1
Q
Describe anatomy of the bladder:
A
- Detrusor : smooth muscle bundles, fibers crisscross & interlace.Intervation ratio 1:1.
2 Bladder wall: 50% collagen
3 Trigone: Located inferior base of the bladderExtends from ureteral orifices to bladder neck
4 Bladder neck
- Urethra: Male 3 parts: prostate, membranous, anteriorFemale 4 cm in length
6 Internal urethral sphincter: smooth muscle/mixed twitch T11-L2: hypogastric n. (sympathetic) Contracts for storage Involuntary
7 External urethral sphincter: skeletal/striated muscle/slow twitchS2-4: pudendal n. Prevents emptyingVoluntary
2
Q
Name the different receptors in neurogenic bladder: and locations (
A
1 Cholinergic muscarinic
(M2 and M3) widely distributed
- Body of the bladder, trigone, bladder neck, and urethra
- Contraction of detrusor
2 Cholinergic nicotinic receptors
- Located in the striated sphincter
- Adrenergic receptors (α1 )
- Trigone, bladder neck, & urethra
Contraction of internal sphincter and bladder neck
- Norepinephrine binds to these receptors to cause contraction - β2- and β3-adrenergic receptors
- Body of the bladder
- Relaxation at the bladder neck on initiation of voiding
- Relax the bladder body to enhance storage.
3
Q
- alpha receptors mostly in:
- beta receptors mostly in:
- cholinergic receptors mostly in:
A
- trigone, bladder neck, urethra
- body of bladder
- diffuse
4
Q
Receptors with function: (bladderO) 1. Norepinephrine 2. Purine receptors 3. Vasointestine Polypeptide 4. Neuropolypeptide Y 5 Tachykinins (in afferent nerves) 6 Prostaglandins 7 PTHrp
A
- Main effector for urethra contraction via A1 receptors
- P1 – adenosine driven; P2 – ATP driven
Inhibitory on pelvic ganglia and facilatory on neuroeffector junction in detrusor - Enhances Ach in pelvic ganglia; inhibits Ach in detrusor
4 Excitatory on detrusor
5 Augment micturition reflex, transmits pain sensationAugment contraction & vascular response in inflammatory states.
6 Slow onset contraction of detrusor
7 Relaxation of detrusor
5
Q
central pathways for bladder: name function
- frontal lobe:
- Pons:
- Spinal cord:
A
1 Frontal lobe - Micturition center
Sends inhibitory signals to PONS until a socially acceptable time and place to urinate is available “Higher voluntary control” over pelvic floor
2 Pons (Pontine Micturition Center) – “reflex center” Major relay/excitatory center Coordinates the urethral sphincter relaxation & detrusor contraction to facilitate urination Affected by emotions (ex: incontinence when excited or scared)
3 Spinal cord
Intermediary between upper and lower control
6
Q
Describe parasympathetic and sympathetic patheways of the bladder
A
Parasympathetic – efferent (S2-S4)
- Pelvic nerves
- Excitatory to bladder, contraction of the body
Sympathetic - efferent (T10-L2)
- Hypogastric nerves to pelvic ganglia
- Inhibitory to bladder body, relaxation of the body
- Excitatory to bladder base/urethra, contracts
Sympathetics “Store”. Parasympathetics “Pee”
7
Q
Bladder:
Efferent:
Afferent:
A
Efferent - somatic
- pudendal nerves (onuf nucleus)
- contraction of the EUS and the pelvic floor muscles
Afferent fibers
- stretch receptors on detrusor muscle
- A-delta fibers respond to bladder distension
- capsaicin or vanilloid receptors subtype 1 (VR1) receptors - pathology (C-fibers)
8
Q
Role of nerves in bladder function:
- hypogastric n:
- Pelvic n
- pudendal n:
A
- T10-L2: To pelvic ganglia.
