minimize the need for invasive and costly investigations.
The history should include fluid intake, daytime voiding pattern, and
the number and time of episodes of bedwetting.
When the history is not clear, request that the family record fluid
intake, daytime voiding, and episodes of bedwetting for at least a
two week period.
A sleep history should include the time that the child goes to bed,
5-The Clinical Features and the Associated Pathologies of Enuresis:
The presence of restless sleep, snoring, and the type and frequency
of nocturnal arousals (e.g. nightmares, sleep terrors, sleepwalking)
should be determined.
Whether the child has experienced periods of dryness and their
circumstances should be determined.
A diet history should include the timing, quantity, and type of fluid
and solid food intake during the day and after supper.
Many children with enuresis do not drink appreciable amounts of
liquids during the school day, usually arrives home from school
thirsty and most drink most of their daily fluids during the school
day, arrive home from school thirsty, and drink most of their daily
fluids in the last four to five hours before bed, a pattern that favours
nocturnal production of urine.
An assessment of the emotional impact on the child is important .
Information should be solicited from both parents and the child.
Basic and revealing information includes whether the child has
experienced teasing by family school mates or friends or has self
restricted participation in school, sleep overs or trips.
Be assertive and inform the Paediatrician firmly that the child is not
likely to be laid back apathetic or daft but most likely have
ADD/AHDH spectrum defects and might need an in-depth evaluation
and intervention.
In some cases, even if the paediatrician has not brought up the topic
of bedwetting, it is likely that this issue could arise if it exists.
Occasionally the parents may demand from the doctor the relevance
of asking for the history of enuresis or of ADHD as co-morbidities.
In the author’s experience, enuresis related individual/familial
neuropsychopathologies were considerable and includes
embarrassments, anxiety, compromised selfesteem/perceptions/interpersonal relationships/quality of life/school
performance.
5-The Clinical Features and the Associated Pathologies of Enuresis:
These were consequential rather than causal.
Finally, data of interest from prospectively observed and managed cases of
enuresis should be acquired and analyzed by the attending clinician for
generating specific figures.
The presence of common underlying problems is indicated by the following:
Patients with overactive bladder or dysfunctional voiding usually present with
frequency, urgency, squatting behaviour and daytime and nighttime wetting.
Constipation and cystitis are common associated problems in patients with
overactive bladder or dysfunctional voiding.
Symptoms of cystitis include dysuria, cloudy, foul smelling urine, visible blood
in the urine, frequency urgency, and day and nighttime wetting.
Compared to adulthood, cystitis could present very covertly in childhood.
In the presence of increased urinary frequency there is usually a tendency to
overestimate the amount of urine passed.
Constipation manifests as infrequent and painful passage of hard white stool,
enuresis and colicky periumbilical pains.
Bowel related problems and gait abnormalities are often present in patients
with neurogenic bladder.
Symptoms of sleep disordered breathing (SDB) include snoring, mouth
breathing, lack of restful sleep, tiredness the following morning.
The hallmark symptoms of urethral obstruction are the need to wait or push to
initiate voiding and a weak or interrupted stream.
When bedwetting a symptom of a major motor seizure disorder, parents may
hear nocturnal sounds associated with abnormal muscle movements.
Girls with ectopic ureters are always wet.
Symptoms of diabetes mellitus include polyuria, polydipsia, and weight loss
notwithstanding a voracious appetite.
Patients with diabetes insipidus present with polyuria, polydipsia and
symptoms related to underlying hypothalamic or renal diseases.
The clinical import of early identifications should be emphasized.
Only about four of every five cases of adult enuretics who on enquiry admits to
the history of bedwetting and remembers those events vividly, while about one
in twelve cases could not recall or have suppressed the awareness entirely.
5-The Clinical Features and the Associated Pathologies of Enuresis:
The Medical and Family History of a Child with Bed-Wetting.
Would be directed to ascertain if there were complications during
the child's birth.
It would be pertinent to ascertain if the child had any history of
problems with his or her nervous system.
Also it would be relevant to ask for the history of any injury or
surgery to her nervous system or genital area in the past.
A flow chart could be more appropriate for easy reference and
comparisons of the child’s progress overtime.
[I]-Severity of the Defect:
[1]-Percentage Number of Continent Nights:
[2]-Percentage of the nights that Continence was achieved without
parental arousal:
[3]-Percentage of the nights that continence was achieved with
parental arousal.
[4]-Percentage Continent with other means of arousal e.g. alarm
clocks or bells:
[5]-Cumulative Nights continent in a row:
[6]-Percentage Nights Continent but Nocturic:
[7]-Depth of Sleep during the continent and incontinent nights .
[8]-Diurnal Urinary Frequencies:
[9]-Diurnal Urinary Urgencies:
[10]-Diurnal Enuresis:
[11]-Urinary Hesitancy:
[12]-Degree of Urinary continence and endurance.
[13]-Degree of Polydipsia
[14]-Frequency of Medical consultations.
[15]-Associated Skin Rash, Infections or Ulcerations.
5-The Clinical Features and the Associated Pathologies of Enuresis:
A careful history should be obtained and a thorough physical examination
should be performed to look for causes of complicated enuresis in children
who present with bed-wetting.
Causes of complicated enuresis include spinal cord abnormalities with
associated neurogenic bladder, urinary tract infection, posterior urethral
valves in boys, and ectopic ureter in girls.
In addition, children who have chronic constipation or encopresis may present
with bed-wetting.
Parents should be questioned about their family history and the child's
medical history.
Careful questioning of parents and children can be extremely helpful in
determining the type of enuresis and a possible cause or contributing factors.
Parents often are not fully aware of their child's daily voiding habits. Thus, a
voiding diary may need to be maintained for a week or more. The family should
keep track of how many times the child voids during the day and how many
nights the child wets the bed.
Children with nocturnal enuresis have a normal physical examination.
However, the physician needs to check carefully for signs that might signal
other problems that can present with bed-wetting. Gait should be evaluated for
evidence of a subtle neurologic deficit.
The flanks and abdomen should be palpated for masses, including an enlarged
bladder.
The lower back should be inspected for cutaneous lesions or an asymmetric
gluteal cleft, which could suggest spinal dysraphism, a variant of spina bifida.
It also can determine the presence of infection or blood in the urine.
If the findings of the physical examination and urinalysis are negative and the
history does not suggest a secondary cause of nocturnal enuresis, no further
work-up is neede
Some organic causes of enuresis may be detected on physical examination.
An exhaustive physical examination should be imperative, which should
include the following points as a minimum:
[A]-A thorough general physical examination.
[B]-Inspection of the external genitalia.
[C]-Palpation in the renal and suprapubic areas to look for enlarged kidneys or
bladder.
[D]-A thorough neurologic assessment of the lower extremities, including gait,
5-The Clinical Features and the Associated Pathologies of
Enuresis:
Deformities of the external genitalia may be associated with other
abnormalities of the urinary tract causing derangement of micturition. An
ectopic ureter may not have an adequate sphincter mechanism.A vaginourethral Fistulae may be suspected on the basis of history and inspection of
micturition.
Inspection:
Associated renal abnormalities may be detected on palpations of the kidneys.
Palpability of the bladder not disappearing with micturition is likely to be
associated with obstructive lesions to the bladder outflow such as the
persistent urethral valves,and palpation of the lumbosacral spine.
Associated renal abnormalities may be detected on palpations of the kidneys.
Palpability of the bladder not disappearing with micturition is likely to be
associated with obstructive lesions to the bladder outflow such as the
persistent urethral valves.
Abnormal physical findings may be found in patients with cystitis,
constipation, neurogenic bladder, urethral obstruction, ectopic ureter,
obstructive sleep apnea (OSA), and hyperthyroidism.
Diastematomyelia or spinal dysraphism or sacral agenesis should be excluded
by inspection of the lower spine and testing the ankle jerks.
A midline dimple, a hairy tuft, a lipoma or a haemangioma may also indicate a
diastematomyelia.
A spinal defect such as a dimple hair tuft or skin discoloration might be visible
in one half cases with intraspinal lesion.
Assessment of the anal wink or the ability of a patient to stand on the toes is a
satisfactory test of the integrity of the S2-4 spinal reflex arc.
In some circumstances observing the child during micturition will be helpful to
assess the urinary stream.
If the child grunts audibly or uses the abdominal muscles to push or if the
stream is weak or interrupted, a urethral obstruction might be present. In girls
with ectopic ureter, a constant, moistness in the introitus, and regular drying
with tissue reveals the persistent leak of urine.
Tonsillar size in a child examined in the awake state and sitting position may
not correlate with obstructive sleep apnea symptoms.
Examination of the child in the prone position and during sleep may be
necessary to visibly document obstruction.
Examination of the endocrine system especially the thyroid will be important if
endocrinopathies such as hyperthyroidism is suspected
BIBLIOGRAPHY AND SUGGESTIONS FOR FURTHER READING
von Gontard A, Mauer-Mucke K, Plück J, Berner W, Lehmkuhl G.
Clinical behavioral problems in day-and night-wetting children.
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5-The Clinical Features and the Associated Pathologies of Enuresis:
Diagnosis:
The best time to investigate a child with enuresis is when the parent or the
child first visits the doctor or raises the issue as a concern.
The range of specific tests which should be carried out in a child presenting
with enuresis will depend on the history and symptomatologies.Urinalysis is
performed to assess for the urinary specific gravity and urinary glucose level.If
urinalysis reveals evidence of infection, the child should be evaluated for
vesicoureteral reflux.
Routine examination of the urine for albumin, sugar and pus cells and urine
culture from a properly obtained specimen, should be carried out in all cases.
The need for an intravenous pyelogram in nocturnal enuresis will depend on
the history and clinical features.
If there is any evidence to suggest infection, or any organic abnormality of the
renal tract, an intravenous pyelogram is indicated.
Where there are obvious emotional factors such as the recent birth of a sibling
or first attendance at school an intravenous pyelogram is indicated.For more
difficult and resistant cases, the currently recommended work-up is a voiding
cystourethrogram and real time renal ultrasonographic examination.
Specific and specialized Investigations will include a
videocystourethrographies and urodynamic and uroflowmetry studies and
endoscopic examinations under anaesthesia.
Enuresis and any specific causes can usually be diagnosed from a history
focusing on enuresis, physical examination, and urinalysis.Workup does not
usually require imaging and urodynamic studies unless specifically indicated
because neurologic or urologic disease is suspected.
Urinalysis and urine culture should help detect urinary tract infection, diabetes
mellitus, or diabetes insipidus.Useful laboratory testing may include blood
count and serum chemistry, serum urea nitrogen and serum creatinine levels
for chronic renal failure, serum glucose levels for diabetes, hemoglobin
electrophoresis for sickle cell disease, and serum thyroid-stimulating hormone
level for hyperthyroidism.
Depending on other findings, specific imaging studies may be indicated, such
as renal and bladder ultrasonography and voiding cystourethrography for
suspected structural abnormality, significant daytime wetting, or recurrent
urinary infections to detect vesicoureteral reflux.
Magnetic resonance imaging of the lumbosacral spine should help diagnose
suspected spinal dysraphism or underlying cause for abnormal neurologic
examination findings.
5-The Clinical Features and the Associated Pathologies of Enuresis:
Diagnosis:
To evaluate bladder dysfunction, urodynamic studies may include
measurement of residual urine and cystometry measurement lines are then
connected to transducers incorporated into the urodynamic apparatus.
These investigations would help to classify these cases further into
complicated and uncomplicated enuresis or regressive or persistent in these
subsets of enuresis, organic pathology could be found in only a very small
number of cases.
Basic physical evaluations and investigative evaluations such as urinalysis
should normally be indicated, but more invasive procedures such as
urography and cystoscopy are not usually warranted and should not usually
be pursued unless there is some indication of an organic lesion.
In children with refractory monosymptomatic primary nocturnal enuresis,
Bladder dysfunction and sleep disturbances should be carefully studied.
Following diagnostic evaluations, most cases of enuresis will belong to the
uncomplicated category.
Investigative studies for the latter category will not ordinarily go beyond a
urine analysis, microscopy, culture and sensitivity to exclude a cystitis which
may cause urinary urgency and then enuresis.
Bacturia has increased urinary frequency in enuretic girls and if suggested
should be investigated and treated, although this will not always lead to
resolution of bedwetting.
Urinalysis should be obtained after an overnight fast and evaluated for specific
gravity or osmolality or both, in order to exclude polyuria as a cause of
frequency and incontinence and to ascertain that the concentrating ability is
normal.
The absence of glycosuria should be confirmed. Urine cultures should be
routinely undertaken.
If there are no daytime symptoms and if the physical examination, urinalysis
and culture are normal, then further evaluations for urinary tract pathology is
not warranted even in older children.
When associated urogenital tract abnormalities are suspected, an intravenous
pyelourogram may be about the most investigation technique applied at the
first instance in the management of enuresis.
Measurement of the urinary flow rate helps rule out obstructive lesions.
5-The Clinical Features and the Associated Pathologies of Enuresis:
Diagnosis:
Cystoscopy is unlikely to be useful if the urinary examination is innocuous, in
that case it should better to avoid, because of the possibility of a worsening of
psychosexual maladaptation in neurotic older children.
Real time ultrasound equipment will normally be required for the assessment of
the bladder wall integrity.
In the author’s experience, leucocytosis and raised erythrocyte sedimentation
rates could be demonstrated in about one in four instances to one in eight
instances respectively in association with urinary tract infections.
Also hyopcreatinineamia, hyperphosphataemias, hypoproteinaemias, raised
alkaline phosphatases and hyponatraemias were occasionally associated
biochemical perturbations.
Studies of enuresis suggest that detrusor and sphincter instability could be
caused by overactivity of integral voiding reflexes.
Children with intractable nocturnal enuresis or enuresis plus daytime urgency
incontinence should be studied by cystometry.
In some instances,both the girls and the boys will have some evidence of
bladder instability.
Children in whom abnormalities were found on preliminary voiding
urodynamics or voiding cystourethrography should also undergoe calibration
and endoscopic examination under anaesthesia.
Initial laboratory test should include urinalysis and, if indicated, urine culture.
Tests to evaluate causes of secondary enuresis are serum glucose level, serum
urea nitrogen, creatinine level, hemoglobin electrophoresis, and thyroidstimulating hormone level.
Patients with daytime symptoms, urinary tract infections, possible renal
anomalies, or refractory symptoms might need renal and bladder
ultrasonography, voiding cystourethrography, magnetic resonance imaging of
the lumbosacral spine, or urodynamic studies.
The differential diagnosis of neurogenic and non-neurogenic voiding
dysfunction, particularly in children with occult neurogenic pathologic findings
without a clinically demonstrable neurologic defect, is a commonly
encountered problem.
Children with voiding dysfunction, including a history of diurnal incontinence,
frequency, urgency, urge incontinence, incomplete bladder emptying, recurrent
urinary tract infection, and persistent vesicoureteral reflux should normally be
evaluated by an MRI.
The magnetic resonance imaging (MRI) has a role in children with voiding
dysfunction and a normal neuro-orthopedic assessment.
5-5- Interventions in Enuresis:Diagnostic Interventions
Diagnosis:
A detailed neuro-orthopedic evaluation should be performed in all patients.
The urologic evaluation consisted of a detailed history, enquiry into bowel
function disturbances), renal sonography or excretory urography, spinal x-ray,
urinalysis and culture, voiding cystourethrography, and multichannel water
cystometry. In more difficult cases of neurogenic bladders, lumbosacral spinal
axial and sagittal T1- and T2-weighted MRI performed with a 1.5-Tesla surface
coil should be undertaken and reviewed possibly by a neuroradiologist.
MRI revealed pathologic findings in two of five patients who had voiding
dysfunction and a normal neuro-orthopedic assessment.
These patients may need to undergo early surgical interventions in a pediatric
neurosurgery department.
In the postoperative period, objective and/or subjective improvement in
voiding symptoms within short and long periods could be observed in one half
to one third of these patients respectively.
Three in five of these patients had a history of voiding dysfunction refractory
to conservative management.
