BLADDER DISORDERS MODERATOR -PROF. N.C. DWIVEDI(MD)(DM) BY-Anil kumar g (JR3)Anatomy ¢ The urinary bladder is a smooth muscle chamber composed of two main parts: — (1) the body, the major part, collects urine — (2) the neck, a funnel-shaped extension of the body, passing inferiorly and anteriorly into the urogenital triangle and connecting with the urethra esr Urachus cor Dome Posterior wall Lateral wall Anterior wall Ureteric orifice «9 Trigone Bladder neck Prostate (not part of bladder) Prostatic urethra (not part of bladder; code to 688.0)On the posterior wall of the bladder, lying immediately above the bladder neck, is a small triangular area called the trigone. The trigone can be identified by the fact that its mucosa, the inner lining of the bladder, is smooth, in contrast to the remaining bladder mucosa, which is folded to form rugae. At the lowermost apex of the trigone, the bladder neck opens into the posterior urethra, and the two ureters enter the bladder at the uppermost angles of the trigone. Each ureter, as it enters the bladder, courses obliquely through the detrusor muscle and then passes another 1 to 2 centimeters beneath the bladder mucosa before emptying into the bladderThe bladder neck (posterior urethra) is 2 to 3 centimeters long, and its wall is composed of detrusor muscle interlaced with a large amount of elastic tissue. The muscle in this area is called the internal sphincter. Traps spittin | Mscosa ‘arin propia Detusor muse Enteral uiataloptcter. Proeen (irtnogeitaldptragen) «* Its natural tone normally keeps the bladder neck and posterior urethra empty of urine and, therefore, prevents emptying of the bladder until the pressure in the main part of the bladder rises above a critical threshold. * Beyond the posterior urethra, the urethra passes through the urogenital diaphragm, which contains a layer of muscle called the external sphincter of the bladder. * External sphincter muscle is a voluntary skeletal muscle, in contrast to the muscle of the bladder body and bladder neck, which is entirely smooth muscle. od * The external sphincter muscle is under" voluntary control of the nervous system and can be used to consciously prevent urination even when involuntary controls are attempting to empty the bladder. Siilaetlion {lve hase perma outa)Blood supply The bladder is supplied by the superior and inferior vesical arteries which are branches of anterior trunk of internal iliac artery. The veins that drain the bladder form a plexus on the infero-lateral surface before ending in the internal iliac vein. Most of the lymph from the urinary bladder ends in the external iliac nodes.Innervation of the Bladder The principal nerve supply of the bladder is by way of the pelvic nerves, which connect with the spinal cord through the sacral plexus, mainly connecting with cord segments S-2 to S-4. Coursing through the pelvic nerves are both sensory nerve fibers and motor nerve fibers. The sensory fibers detect the degree of stretch in the bladder wall. Stretch signals from the posterior urethra are especially strong and are mainly responsible for initiating the reflexes that cause bladder emptying. The motor nerves transmitted in the pelvic nerves are parasympathetic fibers. These terminate on ganglion cells located in the wall of the bladder. Short postganglionic nerves then innervate the detrusor muscle.In addition to the pelvic nerves, two other types of innervation are important in bladder function. Most important are the skeletal motor fibers transmitted through the pudenda! nerve to the external urethral sphincter. These are somatic nerve fibers that innervate and control the voluntary skeletal muscle of the sphincter. Also, the bladder receives sympathetic innervations from the sympathetic chain through the hypogastric nerves, connecting mainly with the L-1,L-2 segments of the spinal cord. These sympathetic fibers stimulate mainly the blood vessels and have little to do with bladder contraction. Some sensory nerve fibers also pass by way of the sympathetic nerves and may be important in the sensation of fullness and, in some instances, pain.Innervation of the urinary bladder and its sphincters Fenal plexus Clac plexus ans = Aeron hors — Eoront fiver Postgangisnc:* As the bladder fills, many superimposed micturition contractions begin to appear. They are the result of a stretch reflex initiated by sensory stretch receptors in the bladder wall, especially by the receptors in the posterior urethra when this area begins to fill with urine at the higher bladder pressures.