Inhibits body – relaxation (B2,3)
Excitatory to base/urethra (A1) - Pelvic N: S2-4 Efferent
Excitatory on detrusor. (Cm) - Pudendal N (Onufs Nucleus) S2-4: somatic
Contracts ex. Sphincter & pelvic floor
9
Q
SNS primarily controls ___ and ____
Somatics (pudendal N) regulates __- and ____
A
bladder and IUS
- Bladder increases capacity but not pressure
- Internal urinary sphincter to remain tightly closed
- Parasympathetic stimulation inhibited
EUS and pelvic diaphragm
10
Q
1 Bladder distension sensed by the
2 Send signal to sacral cord via
3 Message goes to ___ then ___
A
- stretch receptors
2 afferents (A-delta) - Pons to frontal lobe
11
Q
normal voiding: emptying phase:
Socially acceptible situation results in: 3
A
PNS stimulation, SNS is suppressed
Stimulates detrusor to contract
Pudendal nerve is inhibited external sphincter opens facilitation of voluntary urination
12
Q
Infants/Children - “reflex bladders”
1 Empty at ___ volumes
Initially no awareness or voluntary control
2 Detrusor reflex develops by ___ (90%)
3 ____% have immature or “infantile pattern” between voids
A
1 50-100cc
2 5yoa
3 10
corrects by puberty
13
Q
Adults
1. ______: minimal increase in intravesicle pressure despite filling
2 _____ occurs: voluntary relaxation of floor, followed by release of inhibition of detrusor reflex at pontine level.
A
- accomodation
2. normal voiding
14
Q
Common in elderly (bladder dysfunction) 4
A
Common: frequency, urgency, incontinence, incomplete emptying
15
Q
Name the five different classifications of neurogenic bladder
A
1 Anatomical Classification 2 Neurourologic Classification (Hald & Bradley, Bors and Comarr) 3 Functional Classification (International Continence Society, Wein) 4 Neurologic Classification (Bradley) 5 Urodynamic Classification (Lapides, Krane, Siroky)
16
Q
describe anatomical classification of neurogenic bladder
A
Supraspinal (suprapontine) lesions Suprasacral spinal lesions Infrasacral lesions Peripheral autonomic nerve lesions Muscular lesions
17
Q
describe neuro-urologic classification of neurogenic bladder
A
- uninhibited bladder
- upper motor neuron bladder
- mixed type A bladder
- mixed type B bladder
- lower motor neuron bladder
18
Q
Uninhibited bladder has lesions where?
____ is lost
_____ is presevered
A
Lesions above pontine micturition center
ex: stroke, tumor
Inhibition from cortex is lost
Detrusor/sphincter tone preserved
19
Q
in UMN bladder includes lesions:
Can have _____
Results in ____ bladder
_____ occurs
A
Lesions between pontine micturition center and sacral spinal cord (traumatic SCI, MS involving cervicothoracic cord)
Detrusor Sphincter Dyssynergia
Results in high-pressure bladder (up to 80-90cm H2O)
Bladders and sphincters considered “spastic”
Vesicoureteral reflux occurs
20
Q
What is considered “high-pressure” in high pressure bladders?
A
up to 80-90cm H2o
21
Q
Describe differences between mixed type A and B bladders. Where is lesion?
A
Mixed type A bladder: sacral cord lesion
Damaged detrusor nucleus. “detrusor areflexia”
Pudendal nucleus spared – hypertonic/spastic EUS
Low pressure; results in retention
More common
Mixed type B bladder: sacral cord lesion
Spared detrusor nucleus – spastic bladder
Pudendal nucleus damaged – flaccid EUS
Capacity/pressures low, results in incontinence
22
Q
LMN bladder lesions are located:
____ is lost
can have detrusor _____
____ remains intact
Results in ___ and ____
A
Lower motor neuron bladder
Sacral cord lesion or sacral nerve roots
Thoracic SNS outflow to lower urinary tract intact.