The usefulness of Magnetic Resonance Imaging of the lower spinal cord as a
valuable tool in the diagnosis of occult spinal cord disorders, especially in
patients with voiding dysfunction refractory to conservative management
strategies and normal neurologic and orthopaedic assessments has been
previously suggested.
Symptoms and urodynamic and Magnetic Resonance Imaging findings of
patients who had normal neuro-orthopedic assessment and spinal x-ray but
pathologic Magnetic Resonance Imaging results were consistent with a subtle
neurogenic bladder.
Atropine-suppression tests could also be performed preoperatively in some
children with a markedly unstable bladder demonstrated on preoperative
cystometry.
In the majority of children tested, suppression of bladder instability with
atropine was demonstrable.
Voluntary detrusor sphincter dyssynergia was demonstrated in a majority of
the children with daytime urgency incontinence.
Urethral obstructive lesions suspected to be of functional urodynamic
significance are usually more common in girls compared to boys and warrants
satisfactory interventions.
Postoperative cystometry shows more marked improvement in bladder
5-5- Interventions in Enuresis:Diagnostic Interventions
: anticholinergic suppression test was found to have no significant
The
predictive value relative to the cause or surgical curability of bladder
instability.
The pathophysiologic significance of overactivity of integral voiding reflexes
includes enuresis.
Urodynamic studies may need to be carried out in Central Nervous System
defective children with enuresis.
Urodynamic studies could be achieved using filling cystometries.
Videocystourethrography with synchronous pressure and flow-rate recordings
nedds also to be carried out on patients referred for the investigation of
persistent primary enuresis.
Urodynamic studies showed nocturnal enuresis to be associated mainly with
normal detrusor function and nocturnal plus diurnal enuresis mainly with
abnormal detrusor function.
Out of formerly enuretic male patients one half with abnormal detrusor
function showed persistent nocturnal plus diurnal symptoms.
This study dealt with urodynamics during sleep where enuresis was provoked
by filling cystometries a pressure flow studies.
Bladder dysfunction in children with refractory monosymptomatic
primary nocturnal enuresis.
Reduction in nocturnal bladder capacity is a common factor in the
pathogenesis of refractory nocturnal enuresis.Clinical and
urodynamic spectrum of bladder function in children with cerebral
palsy suggests that most children with cerebral palsy has detrusor
muscle instability.
Transurethral incision of congenital obstructive lesions in the
posterior urethra in boys has beneficial efefcts on urinary
incontinence and urodynamic study.
However,routine urodynamic studies is not indicated in all children
with enuresis.Children with unstable bladder will benefit from
clinical and urodynamic observation,and home uroflowmetry for the
evaluation of boys with urinary incontinence.
5- Interventions in Enuresis:Diagnostic Interventions
:Diagnosis:
Relevant systemic evaluations were non-informative, normative
ECGS could exclude heart blocks/arrhythmias.
However, the authors experience, suggests that in most cases of
childhood enuresis, good outcome measures could be achieved by a
comprehensively applied historical enquiry and selective noninvasive evaluations and interventions.
Long standing enuresis can be due to organic causes, as well as
socio-economic deprivation and in most cases an intravenous
urography may not be indicated.
Where there are obvious emotional factors such as the recent birth
of a sibling or the first attendance at school an intravenous
pyelography will not be indicated.
Once an organic cause has been excluded and its exclusion is
important in counseling parents, physical investigations should not
be pursued as this particularly if hospital admission is involved, is
likely to affect functional enuresis adversely.
Food allergy blood Test:
A simple blood test to identify elevated antibodies to food
allergens,helps to discover what should be avoided in the child’s
diet.
A detailed ninety six hours rotation diet, individually created for the
child would identify the food substances that the child is allergic to.
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Therapeutic Interventions for Nocturnal Enuresis.
Therapeutic Interventions for Nocturnal Enuresis.
Interventions For Enuresis
Since no single therapy has been consistently superior, the clinical
setting, family preference, and experience of the practitioner should
dictate the preliminary choice.
Successful treatment refers to continence for a fortnight
consecutively within a sixteen weeks period.
These concepts should be approached in the context of the import
of timely presentations, evaluations, motivational, collaborative
therapies, behavioural modifications, environmental manipulations,
other forms of non-pharmacological interventions, also other current
topical issues should be discussed with the patients.
The most important reason to treat enuresis is to minimize the
embarrassment and anxiety of the child and the frustration
experienced by the parents.
The considerable psychological and emotional solitude experienced
by enuretic children and their families should be appreciated and
addressed.
An exploration of the probable cause of the enuresis should be
undertaken and a possible putative cause for the enuresis proffered
for discussion and explanation to the parents on what the possible
interventions could be.
Older family members with a history of enuresis in childhood should
be encouraged to explore and express their experiences and the
possible strategies that were applied to overcome their enuresis
overtime.
The knowledge that another family member had enuresis and
outgrew the defect over time is usually encouraging.
Interventions in Enuresis: Therapeutic Interventions for Nocturnal Enuresis.
Therapeutic Interventions for Nocturnal Enuresis.
Although at face value,this approach could be
apparently simple and basic,however it proffers
emotional upliftment to the enuretic child. and could
indeed be therapeutic in some instances.
A proactive predisposition,steadfastness,optimism
and determination from the child,his parents and care
givers,are crucial aspects of the intervention, to boost
the childs ego,sustain treatment adherence, diminish
retrogression and lead to the achievement of dryness,
punitive measures should be eschewed.
Incessant follow ups and reiterations of other
behavioral modifications and environmental
manipulations will be pertinent for an overall
successful outcome and appraisals of the impact of
the achievable interventions.
If a child has no daytime symptoms or has experienced
significant dry spells in the past, the presence of a
structural genitourinary abnormality as a cause of the
enuresis is unlikely,as such surgical interventions will
ordinarly not be warranted.
5- Interventions For Enuresis:Non-Pharmacologic Therapeutic Interventions
In clear cut enuresis of functional ,idiopathic or primary origin where surgically
modifiable defects are unlikely associations, an explaination should be offered
to assuage parental anxieties, reassuring them that invasive investigations or
interventions will not otherwise be warranted as such, however their optimal
co-operation will be quite beneficial for a successful outcome.
Whist in the doctors office,the childs parents should be encouraged to proffer
specific examples of their possible pathological concerns leading to the
enuresis in their child for exploration,discussion and management. A keen and
documented attention to a normal daytime micturition pattern is vitally
important. The child should be encouraged to micturate upon awakening, at
common transition times, and approximately every ninety to one twenty
minutes, before leaving home or school for any reason, and always before
bed.Children should be encouraged to micturate regularly at school, at least
two to three times daily whilst at school.A note for the teacher should be
written to authorize regular access to the bathroom. The assistance of the
school teacher should be enlisted,since children should not be expected to
wait for scheduled break periods to micturate.
Micturition postponement until marked urgency arises should be discouraged.
During micturtion,the child should,use a comfortable and an optimal posture,
be attentive and at ease,taking time to empty the bladder completely.
Children should be instructed to drink liberal amounts of fluid during the
day,to maintain an optimal hydration level throughout the entire day. A wellhydrated child is not likely to be thirsty when he or she returns home from
school and is not likely to be very thirsty at bedtime.
Bouts of thirsty sensations,should be prevented such that a child does not
overdrink in the evening hours before going to bed.
Athletic children engaged in sporting activities or who are otherwise physically
active in the evenings after mealtimes should be well hydrated for the activity.
Parents should be asked to take the child to the bathroom to void prior to
bedtime.
Because this therapeutic measure is designed only to minimize the quantity of
fluid in the bladder, full wakefulness is neither necessary nor desirable.
Careful monitoring by a parent is necessary for each of the trip from bed to the
bathroom and back.
5- Interventions For Enuresis: Non-Pharmacological Therapeutic Interventions
Children should go to bed at an hour calculated to offer the optimal
hours of sleep for their age.
An alarm or pharmacologic therapy should be considered, if
attention to the above preliminary management program for up to
twelve weeks does not result in cessation of the enuresis.
Some of these cases could be modified by environmental,
manipulations, behavioural or motivational therapies, and
occasionally by pharmacotherapy.
In some instances the pathologies are surgically amenable.
The Pharmacotherapeutically amenable causes of enuresis include,
but are not limited to:
Urinary Tract Infections.
Diabetes Mellitus
Diabetes Insipidus
Faecal Impaction
Constipation
Obstipation.
Whereas the surgically amenable subsets include:
Ectopic Ureter.
Lower Urinary Tract Infections.
Neurogenic Bladders.
Bladder Calculus
Bladder Foreign Body.
Obstructive Sleep apnoeas secondary to adenoidal hypertrophy.
Occasionally, an idiosyncratic or dose related hypersensitivity
allergy to some food supplements or artificial preservatives in the
food materials themselves could be the implicated factor.
The best approaches for diagnosing and treating childhood-enuresis
have been reviewed.
The scientific medical management of enuresis is dynamic and is
being continually modified and reviewed.
Suggestions for interventional strategies for nocturnal enuresis
should be individualistic and case driven.
5- Interventions For Enuresis: Non-Pharmacological Therapeutic Interventions
:
Environmental Manipulations and Behavioural therapies:
These are usually initial plausible options which should be applied
to most cases of enuresis, even for the most severe cases.
Management of the child with enuresis depends on the
comprehension of the possible specific causative factors suggested
by an adequate psychosocial evaluations and physical examination.
For instance a child could be helped to deal with feelings about a
younger sibling or the parents could be helped to establish proper
attitudes and circumstances for a child’s success in urinary training.
Some enuretic children may be dry while living away from home
such as while in the hospital or whilst living with a relative.
Some general suggestions are as follows.
Since maturation and recovery is the rule in most instances,
treatment should be conservative and modified accordingly.
The placebo effect of kind and firm interest probably cures about
thirty to fifty percent of cases with no other assistance.
Punitive measures, reward or any undue attention to the matter
should be avoided.
5- Interventions in Enuresis:Non-Pharmacological Therapeutic Interventions
:
Environmental Manipulations and Behavioural therapies:
On the basis of the authors experience with these groups of children,
the guidelines outlined below were found quite useful.
[1]-It is important to enlist the cooperation of the child to deal with
the problem.
Rewarding the child for being dry at night is a useful step.
The child or parent could chart the dry nights, and with one or two
dry nights a small reward could be given to the child.
More substantial rewards should be given for increasing success.
[2]-Older children should be encouraged to launder their own bed
wetted clothings.
In many instances, children with enuresis has received inordinate
coercive bladder training.
[3]-Children should be given no liquids before retiring to bed,
and if imperative parents and care givers should ensure that only
minimal quantities of fluids are taken after supper.
[4]-As much as possible encourage bedtime micturition.
[5]-In as much as parental awakenings should be advocated, it is
noteworthy that ,repeated nightly wakings of the child for assistance
to the bathroom for micturition is useful in only a few instances, and
may further engender or aggravate anger in the child or her parent.
[6]-Punishment or humiliation of the child by his parents or others
should be strongly discouraged.
[7]-The total daily urinary output should be estimated in order to
compute the optimal bladder capacity, and to approximate the
average bladder capacity.
[8]- Bladder trainings with stream interruptions should be suggested.
[9]- Parental and siblings praises should be suggested after
continent nights.
[10]- Rewards after continent nights should normally be advocated
for.
[11]-More healthy overnight activities in older children such as
reading or relevant television watching should be encouraged.
5- Interventions in Enuresis:Non-Pharmacological Therapeutic Interventions:
Environmental Manipulations and Behavioural therapies:
Environmental Manipulations and Behavioural therapies:
Although psychiatric consultations should not normally be
indicated, however, many of these children will require references
for multimodal intensive individual or group psychotherapies.
A supportive relationship with Paediatrician and counseling for the
child and the parent’s could be assistive.
These positive reinforcements if systematically executed through
standardized documentations and charting of the child’s progress
were found to be successful in approximately four of five instances.
Nocturnal enuresis is common in young children but persists in as
many as one of twenty children by the age of ten.
Treatment is not appropriate in children under the age of five years
and is usually not needed in those aged less than seven years and in
cases where the child and the parents are not anxious about the
bedwetting, however children over the age of ten years usually
require prompt treatment.
Therapeutic Options for Nocturnal Enuresis:
Aims of Therapeutic Interventions:
[1]-The aim of any treatment programme is to stay dry on particular
occasions such as when visiting friends.
[2]-To reduce the number of wet nights.
[3]-To reduce the impact of enuresis on the child’s lifestyle.
[4]-To initiate successful continence.
[5]-To avoid relapse.
[6]-To intervene pharmacotherapeutically with minimal adverse
effects.
Non-Pharmacological Interventions for Nocturnal Enuresis.
Environmental Manipulations and Behavioural therapies:
With time, primary nocturnal enuresis almost always resolves on its own.
Therefore, treatment should be postponed until the child is willing and able to
comply with the treatment plan.
In children younger than seven years of age, medications are rarely indicated.
Treatment is not necessarily imperative if the child is not distressed about the
enuresis, but parents should be reassured about their child's physical and
emotional health and counseled regarding eliminating undue guilt, shame, and
punitive measures.
When behavioral measures are unsuccessful, enuresis alarms are often
effective in children with primary nocturnal enuresis and should be considered
for older, motivated children from cooperative families.
In children with nocturnal polyuria and normal bladder capacity, desmopressin
is most effective, and typically it works more quickly than alarm systems.
Combined treatment is effective for resistant cases.
Some key clinical recommendations for practice, with acceptable levels of
scientific evidence are as follows:
The first step in treating primary nocturnal enuresis is to educate the child and
parents about the condition.Before primary nocturnal enuresis is addressed,
daytime symptoms should be actively identified and managed.Secondary
causes, if identified, should be managed and treated appropriately.
Treatment of primary nocturnal enuresis is not needed unless the condition is
distressing to the child.
However, the parents should be reassured about their child's physical and
emotional health, and they should be counseled about eliminating guilt,
shame, and punishment.
Management of the child with enuresis depends on the comprehension of the
possible specific causative factors suggested by an adequate psychosocial
evaluations and physical examination.
For instance a child could be helped to deal with feelings about a younger
sibling or the parents could be helped to establish proper attitudes and climate
for a child’s success in urinary training.
Some enuretic children may be dry while living away from home such as while
in the hospital or whilst living with a relative.
Non-Pharmacological Interventions for Nocturnal Enuresis.
In the author’s research experience on this topic with a representative sample,
some other general suggestions noted to be beneficial were as follows:
Since maturation and recovery is the rule in most instances of childhood
enuresis, treatment should be modified accordingly with watchful
conservatism.
The placebo effect of a kind and steadfast interest in the child and his family
with regards to their concerns with enuresis probably cures about one of three
to one half with no other assistance.
Punitive measures, ungraded reward or any undue attention to the matter
should be avoided, in addition, humiliation of the child by his parents or others
should be strongly discouraged.
Rewarding the child for being dry at night is a useful step.
The child or parent could chart the dry nights, and following one or two dry
nights, a small reward could be given to the child.
More substantial rewards should be given for increasing success.
Developing self regulated arousal strategies such as encouraging the child to
void before retiring to bed is usually rewarding, whereas an unduly frequent
nocturnal awakenings of the child at night for micturition purposes following a
walk to the bathroom may be beneficial in only very few instances and may
occasionally, further engender or aggravate anger in the child or his parents.
In the author’s research experience on this topic, these positive
reinforcements if systematically executed through standardized
documentations and charting of the child’s progress were successful in
approximately four of five instances.
Other Interventions and Treatment Options which could be suggested include
bladder trainings with stream interruptions.
Bladder Training Strategies consists of physical manuvers for strengthening
and coordinating muscles of the bladder and urethra, and may assist in the
regulation of micturition.
Pelvic floor muscle retraining for pediatric voiding dysfunction using
interactive computer games could be useful in a selected group of children.
Dry bed training without the use of either bed alarm is a plausible
interventional option, but it does require a high degree of parent child
motivation.
These techniques teach the child to anticipate the need to micturate at
convenience and prevent micturition when in an inconvenient place.
Non-Pharmacological Interventions for Nocturnal Enuresis.
Techniques that may help nighttime incontinence include:
Bladder stretching exrecises through a graded postponement of micturition.