* Sensory signals from the bladder stretch receptors are conducted to the sacral segments of the cord through the pelvic nerves and then reflexively back again to the bladder through the parasympathetic nerve fibers by way of these same nerves.Afferent Efferent Inhibition or facilitation Sensory perception Medial pontine Medial pontine micturition micturition center center Lateral cs spinothalamic Sy tract Stimutate inhi t sacral sacral Sacral IZ parasympathetic somatic sore QS) neurons neurons and and interneurons interneurons Dorsal gang Contraction of detrusor Receptors in muscle wall and mucosa Relaxation of sphincterWhen the bladder is only partially filled, these micturition contractions usually relax spontaneously after a fraction of a minute, the detrusor muscles stop contracting, and pressure falls back to the baseline. As the bladder continues to fill, the micturition reflexes become more frequent and cause greater contractions of the detrusor muscle. Once a micturition reflex has occurred but has not succeeded in emptying the bladder, the nervous elements of this reflex usually remain in an inhibited state for a few minutes to 1 hour or more before another micturition reflex occurs. As the bladder becomes more and more filled, micturition reflexes occur more and more often and more and more powerfully.* Once the micturition reflex becomes powerful enough, it causes another reflex, which passes through the pudendal nerves to the external sphincter to inhibit it. * If this inhibition is more potent in the brain than the voluntary constrictor signals to the external sphincter, urination will occur. If not, urination will not occur until the bladder fills still further and the micturition reflex becomes more powerful.* The micturition reflex is a completely autonomic spinal cord reflex, but it can be inhibited or facilitated by centers in the brain. * These centers include — (1) strong facilitative and inhibitory centers in the brain stem, located mainly in the pons, and — (2) several centers located in the cerebral cortex that are mainly inhibitory but can become excitatoryThe micturition reflex is the basic cause of micturition, but the higher centers normally exert final control of micturition as follows: — 1. The higher centers keep the micturition reflex partially inhibited, except when micturition is desired. — 2. The higher centers can prevent micturition, even if the micturition reflex occurs, by continual tonic contraction of the external urethral sphincter until a convenient time presents itself. — 3. When it is time to urinate, the cortical centers can facilitate the sacral micturition centers to help initiate a micturition reflex and at the same time inhibit the external urethral sphincter so that urination can occur.Fegr Pretronta cortex cortical activation with bladder filling, brain activity increased with increasing bladder volume in the periaqueductal gray- PAG matter in the midline pons, in the mid-cingulate cortex, and bilaterally in the frontal lobe area. Inhibition of micturition was related to activation of parietal cortex, cerebellum, putamen. and supplementary motor area insular, posterior parietal, and prefrontal activation during urinary storage.* Urgency — is the sudden desire to void — in inflammatory conditions such as cystitis or in hyperreflexic neuropathic conditions such as neurogenic bladders resulting from upper motor neuron lesions. + Dysuria — painful urination — associated with inflammation. — The pain is typically referred to the tip of the penis in men or to the urethra in women. * Frequency — is the increased number of voids during the daytime, and = nocturia is nocturnal frequency. — Adults normally void five or six times a day and once at most during the nighttime hours. — Increased frequency may result from increased urinary output or decreased functional bladder capacityHesitancy — isa delay in the initiation of micturition. — results from the increased time required for the bladder to attain the high pressure necessary to exceed that of the urethra in the obstructed setting. Decreased force of stream results from the high resistance the bladder faces and is often associated with a decrease in caliber of the stream. Intermittency is the interruption of the urinary stream Postvoid dribbling the uncontrolled release of the terminal few drops of urine. Obstructive