Detrusor areflexia – high capacity; low pressure
IUS innervation intact
Results in overflow incontinence and UTI
23
Q
Describe functional classification of neurogenic bladder:
A
- failure to store
- bladder: hyperactivity, decreased compliance
- Outlet: denervated pelvic floor, bladder neck descent, intrinsic bladder neck sphincter failure
Failure to empty
- Bladder: areflexia, hypocontractility
- outlet: DSD, nonrelaxing voluntary sphincter, mechanical obstruction
24
Q
Suprapontine/supraspinal lesions
1. examples: 7
2 Characteristics: 4
A
- TBI, stroke, brain tumor, hydrocephalus, CP, MS, parkinsons disease
- Detrusor Hyperreflexia without Detrusor sphincter dyssynergia (DSD)
Urge incontinence
Usually small/absent residual volumes
Failure to store
25
Suprasacral spinal cord lesion:
1. examples 5
2. characteristics 4
1. Myelomeningocele, MS, spinal cord tumor, transverse myelitis, traumatic SCI
2. Detrusor hyperreflexia
Detrusor sphincter dyssynergia
Urge incontinence
High PVRs
26
INfrasacral lesions
1. examples: 5
2. characteristics 3
1. Spinal tumor, sacral SCI, herniated disc, lumbar laminectomy, pelvic trauma
2 Areflexic bladder, DSD may be seen
Urinary retention, overflow incontinence
High PVRs
27
Peripheral autonomic nerve injury (bladder dysfunction)
1. Examples: 4
2. characteristics: 4
1 Example: AIDS, diabetes neuropathy, polio, GBS
2 Urinary retention, overflow incontinence
High PVR
Decreased bladder sensation
Detrusor areflexia
28
_____ is caused by Involuntary contractions of EUS during involuntary detrusor contraction
Caused by lesions:
Types? 3
Detrusor-sphincter dyssynergia
Lesions between brainstem (pons) and sacral spinal cord (sacral micturition center)
Types
1. concomitant increase in detrusor pressure and sphincter EMG activity. Peak detrusor contraction, sphincter relaxes resulting in obstructed void
2. sporadic contractions of EUS throughout detrusor contraction
3. crescendo-decrescendo pattern of contraction resulting in urethral obstruction
29
Name the incontinence:
1. Involuntary leakage from effort or exertion, or sneezing or coughing. Usually related to poor sphincter function
2. Involuntary leakage accompanied or proceeded by urgency. Usually related to detrusor overactivity
3. Associated with over-distention of the bladder, e.g. form detrusor areflexia or bladder outflow obstruction
4 Difficulty in beginning the flow of urine
Associated with prostate enlargement in men & narrowing of the urethral opening in women
1. stress incontinence
2. urge incontinence
3. overflow incontinence
4. urinary hesitancy
30
When to order Urodynamics: 7
```
Urinary incontinence
Recurrent UTIs
Urinary frequency
Large postvoid residuals (retention)
Deterioration of the upper tracts
Monitoring of voiding pressures
Evaluation and monitoring of pharmacotherapy
```
31
urodynamics is made up of what two phases?
1. filling
| 2. voiding
32
```
Filling (storage) phase
1. Bladder is filled with water
2. Evaluates: _____
3 First sensation at _____
4 Fullness at _____
5 Strong desire to void (urgency) at ____
6 Capacity ranges: _____ in adults
Should be little to no rise in pressure, no contractions
```
2. Evaluates bladder sensation, capacity, wall compliance, intravesical pressures, stability
3 First sensation at 100-200ml
4 Fullness at 300-400ml
5 Strong desire to void (urgency) at 450-500ml
6 Capacity ranges: 400-750ml in adults
Should be little to no rise in pressure, no contractions
33
```
Voiding (emptying) phase
1 Measures 3
2 Normal detrusor pressures:
- Women:
- Men:
3 Flow rate analysis: helps identify:
4 H2O cystometry with/without sphincter EMG--helps differentiate
5 Residual urine should be
```
Voiding (emptying) phase
1 Measures leak-point pressure, max viding pressure, urethral sphincter activity.
Normal detrusor pressures:
Women:
34
What are the waves on the urodynamics screen? (top to bottom)
```
bladder pressure
sphincter
EMG
abdominal pressure
flow rate
```
35
___ is the simplest method to evaluate bladder filling.
performed using _____
What we learn: 4
Limitations: 3
Bedside Cystometrogram: Simplest method to evaluate bladder filling
Performed using indwelling catheter
Water is drained by gravity into bladder
Blood pressure and volume of fluid recorded
What we learn:
Sensation of filling
Stability/contraction
Capacity
(can also be used to determine if spinal shock has ended in SCI patient)
Limitations: Foley irritation, cannot assess voiding phase.
36
goals of management of neurogenic bladder: 4
1 achieve/maintain continence avoiding psychological and physical consequences
2 Prevent development of high pressure detrusor that leads to upper tract damage
3 Minimize risk of symptomatic UTI
4 Prevent over-distension of the bladder (produced flaccid, large capacity bladder: myogenic ladder)
37
Behavioral management techniques
| 7
1 Bladder schedule – detrusor hyperactivity
Monitor fluid intakeTimed voids.