Other beneficial measures would include to eencourage more healthy
overnight activities in older children such as reading or relevant television
watching and advocating for rewards following continent nights.
Parental and siblings commendations after continent nights should be
suggested.
In the authors practice experience with these group of
children,overall,however none of the above mentioned strategies alone were
demonstrated to be entirely satisfactory in the management of childhood
enuresis.
Techniques that may assist to ameliorate daytime incontinence includes:
Programmed micturition following a preplanned time schedule, such as paced
voidings undertakings could be carried out up to twelve times daily.
Avoiding caffeine or other foods or drinks that may contribute to a child's
incontinence
Following suggestions for healthy micturition, such as relaxing the pelvic
muscles and gradual micturition over a reasonable period of time instead of
abruptly.
In the treatment of primary nocturnal enuresis, dry-bed training and bladder
training maneuvers alone are not recommended.
Nocturnal and Diurnal Moisture Alarms
Non-Pharmacologic Treatments:
Analyses of response and relapse of the Bed-Wetting Alarm treatment
Systems:
The concept of using an alarm that emits a sound when a child wets the bed
was first introduced in 1938.
Bed alarms appear to be reasonable options for use in older aged school
children with enuresis.
It usually requires a dedicated nursing medical team and highly motivated
parents.
The conventional type of alarm is one consisting of two wire meshed bed mats,
connected to a bell or buzzer that sounds when electrical contact is made by
the child bed-wetting special bed sheets.
Conditioning approaches such as Eneutone apparatus could be offered.
Non-Pharmacological Interventions for Nocturnal Enuresis.
Although the use of these conditioning approaches was not universally
welcomed and should only be resevered for cases where the child’s self
esteem has been grossly eroded.
These devices could only be normally applied only after a pre-requisite
informed consent has been obtained from the child.
These conditioning devices when indicated were found to be successful in well
over nine in ten instances.
The bed-wetting alarm has been shown to be the most effective treatment for
nocturnal enuresis.
Compared with other skill-based or pharmacologic treatments, the bed-wetting
alarm has a higher success rate of about three of four and a lower relapse rate
of two of three. [Evidence level B, nonrandomized clinical trial]
The alarm appears to work by negative reinforcement or avoidance.
It goes off and awakens the child during voiding; the child gets out of bed and
finishes voiding in the toilet or holds urine until later.
For resolution of nocturnal enuresis, the bed-wetting alarm may need to be
used for up to fifteen weeks.
Unfortunately, treatment with bed-wetting alarms has a dropout rate of ten to
thirty percent.
Possible predictors of a poor response include an unstable or chaotic family
situation, behavior deviance in the child, high level of anxiety in the mother,
and lack of concern about bed-wetting on the part of the parents or child.Low
parental education level and high socioeconomic status also may be
predictors of a poor response.
Another cited reason for the relatively high dropout rate is that adults who
used the alarms as children, even those who were cured of bed-wetting,
remember the treatment period as the worst time of their life.
However, a study conducted at a referral center found that when parents were
given a choice of treatment modality, more than nine in ten of those who
selected the alarm had used such an alarm when they were children. [Evidence
level B, nonrandomized clinical trial]
Improved technology has made the bed-wetting alarm a more attractive option
than in the past.
Alarms are now smaller and lighter, and they can be equipped with a buzzer,
rather than a sound alarm, for children who do not respond to an alarm sound
or for households in which an alarm disrupts the sleep of others.A number of
Non-Pharmacological Interventions for Nocturnal Enuresis.
Positive Reinforcement Systems
In one positive reinforcement system, the child puts stickers on a chart or
earns points for every night he or she remains dry.Once a certain number of
stickers or points have been earned, the child is given a prize.
Another technique uses a connect-the-dots picture.The child connects two
dots for every dry night.
When the picture is completed, the child receives a prize.
Responsibility Training
With this technique, the child is given age-appropriate responsibility, in a
nonpunitive way, for the consequences of bed-wetting.Younger children may
be asked to strip wet linens from the bed, whereas older children may be
expected to do the laundry.
Other Approaches
Various nonpharmacologic treatments have been shown to have a positive
effect on bed-wetting in small studies but have not been extensively evaluated
(generally weak strength of evidence).
These approaches include an elimination diet, hypnosis, retention control (i.e.,
holding urine for progressively longer periods), biofeedback, acupuncture,
scheduled awakenings, and caffeine restriction.
In children with monosymptomatic nocturnal enuresis, an enuresis alarm is
effective.
When the child has been continent for fourteen consecutive nights,
overlearning should be included through increasing the child’s bladder
capacity, for this to be achieved, the child should be encouraged to drink extra
fluids before bedtime.
Anticholinergic treatment is useful in children who have urinary urgency,
restricted bladder capacity from nocturnal detrusor hyperactivity and
combined daytime wetting and nocturnal incontinence as well as in children
who do not respond to desmopressin.
Desmopressin is most effective for children with monosymptomatic enuresis,
nocturnal polyuria, and normal bladder capacity.
Pharmacologic therapies are not curative, but they decrease the frequency of
enuresis or temporarily resolve symptoms over time until spontaneous
resolution occurs.
Principal pharmacological options include anticholinergic agents, tricyclic
antidepressants and desmopressin.
Non-Pharmacological Interventions for Nocturnal Enuresis.
Of these therapies, only imipramine and oral desmopressin have been partly
approved for the treatment of enuresis in children.
These are usually initial plausible options which should be applied to most
cases of enuresis, even for the most severe cases.
When behavioural therapy is recommended, the child friendly moisture alarm
should be introduced to alert the parent and the child after micturition.
Moisture alarms could awaken an enuretic child when he or she begins to
micturate.
The proper hygiene schedule in addition to the other recommended
therapeutic procedures although initially cumbersome could be mastered
overtime. These processes could reduce the incidence of primary nocturnal
enuresis (PNE) of childhood.
These devices include a circuit of a fluid-sensor pad worn on the night
pyjamas, a wire connected to a battery-driven control, and an alarm that
sounds when moisture is first detected.
For the enuretic alarm control mechanism to be rewarding,the child must
arouse spontaneously in response to the alarm system or be aroused by his
parents or guardian as soon as the alarm goes off.
For utmost outcome this may imply having the parents or guardian sleep in the
same room with the enuretic child to facilitate the awakening process if this
could not be achieved spontaneously by the child.
An enuresis alarm should be the first line of treatment for well motivated, well
supported children aged over seven years because alarms have a lower
relapse rate than drug treatment on discontinuation.
Use of an alarm could be combined with drug therapy if both techniques are
ineffective on their own.
Selected Bed-Wetting Alarms systems include:
[A]-Nytone Alarm
[B]-Wet-Stop Alarm
[C]-Potty Pager (silent alarm)
[D]-DRI Sleeper
[E]-The Dry Buddy Alarms
An alarm may be covered by insurance if was prescribed by a physician.
Conditioning alarms will give a remission rate in about one half to nineteen of
twenty instances.
With a relapse rate of probably about nine of twenty instances.
Non-Pharmacological Interventions for Nocturnal Enuresis.
[8]-Plausible Pharmacotherapeutic Interventions.
Many parents would ask the physician about the possible advantages or risks
with pharmacotherapies if this has not be mentioned in the treatment plan
during counseling.
Having satisfied himself that the child is physically well, the clinician must
decide whether the enuresis is monosymptomatic and probably developmental
or maturational, or whether it is a transient reaction to anxiety or whether it
represents a more permanent habit resulting from long-term stress or
deprivations.
Further review of the putative causes of nocturnal enuresis would assist to
elucidate the rational behinds its logical interventions.
In thirty three of thirty four instances, the enuresis is non-pathologic and is
usually a consequence of the peculiarities of the maturational process.
A recap of the non-pathological causes of enuresis which could improve with
the passage of time includes:
A small functional bladder capacity.
Lack of the co-ordination/Inability to delay the micturition urge.
Night time polyuria secondary to relatively low antidiuretic hormone levels.
Night time polyuria because of excessive evening fluid intake.
Nonarousability with a full bladder (Deep Sleepers)
In about one in thirty three instances, enuresis could be pathological.
Most children achieved nocturnal continence without being woken up on
several instances at night, so they were not in anyway trained to achieve
nocturnal continence.
Treatment of childhood enuresis must begin with a careful history, physical
examination, urinalysis, urine culture to determine if one is dealing with a
complicated or an uncomplicated enuresis.
There are several treatment options available to the physician that could be
tailored to the individual patient.
Treatment should be related to the type of personality disorder and family
picture.
As suggested historically, over several centuries, very many different
management options for enuresis were applied and evaluated.
Non-Pharmacological Interventions for Nocturnal Enuresis.
All have recorded some degree of positive outcome measures over time,
probably more through the stimulation of hope, familial tensions reduction and
coincidence with maturational or chronologically spontaneous improvement
and recoveries, than through any more specific action as such.
Many families devise their own cures, often based on current medical practices
for example restriction of at nocturnal fluids ingestion, nocturnal awakenings
for micturation purposes, offering rewards for continent nights and other
modifying and manipulative therapies.
When these treatment options are clearly successful, the physician will do well
to support the family in their course of action, even though the support for the
approach may be anecdotal rather than experimentally based robust evidence
supporting the applied strategy to be better than another or than none at all.
On the other hand some parents particularly in the early stages of the disorder
may adopt a frankly punitive treatment approaches such as smaking the child
or humiliating him by revealing his weaknesses to his friends, making him
launder his own clothes manually , despite the possession of a household
washing machine.
In such instances, it is the physicians responsibility to explain to the child’s
parents that their anger is understandable and there is a motive for their
feeling of disgust because they probably have more emotional, psychological
and physical burden due to the enuretic child from having to wash wet bed
sheets more frequently to the financial and time implications for the apposite
interventions for their enuretc child, this may enable them to express their
emotionalities during the interview.
This often have the beneficial effect of diverting the some of the parental
hostilities away from the child, physicians should not reinforce parental
punitive methods and should clearly understand that to increase the child
anxiety is likely to delay the development of bladder regulation.
The importance of tolerance, patience and support for a child likely to be very
concerned about his disability needs to be appreciated.
The belief that the child does not care about his symptoms is usually
unfounded.
His bland smiling face which is a psychological defense mechanism of denial
and regression. should not deceive his clinician.
As soon as he senses that the doctor is non-critical, realizes his real misery
and is anxious to help, he will reveal his sense of shame and eagerness to
become continent.
Non-Pharmacological Interventions for Nocturnal Enuresis.
Parents will be relieved to hear that their child has no organic
disease, but should not be allowed too interpret this as if nothing is
amiss.
Developmental delay is an important and an explanatory concept.
Encouragement and reassurance for parents and child are
particularly effective if there is a programme of regular interviews
with one doctor.
Nonresponse to treatment refers to less than one half decreases in
enuresis.
Initial treatment of primary nocturnal enuresis consists of
motivational therapy and behavioral intervention.
Treatment is usually not indicated until the children are at least aged
seven years and motivated to comply with interventions.
Motivational therapy includes reassurance, support, guilt
elimination, and encouraging child's role in treatment.
Behavioral interventions include awakening the child to void,
positive reinforcement for continence, bladder training, and limiting
fluid and caffeine intake before bedtime.
Non-Pharmacological Interventions for Nocturnal Enuresis.
Alarm therapy
Alarm therapy offers the possibility of sustained improvement of enuresis and should be
considered for every patient.
Alarm therapy is reported to improve bedwetting by increasing nocturnal bladder capacity
or by enhanced arousal.
Alarm therapy does not reduce nocturnal urine output.
Some successfully treated children replace enuresis with nocturia, and others sleep dry
without the need to void at night.
Some improve within the first fortnight of treatment and others only after several months.
A systematic review of a metanalysis of several highly powered randomized clinical trials
involving several enuretic children concluded that alarm therapy is beneficial.
About two thirds of children on alarm therapy were dry, but about half relapsed such that at
six-months follow-up only about a third remained dry. Optimal results occur when the child
is well motivated.
Older children usually have better developed motivation.
Parental motivation and participation are also vitally crucial.
The parent should believe the approach is worthwhile and should be prepared to participate
every night for at least three consecutive months.Numerous alarms are available.
The alarm should be attached at bedtime to the underwear or pajamas in a position chosen
to promptly sense wetness.
Although most children with enuresis do not awaken to the alarm emits its sounds,they
stop emptying their bladders.
When the alarm sounds, a parent must assist the child to wake to full consciousness and to
attend to the bathroom to finish voiding.
After changing the sheets and underwear or pajamas, the child should be returned to bed
and the alarm should be reset.
Close biweekly or monthly follow-up care is important to sustain motivation, troubleshoot
technical issues, and otherwise to monitor the therapy.
In successfully treated children, alarm therapy should be continued for at least three
months and for one month after sustained dryness.
Relapses are common, usually developing in one third to two third of children, and might
respond to further alarm therapy.
If the child is still wet after a minimum of three months of consecutive use, alarm therapy
can be discontinued and considered unsuccessful.
Failure does not preclude future successful treatment in an older, more motivated child.
Enuresis alarms triggered by moisture sensors require use for up to six to sixteen weeks
and are more successful with family cooperation, lack of emotional or behavioral problems,
small bladder capacity, and at least four nocturnal enuretic events weekly.
Relapse rates are considerably decreased if enuresis alarms are combined with behavioral
interventions, such as overlearning (extra fluid intake at bedtime to increase bladder
capacity), dry-bed training (awakening at set intervals), and arousal training (reward for
awakening to alarm).
Children aged at least seven years who do not respond to behavioral interventions might
need to go on medications for initial temporary improvement.
Non-Pharmacological Interventions for Nocturnal Enuresis.
Oral desmopressin is most effective for monosymptomatic enuresis, nocturnal
polyuria, and normal bladder capacity.
Other medications include imipramine and oxybutynin.
These medications can cause adverse effects and, when discontinued, relapse
of symptoms.
Indications for referral to a specialist include persistent enuresis, daytime
wetting or abnormal voiding, straining or poor urinary stream, genital
anomalies, and a history of urinary tract infections.
Interventions for diurnal incontinence or nonmonosymptomatic enuresis
includes treatment of the underlying medical condition, modification of the
voiding regimen, biofeedback, and possible specialist referral.
The evaluation of children with enuresis includes focused history, physical
examination, and urinalysis, and if indicated, urine culture, blood count, serum
chemistry, imaging studies, and urodynamic studies.
Treatment methods of primary nocturnal enuresis includes motivational
therapy, behavioral intervention, and enuresis alarms.
Medications could be used in children aged at least seven years for temporary
relief.
Indications for referral to a specialist include persistent enuresis, daytime
wetting, abnormal voiding, straining or poor urinary stream, genital anomalies,
or a history of urinary tract infections.
The majority of enuretic children are not psychiatrically disturbed.
For these subsets specific treatment focused on only the symptom is usually
helpful.
Dry bed training without alarm systems:
This is a safe easily adaptable and cost effective interventional technique that
requires a high degree of motivation.
Standard Domestic Alarm Clock:
This is a plausible non pharmacotherapeutic option, given its simplicity and
rather more convenience, it is safe cost effective although not very rapidly
reliable.
It does not require any bedwetting to initiate the alarm system.
Enuresis Alarm:
The success of enuresis alarm use in the management of nocturnal enuresis is
supported by the theory of avoidance-learning following repeated acoustic
stimuli from the alarm buzzer to the child.
A successful currently applied technique in the management of enuresis is the
use of a conditioning apparatus which consists of a urine sensitive pad placed
under the enuretic child at bedtime, whenever he micturates, the urine strikes
the pad and triggers a relay in circuit with an electric buzzer.
Non-Pharmacological Interventions for Nocturnal Enuresis.
The noise inhibits micturition and wakes the child up.
The unconditioned stimulus, the noise of the buzzer leads to urethral sphincter
muscular contractions and detrusor muscles relaxation, thus avoiding the
distracting and uncomfortable stimulus of the alarm buzzer.
Before introducing an enuretic alarm buzzer conditioning apparatus, the
parents and the child must have a careful demonstration of how the apparatus
works.