symptoms are most commonly due to benign prostatic hyperplasia, urethral stricture, or neurogenic bladder disorders, prostatic or urethral carcinoma and foreign body are other causes.Urinary incontinence is the involuntary loss of urine. Total incontinence, patients lose urine at all times and in all positions. Stress incontinence is the loss of urine associated with activities that result in an increase in intra-abdominal pressure (coughing, sneezing, lifting, exercising). Uncontrolled loss of urine preceded by a strong urge to void is known as urge incontinence. Chronic urinary retention may result in overflow incontinence. The evaluation and treatment vary with each of the categories.* It isa consequence of a neurological pathology such as spinal injury or multiple sclerosis that disrupts central nervous system regulation of the micturition reflex resulting in dys-coordination of the bladder musculature and the external urethral sphincter. * Instead of the urethral muscle relaxing completely during voiding, it dys-synergically contracts causing the flow to be interrupted and the bladder pressure to rise. * On cystography there is an irregular appearance of the bladder outline due to muscular contraction against the unrelaxed bladder sphincter.60, sNFANS REFLEX VOID BLADDER PRESSURE BLADDER FILLING ENG 100 200 300 > ° 60 VOLUNTARY VOID BLADDER FILLING BLADDER EMG PRESSURE a a 8 6 200 200 300 60, PARAPLEGIC aw REFLEX VOID s2 22 ° BLADDER-SPHINCTER BLADDER FILLING 'DYSSYNERGIA 0 ° 140 200 200Symptoms * Symptomatically, people with this condition generally experience daytime and night time wetting, urinary retention, and often have a history of urinary tract and bladder infections. Constipation and encopresis are often associated with this condition. Diagnosis * Strictly DSD can only be diagnosed from an CMG traceWith regard to the neurologic diseases that cause bladder dysfunction, * multiple sclerosis, usually with urinary urgency, is by far the most common. * degenerative diseases (Parkinson disease and multiple system atrophy) for 14 percent, * spinal cord disorders account for 12 percent of cases, * and frontal lobe lesions for 9 percent.Complete destruction of the cord below T12 — conus lesions — trauma, myelodysplasias, tumor, venous angioma, and necrotizing myelitis. — bladder is paralyzed for voluntary and reflexactivity — no awareness of the state of fullness; — voluntary initiation of micturition is impossible; — the tonus of the detrusor muscle is abolished and the bladder distends as urine accumulates until there is overflow incontinence; — voiding is possible only by the Crede’ maneuver, i.e.,lower abdominal compression and abdominal straining. * Usually the anal sphincter and colon are similarly affected, and there is “saddle” anesthesia and abolition of the bulbocavernosus and anal reflexes as well as the tendon reflexes in the legs. * The cystometrogram shows low pressure and no emptying contractions. * Management: catherisation & anticholinergicsDisease of the sacral motor neurons in the spinal gray matter — autonomic bladder , autonomous bladder — the anterior sacral roots, or peripheral nerves innervating the bladder — lumbosacral meningomyelocele and the tethered cord syndrome. — alower motor neuron paralysis of the bladder. — sacral and bladder sensation are intact. ¢ Various causes pertain in cauda equina disease, the most frequent being compression by epidural tumor or disc, neoplastic meningitis, and radiculitis from herpes or cytomegalovirus. * a hysterical patient can suppress motor function and suffer a similar distention of the bladder.Interruption of sensory afferent fibers — atonic bladder — as in diabetes and tabes dorsalis (tabetic bladder). — motor nerve fibers unaffected * Although a flaccid (atonic) paralysis of the bladder may be purely motor or sensory, as described above, in most clinical situations there is interruption of both afferent and efferent innervation, as in cauda equina compression or severe polyneuropathy. * Neuropathies affecting mainly the small fibers are the ones usually implicated (diabetes, amyloid, etc.), but urinary retention also occurs in certain acute neuropathies such as Guillain-Barre’ syndrome. * Treatment includes intermittent self catheterisationUpper spinal cord lesions, above T12 — reflex neurogenic (spastic) bladder, automatic bladder — multiple sclerosis and traumatic myelopathy, which are the commonest causes; myelitis, spondylosis, arteriovenous