Pathogenesis of erectile dysfunction

Erectile dysfunction is an implication from a combination of organic and psychogenic factors.

Organic etiologies are of hormonal, neurogenic and vascular problems.


Pathogenesis
Arousal difficulties most likely result from a mix of organic and psychogenic etiologies. Organic
causes include vascular, neurogenic, and hormonal etiologies. Vascular arterial or inflow problems
are by far the most common. Regardless of the primary etiology, a psychological component
frequently coexists. Although influenced by other systems, arousal is primarily a neurovascular
process. Optimal function requires an intact nervous system and responsive arterial vasculature.
Sexual stimulation results in nitric oxide release, which initiates a cascade of events leading to a
dramatic increase in blood flow to the penis in men and the vagina and clitoris in women. Nitric
oxide enters into vascular smooth muscle cells causing an increase in the production of cyclic
guanosine monophosphate (cGMP). As cGMP concentrations rise, vascular smooth muscle relaxes,
allowing increased arterial blood flow. The cGMP buildup is countered by
the enzyme phosphodiesterase type 5 (PDE-5).
Inhibiting the action of PDE-5 results in higher levels of cGMP, causing increased and sustained
vasodilation. Arousal disorders appear to increase with age, but it is more likely that increase in
chronic illnesses and their therapeutic intervention are the root cause. Life style factors such as
tobacco, alcohol, exercise, and diet also contribute.

PATHOPHYSIOLOGY
ED may result from three basic mechanisms: (1) failure to initiate (psychogenic, endocrinologic, or neurogenic), (2) failure to fill
(arteriogenic), and (3) failure to store adequate blood volume within the lacunar network (venoocclusive dysfunction). These categories
are not mutually exclusive, and multiple factors contribute to ED in many patients. For example, diminished filling pressure can lead
secondarily to venous leak. Psychogenic factors frequently coexist with other etiologic factors and should be considered in all cases.
Diabetic, atherosclerotic, and drug-related causes account for >80% of cases of ED in older men.
Vasculogenic
The most common organic cause of ED is a disturbance of blood flow to and from the penis. Atherosclerotic or traumatic arterial disease
can decrease flow to the lacunar spaces, resulting in decreased rigidity and an increased time to full erection. Excessive outflow through
the veins despite adequate inflow also may contribute to ED. Structural alterations to the fibroelastic components of the corpora may
cause a loss of compliance and inability to compress the tunical veins. This condition may result from aging, increased cross-linking
of collagen fibers induced by nonenzymatic glycosylation, hypoxemia, or altered synthesis of collagen associated with
hypercholesterolemia.
Neurogenic
Disorders that affect the sacral spinal cord or the autonomic fibers to the penis preclude nervous system relaxation of penile smooth
muscle, thus leading to ED. In patients with spinal cord injury, the degree of ED depends on the completeness and level of the lesion.
Patients with incomplete lesions or injuries to the upper part of the spinal cord are more likely to retain erectile capabilities than are
those with complete lesions or injuries to the lower part. Although 75% of patients with spinal cord injuries have some erectile
capability, only 25% have erections sufficient for penetration. Other neurologic disorders commonly associated with ED include multiple
sclerosis and peripheral neuropathy. The latter is often due to either diabetes or alcoholism. Pelvic surgery may cause ED through
disruption of the autonomic nerve supply.
Endocrinologic
Androgens increase libido, but their exact role in erectile function is unclear. Individuals with castrate levels of testosterone can achieve
erections from visual or sexual stimuli. Nonetheless, normal levels of testosterone appear to be important for erectile function,
particularly in older males. Androgenreplacement therapy can improve depressed erectile function when it is secondary to
hypogonadism; however, it is not useful for ED when endogenous testosterone levels are normal. Increased prolactin may decrease
libido by suppressing gonadotropin-releasing hormone (GnRH), and it also leads to decreased testosterone levels. Treatment of
hyperprolactinemia with dopamine agonists can restore libido and testosterone.
Diabetic
ED occurs in 3575% of men with diabetes mellitus. Pathologic mechanisms are related primarily to diabetes-associated vascular and
neurologic complications. Diabetic macrovascular complications are related mainly to age, whereas microvascular complications correlate
with the duration of diabetes and the degree of glycemic control (Chap. 344). Individuals with diabetes also have reduced amounts
of nitric oxide synthase in both endothelial and neural tissues.
Psychogenic
Two mechanisms contribute to the inhibition of erections in psychogenic ED. First, psychogenic stimuli to the sacral cord may inhibit
reflexogenic responses, thereby blocking activation of vasodilator outflow to the penis. Second, excess sympathetic stimulation in an
anxious man may increase penile smooth-muscle tone. The most common causes of psychogenic ED are performance anxiety,
depression, relationship conflict, loss of attraction, sexual inhibition, conflicts over sexual preference, sexual abuse in childhood, and fear
of pregnancy or sexually transmitted disease. Almost all patients with ED, even when it has a clear-cut organic basis, develop a
psychogenic component as a reaction to ED.
Medication-Related
Medication-induced ED (Table 48-1) is estimated to occur in 25% of men seen in general medical outpatient clinics. The adverse effects
related to drug therapy are additive, especially in older men. In addition to the drug itself, the disease being treated is likely to
contribute to sexual dysfunction. Among the antihypertensive agents, the thiazide diuretics and beta blockers have been implicated most
frequently. Calcium channel blockers and angiotensin converting-enzyme inhibitors are cited less frequently. These drugs may act
directly at the corporal level (e.g., calcium channel blockers) or indirectly by reducing pelvic blood pressure, which is important in the
development of penile rigidity. -Adrenergic blockers are less likely to cause ED. Estrogens,GnRH agonists, H2 antagonists,
and spironolactone cause ED by suppressing gonadotropin production or by blocking androgen action. Antidepressant
and antipsychotic agentsparticularly neuroleptics, tricyclics, and SSRIsare associated with erectile, ejaculatory, orgasmic, and sexual
desire difficulties.