Follow up must be intensive at the outset to ensure effective and continual
use.
In the early stages, following the alarms introduction, the child may not waken
up when the alarm buzzes, and his parents or care giver may need to assist
him.
Normally following the sounding of the enuretic alarm system, the child should
be woken up promptly, however, the buzzer should be left sounding, until the
child is sufficiently awake to turn it off himself.
Clear signs of progress to be expected should be itemized for the family.
Initially, there will be wet patches on the enuretic alarm pads, which should
naturally follow a diminutive pattern until its disappearance which corresponds
with the nights without any sound emission from the enuretic buzzer alarms.
With further progress, there will be an increasingly proportionate nights in
which the child with neither wake up at night to go to void nor wets the bed.
The enuretic alarms buzzer should be regularly in operation nightly until the
child has been continually dry for four weeks.
Four weeks of regular buzzer use constitutes a fair trial.
The strategy of applying the bed wetting alarms were controversially
discussed in the literature while some authors preferred a staggered-alarm
waking procedure on enuretic children amongst others, a standardized waking
regimen was more popular, although overall, the results achieved for both
subsets were comparable
Non-Pharmacological Interventions for Nocturnal Enuresis.Images & Legends
Non-Pharmacological Inteventions for Nocturnal Enuresis.
The alarm clock system:
When a child wishes to nocturnally continent and he is old and
mature enough to co-operate such as at the primary school level, the
alarm clock regimen is advised.
A laid down programme along the following lines is followed:
The last food and drink should be taken by the child at about six
p.m.
The child should be encouraged to void urine and sleep at about
nine p.m.
The child should be awakened, voids urine and the alarm clock set
at about eleven pm.
The enuretic alarm goes on, the child wakes up and voids by two
a.m.
It is pertinent that the child takes over the responsibilities of waking
and voiding
when he is usually dry between nine pm and eleven pm. and eleven
pm and two am, the time for the alarm is slowly advanced to three
a.m, four a.m, five a.m etc until the child remains dry all night.
This has the advantage that the child awakens before voiding
unlike with the bell and pad system as noted with the enuretic
alarms system,
which is a similar pattern of therapy to that described above with the
exception that voiding triggers off an electric bell.
Whatever system that could be conveniently applied in any
particular case, quite a significant number of children remains
enuretic probably for life.
Resistant cases should be sympathetically handled and carefully
screened by psychiatrists and urologists as they proceed to the
second decade of their lives.
On the average medications acts more rapidly, and may offer
reasonable alternatives where the alarms systems and other
environmental or behavioural manipulative therapies seems
ineffective.
Punitive measures as an interventional option are usually
norciceptive and must be discouraged as much as possible to
Non-Pharmacological Inteventions for Nocturnal Enuresis.
Several alarm devices aimed to call the child’s attention to his
micturition needs were reported by parents to be useful in some
instances.
They should be assured that the problem is not their fault and
encouraged to discontinue punishing the child but to instead weight
the management efforts more in favour of honoring the
recommended therapeutic prescriptions, whether it is mainly in the
form of behavioural therapy or environmental manipulations,
preferably for about quarter day to one half day, thereby minimizing
the chances of incontinence.
The use of medical interventions in the management of enuresis is
low globally, although more pronounced in developing countries, it
be possible that only very few parents are aware of the availability of
medical interventions as reasonable alternatives in the management
of enuresis.
Be developing a positive relationship with the child, the
paediatrician could help him with feelings of guilt, shame or
resentment and develop motivation for an independent control with
the help of the prescribed method.
In the context of such a relationship, the physician should explain to
the parents that the child cannot help the enuresis without
assistance and parental support.
In some instances, control has been achieved during the evaluative
process even before the prescription has been written.
Non-Pharmacological Inteventions for Noctunal Enuresis.
Conditioning and Behavioural modifications.
Although many approaches to treating enuresis have included behavioral
modification, by far the most effective of these behavioual manipulations, have
been the use of conditioning alarm units.
The alarm unit is designed to awaken the child when he or she begins to bet
wet.
The small units are self-contained and the child wears it on the shoulder or the
wrist.
The unit is activated by a small electrode sewn or attached directly onto the
child's underclothing.
At present, there are three kinds of alarm units on the market:
One emits sound when it senses that the child has urinated, one vibrates, and
one can do both.
The traditional alarm emits sound.
This method is inexpensive but quite labor intensive, requiring patience.
The major cause of failure is poor compliance on the part of the child and the
parents.
It must be emphasized that this is truly a familial therapy and the parents must
be willing to accept the responsibility of supervising the therapy.
When rigidly adhered to, as many as four of eight children will ultimately show
improved nighttime urinary regulation, although it may take from six to eight
months.
The principle of conditioning therapy is that repetitively arousing the child at
the time of the wetting episode can ultimately condition the child to recognize
that micturition is about to happen, and teach the child to inhibit the voiding
reflex.
Therefore, it's essential during the first few weeks for the parents to wake the
child completely when the alarm goes off.
The major problems with the alarm units are the length of time it takes to get an
adequate result, the disruption of the entire family's sleep pattern and the fact
that many children react sluggishly to the alarm.
As many as three quarters of children may relapse several months after the
family stops using the alarm, but children could be easily retreated within a
short period of time.
Non-Pharmacological Inteventions for Nocturnal Enuresis.
Other techniques may help to reduce relapse.
The last fluid and food intake should be taken two to three hours before the child goes to
bed and voiding or double voiding before lying down to sleep should be advocated for the
child.
These might include increasing fluids during the day and continued use of the moisture
alarm once the child is staying dry at night.
Methods often tried by parents before they seek medical attention, such as limiting fluids
before bedtime, awakening the child at night at random and reward-punishment strategies
are generally ineffective.
In some occasions. treatment of enuresis can be lengthy and frustrating.
Success is in no way assured in all instances.
But ultimately, all children with simple enuresis will outgrow their enuretic pattern
eventually.
Although this strategy is relatively safe and is free of medicinal products or physician
visits,however,remissions of enuresis controlled by behavioural or motivational options
tends to be delayed compared to pharmacological targets, however, if remissions are
achieved eventually, recurrences tends to be less when compared to those subsets where
pharmacological strategies were applied.
For children whose enuretic tendency represents a developmental lag in bladder regulatory
mechanisms, often with a related struggle for achieving micturition regulation, various
pharmacological options could be employed successfully such as the use of atropine or
imipramine (Tofranil)
In introducing pharmacological agents for the management of enuresis, it should be borne
in mind that although a variety of pharmacological and non-pharmacological treatment
modalities were applied in the management of childhood enuresis, there is no consensus
statement on any of the commonly available options.
Most evidence pertaining to the effectiveness of these pharmacotherapeutic agents are
anecdotal, or were occasionally based on poorly designed, powered or evaluated
Systematic reviews of multiple regressional meta-analysis of adequately powered studies
appears to be non-robust or in some instances were completely lacking.
Evaluation of Therapeutic Effectiveness:
Successful initial management of enuresis in childhood is said to have been achieved if
the child remains dry, for fourteen consecutive nights
Other measures of therapeutic effectiveness will include the average number of wet nights
per week.
The number of relapses after initial successes.
The average number of dry nights after interventions was discontinued.
Healthy diets and supplements:
Non-Pharmacological Interventions for Nocturnal Enuresis.
Other important considerations in the management of childhood enuresis is the role of food
allergies. Allergic reactions could begin within minutes or symptoms could appear days
after the ingestion of the offending substance.
Certain food substances seem more likely to cause or aggravate bedwetting.
Eliminating those food substances, from the diet is the beginning of the successful
management of enuresis.
The food substances of most concern were diary products, such as milk, cheese, ice
creams, eggs, wheat, and sugar, soya or yeast, however it is likely that there are other food
substances which were allergenic and could trigger off bouts of enuresis in a child already
having enuretic diathesis.
Effectiveness of Interventions for Nocturnal Enuresis:
If no active interventions were applied, but probably counseling and watchful
conservatisms were followed, a spontaneous cure rate of about one in seven cases
annually could be expected.
Apparently the relapse rates in these subsets with a natural remission appear to be
negligible in the absence of emotional stressors.
With Imipramine pharmacotherapy, the remission rate is probably about three in five
instances but the relapse rate is about seven in ten instances.
Desmopressin (DDAVP) will offer a remission rate of about one in three instances and a
relapse rate of about nine of ten cases.
Unfortunately, although an initial arrest of bed-wetting is often achieved after four to ten
weeks of treatment, relapses occur in one of three to one of two cases warranting
subsequent courses.
However in older children from the age of eight years onwards, the success of the
conditioning alarm method appears to be considerably impressive, especially if indicated
repetitive regimens were accomplished.
However, this success rate is quite selective and case specific and is usually based on the
motivation and resources available to the child in question.
The Dry Buddy is one form of alarm system commonly recommended for enuretic children.
Family structures with limited intellectual resources, restricted room spaces and multiple
reduced social circumstances, may not have the opportunity to prioritize the dry buddy
enuretic alarm regimen considerably.
On the average the non-pharmacological interventions have less relapse rates, but the
responses were usually delayed.
Non-Pharmacological Inteventions for Nocturnal Enuresis.
Other considerations for non-pharmacological interventions for enuresis:
Holistic approach teaches us to see diseases as processes rather than a problem that has
just found a beginning and an end.
Improvement of mental and emotional symptoms in most children suffering from enuretic
diathesis is also an important factor for managing them holistically.
In this way, the purely physical sufferings and inconveniences arising from it could be
ameliorated considerably.
Besides the laundry loads, bedwetting could become such a huge self esteem issue that
the child could bypass sleepovers, daycare naps, camping trips or family vacations.
In the author’s lengthy survey, in about one half instances of enuresis cases seen in his
practice, frequent non-alarm nocturnal wakings were already being practiced by the
parents.
Probably the most important ingredient in all these approaches is a positive doctor child
parent relationship.
The best approach to treatment is to assure parents that the problem is self limited and to
eliminate punitive measures that may adversely affect the psychologic development of the
child.
Since maturation and recovery is the rule treatment of enuresis should be modified
accordingly, the placebo effect of a firm and a kind interest by a Paediatrician cures about
One third to one half of the cases of enuresis with no other assistance.
Punitive measures, non specifically targeted rewards or any undue attention to the matter
should be avoided.
The spontaneous cure rate for enuresis is age dependent and rather doubtful ranging from
about one in six per annum in primary school aged children to about one in five for
secondary school aged children only about one in thirty three of these children will be
enuretic at late adolescence or early adulthood.
As in all childhood developmental disorders, appropriate management involves care of the
child and his family as a whole in addition to attempts in eliminating the symptomatologies.
When enuresis is but one of a constellation of symptoms, in a psychiatrically disturbed
child from an unstable family, one needs to know whether the parents are using the
symptom merely as a covert way of getting medical help for their problems among which
their child’s enuresis may be the least pressing .
Over energetic and unduly enthusiatic treatment of the child’s enuresis may then add to,
rather than reduce the burdens on the family.
Non-Pharmacological Inteventions for Noctunal Enuresis.
Other considerations with conflicting scientific principles:
Homeopathy looks at the underlying causes of enuresis.
In homeopathic principles, bedwetting is a completely treatable medical
condition.
According to its proponents, in the first instance, a major point in support of
the application of homoeopathy for enuresis is said to be its freedom from
deleterious adverse effects.
Anecdotally; the general conception is that homoeopathy, with its dynamic
approach, could cure bedwetting wonderfully.
Secondly homeopathic regimens are palatable and convenient to apply.
It could be conveniently applied at any time and to all age groups.
Lastly it will not only ameliorate the symptomatologies of enuresis, but it also
eradicates the enuretic diathesis without the need for a persistent application
of these pharmacotherapies or dependency on it or adaptation of its habit
forming tendencies.
The results of homoeopathic approach for interventions for enuresis through
some author’s non-standardized ungradable experience, with bedwetting
cases, were far more superior to the conventional strategies treatment with
other systems of medicine.
Electroacupunctural Techniques:
Electro-acupunctures were occasionally applied for the treatment of children
with monosymptomatic nocturnal enuresis with ungradable beneficial effects.
Other special programs were based on individual approaches and includes.
Psychotherapy:
If enuresis has caused emotional turmoil or stress in a child’s life, then these
issues should be addressed and dealt with in a positive manner.
Further considerations for non-pharmacological interventions for enuresis.
In the authors research experience, the management of enuresis involved
multiple strategies mostly behavioural administered by the parents or care
givers:
The response rates for these generic measures had a direct relationship with
the frequency of enuresis.
The most badly affected cases responded least.
In the author’s research experience, an immensely applied survey with
selective
non-invasive evaluations and minimal to modest interventions could suffice in
most instances of persistent and regressional childhood enuresis cases.
Non-Pharmacological Inteventions for Nocturnal Enuresis.
Special Exercises:
Some special exercises were aimed towards strengthening the muscles.
Some useful tips for the child’s parents and care givers should be included in
the management plan, because, proper parental care is much essential, since a
negative attitude of the parents sometimes might further complicate the child’s
condition.
Support and reassurance is more important, than scolding or other punitive
measures which could occasionally cause a life time long deficit in self
confidence and self esteem.
Children who wet the bed were often afraid, worthless, anxious or even
depressed.
They could be quite aloof and feels quite different from other children and
usually they strive as much as possible to avoid the threatened
embarrassments that might be associated with the enuretic phenomena.
Almost always, attendances at overnight school field trips seems out of the
question.
All these psychological harms could be compounded if children do not have
support from their parents.
The parents should be counseled to be kind and patient with the enuretic child.
Do not get irritated or scold the child since they are not aware of the act of
micturating whilst asleep.
Punitive measures or scolding of the children which may worsen the enuretic
diathesis should be eschewed.
The children should be encouraged with positive words and rewards to get out
of the enuretic tendencies.
The child should be assured that the bedwetting is not his or her fault and that
it will likely improve with the passage of time.
The parents should be counseled that their concerns about the child’s
enuresis should not be a matter for discussion with relatives or friends,
otherwise children may feel unnecessarily remorseful and humiliated.
In many instances, enuretic symptoms disappear spontaneously following
some passage of time after a stressful period such as the chronological
alleviation of maternal separation anxiety, particularly in the setting of
assistive and understanding parental figures and other care givers especially
with regards to the reduction of the psychological and emotional pressures on
Non-Pharmacological Inteventions for Nocturnal Enuresis.
The use of pull ups or diapers is better avoided because this could
encourage bed wetting by sending the message that the child is still
a tender baby and as such, that the act of bed wetting is okay for
him or her.
A retrogressive complex that the child does not desire to work
towards maturation adversely affecting his self esteem could be
established, propagated and sustained.
Encourage the child to use the lavatory before he or she goes to
bed.
Encourage him to eschew constipation by having a regular bowel
opening habit.
Have the child eat daily servings of leafy vegetables, which are rich
in vitamins, calcium and magnesium, whole grains such as brown
rice and rolled oats, fresh fruit, and proteins with a minimum of
animal fat.
Avoid sugary pastries, candies or refined carbohydrates such as
white bread and white rice, use fresh food, avoiding prepackaged
and processed ones.
Bladder training exercises:
During micturition, the child should be encouraged to interrupt his
urinary stream midstream one or two times for a second.
Herbal tea remedies:
Dried herbs such as Cleaver and Horsetail steamed -use a teaspoon
of each herb per cup of boiling water. You could try Let steam for 15
minutes. Children could drink 1-2 cups early in the day.
Non-Pharmacological Interventions for Nocturnal Enuresis.
Concomitant nonpharmacologic therapy in the treatment of primary
nocturnal enuresis and other rational interventions:
Reassurance, periodic feedbacks, and encouragement of the
parents and child by the physician are necessary for optimal results.
In the author’s clinical and research experience on this topic, the
applications of multimodal evidence based non-pharmacologic with
only occasional-pharmacological interventions implied overall
satisfactorily response rates with the persistent forms of enuresis
being more readily interventionally amenable compared to the
regressive subsets.
Various bladder training programmes were effective for some day
time enuretic cases.
The anecdotal evidence in favour of other unorthodox interventions
sought or obtained elsewhere were unfounded.