malformation (AVM), syringomyelia, and tropical spastic paraparesis — If the cord lesion is of sudden onset, the detrusor muscle suffers the effects of spinal shock. At this stage, urine accumulates and distends the bladder to the point of overflow. — As the effects of spinal shock subside, the detrusor usually becomes reflexly overactive (detrusor hyperreflexia), and since the patient is unable to inhibit the detrusor and control the external sphincter, urgency, precipitant micturition, and incontinence result. — Incomplete lesions result in varying degress of urgency in voiding.With slowly evolving processes involving the upper cord, such as multiple sclerosis, the bladder spasticity and urgency worsen with time and incontinence becomes more frequent. In addition, initiation of voluntary micturition is impaired and bladder capacity is reduced. Bladder sensation depends on the extent of involvement of sensory tracts. Bulbocavernosus and anal reflexes are preserved. The cystometrogram shows uninhibited contractions of the detrusor muscle in response to small volumes of fluid.* Some patients can still control urination in this condition by stimulating the skin (scratching or tickling) in the genital region, which sometimes elicits a micturition reflex. * Management: — Decompress the rectum or bladder - reverses the effects of unopposed sympathetic outflow. — Terazosin/ spinal anesthetic may be used as prophylaxis.Mixed type of neurogenic bladder. * In diseases such as multiple sclerosis, subacute combined degeneration, tethered cord, and syphilitic meningomyelitis, bladder function may be deranged from lesions at multiple levels, i.e., spinal roots, sacral neurons or their fibers of exit, and higher spinal segments. * The resultant picture is a combination of sensory, motor, and spastic types of bladder paralysis.Stretch injury of the bladder wall, as occurs with anatomic obstruction at the bladder neck and occasionally with voluntary retention of urine, as in hysteria. Repeated overdistention of the bladder wall often results in varying degrees of decompensation of the detrusor muscle and permanent atonia or hypotonia, although the evidence for this mechanism is uncertain. The bladder wall becomes fibrotic and bladder capacity is greatly increased. Emptying contractions are inadequate, and there is a large residual volume even after the Crede’ maneuver and strong contraction of the abdominal muscles. As with motor and sensory paralyses, the patient is subject to cystitis, ureteral reflux, hydronephrosis and pyelonephritis, and calculus formation.* Frontal lobe incontinence Often the patient, because of his confused mental state, ignores the desire to void and the subsequent incontinence. There is also a supranuclear type of hyperactivity of the detrusor and precipitant evacuation. ¢ Nocturnal enuresis or urinary incontinence during sleep, due presumably to a delay in acquiring inhibition of micturition.1.Noninvasive Bladder “orm monn Investigations voiding diary may be kept by either the patient or the caregiver of the approximate amount drunk, frequency of micturition, and Se A tom episodes of incontinence, recorded over the course of several days. This gives a useful indication of the | 7~ severity of the bladder complaints ome ae et: ‘Touay' Date: buming.feguency 136 68 more cane of ing, if manure, tary aceldeat BAC bowel me 12 Midnight—7 ase on which management decisions ne can be based. in mna.Urinary flowmetry: * noninvasive investigation, valuable particularly when combined with an ultrasound measurement of the postmicturition residual volume. + Itasa base of the collecting system is a spinning disk, and flow of urine onto this disk tends to slow its speed of rotation, which a servomotor holds constant. * — Urine flow is derived from measurement of the power necessary to maintain rotation speed, and the machine usually produces a graphic printout, together with an analysis, for the time taken to reach maximal flow, maximum and average flow rates, and the voided volume b.simple ultrasound machines are now available that require little operator training and make it easy to determine whether the postmicturition residual is negligible or in excess of 100 mL A |Past processine trem oo oeosor Wai8 io Yoo. ‘A, Urinary flow meter. The side of the uroflow transducer has been cut away to show the disk at the base of the funnel, which rotates as urine passes into the collecting vessel. B, Typical (normal) printout from the urotiowmeter. Atotal of 280 mL was voided (upper trace), with a maximum flow rate of 30 mL per second (lower trace).