1. PHYSIOLOGY OF PENILE ERECTION
&
PATHOPHYSIOLOGY
OF
ERECTILE DYSFUNCTION
Dr. V.Priyadarshi

2. Physiology of Penile Erection

3. An Erection Requires a Coordinated
Interaction of Multiple Organ Systems
 Psychological
 Endocrine
 Neurologic
 Vascular

4. Physiology of penile erection
Sexual stimulation Nitrix oxide synthesized in nerve
and vascular tissue of penis
Nitrix oxide activates
GTP  cGMP guanylate cyclase
cGMP relaxes smooth muscles of Vasocongestion of
corpus cavernosum/penile arterioles penile tissues
17

5. Three types of erections
1. Genital stimulated (contact or reflexogenic)
- induced by tactile stimulation of the genital area.
- can be preserved in upper spinal cord lesions.
- usually short in duration and poorly controlled .
2.central-stimulated (noncontact or psychogenic)
- more complex,
- resulting from memory, fantasy, visual, or auditory stimuli.
3. central-originated (nocturnal)
- can occur spontaneously without stimulation or during
sleep
- most sleep erections occur during REM sleep.
- occurs due to differential activation of cholinergic neurons
at RAS while deactivation of adrenergic and serotonergic neurons
during REM sleep.
.

6. Internal structure of the penis: top view
(internal, in
(between glans and the body) pelvic cavity)
Male Sexual Anatomy (cont.)
(engorge with blood
(head of the (expands during arousal)
penis; lots of to form
nerve endings) the glans)
Fig 5.1a Interior structure of the penis: (a) view from above.

7. cross-section of the penis
 Tube within tube pattern.
 Three corpora
 Thick bilayered T.albuginia with
elastic fibers which can expand
and strech.
 Incomplete outer longitudinal
layer b/w 5-7 0’clock.
 Spongiosa lacking outer long.
Layer of T. albuginea.
 Intracavernosal pillars and
incomplete incavernosal septum.
 suspended to lower ischiopubic
ramii through fundiform and
suspensory ligaments.

8. Blood supply of penis

9. Hemodynamics of Erection
 In the flaccid state, the arteries, arterioles, and sinusoids are contracted.
The intersinusoidal and subtunical venous plexuses are wide open, with free
flow through the emissary veins. The pO2 is venous(35 mm Hg).
 In the erect state, the muscles of the sinusoidal wall and the arterioles relax,
allowing maximal flow to the compliant sinusoidal spaces.
 Most of the venules are compressed b/w expanding sinusoids. Larger
venules of sub tunicial plexus are sandwiched b/w the distended sinusoids
and the t.albuginea that effectively reduces the venous capacity to a
minimum. The pO2 here is arterial(> 90 mm Hg) and ICP >100mmHg.

10. How blood inflow helps maintain
erection
 Inside the penis: like a tube within a tube
 When the inner tube fills with blood and expands,
it fills the space between the tubes and blocks the
outflow of blood, helping to maintain erection.

11. Phases of the Erection Process
(o) Flaccid phase
 Minimal arterial and venous flow; blood gas values equal
those of venous blood.
(1) Latent (filling) phase
 Increased flow in the internal pudendal artery during both
systolic and diastolic phases. Decreased pressure in the
internal pudendal artery; unchanged intracavernous
pressure. Some elongation of the penis.
(2) Tumescent phase
 Rising intracavernous pressure until full erection is achieved.
 arterial flow rate decreases as the pressure rises.
 When intracavernous pressure rises above diastolic pressure,
flow occurs only in the systolic phases.

12. Phases of the Erection Process
(3) Full erection phase
 Intracavernous pressure rises to as much as 80–90% of the systolic pressure.
 Pressure in the artery increases but remains slightly below systemic pressure.
 Arterial flow is much less than in the initial filling phase but is still higher than
flaccid phase.
 The venous channels are mostly compressed.
 Blood gas values approach those of arterial blood.
(4) Skeletal or rigid erection phase
 As a result of contraction of the ischiocavernous muscle,
 the intracavernous pressure rises well above the systolic pressure, resulting in
rigid erection.
 almost no blood flows through the cavernous artery.
(5) Initial detumescent phase
 After ejaculation or cessation of erotic stimuli, sympathetic discharge resumes,
 contraction of the smooth muscles around the sinusoids and arterioles.
(5) Slow detumescent phase – slow opening of venous channels.
(6) Fast detumescent phase
 Expelulsion of a large portion of blood from the sinusoidal and diminition of the
arterial flow to flaccid leve. The penis returnsto its flaccid length and girth

13. Neurophysiology of Erection

14. Neurophysiology of Erection
Peripheral and spinal
 At glans penis, high density free nerve endings and
receptors.
 Dorsal nerve of penis carries somatosensory fibers.
 Sympathetic innervation from T10-T12 segments.
causes detumescence.
 Parasympathetic supply through cavernous nerve from
pelvic plexus carrying S2-4segments.induces erection.
 Pudendal nerve from Onuf’s nucleus(S2-4) is
somatomotor, supplying muscles.
 Contraction of the ischiocavernosus muscles produces
the rigid-erection phase. Rhythmic contraction of the
bulbocavernosus muscle helps in ejaculation.