Aetiologies of coronary artery disease include
The etiology of CAD is primarily atherosclerosis. The disease is multifactorial, with the primary risk factors being hyperlipidemia,
smoking, diabetes, hypertension, obesity, sedentary lifestyle, and male gender. Newly identified risk factors include elevated levels of C-
reactive protein, lipoprotein (a), and homocysteine. The atherosclerotic process results in the formation of obstructive lesions in the
aorta, the peripheral vessels, and the coronary arteries. Atherosclerosis is the leading cause of death in the Western world, and acute MI
alone accounts for 25% of the deaths in the United States each year. The most important factor in the long-term treatment of coronary
disease is modification of risk factors, including the immediate cessation of smoking, control of hypertension, weight loss, exercise, and
reduction of serum cholesterol. If dietary control of cholesterol cannot be achieved in patients with coronary disease, evidence suggests
that the early use of medications (such as statins) to lower cholesterol can significantly reduce cardiovascular risk.
The basic lesion is a segmental plaque within the coronary artery. Involvement of small distal vessels is usually less extensive, while
arterioles and intramyocardial vessels are usually free of disease. This segmental localization makes CABG possible. Among the three
major coronary arteries, the proximal LAD is frequently stenosed or occluded, with the distal half of the artery remaining patent. The
right coronary artery is often stenotic or occluded throughout its course, but the posterior descending and left AV groove branches are
almost always patent. The circumflex artery is often diseased proximally, but one or more distal marginal branches are usually patent.
With progressive disease, platelet aggregation in the narrowed lumen or plaque hemorrhage or rupture may lead to unstable symptoms
or to acute thrombosis and MI.

ETIOLOGY AND PATHOPHYSIOLOGY
CHD is one of several manifestations of atherosclerotic disease, which begins with endothelium dysfunction.
2

Endothelium, when normal, balances vasoconstrictors and vasodilators, impedes platelet aggregation, and
controls fibrin production.
Dysfunctional endothelium encourages macrophage adhesion, plaque growth, and vasoconstriction by
recruiting inflammatory cells into the vessels walls, the initiating step of atherosclerosis.
The vessel wall lesions develop a cap of smooth muscle cells and collagen to become fibroadenomas.
The vessels with these lesions undergo enlargement, allowing progression of the plaque without
compromising the lumen.
Plaque disruption and thrombus formation, instead of progressive narrowing of the coronary artery lumen, is responsible for
two- thirds of acute coronary events.
2

Plaques most likely to rupture (high-risk plaques) have a large core of lipids, many macrophages,
decreased vascular smooth muscle cells, and a thin fibrous cap.
After plaque rupture, the exposed lipid core triggers a superimposed thrombus that occludes the vessel.
Increased thrombosis is triggered by known cardiac risk factors including elevated low-density lipoprotein
(LDL) cholesterol, cigarette smoking, and hyperglycemia.

Coronary artery disease (CAD) is the most common type of heart disease. It is the leading
cause of death in the United States in both men and women.
CAD happens when the arteries that supply blood to heart muscle become hardened and
narrowed. This is due to the buildup of cholesterol and other material, called plaque, on their
inner walls. This buildup is called atherosclerosis. As it grows, less blood can flow through
the arteries. As a result, the heart muscle can't get the blood or oxygen it needs. This can lead
to chest pain (angina) or a heart attack. Most heart attacks happen when a blood clot suddenly
cuts off the hearts' blood supply, causing permanent heart damage.
Over time, CAD can also weaken the heart muscle and contribute to heart failure and
arrhythmias. Heart failure means the heart can't pump blood well to the rest of the body.
Arrhythmias are changes in the normal beating rhythm of the heart.


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ysfunction#8151443 Current Diagnosis and treatment in family medicine 3 edition