* Cystometry, the registration of bladder W CYSTOUROFLONMETRY 94.0208 15:14 ID. pressure, can be performed during filling eae and voiding . * Detrusor pressure is derived by subtraction Vids of the abdominal pressure (measured using " aaa mt san ue a rectal line) from the intravesical pressure ee eee se (measured using a vesical line). The . t i Ra efficiency of the subtraction usually is 10.cm/H,0 checked at the beginning of cystometry by abd asking the subject to cough. “ 100m H,0 * This produces an increase in abdominal 120220920 4). B:20 pressure and hence in intravesical pressure, —_""S but no increase in detrusor pressure. Cystometry during bladder filing. The bladder was filled (top trace) at 50 mL per minute (Vinfus) to a total of 300 mL. Detrusor pressure (Pdet) is derived by subtracting pressure in the rectum (Pabd) from the measured intravesical pressure (Pves). At the beginning of the trace, these two values can be seen to be subtracting effectively because on coughing there is an abrupt increase in intravesical pressure but no increase in detrusor pressure. The detrusor pressure did not exceed 10 cm H.O, which is normal.VIDEOCYSTOMETRY : When cystometry is carried out using a contrast filling medium and the procedure is visualized radiographically, the technique is known as videocystometry. CATHETER-MOUNTED TRANSDUCER: » Urethral pressure profile is measured using a catheter-mounted transducer that is drawn slowly through the urethra by a motorized armature. The test is called static if no additional maneuver such as coughing or straining is performed. > If intravesical pressure is measured simultaneously while the patient coughs repeatedly during withdrawal of the catheter, the transmission of the cough impulse in the urethra and bladder can be measured and expressed as a ratio—the transmission pressure ratio. measurements of the urethral pressure profile and parameters derived from it would be useful in assessing genuine stress incontinence VvElectromyography: To assess the extent of relaxation of the urethral sphincter during voiding. Interruption of the neural pathways between the pons and the sacral cord results in loss of coordination of sphincter and detrusor muscle activity, a condition known as detrusor-sphincter dyssynergia. Neuroimaging: MRIGoals in treatment: * Preservation of upper urinary tract * Maintain adequate bladder capacity with good compliance * Promote low-pressure micturition * Avoid bladder over-distension * Prevent urinary tract infection * Minimize use of Foley catheter * Choose therapy that minimizes patient risks while maximizing social, emotional, and vocational acceptabilityMANAGEMENT OF BLADDER DISORDERS 1.Detrusor Overactivity: Antimuscarinic medications are the mainstay of treatment GENERIC DOSE |FREQUENCY|RECEPTOR MOLECULE ELIMINATION NAME img) SELECTIVITY TYPE HALF-LIFE (hr) Propantheline |15 tds Nonselective Quatemary = <2 amine Tolterodine [2 bd Nonselective Tertiary amine Tolterodine XL |4 od Tertiary amine Trospium [20 bd ‘Quatemary amine JOxybutynin —[2.5-5 bd-qds Tertiary amine JOxybutynin XL [5-30 od Tertiary amine Propiverine [15 od-qds _[Nonselective Ester 44 Darifenacin |7.5-15 od M3-specific Tertiary amine [3.1 antagonist Solifenacin [5-10 od M2/3-specific Tertiary amine = antagonist* main side effect is dry mouth, with less common effects of blurred vision, drowsiness, and constipation. Darifenacin and solifenacin are newer anticholinergics, with greater specificity for the M3 receptor. * Botulinum A toxin (BONT/A): introduced in the treatment of bladder overactivity by injection into the detrusor smooth muscle under cystoscopic guidance.Normal N-M transmission Fic. 1. Normal fusion and reloase of acetylcholi erminal vin interaction of veeide and membrane bound (SNARE)| 2 rotein. Inst. parasympathetic nerves innervating Hader With laying numerous vesicles| snislang ecretoeneaiiar ACh SNAPSS. sroaposomal ao ted membrane protein. B, Slering me adam, assembly of SNARE protein Bote (eg synaptobrevin, SNAP-25 and syntaxin| cours, which loads to (C) release of ACh and activation of postjune- ional muscarinic a eh ‘resulting in bladder contraction. Mechanism of Action Botulinum toxin ww wv. ] > 6? 