Voiding Dysfunction Flashcards
Avg. Capacity of Adult Bladder
- Male: 400-500cc
- Female: 350-450cc
- Bladder lies behind the symphysis unless overdistended
Bladder microstructure layers
- Urothelium
- Lamina propria
- Muscularis propria
- Serosa
Urothelium
- 4-7 layers thick, attenuated to 2-3 when fully distended
- 3 distinct layers
*basal- small cuboidal progenitor cell from which other layers arise
*intermediate- polygonal structure w/ ability to stretch and flatten
*superficial “umbrella” cell- release multiple chemical mediators which contribute to micturition signaling pathway
Lamina propria
- Connective tissue bed supporting overlying urothelium
*seperated by basement membrane
- Rich in capillaries, lymphatics and nerve endings
- Contains elastin fibers, and thin poorly differentiated layer of smooth muscle fibers, muscularis mucosae
*distinct from muscularis propria
*variable position within urothelium
Interstitial cells of cajal
- Signaling cells within lamina propria include interstitial cells of cajal (ICC)
- ICC cells form a functional communication network thru gap junctions which facilitate communication b/w the bladder and afferent nerve pathways
- ICC cells may also play a role in detrusor function
- Neurologic injury is assoc. w/ changes in the urothelium which ultimately contributes to neurogenic voiding dysfunction
Muscularis propria
- 3 layers
*inner and outer longitudinal
*intermediate circular
- Randomly oriented smooth muscle which provides ability to maintain continuous tension at diff. muscle lengths
*an extracellular matrix (ECM) surrounds the muscle and acts as scaffold
*ECM is constantly remodeled containing collagen (type 1 and 3), elastic fibers, adhesive proteins, glycans and glycoproteins
*strain from neurologic injury may result in stiffening of the matrix, increasing type 3 collagen and leading to reduced detrusor capacity which ultimately contributes to neurogenic voiding dysfunction
Bladder storage physiology
- Requires stimulation of the sympathetic nervous system via adrenergic receptors
- Primary subtype alpha1 is responsible for contraction to the bladder outlet to prevent incontinence
- Smooth muscle relaxation of detrusor mediated by beta3 receptors
Bladder emptying physiology
- Facilitated by parasympathetic stimulation of muscarinic receptors
- M3 is primarily responsible for detrusor contraction
- Medications bind to M2 and M3 recetpros to reduce detrusor contractility
Alpha -1a adrenergic receptors locations
- Smooth muscle of prostate
- Bladder neck
- Ureter
- Seminal vesicles
- Vas deferens
Alpha-1b adrenergic receptors locations
- Blood vessels
Alpha-1d adrenergic receptors locations
- Nasal passages
- Bladder
Alpha blockers 1st generation
- Terazosin, doxazosin, alfuzosin
- Non-selective alpha blockers
- Equal long term efficacy to 2nd gen agents
- Traditionally used by primary care physicians in dual therapy to treat concominant hypertension
Alpha blockers 2nd generation
- Tamsulosin, silodosin
- High affinity for alpha-1A receptors
Alpha blockers side effects
- Dizziness
- Fatigued
- Nasal congestion
- Orthostatic hypotension
- Syncope
- Retrograde ejaculation
- Intraoperative floppy eye syndrome
Antimuscarinic drugs
- Oxybutinin
- Tolteridone
- Trospium
Antimuscarinic drugs pharmacology
- Used antagonize miuscarinic receptors in the bladder
- Used for over active bladder (OAB)
- Off label use for bladder spasm
Antimuscarinics side effects
- Urinary retention
- Dry mouth
- Constipation
- Altered mental status
Beta3- adrenoreceptor agonists
- Mirabegron
Beta3-adrenoreceptor agonist pharmacology
- Stimulates beta3-adrenoreceptors in detrusor muscle to facilitate storage
- Used for OAB and lower urinary tract symptoms (LUTS) related to BPH
Beta3- adrenoreceptor agonist side effects
- Elevated BP
- Retention
*UTI
- Tachycardia
- Dry mouth
Normal bladder voiding mechanism relies on
- External sphincter relaxation
- Detrusor muscle contraction
Key CNS structure in micturition
- Periqueductal grey (PAG)
*midbrain area known for its role in nociception and emotional responses
- Pontine micturition center (PMC)
*aka Barringtons nucleus: located in dorsomedial pontine tegmentum
- Onufrowicz’s nucleus
*small motor neuron group in ventral horn of sacral spinal cord (S2-4)
Basic voiding mechanics
- Distention of the bladder sends signals to periaqueductal grey and pontine micturition center (PMC)
- PMC communicates w/ periaqueductal grey
- PMC inhibits spinal guarding (sympathetic and somatic outflow to urethra)
- Synergic micturition via long descending pontinespinal pathway
- Acetylcholine binds to M2 and M3 receptors in detrusor
- Sympathetic/somatic inhibit voding
*voluntary relaxation of sphincter inhibits this system
Supraspinal vesicovesical reflex
- Brain is responsible for inhibtion of voiding at all times
- Bladder fills up sends a signal to the spine up to the pontine micturition center (PMC), cross talk b/w the PMC and the periaqueductal grey results in a signal that comes down thru the spine thru Onuf’s nucleus to the bladder and you get voiding
- Parasympathetic goes up and sympathetic goes down and you can pee