15. Neurophysiology of Erection contd .
Supraspinal centers
 Medial Pre Optic Area (MPOA) and paraventricular nucleus
(PVN) of the hypothalamus and hippocampus are important
integration centers for sexual function and penile erection
( Sachs and Meisel, 1988 ; Marson et al, 1993 )
 Medial preoptic area (MPOA) recognizes a sexual partner
and integrate hormonal and sensory cues.
 Efferent pathways from the MPOA passes through the
medial forebrain bundle and the midbrain tegmental region.
Pathologic processes in these regions, such as PD or CVA,
are often associated with ED.
 Paraventricular nucleus (PVN) facilitates penile erection
through oxytocin neurons to spinal sympathetic efferents –
Psychogenic erection that persist even in lumbar and
sacral cord injuries.

16. Spinal Reflexes Involved in Stimulation of Penile
Dorsal Nerve
Stimulation Spinal Center Efferent Effect
Noxious, abrupt Sacral motor Pudendal nerve Bulbocavernous
stimulation neurons (motor) reflex
Low-intensity Sacral 1. Pelvic nerves 1.Closure of
continuous (e.g., parasympathetic bladder neck and
vibratory, manual) neurons and Bladder inhibition
interneurons 2. Cavernous 2. Penile erection
nerve
High-intensity Sacral motor and Pudendal, pelvic, Ejaculation
continuous parasympathetic and cavernous
Thoracolumbar nerves
sympathetic
neurons

17. Neurotransmitte
rs

18. Neurotransmitters
Peripheral Neurotransmitters
 Adrenergic neurotransmission, and endothelium-
derived contracting factors such as angiotensin II,
PGF2α, and endothelins maintain the flaccid state.
 NO released from nonadrenergic, noncholinergic
neurotransmission and from the endothelium is the
principal neurotransmitter mediating penile erection.
NO increases the production of cGMP, which in turn
relaxes the cavernous smooth muscle.
 Detumescence after erection may be a result of
cessation of NO release, the breakdown of cyclic
guanosine monophosphate (cGMP) by
phosphodiesterases, or sympathetic discharge during
ejaculation.

19. Neurotransmitters
 Central Neurotransmitters
 Dopaminergic and adrenergic receptors promote sexual
function. (Apomorphine / Yohimbine)
 Serotonin inhibit sexual drive. (SRI /Buspirone)
 Low levels of DA stimulation causes erection (D1) while higher
levels or prolonged stimulation produces seminal emission
( D2 ).Act through Oxytocin release from PVA.
 Prolactin suppress sexual function through inhibition of
dopaminergic activity in the MPOA and decreased testosterone.
has a direct contractile effect on the cavernous smooth muscle.
 GABA, NO, Opioids and melanocortins are other modulators.

20. Physiology of
Smooth Muscle Relaxation

21. Physiology of
Smooth Muscle Relaxation
▪ Relaxation of the cavernous smooth muscle is the key to penile erection.
▪ Low cytosolic calcium favors smooth muscle relaxation.
▪ Nitric oxide released by nNOS contained in the terminals of the
cavernous nerve initiates the erection process, and nitric oxide released
from eNOS in the endothelium helps maintain erection.
▪ Upon entering the smooth muscle cells, NO stimulates the production of
cGMP.
 PGE1and PGE2 activate adenyl cyclase to produce cAMP.
▪ Cyclic GMP and AMP activate protein kinases A & G , which in turn
opens potassium channels and closes calcium channels and
sequestration of intracellular Ca by EPR.
 The resultant fall in intracellular calcium leads to smooth muscle
relaxation.
▪ The smooth muscle regains its tone when cGMP and cAMP are
degraded by phosphodiesterase and it leads to detumesence.
 PDE5 is the principle phosphodiesterase that is inhibited by Sildenafil.
Papaverine is a nonspecific phosphodiesterase inhibitor.