2 Reflex voiding: must have intact micturition reflex
3 Bladder stimulation: stroking & pinching peripheral skin
4 Valsalva Maneuvers
5 Crede Maneuvers Performed by attendant Mechanically pushes urine out of the bladder in pts with tetraplegia
6 Anal stretch voidingInvolves relaxing the pelvic floor by stretching the anal sphincter & then emptying by the valsalva maneuvers
7 Pelvic floor exercises: stress incontinence
38
What are the 5 ways to collect urine?
1 External condom catheter: incontinence
Skin breakdown
2 Clean intermittent cath:
if PVR> 100 cc
Retention > 400 cc, q4-q6 hrs
Allows for independence
3 Indwelling catheter (IC): retention
Weigh risk vs. benefit
Non compliance with intermittent cath
Refuses intermittent cath
4 Suprapubic catheter: long term use, difficult IC, tetra
5 Adult diapers: incontinence with dementia
39
____ are first line for detrusor hyperactivity.
MOA:
Side effects:
Anticholinergics
(First line for Detrusor hyperactivity)
MOA: reduces reflex (involuntary) detrusor activity
Side effects: dry mouth, HA, dyspepsia, constipation, and dry eyes (based on muscarinic effects/selectivity)
40
nonseletive anticholinergics bind more M-receptors, giving more side effects.
Name the effects based on these specific receptors:
M1:
M2:
M3:
Nonselective bind more M-receptors; more side effects
M1: memory/cognitive impairment
M2: Prolonged QT interval
M3: blurry vision, xeorstomia, constipation
Selective agents (M2, M3) – more tolerable
Sustained released formulations also help
41
Name the non-selective anticholinergics used for bladder treatment
```
1 Oxybutinin (Ditropan) 1st drug approved
(5mg BID-TID, XL 50-30mg QD; transdermal 2x/wk)
```
2 Tolterodine (Detrol) Less xerostomia/ cognitive effects (IR 1-2mg BID, XL 2-4mg QD)
3 Trospium (Sanctura) IR & XL - Does not cross blood brain barrier Less drug interactions; better for hepatic impairment
4 Propantheline (Pro-Banthine)
5 Hyoscyamine (Daturine)
42
Which anticholinergic drug was first approved for neurogenic bladder management?
Which has less xerostomia/cognitive effects?
Which does not cross the blood brain barrier
1. oxybutinin (ditropan)
2. Tolterodine (Detrol)
3. Trospium (Sanctura)
43
Name the 3 selective anticholinergics
1 Solifenacin (Vesicare) More selective for M3
2 Fesoterodine (Toviaz) Competitive muscarinic antagonist that does not cause CV or cognitive effects. Less drug interaction; better in hepatic impairment
3 Darifenacin (Enablex) Does not need adjusting for renal impairment Dose: 7.5-15mg QD
44
Which selective anticholinergic does not cause CV or cognitive effects? better for hepatic patients
Which does not need adjusting for renal involvement?
1 Fesoterodine (Toviaz) Competitive muscarinic antagonist that does not cause CV or cognitive effects. Less drug interaction; better in hepatic impairment
2 Darifenacin (Enablex) Does not need adjusting for renal impairment Dose: 7.5-15mg QD
45
Name the three TCAs used in neurogenic bladder:
1 Imipramine (Tofranil) – reduces detrusor tone (Anticholinergic), increases IUS (A1 adrenergic agonist), reduce urgency
Pros: local anesthestic on bladder
Side effects: sedation, orthostasis, CV conduction block
Caution: pregnancy, elderly
```
2 Amitriptyline (Elavil) – less anticholinergic effect than Imipramine. Same effects
Strong sedation properties; useful in neuropathic pain & insomnia.
```
3 Doxepin (Sinequan)
46
Cholinergic agonists are treatment of choice in which patients with neurogenic bladder?
example:
hyporeflexia, areflexia
Urecholine (Bethanechol)
No nicotinic effects
Best in Mixed type A or LMN lesions
Taken 1 hour AC&HS + behavior modifications
Side effects: hypotension, bradycardia, bronchoconstriction, N/V, abd cramping, diarrhea.