Interventions in secondary enuresis due to systemic or localized
pathologies, although plausible and important ,may not necessarily
result in an instant cure of the enuresis in all instances, the
success rate in this circumstance is considerably less than one half,
probably in the range of one of four instances to about one of five
instances.
Given this restricted instant remission for this subset with
secondary enuresis, investigative evaluations and therapeutic
interventions should not be unduly undertaken, but rather its
application should be appropriately weighted.
Otherwise, unaccomplished management goals may further
compromise the child’s positive expectations and further undermine
the clinician-child relationship.
However, given the temporal diminutions and ameliorations of
symptomatologies in both the primary and secondary enuresis with
chronological progressions in bladder control, there is enough room
for a positive approach to the counseling delivered, which could
contribute to psychological enhancement and improved bladder
control.
Images for The Non-Pharmacological Inteventions for Noctunal Enuresis.
Non-Pharmacological Inteventions for Nocturnal Enuresis.
In accordance with the rules of traditional Chinese medicine
nocturnal enuresis is considered to be due to a deficiency of chienergy in the kidneys and the bladder leading to some weaknesses
in their regulatory functions.
Several authors have claimed positive results from the application of
laser puncture in the treatment of children suffering from nocturnal
enuresis.
The laser puncture technique is more child friendly, because unlike
the acupunctural techniques, it circumvents the concerns with
needle pricking and, the vegetative effects accompanying several
acupunctural procedures, it also gives reliable results.
Eliminating food stuffs such as citrus fruit and caffeine may benefit
them.
Treatment often utilizes bedwetting alarms to awaken the patient and
DDAVP (Desmopressin) to reduce urine formation.
These approaches do not always ameliorate the problem, and the
problem often recurs when the treatment is discontinued.
Punitive measures or exposing the child socially makes the
complete and early recovery unlikely.
Other Considerations:
Enuresis nocturna or diurna is a paediatric public health problem
and concerted efforts at all levels such as professional, promotional,
educational and the community should be made to address its
multiple domains such as its preventive, etiological and curative
aspects.
The misconceptions among the parents will require health
educational interventions.
Children with enuresis were commonly punished and were at
significant risk of emotional and physical abuse
The emotional impact of enuresis on a child and family could be
considerable.
Non-Phamacological Inteventions for Nocturnal Enuresis.
In most settings enuretic children most likely do not receive
adequate attention concerning their enuresis, and most of them will
certainly not receive any professional treatment.
Feelings of embarrassment and anxiety, low self esteem, low self
perceptions, poor interpersonal relationships, poor quality of life
and compromised school achievements and performance are more
frequent in children with nocturnal enuresis even in children with
one enuretic event in twenty eight days.
There is a more cultural acceptance of enuresis as a developmental
phenomenon in some developing settings, hence initial
interventions sought most were usually traditional management
options.
Diabetes Mellitus
Diabetes Insipidus
Faecal Impaction
Constipation
Obstipation.
Whereas the surgically amenable subsets include:
Ectopic Ureters.
Lower Urinary Tract Infections.
Neurogenic Bladders.
Bladder Calculus
Bladder Foreign Body.
Obstructive Sleep apnoeas secondary to adenoidal hypertrophy.
Unlike other diathesis, the paraphrase once enuretic always enuretic
is very untrue for enuresis, because the natural history is for the
frequency of bedwetting to diminish chronologically.
In some cases, it may be that bedwetting could occur several times
in a four year old child, and only once when the child is five year
olds and never again.
Bedwetting is not supposed to happen at all in five year olds.
In general, diurnal enuresis is more difficult to treat with the
conventional methods than the nocturnal type.
Non-Pharmacological Inteventions for Nocturnal Enuresis.
Nocturnal enuresis is a common problem that can be troubling for
children and their families.
Recent studies indicate that nocturnal enuresis is best regarded as a
group of conditions with different etiologies.
A genetic component is likely in many affected children.
Research also indicates the possibility of two subtypes of patients
with nocturnal enuresis: those with a functional bladder disorder
and those with a maturational delay in nocturnal arginine
vasopressin secretion.
The evaluation of nocturnal enuresis requires a thorough history, a
complete physical examination, and urinalysis.
Nocturnal enuresis is a common problem, affecting many children
globally and occurring three times more often in boys than in girls.
Unfortunately, only about one third of the families of children with
this frequently troubling problem seek help from a physician.
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Berg I, Forsythe I, McGuire R. Response of bedwetting to the enuresis
alarm. Influence of psychiatric disturbance and maximum functional
bladder capacity. Arch Dis Child. 1982;57:394–6. [PMC free article]
[PubMed] [Google Scholar]
Van Hoeck KJ, Bael A, Lax H, Hirche H, Bernaerts K, Vandermaelen V, et
al. Improving the cure rate of alarm treatment for monosymptomatic
nocturnal enuresis by increasing bladder capacity - A randomized
controlled trial in children. J Urol. 2008; 179:1122–6. [PubMed] [Google
Scholar]
Bower WF, Diao M, Tang JL, Yeung CK. Acupuncture for nocturnal
enuresis in children: A systematic review and exploration of rationale.
Neurourol Urodyn. 2005;24:267–72. [PubMed] [Google Scholar]
Bower WF, Diao M, Tang JL, Yeung CK. Acupuncture for nocturnal
enuresis in children: A systematic review and exploration of rationale.
Neurourol Urodyn. 2005;24:267–72. [PubMed] [Google Scholar]
BIBLIOGRAPHY AND SUGGESTIONS FOR FURTHER READING
Bower WF, Diao M, Tang JL, Yeung CK. Acupuncture for nocturnal
enuresis in children: A systematic review and exploration of
rationale. Neurourol Urodyn. 2005;24:267–72. [PubMed] [Google
Scholar]
Rational Treatment for Enuresis.
Rational Treatment for Enuresis.
[B]-Temporary and often placebo improvement follows any drug
therapy.
This best reserved for children aged five years or more and should
not exceed ten weeks in duration.
All drugs are certainly dangerous and this includes imipramine.
The concept of usefulness of any pharmacotherapeutic agent is
rather doubtful.
THE CHEMICAL STRUCTURE OF DESMOPRESSIN
RATIONAL TREATMENT FOR NOCTURNAL ENURESIS.
Recent studies have provided more information about nocturnal
enuresis, and generally effective therapeutic interventions are
available.
Treatment options include nonpharmacologic and pharmacologic
measures.
Continence training should be incorporated into the treatment
regimen.
Use of a bed-wetting alarm has the highest therapeutic rate and the
lowest relapse rate, however, some families may have difficulty with
this treatment approach.
Kegel exercises could help to strengthen weak muscles around the
bladder.
The exercise involves contracting and relaxing the pelvic muscles.
The child’s progress could be monitored through feedback
mechanisms, to ensure that the exercise was being properly
undertaken.
This procedure is non-invasive.
It usually involves the placement of two sticky patches on the child’s
buttocks which will then be connected to a biofeed back machine.
The biofeed back exercises if properly undertaken, the machine will
indicate by giving out a lightning signal.
A child goes for therapy every two to four weeks over the course of
three to six months period, to be effective the child must practice at
home, about three times in a day.
Rational Treatment for Nocturnal Enuresis.
Behavioural modifications-essentially the use of a bed alarm is often
added to the regimen.
The uniqueness of the Dry Buddy system is to alert the caregiver,
sleeping in the comfort of his or her own bedroom and privacy.
The effective wetness signal alarm could be an automated light,
radio music, an alarm clock, or any other alarm.
A parent or caregiver often has to supervise the child when an
incident occurs.
Various studies suggest that enuresis or bedwetting alarms are the
preferred method for treatment.
The caregiver is essential to improving the success rate of alarm
therapy.
The typical success rates of these wetness alarm systems are about
one of four cases to stop bedwetting in a month, one half success
rates in two months, and nine in ten success rates in three months.
RATIONAL TREATMENT FOR NOCTURNAL ENURESIS.
In the functional microscopic
anatomy and physiology sections
of this monograph, I have
compiled an encyclopaedic
itemised list of these given
bibliography, references and
suggestions for further reading on
the experimental animal
preclinical phase trials ,several
promising pharmacotherapeutic
agents were mentioned, but also I
have equally proffered these
bibliographic sources, in the other
relevant sections of this text as
well.
7-Pharmacotherapy For Enuresis
Pharmacologic Treatments:
Pharmacotherapeutic Principles: Note the Type of
Drugs, their dosages and their adherence pattern.
Micturition is coordinated and regulated at the pontine
mesencephalic micturition centre
and the locus ceruleus levels, so drugs that were
found to be effective appears to be working centrally.
Although for a long time,the only therapies that have
been demonstrated to be effective in randomized
clinical trials include alarm therapy and treatment with
desmopressin acetate (DDAVP) and
imipramine,however it is equally encouraging and
heartening that the data from numerous fairly recent
experimental animal test system models have
demonstrated a lot of promising potential for several
pharmacotherapeutic agents including
desmopressin,imipramine and several other
anticholinergics ,in addition to biologicals.
I have reviewed several mentioned articles on the
translational preclinical phase of the scientific
pharmacotherapy for enuresis employing experimental
rodent animal test system models, but also the porcine
and primate models as well.
In the bibliography, references and suggestions for
further reading aspect of the functional microscopic
anatomy and physiology sections of the urinary
system,I have made an itemised encycopaedic
compilations of these bibliographic sources.
PHARMACOTHERAPY FOR ENURESIS
Desmopressin and imipramine are the primary medications used to
treat nocturnal enuresis, but both are associated with relatively high
relapse rates.
Desmopressin (DDAVP) and imipramine (Tofranil) are the primary
drugs used in the treatment of nocturnal enuresis.
Pharmacologic treatment is not generally recommended for children
under seventy two months of age.
Rational Treatment for Nocturnal Enuresis-DESMOPRESSIN
Rational Treatment for Nocturnal Enuresis.
Desmopressin
DDAVP, a synthetic analogue of the naturally occurring antidiuretic
hormone that affects water conservation in the kidneys, could stop
bedwetting, but does so by drastically reducing the ability of the
kidneys to make urine.
The plasma vasopressin level had an inverse relationship to the
therapeutic responsiveness of interventions of vasopressin in the
treatment of primary nocturnal enuresis.
A synthetic analog of arginine vasopressin, desmopressin works by
decreasing urine volume at night and by decreasing intravesicular
pressure.
Commonly available presentations include nasal sprays or tablets.
Treatment using the nasal spray is initiated with 0.2 mcg/kg given at
bedtime, one half of the dose in each nostril.
If necessary, the dosage can be increased to 0.4 mcg/kg and then 0.8
mcg/kg at bedtime.
The tablets could be taken in crushed forms by children at a dose of
0.004mg/kg at bedtime, if necessary, the dose can be titrated to 0.012
mg/kg.
These bedtime dosages should last for one week, and if the child is
continent, these dosages should be continued.
If an acceptable level of dryness is not achieved within this period,
the medication should be discontinued and advice should be sought
from a responsible health care provider.
As a rule, desmopressin is usually well tolerated.
Side effects, which include nasal irritation, nosebleeds, and
headache, are generally very mild and transient .Occasionally,
emotional disturbances, including aggressive behaviors and
nightmares, which resolved with discontinuation of the medications
were observable.
Despite its rapid efficacy, even though symptomatic improvement
could be induced, most parents may be uncomfortable with this
approach in the management of enuresis, because of its unnatural
influence on the basic innate haemostatic mechanisms and its
frequent high relapse rates.
DDAVP (desmopressin acetate) mimics the natural hormone that
causes the kidneys to conserve body water and concentrate the
urine, decreasing urine output during sleep.
Rational Treatment for Nocturnal Enuresis-DESMOPRESSIN.
Rational Treatment for Nocturnal Enuresis-DESMOPRESSIN
DDAVP:
Significantly improves bedwetting in a quarter to three of five of
affected children, one of eight to two of five of affected children will
achieve complete resolutions of their enuretic diathesis.
DDAVP is generally recommended in children older than seventy two
months.
It is child friendly and could be used as needed for overnight trips
once the correct dosage has been established, side effects are
usually minimal if any.
However, the drug is expensive and about four of five children who
stop taking it will relapse.
The optimal duration of treatment is unknown.
If the medication works, use it for three to six months and then
gradually taper the dose over several weeks.
DDAVP is safe and often effective, but it's important to use it only at
bedtime to reduce the risk of fluid overload and electrolyte
abnormalities.
It is a drug that' could prove useful when an enuretic child goes for
sleepovers, camping, vacations and the like.
However, it is expensive and is not a definitive interventional
approach.
Desmopressin acetate therapy is usually a reasonable choice in the
management of enuresis.
DDAVP is the preferred medication to treat children with enuresis.
A systematic review of metanalysis of several randomized clinical
trials concluded that DDAVP therapy reduces bedwetting.
Children treated with DDAVP had on the average fewer wet nights
per week.
The tablet and oral slow release formulations have similar
efficacy,although the risk for severe hyponatremia that can cause
seizures and death made the intranasal formulation unpopular.
RATIONAL TREATMENT OF ENURESIS-DESMOPRESSIN-CHEMICAL STRUCTURE.
Rational Treatment for Nocturnal Enuresis-DESMOPRESSIN.
DDAVP tablets or oral disintegrating tablets should be administered
one hour before bedtime.
The equivalent starting dosage for the melt is 2.4micrograms/kg and
the maximum dose is 7.2 microgram/kg.
The immediate onset of action of DDAVP allows the flexibility of
intermittent administration for special occasions or long-term use to
maintain dryness.
For long-term use, DDAVP can be prescribed in twelve weekly
quantities and discontinued between prescriptions to determine if
the wetting persists and, therefore, to justify continued use.
The safety profile of DDAVP is favorable, and many studies have
documented low rates of adverse effects.
Sedatives, stimulants, or sympathomimetic agents have not proved
beneficial.
Because treatment with medication may be effective even in children
with an organic problem such as infection or neuropathy, patients
should always be evaluated carefully before drug therapy is started.
Of the tricyclic antidepressants, imipramine has been investigated
and used the most extensively.
DESMOPRESSIN ACETATE 0.2 MG TABLETS
RATIONAL TREATMENT OF ENURESIS-DESMOPRESSIN
RATIONAL TREATMENT OF ENURESIS-DESMOPRESSIN
RATIONAL TREATMENT OF ENURESIS-DESMOPRESSIN
The only serious adverse effect reported in patients with enuresis
treated with desmopressin is seizure or other CNS symptoms due to
water intoxication.
A review of case reports of water intoxication associated with
desmopressin confirmed excess fluid intake was a feature in at least
six of eleven instances.
This serious adverse effect is preventable with careful patient
education not to consume an excess of fluids on any evening that
desmopressin is administered.
A maximum of one cup of fluid should be offered at the evening
meal, no more than one cup between mealtime and bedtime, and
nothing to drink within two hours prior to bedtime.
Early symptoms of water intoxication include headache, nausea, and
vomiting.
If these symptoms develop, the medication should be discontinued
and the child promptly assessed by a physician.
Hyponatremic-related seizures associated with the use of
desmopressin were established in several instances,the combintion
of hyponatreamia and seizures are usually associated with cerebral
oedemas and mortalities were frequent with these combinations.
These morbidities and mortalities of hyponatreamia and seizures
seems to be associated most with the intranasal formulations,
especially with the younger age groups and occasionally with the
latter teenage age groups.
The most commonly reported indication for the use in this drug in
the pediatric age group was enuresis.
In a few other instances,a concomitant use of a drug or disease
condition that is associated with hyponatremia, seizures, or both
could be established.
A combination of the alarm therapy with DDAVP is reported to result
in dryness not achievable with either therapy alone.
ANTICHOLINERGICS
Other pharmacotherapeutic agents employed in the
management of enuresis are either anticholinergic
drugs or combined anticholinergics and smooth
muscle relaxants. Anticholinergic (antimuscarinic)
drugs have been variably considered as plausible
pharmacotherapeutic options for enuresis.
Their mechanism of action is to relax the bladder by
inhibiting involuntary detrusor muscle contractions.
