Dr.Ajit Saxena

8/9/2019 Dr.Ajit Saxena

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Erectile DysfunctionErectile Dysfunction

Normal erectile function involves 3Normal erectile function involves 3

synergistic and simultaneoussynergistic and simultaneous

processes:processes: 1) neurologically mediated increase in1) neurologically mediated increase in

penile arterial inflowpenile arterial inflow

2) relaxation of2) relaxation of cavernosalcavernosal smoothsmoothmusclemuscle

3) restriction of venous outflow from the3) restriction of venous outflow from the

penispenis


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Erectile dysfunctionErectile dysfunction ED is predominately a disease ofED is predominately a disease of

vascular origin.vascular origin.

The incidence ofED dramaticallyThe incidence ofED dramatically

increases in men with diabetesincreases in men with diabetesmellitus, hypercholesterolemia, andmellitus, hypercholesterolemia, and

cardiovascular disease.cardiovascular disease.

Loss of the functional integrity of theLoss of the functional integrity of theendothelium and subsequentendothelium and subsequent

endothelial dysfunction plays anendothelial dysfunction plays an

integral role in the occurrence ofED inintegral role in the occurrence ofED in

this cohort of men.this cohort of men.


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Erectile dysfunctionErectile dysfunction

The corpusThe corpus cavernosumcavernosum of the penisof the penisis composed of a meshwork ofis composed of a meshwork of

interconnected smooth muscle cellsinterconnected smooth muscle cellslined by vascular endothelium.lined by vascular endothelium.

Endothelial cells and underlyingEndothelial cells and underlyingsmooth muscle also line the smallsmooth muscle also line the small

resistanceresistance helicinehelicine arteries thatarteries thatsupply blood to the corpussupply blood to the corpuscavernosumcavernosum during penileduring peniletumescence.tumescence.


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Role of Endothelium in ErectionsRole of Endothelium in Erections

NO production from nNOS in theNO production from nNOS in the

NANC nerves innervating the penis isNANC nerves innervating the penis is

essential for the initiation ofessential for the initiation ofcavernosal smooth muscle relaxationcavernosal smooth muscle relaxation

and subsequent erectionand subsequent erection

The relative importance of endothelialThe relative importance of endothelial--derived NO from eNOS in thederived NO from eNOS in the

endothelial cells of the corpusendothelial cells of the corpus

cavernosum and arteries supplyingcavernosum and arteries supplying

the enis has recentl been elucidatedthe enis has recentl been elucidated


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Role of Endothelium inRole of Endothelium in

ErectionErection NO diffuses to adjacent smoothNO diffuses to adjacent smooth

muscle cells stimulatingmuscle cells stimulating guanylateguanylate

cyclasecyclase. This interaction converts. This interaction convertsguanosineguanosine triphosphatetriphosphate (GTP) to(GTP) to

cycliccyclic guanosineguanosine monophosphatemonophosphate

((cGMPcGMP), which induces a substantial), which induces a substantialincrease in intracellularincrease in intracellular cGMPcGMP,,

causing smooth muscle relaxationcausing smooth muscle relaxation


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Role of EndotheliumRole of Endothelium

The vascular endothelium not only servesThe vascular endothelium not only serves

as a passive barrier for the arterial andas a passive barrier for the arterial and

venous blood, but also plays a pivotal rolevenous blood, but also plays a pivotal role

in modulating vascular tone and blood flowin modulating vascular tone and blood flow

in response toin response to humoralhumoral, neural, and, neural, and

mechanical stimulimechanical stimuli


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ENDOTHELIAL DYSFUNCTION

Also seen in

Heart disease Hypertension

Diabetes mellitus

Metabolic syndrome


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ArteryArtery Size (mm)Size (mm) ClinicalClinical

Event

Event

PenilePenile 11--22 EDED

CoronaryCoronary 33--44 CADCADCarotidCarotid 55--77 TIA/StrokeTIA/Stroke

FemoralFemoral 66--88 ClaudicationClaudication

Artery size and Atherothrombosis

Montorsi et alEur Urol2003; 44:352-4


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ED and Cardiac PatientsED and Cardiac Patients

MMASMMAS men with cardiovascular disease,men with cardiovascular disease,

diabetes or hypertension 4 times thediabetes or hypertension 4 times the

incidence of complete EDincidence of complete ED

Myocardial infarction 44%Myocardial infarction 44%

Untreated hypertension 17%Untreated hypertension 17%

Treated hypertension 25%Treated hypertension 25%

ED increases with increasing CADED increases with increasing CAD


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Endothelial Dysfunction and Diabetes

Peripheral vascular disease and neuropathyPeripheral vascular disease and neuropathyof autonomic nerves are establishedof autonomic nerves are establishedcomplications associated with diabetescomplications associated with diabetes

mellitusmellitus Such alterations in the peripheralSuch alterations in the peripheral

vasculature may underlie the highvasculature may underlie the highprevalence (.50%) of diabetic ED in menprevalence (.50%) of diabetic ED in men

(Hakim and Goldstein, 1996)(Hakim and Goldstein, 1996)


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Oxidative stress

Endothelial

cell injury

Diabetes

Hypertension

Vasoconstriction

Erectile dysfunction Thrombosis

Atherosclerosis

Smoking

Dyslipidemia

Precursors

Outcomes

Endothelial Insults:Endothelial Insults:

The ED LinkThe ED Link


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The recognition ofED as a warning signThe recognition ofED as a warning sign

of silent vascular disease has led to theof silent vascular disease has led to the

concept that a man with ED and noconcept that a man with ED and no

cardiac symptoms is a cardiaccardiac symptoms is a cardiac

(or vascular) patient until proven(or vascular) patient until proven

otherwise.otherwise.

Princeton II: Jackson G et al. 2006.Princeton II: Jackson G et al. 2006. J Sex Med 3:28J Sex Med 3:28--3636


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Diagnosis of ED : Why is itDiagnosis of ED : Why is it

important?important?

ED often leads to

- Anxiety, depression, loss of self-esteem, and diminished quality of life

- Diminished willingness to initiate sexual relationships withdrawal from

intimate relationships

- Negative effect on their overall health

- Screening patients forED may actually uncover underlying factors

important to their patients' health


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