Caution: COPD, asthma, hyperthyroidism, PUD, CAD, PD
Take on empty stomach to avoid n/v
47
```
_____ is the treatment of choice in spastic IUS in DSD and UMN disorders.
Cause ____ reduction of norepi
Enhance _____
Seldom used as ______
Side effects:
```
Example drugs: 2
Alpha-2 Adrenergic Agonists - Treatment of choice in spastic IUS in DSD and UMN disorders
Cause pre-synaptic reduction of norepi
Enhance bladder emptying by reducing bladder neck tone
Seldomly used as monotherapy
Side effects: fatigue, dizziness, dry mouth, constipation
Clonidine (oral, transdermal), Tizanidine (oral)
Also treat pain, skeletal muscle tone
48
1 ______ Produce peripheral postsynaptic blockade of Alpha-adrenergic receptors in bladder neck and proximal urethra
2. Reduces ____ incontinence
Reduces ____
3 Examples: 5
```
1. Alpha-1 Adrenergic Antagonists
2 urinary outflow incontinence, BP
3. Phenoxybenzamine (Dibenzyline)
Terazosin (Hytrin)
Tamsulosin (Flomax)
Alfuzosin (Uroxatral)
Doxazosin (Cardura)
```
49
Name the drug approved for detruosor hyperactivity that affects Beta-3 adrenergic agonists
dose?
side effects?
Beta-3 Adrenergic Agonists
Mirabegron (Myrbetriq)
Approved for detrusor hyperactivity
IR 25 – 50mg daily.
Side effects: HA, nausea, Hypertension, diarrhea, constipation, dizziness, tachycardia/Afib
50
"other" neurogenic bladder drug treatment:
1. BDZ leaves a _____ effect and targets ____ thereby reducing
2. Baclofen leaves a ____ effect
3. Dantrium affects ____ and targets:
4. Botox A targets ____ and treats ____
5. Opioids: interfere with ____. ____ helps this.
_____ inhibits micturition reflex. helps in neurogenic incontinence
1. GABA-A, EUS (UMN or Mixed A) reduing bladder outflow resistance
2. GABA-B
3. Ca Channel blocker - EUS;DSD
4. NMJ presynaptic vesicle, blocking signal; treats detrusor overactivity, incontinence
5. voiding, naloxone
nociceptin (orphanin FQ)
51
Role in neurogenic bladder:
1. Vanilloids:
2. Nerve Growth Factor:
3. Nitrous oxide agonists
4. 5-alpha-reductase inhibitors:
1 Vanilloids
Capsaicin/resiniferatoxin (RTX) reduce overactivity
Selectively desensitize C-fiber sensory nerves
TR1 receptors
2 Nerve Growth Factor
Elevated in detrusor overactivity.
Induces changes in excitability of bladder afferents
3 Nitrous Oxide Agonists
NO-synthase staining neurons present in sphincters
Activation results in reduced urethral pressure
PO nitrates could treat DSD
4 5-alpha-reductase inhibitor
Finasteride (Proscar)
BPH/Outlet obstruction
52
Name the procedures used to enhance detrusor storage: 3
1. neuromodulation for neurogenic detrusor overactivity
2. augmentation cystoplasty
3. ureterocystoplasty
53
what surgeries can be performed to enhance detrusor emptying5`
1. urinary diversion
2. sphincerotomy
3. urethral stents, balloon dilatation
4. artificial urinary sphincter
5. sling procedures
54
Neuromodulation for Neurogenic detrusor overactivity
1 Unilateral or bilateral_____ stimulation technology
2 ___ % success rate
3 ____% complication rate; lead migration, pain at site of implant
4 Efficacy may disappear after ___
5 Combined neuromodulation & ____ to reduce detrusor pressure
UMN bladder; Most often for female patients
Erectile dysfunction
Chronic Pudendal N stimulation
```
1 sacral nerve root
2. ___ success rate
3. ____ complication rate
4. 1-4 years
5 dorsal rhizotomy
```
55
Augmentation Cystoplasty
1 Enterocystoplasty - _____ have been used
2 ___ is procedure of choice (low pressure, high capacity)
3 Success rate ____%
4 Alternative: 2
5 Complications: 4
6 Ureterocystoplasty: ______ utilized (megaureter)
7 Experimental:
1 Gastric, small and large intestine
2 Ileocystoplasty
3 90
4 Demucosalized enterocystoplasty, autoaugmentation
5 bladder perforation, stone formation, neoplasm, Fibrosis
6 Dilated portion of damaged upper tract
7. Tissue engineering using biodegradable biomatrices
56
1 Urinary Diversion Used in
2 two examples?