Several antimuscarinic pharmaco-chemical entities
have been employed in the therapeutic interventions
for enuresis such as oxybutynin, tolterodine,
trospium, solifenacin, and darifenacin.
Several clinical practice guidelines recommend
oxybutynin as first-line treatment.
Oxybutynin is the main pharmacotherapeutic agent
approved drug for use in the paediatric enuretic
patients.
Antimuscarinic drugs have been associated with
high incidence of anticholinergic adverse events
(AEs) such as dry mouth, constipation, and blurred
vision that may result from antagonism of
muscarinic receptors at the salivary gland,
gastrointestinal tract, and central nervous system.
In the elderly, there is also the risk of cognitive
impairment.
Rational Treatment for Nocturnal Enuresis.
ANTICHOLINERGICS.
Oxybutynin.
Oxybutynin is a drug with anticholnergic properties
used for the treatment of detrusor instability.
Oxybutynin is beneficial for children with small bladder
capacity and daytime enuresis.
For the tablet, incidence of minor adverse events is not
significantly different from a placebo.
ANTICHOLINERGIC DRUGS Propiverine hydrochloride (propiverine)
Propiverine hydrochloride (propiverine) is a detrusor relaxant drug
with antimuscarinic and calcium-modulating properties for the
treatment of enuresis.
Propiverine was first approved in some industrialised regions as a
15 mg immediate-release formulation (IR) although the 15 mg IR was
never marketed in some other industrialised regions.
The modified-release formulation (MR) and extended-release
formulations (ER) were developed in order to improve patients’
compliance by means of a once daily dosage regimen, and to allow
for improved steady-state plasma concentrations. Commonly,
propiverine ER is available as 30 mg and 45 mg capsules for adult
use, and as propiverine-pediatric that is available in 5 mg tablets.
ANTICHOLINERGICS-PROPIVERINE HYDROCHLORIDE
ANTICHOLINERGICS-PROPIVERINE HYDROCHLORIDE
ANTICHOLINERGICS-PROPIVERINE HYDROCHLORIDE
ANTICHOLINERGICS-PROPIVERINE HYDROCHLORIDE
SOLIFENACIN SUCCINATE-CHEMICAL STRUCTURE
ANTICHOLINERGICS-SOLIFENACIN SUCCINATE
ANTICHOLINERGICS-SOLIFENACIN SUCCINATE
ANTICHOLINERGICS-SOLIFENACIN SUCCINATE
ANTICHOLINERGICS-SOLIFENACIN SUCCINATE
ANTICHOLINERGICS-SOLIFENACIN SUCCINATE
ANTICHOLINERGICS-SOLIFENACIN SUCCINATE
ANTICHOLINERGICS-SOLIFENACIN SUCCINATE
SOLIFENACIN SUCCINATE AND MIRABEGRON(EXTENSIVE RELEASE TABLETS
ANTICHOLINERGICS-SOLIFENACIN SUCCINATE
ANTICHOLINERGICS-SOLIFENACIN SUCCINATE
ANTICHOLINERGICS-SOLIFENACIN SUCCINATE
ANTICHOLINERGICS-SOLIFENACIN SUCCINATE
ANTICHOLINERGICS-SOLIFENACIN SUCCINATE
ANTICHOLINERGICS-SOLIFENACIN SUCCINATE
ANTICHOLINERGICS-SOLIFENACIN SUCCINATE
ANTICHOLINERGICS-TROSPIUM-CHEMICAL STRUCTURE
ANTICHOLINERGICS-TROSPIUM
ANTICHOLINERGICS-TROSPIUM-CHEMICAL STRUCTURE
ANTICHOLINERGICS-DARIFERACIN CHEMICAL STRUCTURE
RATIONAL MANAGEMENT OF ENUREISANTICHOLINERGICS-DARIFERACIN.
RATIONAL MANAGEMENT OF ENUREISANTICHOLINERGICS-DARIFERACIN.
Rational Treatment for Enuresis.
Rational Pharmacotherapeutic Interventions for Enuresis.
Anticholinergic therapy
An anticholinergic medication may be helpful in some patients,
especially those with overactive bladder, dysfunctional voiding, or
neurogenic bladder.
These medications reduce uninhibited detrusor contractions,
increase the threshold volume at which an uninhibited detrusor
contraction occurs, and enlarge the functional bladder capacity.
Oxybutynin chloride (Ditropan) and tolterodine (Detrol) are
commonly prescribed medications.
Oxybutynin chloride also has antispasmodic and analgesic
properties.
Anticholinergic adverse effects include dry mouth, blurred vision,
facial flushing, constipation, poor bladder emptying, and mood
changes.
Constipation as an adverse event is especially problematic since
this might increase the risk for wetting.
These medications should not be administered during a fever
because a decrease in sweating is an anticholinergic effect.
Similarly, these medications should be used cautiously in children
who exercise or play strenuously, especially on hot days.
The dosage of oxybutynin is 2.5-5 milligrams administered at
bedtime.
The combination of DDAVP and oxybutynin chloride may be
efficacious in children with overactive bladder or dysfunctional
voiding who respond to anticholinergic therapy with improved
daytime symptoms but who continue to wet at night.
A long-acting preparation is available but has not been approved for
use in children.
In primary nocturnal enuresis associated with ADD/ADHD, the
tricyclic antidepressants especially Imipramine is my initial option
and best choice because, this drug is effective in both ADD/ADHD
and primary nocturnal enuresis with reasonable response rates and
predictable side effects.
Rational Pharmacotherapeutic Interventions for Enuresis:
Flavoxate Hydrochloride.
FlavoxateHCl (Urispas), a urinary spasmolytic, may be helpful in
some patients with overactive bladder and dysfunctional voiding but
is approved only for children older than sixty months.
FLAVOXATE HYDROCHLORIDE TABLET
Tolterodine
Tolterodine is not approved for use in children younger than twelve
years for enuresis pharmacotherapeutic interventions.
Tolterodine ER is a nonselective competitive muscarinic receptor
antagonist. After oral administration, tolterodine is metabolized in
the liver, resulting in the formation of the 5-hydroxymethyl
derivative, a pharmacologically active metabolite.
The 5-hydroxymethyl metabolite, which exhibits an antimuscarinic
activity similar to that of tolterodine, contributes significantly to the
therapeutic effect. Compared with the IR formulation, once-daily
tolterodine ER releases the drug in a steady but constant manner,
lowering peak and trough drug levels.
Rational Pharmacotherapeutic Interventions for Nocturnal Enuresis:
Imipramine Hydrochloride.
Rational Pharmacotherapeutic Interventions for Nocturnal Enuresis:
Imipramine Hydrochloride.
Imipramine provides some benefit in approximately one half of
children with nocturnal enuresis.
Imipramine is one useful tricyclic antidepressant at a dosage of one
milligrams per kilograms body weight at bedtime.
However, only a quarter of enuretics experience complete
elimination of enuresis, a rate that is only slightly better than that for
placebo when the one in seven cases of spontaneous remission rate
is taken into consideration.
Following the discontinuation of imipramine, relapse rates are high.
Side effects, including cardiotoxicity at high doses, occur frequently
enough that imipramine probably should not be considered a firstline treatment for nocturnal enuresis.
If other treatments fail, imipramine, given once daily one hour before
bedtime, can be used at an average dosage on one mg per kilograms
body weight.
After three to six months of treatment, imipramine should be
discontinued slowly.
The dose is decreased by one half for two weeks; the reduced dose
is then given every other night for an additional two weeks.
Rational Pharmacotherapeutic Interventions for Nocturnal Enuresis.
Developing a Treatment Plan
About a quarter to a third of parents had used punishment as their
primary means of dealing with bed-wetting.
Hence, family education is crucial.
Parents and the affected child need to know that bed-wetting is a
common problem, and parents should be instructed not to blame or
humiliate the child.
The physician can foster a sense of optimism about the potential for
improvement while at the same time giving the child responsibility
for achieving urinary control at night.
Sometimes the very process of seeking help leads to improvement
of nocturnal enuresis.
In several author’s experience, using desmopressin plus behavior
therapy, placebo plus behavior therapy, and desmopressin therapy
alone found improvement in all three groups in the first weeks after
enrollment, before the actual study actually began.
The timing of treatment should be individualized.
It is important that the child be motivated to take an active role.
The younger the child, the more fragile his or her motivation may be.
The depth of this motivation can be assessed by assigning the child
the task of keeping the voiding log.
If the child seems inadequately motivated, it may be best to ask the
family to postpone treatment until the child is ready.
All treatments should be explained carefully.
When choices were well explained, slightly more parents selected no
treatment at all than treatment with desmopressin, indicating that
many parents simply want reassurance.
Information obtained in the initial voiding diary may give clues about
the best choice of initial treatment.
Rational Pharmacotherapeutic Interventions for Nocturnal Enuresis.
The child who voids frequently during the day (seven times or
more), voids small amounts, has few or no dry nights during the
week, and wets the bed more than once a night is more likely to
have low functional bladder capacity.
This child may benefit most from the use of a bed-wetting alarm.
On the other hand, the child who has a normal voiding pattern
during the day, voids large amounts at night, and wets only one to
two nights per week may have nocturnal polyuria and therefore may
be an appropriate candidate for desmopressin therapy.
A child who fails one treatment modality is likely to benefit from
another treatment.
Continence training should be part of any treatment plan.
Given its higher success rate and lower relapse rate, an alarm
system should be considered as first-line treatment for many
children.
Desmopressin is rapidly effective, but sole use of the drug neglects
continence skills. The alarm system and desmopressin can be used
in combination.
Whatever the treatment plan, follow-up, support, and encouragement
are important components.
One study of the psychologic benefits of treatment for nocturnal
enuresis found that children rated their self-concept as being
improved after all treatments (even placebo) and that parents'
perception of their child's behavior improved, no matter what
treatment was used or how successful it was.
Treating bedwetting is not always very straight forward.
Given its frequent occurrence in most children, it may be worthwhile
to withhold treatment before the age of seventy two months of age.
At any age, decisions regarding treatment should consider to what
extent the problem affects the child and the child's social
development.
Rational Pharmacotherapeutic Interventions for Nocturnal Enuresis.
Many young children and their parents are better served by reassurance that
there's no physical abnormality than by long-term and expensive therapy of
uncertain effectiveness and toxicity implications.
Treatment may consist of medication, conditioning and behavior modification,
or a combination of approaches.
There appears to be no medication that could offer a more lasting positive
influence on enuresis rather than the natural maturational mechanisms of
urinary regulation.
Although drug therapy is not appropriate for children under the age of seven, it
could be used as alternative measures when other behavioural or motivational
and environmental manipulations fail, preferably on a short term basis for
example to cover periods away from home, or if the child and family are very
anxious about the condition.
The possible side effects of the various drugs should be borne in mind on
introduction.
However, medications are relevant for brief symptomatic controls.
When the drug is stopped, the enuresis will usually return unless the child has
naturally outgrown it.
Success has been reported with tricyclic antidepressants (imipramine),
anticholinergics (oxybutynin), and desmopressin acetate (DDAVP).
Two commonly used drugs are Tofranil (imipramine) and DDAVP
(desmopressin acetate).
A systematic review found that desmopressin reduced the number of wet
nights more effectively in children older than nine years and in children who
had the fewest number of wet nights. [Evidence level A, systematic review of
randomized controlled trials]
The studies examined in the review found that frequency of wetting decreased
anywhere from one in ten to nine in ten, but that only a quarter of the
children achieved complete dryness.
Once desmopressin therapy is stopped, relapse rates can range from four in
five to or it could be universal.
If children respond to desmopressin, treatment is continued for three to six
months.
To minimize the possibility of relapse, the drug should be discontinued slowly,
with the dose decreased by as little as ten micrograms per month.
Rational Pharmacotherapeutic Interventions for Nocturnal Enuresis.
Imipramine
The mechanism for the benefits of imipramine
in the treatment of nocturnal enuresis is not
understood.
One theory is that the anticholinergic effect of
the drug may result in a decrease in bladder
contractility that leads to increased bladder
filling and improved functional bladder
capacity.
Rational Treatment for Nocturnal Enuresis: Imipramine
Pharmacotherapy with an enuresis bed alarm adjunct.
Behavioural modifications-essentially the use of a bed alarm is often
added to the imipramine pharmacotherapeutic regimen.
The uniqueness of the Dry Buddy system is to alert the caregiver,
sleeping in the comfort of his or her own bedroom and privacy.
The effective wetness signal alarm could be an automated light,
radio music, an alarm clock, or any other alarm.
A parent or caregiver often has to supervise the child when an
incident occurs.
Various studies suggest that enuresis or bedwetting alarms are the
preferred method for treatment at the first instance with imipramine
adjunct.
The caregiver is essential to improving the success rate of
imipramine with alarm therapy adjunct.
The typical success rates of these wetness alarm systems are about
one of four cases to stop bedwetting in a month, one half success
rates in two months, and nine in ten success rates in three months
and it has been observed that these success rates are positively
modified by an imipramine based pharmacotherapy for those cases
that were not amenable to the isolated alarm .
Rational Treatment for Nocturnal Enuresis: Imipramine
Pharmacotherapy with an enuresis bed alarm adjunct.
.
Rational Treatment for Nocturnal Enuresis: Imipramine
Pharmacotherapy with an enuresis bed alarm adjunct.
Rational Treatment for Nocturnal Enuresis: Imipramine
Pharmacotherapy with an enuresis bed alarm adjunct.
Rational Treatment for Nocturnal Enuresis: Imipramine
Pharmacotherapy with an enuresis bed alarm adjunct.
Rational Treatment for Nocturnal Enuresis: Imipramine
Pharmacotherapy with an enuresis bed alarm adjunct.
STRUCTURES OF IMIPRAMINE AND DESIPRAMINE.
C19H25CLN2
Rational Treatment for Nocturnal Enuresis: Imipramine
Pharmacotherapy with an enuresis bed alarm adjunct.
Rational Pharmacotherapeutic Interventions for Enuresis
Imipramine
Imipramine provides some benefit in approximately one half
of children with nocturnal enuresis.
Imipramine is one useful tricyclic antidepressant at a dosage
of one milligrams per kilograms body weight at bedtime.
However, only a quarter experience complete elimination of
enuresis, a rate that is only slightly better than that for
placebo when the one in seven cases of spontaneous
remission rate is taken into consideration.
Following the discontinuation of imipramine, relapse rates
are high.
Side effects, including cardiotoxicity at high doses, occur
frequently enough that imipramine probably should not be
considered a first-line treatment for nocturnal enuresis.
If other treatments fail, imipramine, given once daily one
hour before bedtime, can be used at an average dosage on
one mg per kilograms body weight.
After three to six months of treatment, imipramine should be
discontinued slowly.
The dose is decreased by one half for two weeks; the
reduced dose is then given every other night for an
additional two weeks.
Pharmacologic Treatments:
Developing a Treatment Plan
About a quarter to a third of parents had used punishment as their
primary means of dealing with bed-wetting.
Hence, family education is crucial.
Parents and the affected child need to know that bed-wetting is a
common problem, and parents should be instructed not to blame or
humiliate the child.
The clinician can foster a sense of optimism about the potential for
improvement while at the same time giving the child responsibility
for achieving urinary control at night.
Sometimes the very process of seeking help leads to improvement
of nocturnal enuresis.
In several author’s experience, using desmopressin plus behavior
therapy, placebo plus behavior therapy, and desmopressin therapy
alone found improvement in all three groups in the first weeks after
enrollment, before the actual study actually began.
The timing of treatment should be individualized.
It is important that the child be motivated to take an active role.
The younger the child, the more fragile his or her motivation may be.
The depth of this motivation can be assessed by assigning the child
the task of keeping the voiding log.
If the child seems inadequately motivated, it may be best to ask the
family to postpone treatment until the child is ready.
All treatments should be explained carefully.
When choices were well explained, slightly more parents selected no
treatment at all than treatment with desmopressin, indicating that
many parents simply want reassurance.
Pharmacologic Treatments:
Information obtained in the initial voiding diary may give clues about
the best choice of initial treatment.
