5/7 Male Sexual Fxn: Physiology & Disease

Question 1

Basic Cross-sectional anatomy of the penis:

what are the 3 main compartments?

where is the sinusoidal erectile tissue?

Answer 1

3 compartments: 2x Corpus Cavernosa, 1x Corpus Spongiosum

Sinusoidal erectile tissue is in the 2 corpus cavernosa.

(Urethra is in the corpus spongiosum)

Remember there are 2 Corpus Cavernosa: CC

Question 2

Erection: is it a parasympathetic or sympathetic process?

Answer 2

Parasympathetic process.

(remember this because you don’t want to be running from a bear and also have an erection)

To have an erection you need to be relaxed.

Question 3

Penis innervation: 3 types, and what they are each responsible for?

Answer 3

• Parasympathetic: erection (aka tumescence). via NO, cGMP
• Sympathetic: detumiscence (you are running from a bear, you lost your erection)
• Somatic: sensation

Question 4

Three catgories of erection?

MoA for each?

Answer 4

-Psychogenic: audiovisual, fantasy. Cortical output –> activates spinal erection center (S2-S4)

-Reflexogenic: via tactile stimulus. Dorsal nerve –> activates spinal erection center (S2-S4)

-Nocturnal: during REM, unknown mech –> activates spinal erection center (S2-S4)

Question 5

During the flaccid state, smooth muscle is contracted or relaxed?

arterial inflow is high or low?

Answer 5

Flaccid state: Muscles are contracted around the sinusoidal erectile tissue (yellow arrow)

arterial inflow is low (red arrow)

Question 6

During the erect state, smooth muscle is contracted or relaxed?

arterial inflow is high or low?

venous outflow is high or low?

Answer 6

smooth muscle is relaxed: allows filling of the sinusoidal erectile tissue (yellow)

arterial inflow is high (red)

venous outflow low: less blood is escaping (blue)

Question 7

what physiologically contributes to an erection (aka tumescence)?

Answer 7

• release of neurotransmitters –> smooth muscle relaxation in sinusoids
• Arterial dilation –> incr blood flow in to sinusoidal space
• expansion of sinusoids –> compresses outflow veins, blood is trapped

end result = increased intracavernosal pressure -> erection

Question 8

what is the role of NO in the erection-causing cascade?

roles of GTP, cGMP

Answer 8

NO allows GTP to convert to cGMP.

cGMP then catalyzes a whole cascade (dntk) - end result is decreased intracellular Ca.

Decr intracellular Ca –> muscle relaxation -> allows blood to fill the sinusoids.

Question 9

what is the role of PDE5 in the erection-causing cascade?

what can inbihit it?

Answer 9

PDE5 breaks down cGMP –> less cGMP means increased intracell Ca, muscle is less able to relax.

Sildafenil, etc (Viagra) inhibits PDE5 –> decreases intracell Ca–> increases relaxation –> erection

PDE5 is opposed by Viagra!

Erection is easier with less Ca in cell.

Question 10

Common risk factors for ED? (4, w some overlap..)

(list; details later)

Answer 10

Aging

Lifestyle issues

Smoking

HTN

Question 11

Lifestyle issues that contribute to ED?

Answer 11

Bottom line is that an erection requires good arterial input.

Sedentary lifestyle, obesity, heavy drinking, illicit drugs, smoking.

Smoking = most impt lifestyle issue for ED

Question 12

Smoking increases the risk of ED by how much?

generally, what is the mech?

is it reversible?

Answer 12

incr risk of moderate to complete ED 2x above baseline

nicotine is a vasoconstrictor -> less blood flow to penis

somewhat reversible with smoking cessation

Question 13

Categories of ED (5)?

(list; details later)

Answer 13

• psychogenic
• neurogenic
• arteriogenic
• drug induced (side effect)
• Endocrine

Question 14

Neurogenic ED:

central causes?

spinal cord causes?

peripheral causes?

Answer 14

• Central: tumor, trauma, neurodegen disease
• Spinal cord: trauma, disc, tumor, MS
• Peripheral (pelvic autonomics): trauma, post-prostacectomy (impossible to remove prostate without disrupting nerves)

**he talked mostly about the prostacectomy part

Question 15

Arteriogenic ED:

what does ED tell us about the general health of a patient?

Answer 15

ED can be a function of generalized atherosclerosis: a sx of a larger health problem. Same risk factors for ED as for an MCI.

Loss of erectile function can be a big motivator for lifestyle modifacation!

Question 16

Endocrine causes of ED?

Answer 16

Diabetes - not due to sugar levels, due to microvascular and microneural disease.

