JC75 (Surgery) - Erectile dysfunction Flashcards
List the layers of the penis from outer to inner
- Skin
- Superficial Dartos fascia + superficial dorsal vein
- Deep Buck’s fascia with deep dorsal vein and dorsal artery
- Tunica albuginea: outer longitudinal and inner circular
- Subtunical space
- Corpus spongiosum and corpa cavernosa
- Cavernosal arteries in corpa cavernosa, penile urethra in corpus spongiosum
Arterial supply of penis
Internal pudendal artery»_space; dorsal and circumflex artery»_space; Cavernous and Bulbourethral artery
Ligaments attached to penis
Fundiform ligament and suspensory ligament
Ligaments attached to penis
Fundiform ligament and suspensory ligament
Venous drainage of penis
Dorsal penis:
Subtunical plexus»emissary veins»Deep dorsal vein»Superficial dorsal vein»branch off:
- Saphenous vein»External iliac vein
- Dorsal venous complex»Peri-prostatic plexus»Internal iliac vein
Ventral penis:
Bulbourethral vein»circumflex veins to dorsal penis OR cavernous vein»Crural vein»Internal pudendal vein»Internal iliac vein
7 phases of penile erection and detumescence
Which phase is controlled by pudendal nerve and cavernous nerve?
Flaccid > Latent > Tumescence > Full erection > Rigid erection > Initial detumescence > slow detumescence
Phase 4 - Rigid erection, controlled by cavernous nerve and pudendal nerve
Physiology of penis blood flow in Flaccid/ Detumescence phase
Tonically contracted:
Arteriole wall smooth muscle + Smooth muscle separating sinusoids inside corporeal bodies
> > Minimal amount of arteriolar blood flow into corporeal bodies
Subtunical venous plexus and emissary vein drainage is normal
Low arterial inflow but good venous outflow = low blood stasis = flaccid
Physiology of penis blood flow in tumescence/ erect state
Smooth muscles Relaxed:
Arteriole wall smooth muscle and smooth muscle in-between sinusoids
> > Rapid arterial inflow into sinusoids
Sinusoid expansion/ Engorgement compresses on Subtunical plexus and tunica with emissary veins
Blood trapped inside corporeal bodies
Good arterial inflow with poor venous drainage = Blood stasis = erection
Innervation of penis
Sympathetic, parasympathetic, somatic
Sympathetic: T11-L2»_space; pelvic plexus
Parasympathetic: S2-S4»_space; pelvic plexus
Pelvic plexus»_space; cavernous nerve (pass through postero-lateral aspect of prostate, commonly damaged in surgery)
Somatic: Onuf’s nucleus at S2-S4»_space; dorsal nerve of penis > Ischiocavernosus (erection) and bulbocavernosus (ejaculation)
Effect of sympathetic firing on penile erection
Sympathetic firing (Norepinephrine)
- Increase intracellular calcium»_space; activate muscle contraction in arterioles and walls of sinusoids»_space; Decrease arterial blood inflow»_space; Decrease rigidity of corporeal tissue»_space; Detumescence
Effect of parasympathetic firing on penile erection
Parasympathetic (Ach)
- Inhibits pre-synaptic sympathetic firing (blocks detumescence)
- Stimulates nitric oxide release from endothelium* most important*
- Influx of Potassium into neuron, blocking Ca influx and sequestration of Ca into ER
> > activate cAMP pathway by PGE1 and cGMP pathway by NO
> > arteriole and sinusoid wall relaxation/ vasodilation»_space; Increase arterial inflow into corporeal tissue»_space; Increase corporeal bodies engorgement and compression on Subtunical plexus and emissary veins »_space; Tumescence
Molecular pathways for penile arteriole smooth muscle relaxation
- cAMP pathway activated by PGE1:
PGE1 activates adenylyl cyclase»_space; increase conversion of ATP to cAMP»_space; cAMP activate PKA
cAMP is degraded by phosphodiesterase-2,3,4 - cGMP pathway activated by NO:
Activates guanylyl cyclase»_space; Increase conversion of GTP to cGMP»_space; activate PKG
cGMP is degraded by phosphodiesterase 5
Which molecular target is most important in penile arteriole smooth muscle relaxation?