The child who voids frequently during the day (seven times or more),
voids small amounts, has few or no dry nights during the week, and
wets the bed more than once a night is more likely to have low
functional bladder capacity.
This child may benefit most from the use of a bed-wetting alarm.
On the other hand, the child who has a normal voiding pattern
during the day, voids large amounts at night, and wets only one to
two nights per week may have nocturnal polyuria and therefore may
be an appropriate candidate for desmopressin therapy.
A child who fails one treatment modality is likely to benefit from
another treatment.
Continence training should be part of any treatment plan.
Given its higher success rate and lower relapse rate, an alarm
system should be considered as first-line treatment for many
children.
Desmopressin is rapidly effective, but sole use of the drug neglects
continence skills. The alarm system and desmopressin can be used
in combination.
Whatever the treatment plan, follow-up, support, and encouragement
are important components.
One study of the psychologic benefits of treatment for nocturnal
enuresis found that children rated their self-concept as being
improved after all treatments (even placebo) and that parents'
perception of their child's behavior improved, no matter what
treatment was used or how successful it was.
Treating bedwetting is not always very straight forward.
Given its frequent occurrence in most children, it may be worthwhile
to withhold treatment before the age of seventy two months of age.
Pharmacologic Treatments:
At any age, decisions regarding treatment should consider to what
extent the problem affects the child and the child's social
development.
Many young children and their parents are better served by
reassurance that there's no physical abnormality than by long-term
and expensive therapy of uncertain effectiveness and toxicity
implications.
Treatment may consist of medication, conditioning and behavior
modification, or a combination of approaches.
There appears to be no medication that could offer a more lasting
positive influence on enuresis rather than the natural maturational
mechanisms of urinary regulation.
Although drug therapy is not appropriate for children under the age
of seven, it could be used as alternative measures when other
behavioural or motivational and environmental manipulations fail,
preferably on a short term basis for example to cover periods away
from home, or if the child and family are very anxious about the
condition.
The possible side effects of the various drugs should be borne in
mind on introduction.
However, medications are relevant for brief symptomatic controls.
When the drug is stopped, the enuresis will usually return unless the
child has naturally outgrown it.
Success has been reported with tricyclic antidepressants
(imipramine), anticholinergics (oxybutynin), and desmopressin
acetate (DDAVP).
Two commonly used drugs are Tofranil (imipramine) and DDAVP
(desmopressin acetate).
A systematic review found that desmopressin reduced the number
of wet nights more effectively in children older than nine years and
in children who had the fewest number of wet nights. [Evidence level
A, systematic review of randomized controlled trials]
Pharmacologic Treatments:
The studies examined in the review found that frequency of wetting
decreased anywhere from one in ten to nine in ten, but that only a
quarter of the children achieved complete dryness.
Once desmopressin therapy is stopped, relapse rates can range
from four in five to or it could be universal.
If children respond to desmopressin, treatment is continued for
three to six months.
To minimize the possibility of relapse, the drug should be
discontinued slowly, with the dose decreased by as little as ten
micrograms per month.
Imipramine
The mechanism for the benefits of imipramine in the treatment of
nocturnal enuresis is not understood.
One theory is that the anticholinergic effect of the drug may result in
a decrease in bladder contractility that leads to increased bladder
filling and improved functional bladder capacity.
Rational Treatment for Nocturnal Enuresis: Imipramine
Pharmacotherapy with an enuresis bed alarm adjunct.
Rational Treatment for Nocturnal Enuresis: Imipramine
Pharmacotherapy with an enuresis bed alarm adjunct.
Rational Pharmacotherapeutic Interventions for Nocturnal Enuresis.
Imipramine
3-(10, 11- dihydro-5H-dibenzozepine-5-yl)-NN-dimethylpropan-1amine.
The chemical Formular of Imipramine is C19 H24 N2.
Imipramine has a Molecular Mass of about Two hundred and eighty
micrograms and is usually excreted renally.
Imipramine has a half life of about eleven to twenty five hours.
In the liver, it is metabolized to its main active metabolite
desipramine.
It usually administered orally and has been known to be harmful to
the fetus.
Imipramine,is an antidepressant medication, a tricyclic
antidepessant of the dibenzazepine group.
Imipramine is mainly used in the treatment of major depression and
enuresis(inability to control urination).
It has also been evaluated for use in panic disorders.
Therapeutics:
Imipramine is used in the treatment of depression, such as
depression associated with agitation or anxiety and has similar
efficacy to the antidepressant drug meclobimide.
Mechanisms of Action:
Although, Imipramine was the first drug introduced to treat enuresis,
however its exact mechanism of action is still elusive.
However, it is known to relax the bladder smooth muscle, and it may
also attenuate the depth of sleep.However its benefit is confined to
the period of its application.It is generally used in children older than
seventy two months.Has a success rate of one in ten to one half.
Starts working in a few days
It is relatively cost effective, however there are no child's friendly
Pharmacotherapy with an enuresis bed alarm adjunct.
Pharmacologic Treatments:
Imipramine is ,a tertiary amine affects numerous neurotransmitter
systems known to be involved in the etiology of depression, anxiety,
attention deficit hyperactivity disorders, enuresis and numerous
other mental and physical conditions.
Imipramine is similar in structure to some muscle relaxants, and has
a significant analgesic effect and, thus, is very useful in some pain
conditions.The mechanisms of Imipramine's medicinal action
include, but are not limited to, effects on:
Imipramine incites a Moderate to strong reuptake inhibition of Serotonin(5-HT).
Imipramine's serotonin reuptake inhibition is almost comparable but
still less than its reuptake inhibition of norepinephrine.
When compared to other tricyclic antidepressants (with the
exception of clomipramine)Imipramine's strong serotonin reuptake
inhibition make it more akin to the serotonin reuptake inhibitors
class of antidepressants than its metabolite desipramine which has
almost purely noradrenergic effects.
Imipramine exerts a Strong reuptake inhibition of Norepinephrine(NE):.
Imipramine induces Dopamine (DA): Reuptake and release at D1 and
D2 receptors.
Similar but less potent than psychostimulants, dopamine agonists,
and the atypical antidepressant bupropion on dopaminergic
mechanisms (increase in release and blockade of reuptake
inhibition).
While this effect is much less than the primary effects on NE, SER
and ACh, it is nonetheless significant and is partially responsible for
the therapeutic benefits of treatment with Imipramine.
Enhancement of brain dopamine activity has been implicated in
Imipramine's ability to stimulate motor activity and prolong time
spent in escape in mice.
Regarding dopamine uptake, imipramine is far less potent than most
other antidepressants (for example, it has only five percent of the
potency of amitryptilline or paroxetine.
IMIPRAMINE HAS A SIGNIFICANT ANTICHOLINERGIC PROPERTY
Acetylcholine(ACh): Imipramine has a significant anticholinergic
effect, thus, it is prescribed with caution to the elderly and with
extreme caution to those with psychosis, as the general brain
activity enhancement in combination with the dementing effects of
anticholinergics increases the potential of Imipramine to cause
hallucinations, confusion and delirium in this population.
Imipramine is an antagonist at M2 muscarinic acetylcholine
receptors.
The blockade of cholinergic (muscarine) receptors is known to
cause euophoria potentially contributing to the mood lifting effects
of Imipramine as well.
Antimuscarinic effect is also responsible for rapid heart rate
(tachycardia).
Rational Treatment for Nocturnal Enuresis: Imipramine
Pharmacotherapy with an enuresis bed alarm adjunct.
Rational Pharmacotherapeutic Interventions for Nocturnal Enuresis.
Pharmacologic Treatments:
Epinephrine:
Imipramine antagonizes adreno-receptors (II), thus sometimes
causing increased heart rate (contributed to by other effects as well),
orthostatic hypotension, and a general decrease in the
responsiveness of the central nervous system (hence, a contribution
to its potent anti-anxiety properties).
Compared to amitryptiline ,its activity on σ-receptors and
enkephalinase is negligible.
Histamine:Imipramine is an antagonist at histamine H1 receptors.
This contributes to the acute sedative effect that it has in most
people.
In turn, its anti-histaminergic and general calming effects take place
immediately, and, thus, Imipramine is sometimes prescribed as a
sleep aid in low doses.
Dimunitive hippocampal neurogenesis , is implicated in reactively or
endogenously driven depressive states,although,it is not clear how
neurogenesis restores mood, as ablation of hippocampal
neurogenesis in murine models do not show anxiety related or
depression related behaviours.
Chronic Imipramine administration results in increased histone
acetylation (which is associated with transcriptional activation and
decondensed chromatin) at the hippocampal neurogenesis.
Imipramine has been shown to increase the expression of μ-opioid
receptors in rat forebrain.
In comparison with other antidepressants,
The potency (affinity) of imipramine and other antidepressants on
various transporters and receptors .
Imipramine has effects on serotonin and nor-epinepherine
transporters ,alpha 1,dopamine 2,histamine 1 ,muscaranic,and
serotonin receptors blocking effects.
PHARMACOTHERAPY FOR ENURESIS-IMIPRAMINE
IMIPRAMINE HYDROCHLORIDE TABLETS.
Rational Pharmacotherapeutic Interventions for Nocturnal Enuresis.
Pharmacologic Treatments:
Metabolism:
Imipramine is converted to desipramine, another tricyclic
antidepressant, in the body.
Side effects of Imipramine could be mild,moderate,moderately
severe,severe ,profound,idiosyncritic or life threatening.
Central Nervous System: Dizziness, drowsiness, confusion,seizures,
headache, anxiety, tremors, stimulation, weakness, insomnia,
nightmares, extrapyramidal symptoms in geriatric patients,
increased psychiatric symptoms, paraesthesia.
It is not surprising, therefore, that Imipramine is also known to cause
a high rate of manic and hypomanic reactions, especially in patients
with preexisting bipolar disorder.
It is estimated that up to one quarter of such patients maintained on
Imipramine will switch on to mania or hypomania.
Cardiovascular: orthostatic hypotension, ECG changes, tachycardia,
hypertension, palpitations, dysarhythmias.
Eyes, Ears, Nose and Throat: Blurred vision, tinnitus, mydriasis.
Gastrointestinal:
Dry mouth, nausea, vomiting, paralytic, increased appetite, cramps,
epigastric distress, jaundice, hepatitis, stomatitis, constipation, taste
changes.
Genitourinary: urinary retention, acute renal failure.
Hematological:agranulocytosis,thrombocytosis, eosinophilia,
leukopaenia.
Skin: Rash, urtacaria,diaphoresis,pruritis,photosensitivity
Its initial dose should normally be the lowest recommended
dose,increasing gradually for the most difficult and resistant cases.
Folowing remission the dose should often be reduced gradually.
Almost always the management of enuresis is usually undertaken on
ambulatory basis.
Like most drug administrations in Pediatric patients,the dose of the
drug should be adjusted according to the severity of the symptoms
being managed,its associated ongoing advers-effects and the weight
or the body surface area of the child.
Rational Pharmacotherapeutic Interventions for Nocturnal Enuresis.
Pharmacologic Treatments:
The symptoms and the treatment of an imipramine overdose are
more or less similar to those of other tricyclic antidepressants.
In childhood,any toxicity should be considered significant ,
potentially lethal and should be taken very seriously and addressed
appropriately..
The principal and potentially life threatening ones are related to the
cardiopulmpnary system and includes tachycardia, widened QRS
complexs and wide ranged neuropsychiatric pertubartions.
The dosage for children is about one milligram per kilogram body
weight, given one hour before bedtime.
Side effects of Imipramine include:
Anxiety
Irritability
Insomnia
Loss of appetite
Moodiness
Overdosage could cause cardiac irregularities and convulsive
seizures.
Because taking too much could cause cardiac irregularities and
convulsions, an adult should administer the imipramine to the child
personally and keep the drug out of children's reach.
The prescribed dose would not normally cause cardiac irregularities.
Due to this medication's side effects, risks with overdosage and
limited success rate, we prescribe it infrequently.
Typically, imipramine should be used only on adolescents who could
not respond to all other interventions.
Pharmacologic Treatments: Pharmacotherapy for a short term relief
of symptoms:
Pharmacotherapy for a short term relief of symptoms:
Application of Desmopressin and Tricyclic antidepressant drugs are
pharmacotherapeutic techniques which are rapidly effective within a
few days of treatment initiation.
Tricyclic antidepressants drugs such as imipramine, amitriptyline,
clomipramine, viloxazine, desipramine were useful in nocturnal
enuresis, of all these but especially imipramine hydrochloride were
the most frequently prescribed drug for the management of
childhood enuresis.
At a dose of 0.5/kg mg to 1 mg/kg in the evening well before bedtime.
Side effects such as initial drowsiness and difficulty in
concentrating on school work could occur but were seldom serious
to warrant the discontinuation of the drug.
Other recognized side effects included anorexia, anxiety,
constipation, mood swings, behavioural disturbances could occur
and relapse is more common after withdrawals.
Rational Pharmacotherapeutic Interventions for Nocturnal Enuresis.
Pharmacologic Treatments: Imipramine therapy
Imipramine therapy
A systematic review of metanalysis of several randomized clinical
trials concluded that imipramine is effective in reduce bedwetting.
Children treated with imipramine had fewer wet nights per week.
Although,the relapse rate is high when the medication is
discontinued.
The usual dose, taken one-two hours before bedtime, is about one
milligram per kilogram body weight.
Adverse effects include constipation, difficulty initiating voiding,
irritability, drowsiness, reduced appetite, and personality changes.
Imipramine overdose can be fatal, and a cautionary warning is
necessary with every prescription.
Because of the unfavorable adverse effect profile and significant risk
of death with overdose, the World Health Organization (WHO) does
not recommend imipramine for the treatment of enuresis.
Surgical Care
Ectopic ureter and OSA respond to specific surgical interventions.
Enuresis is not a surgically treated condition.
Previous
Consultations
Referral to a pediatric otolaryngologist or a pediatric sleep specialist
may be appropriate if OSA is suspected.
Previous
Rational Pharmacotherapeutic Interventions for Nocturnal Enuresis.
Pharmacologic Treatments:
Diet
Children should be instructed to drink a liberal amount during the
day, to maintain good hydration throughout the day, and to drink
enough to prevent thirst when they arrive home from school and at
bedtime. Children who play sports in the evening should be
optimally hydrated for the activity.
Pharmacotherapy
Treatment should not normally exceed three months unless a
physical examination is made and the child is fully reassessed,
toxicity following overdosage with tricyclic antidepressants is a
cause for concern.
Diarrhea, dizziness, drowsiness, dry mouth, cephalgias, irritabilities,
lethargy, sleep disturbances, gastric upset and vomiting.
If successful, treatment should be continued for many months, since
relapses may not respond to a second course of medication.
Possibility of a lethal overdose is a major concern with this
therapeutic intervention.
These drugs may not be very useful over a longer period if they were
not useful initially ,chronological tolerance ,its rebound effect on
drug discontinuation and toxicities concerns precludes their longer
term continual or extensive use.
In nocturnal enuresis, urine volume reduction could be achieved by
the use of Oxytocin/ADH analogue a synthetic peptide derived by
altering amino acid residues in the parent compounds there by
giving them a more selective activity such as
1-deamino-8-D-arginine vasopressin [DDAVP desmopressin] has
very high antidiuretic activity with very little pressure effect given at
20 micrograms given orally, sublingually but not usually intranasally
at bed time is usually effective, numerous side effects with the
intranasal route precludes the use of the drug through this route.
This drug usually leads to the reduction of urine volume
considerably it has been found to be useful in a proportion of cases.
Rational Pharmacotherapeutic Interventions for Nocturnal Enuresis.
Pharmacologic Treatments:
However, particular care is needed to avoid fluid overload and
treatment should not be continued for longer than three months
without an interruption for a week for a complete evaluation.
Upgradable or unqualifiable systematic reviews, suggested that
Desmopressin, is effective and better than no treatment for short
term accelerated symptomatic controls.
It is equally heartening that the data from numerous fairly recent
experimental animal test system models have demonstrated a lot of
promising potential for several pharmacotherapeutic agents
including desmopressin.I have reviewed several mentioned articles
on the translational preclinical phase of the scientific
pharmacotherapy for enuresis employing experimental rodent
animal test system models, but also the porcine and primate models
as well.