Thyroid disease (didn’t say much abt this)

Testosterone Deficiency: mainly a commercialized load of crap made up by pharma companies. People can have fine libido/function at levels below what pharma companies think is normal.

Question 17

basic workup of ED includes…

Answer 17

History:

• Duration of impotence (? morning erections), Libido, Inventory of partners
• CAD, Diabetes, PVOD (periph vasc dz??), Renal function
• ETOH and tobacco use

Physical:

• Penis (micropenis?, Peyronies? (= curvature)) and testicles (size and consistency)
• Complete neurological/vascular exam
• **Neuro and vascular are a theme here…..*

Question 18

Labs as part of a basic ED workup?

Answer 18

Testosterone, LH levels

TSH

Lipid, cholesterol panel

(If they haven’t already had these looked into in primary care, we do them now)

Question 19

Treatment options? (list 5)

Answer 19

• Oral tablet (ie viagra)
• vacuum device
• uterhral suppository
• cavernosal injection
• implant (a few options)

Question 20

First place to start in treating ED?

Answer 20

• Try a few months of lifestyle modifications (with them knowing that you will give them a pill if they need it in a few months)
• then go for the pills

Question 21

biochemically, what is the key to this whole erection thing?

Answer 21

need to increase cGMP levels in the smooth muscle.

do this by opposing PDE5 (which breaks down cGMP).

Viagra, Sildenafil.

Question 22

the cavernous smooth muscle cells are affected by several neuromodulators (norepi, VIP, endothelin, NO…) what is the most important neuromodulator to erectile function?

Answer 22

NO = most impt

(really dntk anything but NO)

Question 23

what is the significance of the pharmacokinetics of the various PDE5 inhibitors?

Answer 23

Halflife corresponds to the length of efficacy… but also the duration of the side effects.

Ex: Cialis has a longer halflife than Viagra, (17h vs 4h) but you may have a 17h headache

Question 24

What is a conraindication to Viagra use?

For what patients should we not prescribe Viagra?

Answer 24

Contraindication = use of Viagra and exogenous organic nitrates

Be cautious if prescribing Viagra for pts with poor heart health. Make sure they are healthy enough to have sex. Consult with primary care of cardiology.

Question 25

Common side effects of Viagra?

what information can we take from the side effects?

Answer 25

all are generally transient, mild/mod.

headache (16%)

flushing (10%)

dyspepsia (7%)

the presence of side effects tells us that the med got into the pt’s system – if it didn’t work, but he had side effects, then we at least know he absorbed it. if he had no side effects we wonder if he didn’t absorb it for some reason

Question 26

Problem with vacuum erection device?

Answer 26

some guys like it, BUT it only works with the tissues that are external. Penis and tissues extend into abdomen.

Question 27

Intracavernosal injection: what is this?

what meds are in it?

Answer 27

guy injects some prostaglandins etc directly into the corpora. omg.

done whenever you’d want an erection.

Meds= 3P’s

• Papavarine: inhibits phosphodiesterase, blocks Ca2+ influx
• Phenoxy/Phentol: alpha-blockers
• -Prostaglandin E1: vasodilation*

Question 28

what are the 2 forms of priapism?

which is more concerning?

Answer 28

1. Painless erection without detumescence

(arterial cause or trauma; high-flow)

2. Painful erection without detumescence**

(venous cause. low-flow)

**painful is far more concerning and is a medical emergency

Question 29

Painless priapism: why is this not as concerning as painful priapism?

Answer 29

Painless priapism: high blood flow state –> not having tissue ischemia.

the priapism may be due to trauma, blood flowing unabated into the corpora. may be due to a fistula (unregulated arterial blood flowing directly into corpora, maybe due to a lacerated artery)

Question 30

Painful priapism: why is this a medical emergncy? what causes it?

Answer 30

this is the low-flow type: not much blood is flowing out of the penis, but nothing is getting in either -> tissue ischemia.

tissue fibrosis begins after 4h of low-flow priapism.

can be caused by IVDU, trazodone, cocaine use. then once tissue begins to be ischemic we have to work harder to correct it bc the tissue is not responding as well.

Question 31

Most important points:

Most ED is psychogenic, vasculogenic or neurogenic?

Answer 31

vasculogenic

(remember smoking, atherosclerosis, HTN)

Question 32

Treatment begins with what?

Answer 32

He told me in person lifestyle changes, but on the slides it says….

-oral agents (PDE5 inhibitors)

…. which increase intracellular cGMP, to increase intracavernosal smooth muscle relaxation

Question 33

which form of priapism is an emergency (high flow or low flow)?

Answer 33

low flow