Phosphodiesterase 5 (PDE-5)
Most important in termination of cGMP- induced smooth muscle relaxation
Blocking PDE-5 = sustain penile arteriole relaxation = sustain erection
Role of Nitric oxide in penile erection
Produced by endothelial cells via NO synthetase
nNOS (nervous tissue) - initiate erection
eNOS (endothelium) - sustain erection
iNOS (all other cell types)
Release of NO from nerves = Non-adrenergic/ Non-cholinergic (NANC) neurotransmission
Outline the stimuli, neural pathway, vascular changes in penile erection
Stimuli:
- Psychogenic, Tactile/ reflexogenic, Nocturnal (REM sleep)
- Causes cavernous nerve to generate nNOS
Parasympathetic firing also generate eNOS
NO stimulate cGMP pathway»_space; arteriole and intersinusoidal smooth muscles RELAX»_space; arterial inflow into corporeal bodies»_space; Blood engorgement and trapping in corporeal bodies
Ischiocavernosus muscle contraction compress base of engorged corpora cavernosa
List disease entities under male sexual dysfunction
Erectile dysfunction
Ejaculatory dysfunction:
- Premature ejaculation
- Anejaculation
- Retrograde ejaculation
Reduced libido
Erectile dysfunction
Clinical definition
Persistent inability to achieve/ maintain erection
Sufficient to permit satisfactory sexual performance
Not associated with anxiety, alcohol or fatigue
Diseases associated with erectile dysfunction
DM Dyslipidemia Obesity Metabolic syndrome Smoking Cardiovascular disease Depression BPH
ED is a barometer of cardiovascular health, strong association with cardiovascular disease mortality
Classify the causes of erectile dysfunction
** Multi-factorial in etiology in reality **
- Organic:
- Vasculogenic: arterial or venogenic
- Neurogenic
- Endocrine - Psychogenic
- Generalized
- Situational: partner, performance, distress related… - Drug-induced
Drugs associated with erectile dysfunction
Antiandrogens - 5-ARI, LHRHa
Antihypertensives - Thiazides, B-blockers
Antidepressants - SSRI, TCA
Antipsychotic - Neuroleptics
Recreational - Heroin, marijuana, methadone
History taking for erectile dysfunction
- Aims
Aims:
- Find underlying causes
- Find contra-indications for Tx
- Find asso. medical illness
- Readiness for invasive treatment
Outline History taking for erectile dysfunction
- Sexual history:
- Characterize ED
- Severity
- Libido, ejaculation, orgasmic responses
- Any morning erection - Medical history: CVD, Neurological, Urological
- Social: smoking, drinking
- Drug history: causative CVD drugs, nitrates, recreational/ hardcore drugs
Compare psychogenic vs organic caused Erectile dysfunction
Psychogenic:
- Sudden onset
- Complete/ immediate loss of erection
- Situational dysfunction
- Waking erections present
Organic:
- Gradual onset
- Incremental progression
- Global dysfunction
- Waking erections poor/ absent
Outline P/E for erectile dysfunction
General:
- Stature- global
- Gynecomastia - endocrine
- Lower limb neurological exam, gait - neurological
Abdomen:
- Secondary sexual characteristic
- Femoral pulses and distal limb pulses - CVD
External genitalia:
- Phallus deformity
- Testes position, Genital/ perineal sensation
- Bulbocavernosus reflex
Outline a subjective clinical assessment tool for erectile dysfunction
International Index of Erectile Function (IIEF-5) Questionnaire
5 questions: e.g. rate confidence about getting an erection, how difficult to maintain erection to end of intercourse …etc
No ED: 22-25 Mild ED: 17-21 Mild to moderate ED: 12-16 Moderate ED: 8-11 Severe ED: 5-7
First-line investigations for erectile dysfunction
Medical:
- Fasting blood sugar
- Lipid profile
- Cardiovascular disease screen: CHD
Sexual characteristics:
- Testosterone/ LH levels
Outline flowchart for ED risk stratification
Indications for specialized testing of ED
Primary ED: no erection ever, endocrine cause likely
Young ED with pelvic/ perineal trauma
Complex psychiatric/ psychosexual disorder
Complex endocrinopathies
Medico-legal/ rape
Treatment options for ED
Lifestyle, first-, second-, third- line
step-wise approach
Life-style:
- Stop smoking, better DM and CVD control, adjust inciting drug
First-line:
- Oral PDE-5 inhibitor (Sildenafil/ Viagra)
- Topical/ Intraurethral alprostadil
- Vacuum constriction device
- Low intensity SWL
Second line:
- Intracavernosal injection s
Third line:
- Penile prosthesis
PDE-5 inhibitor
- MoA
- Examples
- Effectiveness
MoA:
Inhibit PDE-5 from degrading cGMP pathway»_space; Maintain penile arteriole and intersinusoidal smooth muscle relaxation
Examples: Sildenafil - Viagra Tadalafil - Cialis Vardenafil - Levitra Avanafil - Spedra
70% successful intercourse
Compare Sildenafil, Vardenafil and Tadalafil
Onset Duration of effectiveness Starting dose Lead-time before sex Max dosing frequency
PDE-5 inhibitors
Side effectives
C/I
Headache Flushing Nasal congestion Abnormal vision (blue/ green vision) - Sildenafil, vardenafil only Back pain/ Myalgia - Tadalafil only
C/I:
Any NITRATE USE»_space; cGMP accumulation»_space; hypotension»_space; death
MI, Stroke or arrhythmia in the last 6 months
Heart failure, CAD, Unstable angina
Resting hypotension under 90/50
Hereditary degenerative retinal disorders
Severe hepatic impairment Child-Pugh-C
end-stage CKD with dialysis
PDE-5 inhibitor
Timing and daily dosage
Timing: 1 hour before sexual intercourse
Daily dosage: 1 dose maximum per day
Intracavernosal injection
- Drug of choice
- MoA
- Effectiveness
- S/E
Alprostadil injection (Synthetic Prostaglandin E1)
MoA: smooth muscle relaxation via cAMP pathway, independent of NO release
Effectiveness: 80%, even for DM and post-RP
S/E: Painful erection Prolonged erection Priapism Penile fibrosis
Vacuum constriction device
Disadvantages
C/I
Unnatural semi-erect penis
Inability to ejaculate
Bruising and numbness
C/I: anticoagulants
Penile prosthesis
- Indications
- Main types
- Advantage and disadvantage
- Complications
Indications:
ED refractory to all other treatment
Patient preference for permanent solution
Types:
Malleables (Semi-rigid rods)
Inflatables
Adv: High success and satisfactory rates
Disadv: Cost, irreversible damage to corporeal bodies
Complications: infection, erosion, mechanical failure