23. Ejaculation
 Ejaculation: the process by which semen is expelled
through the penis outside the body.
 Ejaculation is a separate process from orgasm, and
the two may not always occur simultaneously.
 It is possible for men to experience multiple orgasms w/o
ejaculation.
 2 phases (see next slides for details):
1) Emission phase: semen collects in the urethral bulb
 This stage is usually sensed by the man as the
“point of no return”
2) Expulsion phase: semen is expelled

24. Emission phase of ejaculation (phase 1)
 Contractions in the prostate, seminal vesicles, and vas
deferens force secretions into urethral bulb.
 Both the internal and external urethral sphincters close,
trapping semen in the urethral bulb
(like a balloon)

25. Expulsion phase of ejaculation (phase 2)
 Collected semen is expelled out of the body by rhythmic
contractions of muscles surrounding the urethral bulb and also
on the urethra.
 External urethral sphincter relaxes to allow semen out; internal
urethral sphincter stays contracted to prevent the escape of
urine.

26. Erectile
Dysfunction

27. Definitions
Erectile dysfunction is defined as the
“Inability to achieve or maintain an erection
sufficient for satisfactory sexual performance.”
-The National Institutes of Health (NIH) Consensus Development
Conference on Impotence(December 7-9, 1992)

28. ED vs Impotence
“ED is the more precise term, especially
given the fact that sexual desire and the
ability to have an orgasm and ejaculate may
well be intact despite the inability to achieve
or maintain an erection.”
- American Urological Association Education and Research

29. Epidemiology

30. Incidence and prevalance
 Incidence of 25 to 30 per 1000 man-years
-Moreira et al, 2003 ; Schouten et al, 2005
 Age dependent
 2%men at age <40 years
 25% men age 65
 75% men >75 years
-Kinsey et al ,1948
 Not a necessary occurrence of the aging process
 Rising trend of prevalance of ED
-international studies reported between 1993 and 2003

31. Massachusetts Male Aging Study (MMAS)
 Prevalence rates of ED between the ages of 40 and
70 years, the probability of complete ED increased
from 5.1% to 15%, moderate dysfunction increased
from 17% to 34%, and mild dysfunction remained
constant at about 17%.
 Crude incidence rate of impotence in white men in
the United States was 25.9 cases per 1000 man-
years.
 ED was higher for men with diabetes mellitus (50.7
cases), treated heart disease (58.3 cases), and
treated hypertension (42.5 cases) per 1000 man-
years.

32. Risk Factors
 Diabetes 27% - 59%
 Chronic renal failure 40%
 Hepatic failure 25% - 70%
 Multiple Sclerosis 71%
 Severe depression 90%
 Other (vascular disease, low HDL, high
cholesterol)
-Benet et al. Urol Clinic North Am. 1995; 151:54-61

33. Other risk factors
 General health status
 Concurrence of other genitourinary disease
 Psychiatric or psychologic disorders
 Other chronic diseases
 Sociodemographic conditions.
 Smokingng and medications
 Hormonal factors
 Endothelial dysfunction - common etiologic pathway

34. Classification

35. Classification of ED
International society of Impotence Research
 Psychogenic
 Organic
 Mixed organic/psychogenic (most
common type)

36. Psychogenic
ED

37. Psychogenic ED
 Sexual behavior and penile erection are controlled
by the hypothalamus, the limbic system, and the
cerebral cortex.
 Direct inhibition of the spinal erection center by the
brain as an exaggeration of the normal suprasacral
inhibition ( Steers, 1990 )
 Excessive sympathetic outflow or elevated
peripheral catecholamine levels, which may
increase penile smooth muscle tone to prevent its
necessary relaxation (Kim and Oh,1992)

38. Classification of ED
International society of Impotence Research
Psychogenic ED
1. Generalized type
A. Generalized unresponsiveness
a. Primary lack of sexual arousability
b. Aging-related decline in sexual arousability
B. Generalized inhibition
a. Chronic disorder of sexual intimacy
2. Situational type
A. Partner related
a. Lack of arousability in specific relationship
b. Lack of arousability due to sexual object preference
c. High central inhibition due to partner conflict or threat
B. Performance related
a. Associated with other sexual dysfunction/s (rapid ejaculation)
b. Situational performance anxiety (eg, fear of failure)
C. Psychological distress or adjustment related
a. Associated with negative mood state (eg, depression)
b. major life stress (eg, death of partner)

39. Differentiating Psychogenic
from Organic ED
Psychogenic ED:
 Younger patient (<40)
 Preservation of morning erections and
nocturnal erections
 Achieve erection with masturbation
 May be partner-specific
 Often sudden onset

40. Organic ED

41. Differentiating Psychogenic from
Organic ED
Organic ED:
 Gradual deterioration
 Decrease in morning erections and nocturnal
erections
 No erections with masturbation
 No loss of libido
 Presence of co-morbid conditions

42. Classification of ED
International society of Impotence Research
Organic ED
 1. Neurogenic
 2. Hormonal
 3. Arterial
 4. Cavernosal (venogenic)
 5. Drug induced