0 . e 6, Fin, 2 Parasympatbetic nerve terminal. A, binding oftocin henry chain to as yet unidentified receptor and internalization of toxin ‘within nerve terminal. B, translocation of light chain into cytosol. C, inhibition of reurotranamitter release by cleavage of specific SNARE proteins. A to G, botulinum toxin serotypes.Desmopressin spray: First introduced to treat DI, Widely prescribed for children with nocturnal enuresis, patients with MS and nighttime frequency also have used it. Disabled patients and their caregivers, the difficulties of the patient having to get up to go to the toilet several times in the night can be considerable. One or two nasal puffs of desmopressin from a metered-dose spray administered on retiring reduces urine output for the following 6 to 8 hours and may significantly lessen nighttime urinary frequency. An oral preparation of desmopressin is now available. Used once in 24 hours Not be given to the elderly, in whom its use may precipitate congestive heart failure.2.Incomplete Bladder Emptying or Urinary Retention Sterile intermittent catheterization * Most patients are advised initially to perform the technique at least twice a day * Although bacteriuria is noted in 50% of patients doing clean intermittent self- catheterization, the incidence of symptomatic urinary tract infections fortunately is low .In spinal cord disease, a combination of intermittent self-catheterization 4 and an oral anticholinergic deals effectively with both aspects of bladder malfunction. No \ Yes In a borderline significant residual volume, starting an anticholinergic ES may have the effect of increasing it . This should be suspected if the medication has some initial beneficial Treat with anticholinergics effect for several days that then 4 disappears. This combined approach works well in patients with spinal cord disease v \ such as MS, provided that the patient is not too severely disabled. recommended management of naurlogical incontinence. CISG, ean intermitient sel catheterization; PVR, postvoid residualPermanent Indwelling Catheters: When the patient is no longer able to perform self- catheterization, or when urge incontinence and frequency are unmanageable. No longer weight-bearing and is chair-bound. Suprapubic catheter is a better long-term alternative to an indwelling urethral catheter and often is the method of choice in managing incontinence in patients for whom other means are no longer effective.BLADDER MANAGEMENT OPTIONS, WITH PROGRESSION OF MS Walking unaided & Walking mostly without aids. Walking mostly with aids: Chairbound Oral Oral Oral anticholinergic anticholinergic anticholinergic = DDAVP +CISc + CISC = DDAVP = DDAVP Bedbound 2 CBME 2 BONT/A ? BONT/A ?. CBME ioc Time ——> The bladder symptoms in multiple sclerosis (MS) become increasingly difficult to manage with progression of spinal cord disease. This diagram summarizes the various measures that may be effective at each stage. BoNT/A, botulinum toxin A; CBME, cannabis-based medicinal extract, CISC, clean intermittent self-catheterization; DDAVP, trademark for preparation of desmopressin; IDC, indwelling catheterExternal Device: Urge incontinence is the main problem and the bladder empties completely, some men are able to wear an external device attached around the penis. The simplest and least obtrusive is a self-sealing latex condom sheath, which can be put on each night or kept in place for up to 3 days. Sacral Nerve Stimulators ¢ An extradural sacral nerve stimulator can be highly effective in lessening detrusor overactivity that is resistant to anticholinergic medication. * It seems highly likely that the mechanism of action of this device is stimulation in the presacral region of the pelvic afferents, which are known to have an inhibitory effect on the detrusor.* Surgery: * range from minimally invasive procedures, (TVT, TOT) to increase bladder outflow resistance, or implantation of an artificial urethral sphincter, to the surgical techniques of increasing bladder capacity by cystoplasty or urinary diversion into a conduit or catheterizable reservoir BLADDER DISORDER /SURGICAL PROCEDURE \Genuine stress Bladder neck suspension; transvaginal tape (TVT); transobturator ‘incontinence tape (TOT) ‘Detrusor overactivity Augmentation cystoplasty ‘Sphincter failure Artificial sphincter Intractable incontinence [Urinary diversion with stoma collection bagREFERENCES * Neurology in Clinical Practice e-dition, 5th Edition Bradley, Daroff, Fenichel & Jankovic. * ADAMS AND VICTOR’S PRINCIPLES OF NEUROLOGY Eighth Edition.