Sphincterotomy
3 Indications: 4
4 Reduces , reflex voiding occurs
Pros: reduce risk of AD, fewer UTIs
Cons: incontinence
Reserved for quadriplegic males
Complications: hemorrhage, ED, stricture
```
1 LMN bladder, Mixed Type A (incomplete emptying)
2 Mitrofanoff (appendicovesicostomy)
Monti tube (ileovesicostomy)
```
Sphincterotomy
3 DSD w/ hydronephrosis, reflux, AD, recurrent UTI\
4 outlet obstruction
57
Urethral stents, balloon dilatation
- Complications: 2
- Relative CI: 1
Artificial Urinary Sphincter
- Gold Standard to treat _____
- Implantable artificial device
- Must have _____, _____ to operate pump/valve mechanisms
- Relative CI: 3
- Cons: 2
Sling procedures
______ sling procedure
Can be used in conjuction with augmentation
Urethral stents, balloon dilatation
Complications: encrustation, migration
Relative CI: recurrent UTIs
Artificial Urinary Sphincter
Gold Standard to treat incontinence
Implantable artificial device
Must have learning capacity, hand strength/dexterity to operate pump/valve mechanisms
Relative CI: recurrent bladder stones, >grade 2 reflux, bladder tumors
Cons: repeat procedures, implant lasts 10 years
Sling procedures
Bulbourethral sling procedure
Can be used in conjuction with augmentation
58
two future surgical developments for neurogenic bladder?
```
1 Lumbar to Sacral Nerve Rerouting
Skin-central nervous system bladder reflex arc via L5 motor to S3 nerve.
Trialed in Spina Bifida patients
Success rate 87%
Complications: peripheral n injury
```
2 Spinal Cord Regeneration
Transplantation of:
Fibroblasts genetically modified to express brain-derived neurotrophic factor (BDNF)
Neurotrophin 3 (NT-3), NT-secreting schwann cells,
Olfactory ensheathing cells (OEC),
Pharmacological blockade of epidermal growth factors (EGF) on astrocytes mitigates fibrosis
Intrathecal Chondroitinase ABC
59
peds considerations for treatment of neurogenic bladder? 2
1 Biofeedback
Involves listening to sphincter EMG patterns during voiding
Seen with incomplete emptying and DSD caused by non-neurogenic learned disorder
2 Surgical: anterior fascial sling, artificial urinary sphincter
Severe incontinence
90% long-term success rate
60
Spinal Shock
- In suprasacral injuries, no ____
- Can last from _____ post-injury
- Treat initially with indwelling cathter
- d/c and start intermittent caths if: 3
Once resolved
______ begin
Men: Perform IC or reflexively void
Women: No “good” option
Spinal Shock
In suprasacral injuries, no bladder contraction
Can last from 2 weeks to 6 months post injury
Treat initially with indwelling catheter
d/c and start intermittent caths if:
No longer receiving IVFs
Fluid output
61
complications of urinary retention: 6
1 Supplies urine culture medium for bacteria: UTI
2 Vesicoureteric reflex: Pyelonephritis
3 Bladder stones
4 Hydronephrosis
5 Hypertrophy of the detrusor muscle
6 Diverticula (the formation of pouches) in the bladder wall (which can lead to stones and infection)
62
3 criteria for "true" uti
Bacteriuria
Pyuria (Gram – vs Gram +)
New onset of symptoms
63
Why is constant high pressure bladder bad?
Ureters can’t drain into high-pressure bladder, so hydronephrosis develops
May damage bladder
May induce vesicoureteral reflux
64
______ has a Higher risk seen with SCI patients who require indwelling catheters or bladder augmentations
bladder cancer
65
possible causes of bladder cancer in SCI patients
Chronic irritations from UTIs/catheter
Stasis of urine
Bladder stones
Exposure of bowel mucosa to urine following augmentation or diversion.
66
type of cancer in SCI bladder cancer
Squamous cell carcinoma
IAP part II
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