43. Neurogenic
 10% to 19% of ED is neurogenic ( Abicht 1991 ;
Aboseif et al, 1997 ).
 Pathologic processes in the region of higher center,
such as Parkinson's disease, stroke, encephalitis, or
temporal lobe epilepsy ,tumors, dementias,
Alzheimer's disease, and trauma .
 Spinal cord injuries: 5% - 80%
 Reflexogenic erection is preserved in 95% of patients
with complete upper cord lesions but in only about
25% of those with complete lower cord lesions.
( Eardley and Kirby, 1991 ).
 disorders at the spinal level e.g., spina bifida, disk
herniation, syringomyelia, tumor, transverse myelitis,
and multiple sclerosis
 Injury to cavernosal nerve and pelvic plexus in pelvic
surgery ( Iatrogenic ED)

44. Iatrogenic impotence resulting from
various pelvic surgical procedures
 radical prostatectomy - 43% to 100%
 Nerve sparing radical prostatectomy
-30% to 50%
 perineal prostatectomy for benign disease
- 29%
 abdominal perineal resection
-15% to 100%
 external sphincterotomy at the 3 and 9
o'clock positions -2% to 49%

45. Hormonal
 Hypogonadism is a not-infrequent finding in the impotent
population.
 Testosterone enhances sexual interest, increases the
frequency of sexual acts, and increases the frequency of
nocturnal erections but has little or no effect on fantasy-
induced or visually stimulated erections.
 However, exogenous testosterone therapy in impotent men
with borderline-low testosterone levels reportedly has little
effect ( Graham and Regan, 1992 ).
 Hyperprolactinemia,results in both reproductive and sexual
dysfunction and is associated with low circulating levels of
testosterone, which appear to be secondary to inhibition of
gonadotropin-releasing hormone secretion by the elevated
prolactin levels.
 In hypothyroidism, low testosterone secretion,increased
circulating estrogen and elevated prolactin levels contribute
to ED.

46. Arteriogenic
 Atherosclerotic or traumatic arterial occlusive disease
of the hypogastric-cavernous-helicine arterial tree can
decrease the perfusion pressure and arterial flow to
the sinusoidal spaces,
 This increases the time to maximal erection and
decreases the rigidity of the erect penis.
 An atherosclerotic process may decrease expansibility
of cavernous smooth muscles by decreasing NOS
activity.
 Common risk factors associated with arterial
insufficiency include hypertension, hyperlipidemia,
cigarette smoking, diabetes mellitus, blunt perineal or
pelvic trauma, and pelvic irradiation.
 As, ED and cardiovascular disease share the same
risk factors, ED may present as a manifestation of
generalized or focal arterial disease (Sullivan et
al,1999).

47. Cavernous (Venogenic)
 Failure of adequate venous occlusion is one of the
most common causes of vasculogenic impotence
( Rajfer et al, 1988 ).
 Veno-occlusive dysfunction : degenerative tunical
changes, fibroelastic structural alterations (increased
deposition of collagen and decreased elastic fiber) ,
insufficient trabecular smooth muscle relaxation, and
venous shunts.
 Degenerative changes as old age, and diabetes or
traumatic injury to the tunica albuginea (penile
fracture) can impair the compression of the subtunical
and emissary veins.
 In Peyronie's disease, the inelastic tunica albuginea
may prevent the emissary veins from closing. ( Metz et
al, 1983 ).

48. Diabetes and ED
 The prevalence of ED is three times higher in diabetic men
(28% versus 9.6%) ( Feldman et al, 1994 ), occurs at an
earlier age, and increases with disease duration.
 Associated with a decreased desire and orgasmic
dysfunction as well .
 ED occurs due to dysfunction of one or a combination of :
psychologic function, CNS function, androgen secretion,
peripheral nerve activity, endothelial cell function, and
smooth muscle contractility ( Dunsmuir and Holmes, 1996 ).
 A higher odds ratio is seen with insulin-dependent diabetes
mellitus; diabetes present for over 10 years; fair or poor
control based on glycosylated hemoglobin; management by
means other than diet; a history of diabetes-related arterial,
renal, or retinal disease and neuropathy; and concurrent
cigarette smoking.

49. Drug induced ED
 Most common cause of ED in men >50 years.
 Antihypertensives
- thiazides
- β- Blockers
- α1 blockers
- α2 agonist
- ACE inhibitor and AT II antagonists
 Antipsychotics
 Antidepressants.
-Tricyclics
- Monoamine oxidase inhibitors
- Selective serotonin reuptake inhibitors (SSRIs)
 Anxiolytics
 Antiandrogens
 Digitalis
 Opioids
 Protase inhibitors
 Tobbaco and alcohol
 H2 receptor antagonist

50. THANK YOU!