Desmopressin should only be used for a limited period of time
usually for about four weeks.
It may have a role in the short term management of the child such as
when a child is living away from home or wishes to attend a camp.
Adverse effects such as anorexia, cephalgias, unpleasant taste in
the mouth, visual difficulties, epistaxis and nasal discomfort in
addition to very rarely water intoxication were reported in some
cases.
Application of Indomethacin suppositories to children with primary
enuresis was found to be beneficial especially in children with
primary functional enuresis.
There were no toxicity concerns as such when indomethacin was
used within the recommended dose range in some selected group of
children with primary functional enuresis.
Pharmacologic Treatments:
Carbamazepine
Carbamazepine was opined to have a fair role in secondary enuresis
related to neurogenic mechanisms especially those related to
bladder detrusor muscle instability.
A prolonged enuretic interval was achieved in some selected group
of patients with secondary enuresis related to dysfunctional bladder
commenced on carbamazepine.
In the author’s experience, toxicity concerns were not much of an
issue in these subsets who needed carbamazepine for other
paroxysmal events related to cerebral dysarrythmias.
A comparative averaging of these plausible or anecdotal therapeutic
interventions for their therapeutic benefits against their toxicities
profiles suggests that toxicity concerns were most for imipramine
and other tricyclic antidepressants compared to desmopressin,
Indomethacin or other putative therapeutic agents.
Oxybutynin and other anticholinergic could also be used in diurnal
enuresis due to detrusor muscle instability.
There is very little evidence that drugs such as phenobarbitone or
meprobamate were useful except in those instances where their
therapeutic benefit could have been related to their antiepileptic
activities, in such instances, enuresis could have been a component
of the automaticities related to a seizure event.
The roles of Hydroxyzine hydrochloride and methylphenidate
hydrochloride in the management of nocturnal enuresis were
controversially discussed.
If enuresis were related to a defective urinary training adaptive skills
acquisition perturbations in attention deficit hyperactivity spectrums
disorders, then amphetamine like drugs or methylphenidate would
have a beneficial modulating effect.
Rational Pharmacotherapeutic Interventions for Nocturnal Enuresis.
Pharmacologic Treatments:
In the authors experience, the anticholinergic properties of
atropine, propantheline bromide, hyoscine hydroxyl butyrl methyl
bromide or emepronium bromide on the bladder detrusor could
occasionally be exploited beneficially to achieve selective muscle
relaxation, although overall these may not be very satisfactory
options as longer terms interventional strategies.
There appears to be a good body of evidence that overall they may
not be beneficial after all.
A rational approach to treating enuresis is to first start a trial of
DDAVP.
This gives the child a treatment option that ensures dryness during
times when bedwetting would be particularly inconvenient or
traumatic.
After a trial of DDAVP, it is generally recommend that the parents
consider a subsequent trial of a behavior-conditioning program.
A carefully regulated intervention with desmopressin and behavioral
therapy for nocturnal enuresis suggests that the intermittent use of
DDAVP along with a conditioning retraining therapy is often effective
in increasing self-confidence while working toward a cure that may
not necessarily be pharamacotherapeutically driven.
Also, from the other perspective, the social aspects of nocturnal
enuresis and its interventions needs to be scrupulously addressed
for an overall utmost outcome.
Furthermore, it should be worthwhile to follow up the difficult cases
of childhood enuresis up to the adult age, especially with regards to
primordial preventive measures for their off springs with enuretic
diathesis.
BIBLIOGRAPHY AND SUGGESTIONS FOR FURTHER READING
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In the authors experience with a heterogeneous paediatric sample,
the evaluation of the effectiveness of interventional options for
nocturnal enuresis was comparable to that of other authors,
although the settings were somewhat different, the following
deductions could be proffered.
If no active interventions were applied but probably counseling and
watchful conservatisms are followed a spontaneous cure rate of
about one of seven cases annually is expected.
Apparently the relapse rates in these subsets with a natural
remission appear to be negligible in the absence of emotional
stressors.
Conditioning alarms will give a remission rate of about one half to
nineteen of twenty cases.
With a relapse rate of probably about one half instances.
With Imipramine, the remission rate is probably about three of five
but the relapse rate is about seven of ten.
Desmopressin (DDAVP) will offer a remission rate of about one of
three and a relapse rate of about nine of ten.
The evaluations for the effectiveness of therapies for enuresis will
not normally end with the cessations of either pharmacological or
non-pharmacological interventions but will continue with interval
assessments of behavioral and self-concept changes after three, six
twelve months or more of interventions for enuresis.
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Metadata,Subjects and Topics Index: Abbreviations Key Words.
Medical Science Headings(MeSH)
Metadata,Subjects and Topics Index: Abbreviations Key
Words.Medical Science Headings(MeSH)
Abuse of children with enuresis:
emotional
physical
Acetylcholine:
Actinomycosis:
as a cause of enuresis
Adenoidal hypertrophy:
adreno-receptors:
effects of imipramine on
Arterioles:
afferent:
efferent:
Anionic-cationic synports:
Attention Deficit hyperactivity disorders:
Alarms systems:
Aldosterone:
Anoxia:
Anticholinergics:
Antidiuretc hormones:
Apothecaries regimen in enuresis:
Aristotle:
Atrial natriuretic peptide factors:
Metadata,Subjects and Topics Index: Abbreviations Key
Words.Medical Science Headings(MeSH)
Assynergia:
Basal Lamina:
Behaviour conditioning programs:
Bladder:
control
innervations
instability
regulation
training programmes
Bowman’s Capsules:
Capillaries:
Carbamazepine
Ciba Drug Company:
Chinese Medicine:
for the treatment of enuresis:
Conditioning alarms:
Cyclic AMP:
role in humoural mediation.
Constipation:
as a cause of enuresis
Control:
urinary
Continence Training:
Cost effectiveness of Interventions:
alarm systems
behavioural therapies
Metadata,Subjects and Topics Index: Abbreviations Key Words.
Medical Science Headings(MeSH)
bladder training programmes
carbamazepine
desmopressin
environmental manipulations
imipramine
tricyclic antidepressants
Cystometry:
Cyclic AMP:
role in renal physiology.
Decreased bladder capacity:
and enuresis:
Definitions:
of enuresis
of subtypes of enuresis:
Desmopressin:
adverse effects
drug history
Detrusor:
detrusor instability
detrusor dyssynergia
Developmental delay:
association with enuresis.
Metadata,Subjects and Topics Index: Abbreviations Key Words.
Medical Science Headings(MeSH)
Diuresis:
osmotic
water
Diuretics:
as causes of enuresis.
Dopamine:
Drugs:
as causes of enuresis.
Dysfunctional bladder syndrome:
Ectopic ureters:
as a cause of enuresis.
Effective filtration:
Encephalitis:
as a cause of enuresis.
Endothelium:
Environmental manipulations as interventions for enuresis:
Enuresis:
aetiopathogenesis
behavioural therapies for
clinical features of
definitions
drug treatment
Metadata,Subjects and Topics Index: Abbreviations Key Words.
Medical Science Headings(MeSH)
environmental manipulations for
epidemiology
functional
historical perspectives
incidence
investigations for
natural history of
nocturnal
nomenclatures
non-pharmacological interventions for
persistent
pharmacological interventions for
prevalence
primary
regressive
risk factors
secondary
treatments
Epinephrine receptors:
Equisetums as therapy for nocturnal enuresis:
Failure:
Renal:
Family education for enuresis:
Follow up:
of cases of childhood enuresis.
Food allergy:
as a cause of enuresis.
Folklore therapies for enuresis:
Functional Renal Anatomy:
Metadata,Subjects and Topics Index: Abbreviations Key
Words. Medical Science Headings(MeSH)
Genetic determinants for enuresis:
Giggle Incontinence
Glomerulus:
traberculations
tortousities
viscosity of
conductivity coefficients.
permeability coefficients
hydrostatic pressures.
osmotic pressures.
oncotic pressures gradients across the glomerular capillary stroma
the net ultrafiltration surface area relative to the osmotic pressure of
the tubular filtrates.
size of the glomerular capillary stroma in influencing glomerular
capillary filtration.
capillary mesh works:
Glomerular filtration rate:
Normo-equilibrium:
The glomerular capillary hydrostatic pressure
osmotic pressure gradient across the glomerular capillaries
the hydrostatic pressures in the Bowman’s Capsules
Glomerular efferent capillaries constrictive pressures:
Glomerular afferent capillaries constrictive pressures:
Glomerular ultrafiltration:
flow velocity
diffusability co-efficients.
Haemoglobinopathy
Metadata,Subjects and Topics Index: Abbreviations Key Words.
Medical Science Headings(MeSH)
mechanisms of enuresis in
Heart block:
as a cause of enuresis:
Histiocytosis X:
mechanisms of enuresis in
Historical aspects of enuresis:
Horsetails:
as therapy for nocturnal enuresis:
Humoural Factors:
Hydroxyzine hydrochloride:
as an adjunct in the management of enuresis.
Hyponatremic related seizures:
in desmopressin therapy.
Hypostenuria:
as a cause of enuresis.
Hypothyroidism:
as a cause of enuresis
Idiopathic factors:
as aetiological mechanisms in enuresis.
Imipramine:
adverse effects
cardiotoxicities
chemical formular
drug history
pharmacodynamics and receptor effects:
activity on σ-receptors and enkephalinase
comparative pharmacodynamics to amitryptiline
norepinephrine receptors.
Metadata,Subjects and Topics Index: Abbreviations Key Words.
Medical Science Headings(MeSH)
Increased renal blood flow:
Indomethacin:
toxicities profile
Infrequent voiding:
as a cause of enuresis.
Inheritance pattern in enuresis:
Intercalated Cells (I cells):
Interlobular arteries:
Interlobular veins:
Interventions for enuresis:
comparisons
Effectiveness
Investigations for enuresis:
basic investigations for enuresis.
minimum investigations for enuresis.
indications for invasive investigations in enuresis.
Irritable bladder diathesis:
as a cause of enuresis.
Juxtaglomerular apparatus:
Juxtaglomerular cells:
Kegel exercises:
Lacis cells:
Metadata,Subjects and Topics Index: Abbreviations Key Words.
Medical Science Headings(MeSH)
Lymphoproliferative disorders:
as causes of enuresis.
Macula densa.
Magnetic Resonance Imaging:
Meatal stenosis:
as a cause of enuresis.
Mesangial capillary cells:
dilatation
relaxability
retractability
contractibility
Methylphenidate hydrochloride:
in the treatment of enuresis.
Medically plausible treatment options for enuresis:
Medullary interstitial cells Type I:
Medullary pyramids:
Monosymptomatic enuresis:
Nephrons:
Neurotransmitters:
Night time continence:
Time of attainment
daytime incontinence:
time of attainment.
Nocturnal enuresis:
nocturnal polyuria and enuresis.
Nocturnal bladder capacity:
in the aetiopathogenesis of nocturnal enuresis.
Obstipation:
as a cause of enuresis.
Obstructive Sleep Apnoeas:
Organs organun vasculosum of the lamina terminalis [OVLT]
Oxybutynin:
Metadata,Subjects and Topics Index: Abbreviations Key
Words. Medical Science Headings(MeSH)
Overactive bladder and dysfunctional voiding:
in the aetiopathogenesis of enuresis.
Nocturnal polyuria:
as a cause of enuresis.
PANDAS: [pediatric autoimmune neuropsychiatric disorders
associated with streptococcal infections]
PANS:Paediatric Autoimmune Neuropsychiatric Disorders
Associated Associated with Streptococcal Infection.
Pars convoluta:
Pars recta:
Papyrus of Ebers:
Parental history of enuresis and likelihood of child’s affectation:
Pericytes:
Physical examinations for enuresis:
assessment of the lower extremities.
gait evaluation for enuresis.
inspection of the external genitalia.
muscle power evaluation.
neurologic assessment.
perianal reflexes examination.
plantar responses assessment.
muscle tone evaluation
anal tone and sensation
palpation in the renal and suprapubic areas.
Metadata,Subjects and Topics Index: Abbreviations Key Words.
Medical Science Headings(MeSH)
Physiology:
Renal
Podocytes:
Polygenic pattern of inheritance in enuresis:
Polysymptomatic enuresis:
Principal (P) cells:
Prostaglandins:
Proximal tubules:
Psychiatric disorders:
as causes of enuresis
Psychogenic factors:
as causes of enuresis.
Renal Plasma Flow:
Renal Transport maxima:
Renal tubular function:
Rennin:
Responsibilty training for enuresis:
Restricted bladder capacity as a cause of enuresis.
Sarcoidosis:
as a cause of enuresis.
Secondary causes of enuresis:
chronic renal failure
constipation
diabetes insipidus
diabetes mellitus
Metadata,Subjects and Topics Index: Abbreviations Key Words.
Medical Science Headings(MeSH)
hyperthyroidism
obstructive sleep apnea
worm infestations
psychological stress
urinary tract infection
seizure disorder
Sickle cell disease.
as a cause of enuresis.
Seizure disorders:
as a cause of enuresis.
Serotonin receptors:
Sleep disorders.
as a cause of enuresis.
Sleep related respiratory difficulties:
as a cause of enuresis.
Sleep disordered breathing:
as a cause of enuresis.
Sodium-Potassium-Chloride co-transport synport:
Social Factors:
propagating enuresis
Stellate cells:
Sub Fornical Organs:
Subfornical organs :(SFO)
Metadata,Subjects and Topics Index: Abbreviations Key Words.
Medical Science Headings(MeSH)
Surgically amenable treatments for enuresis:
Treatments for enuresis:
when to start treatment for enuresis
sustainable treatment options
tentative symptomatic relieves
Tuberculosis:
Causes of enuresis in reset osmostat.
Tubular function:
Septo-optic dysplasias:
as associations of enuresis.
Urea:
role in the countercurrent and urine concentrating processes.
Urethral stenosis:
as a cause of enuresis.
Urinary:
difficulties
frequency
urgency
Urinary tract infections
as a cause of enuresis.
Urgency Incontinence:
Urodynamic studies:
Vagino-urethral fistula
as a cause of enuresis.
Vasa Recta:
Videocysturethrographies:
Wenguenguo trees seeds for the management of enuresis:
Wolframs syndrome:
World Health Organisation (WHO):
THE SCIENTIFIC FUNDAMENTALS IN THE
SPECIFIC INTERVENTION FOR ENURESIS
THE SCIENTIFIC FUNDAMENTALS OF THE SPECIFIC INTERVENTIONS FOR ENURESIS
BY.PROF.DOTT.EMMANUELUDEMEZUE ONYEKWELU.
CSci,CSciTeach,BChir(Hons),BM,(Hons)MD,MRQA,FRSA,FCILED,FRGS,FRSH,FRCEM,FRSPH,FRSB,DSc/PhD(Hon)
THE SCIENTIFIC FUNDAMENTALS IN THE
SPECIFIC INTERVENTION FOR ENURESIS
THE SCIENTIFIC FUNDAMENTALS IN THE
SPECIFIC INTERVENTION FOR ENURESIS
THE SCIENTIFIC FUNDAMENTALS IN THE
SPECIFIC INTERVENTION FOR ENURESIS
The Scientific Fundamentals of the Specific Interventions for
Enuresis by.
Prof.Dott.EmmanuelUdemezue Onyekwelu.
CSci,CSciTeach,BChir(Hons),BM,(Hons)MD,MRQA,FRSA,FCILED,FRGS,FRSH,FRCEM,FRSPH,FRSB,DSc/PhD(Hon)
This is the second edition of The Scientific Fundamentals of
the Specific Interventions for Enuresis published by
Prof.Dott.Emmanuel Udemezue Onyekwelu.
CSci,CSciTeach,BChir(Hons),BM,(Hons)MD,MRQA,FRSA,FCILED,FRGS,FRSH,FRCEM,FRSPH,FRSB,DSc/PhD(Hon)
AT C L A S S I C S A N D R E V I S I T S I N S C I E N T I F I C M E D I C I N E
Classics Revisits Sci.Med. 2024.