Pathophysiology

The penis consists of three components, two dorsolateral corpora cavernosa and a ventral corpus spongiosum that surrounds the penile urethra and distally forms the glans penis. The corpora cavernosa consist of blood-filled sinusoidal or lacunar spaces, which are lined with endothelial cells, supported by trabecular smooth muscle, and surrounded by a thick fibrous sheath called the tunica albuginea. The cavernosal arteries, which are branches of the penile artery, penetrate the tunica albuginea and supply blood flow to the penis.

Sympathetic and parasympathetic nerves innervate the penis. In the flaccid state, a2-adrenergic receptors mediate tonic contraction of the arterial and corporal smooth muscles. This maintains high penile arterial resistance and a balance exists between blood flow into and out of the corpora. With sexual stimulation, nerve impulses from the brain travel down the spinal cord to the thoracolumbar ganglia. A decrease in sympathetic tone and an increase in parasympathetic activity then occurs, causing a net increase in blood flow into the erectile tissue. Erections may also occur as a result of a sacral nerve reflex arc while patients are sleeping (nocturnal erections). Acetylcholine-mediated parasympathetic activity leads to production of the nonadrenergic-noncholinergic transmitter nitric oxide (NO). By enhancing the activity of guanylate cyclase, NO increases the production of cyclic guanosine monophosphate (cGMP). Vasoactive peptide and prostaglandins E1 and E2 stimulate increased production of cyclic adenosine monophosphate (cAMP). Both cAMP and cGMP ultimately lead to a decrease in calcium concentration within smooth muscle cells of the penile arteries and the sinusoidal spaces, leading to smooth muscle relaxation and increased blood flow. As the sinusoidal spaces become engorged, intracavernosal pressure increases, subtunical venules are compressed, and the penis becomes rigid and elongated (Fig. 51-1).

FIGURE 51-1. Mechanism of erection and sites of action of various treatment modalities for erectile dysfunction (ED). Penile erection is achieved through relaxation of smooth muscle cells lining arterial vessels and sinusoidal spaces in the corpora cavernosa, which leads to increased arterial inflow and pressure, decreased venous outflow, and increased intracavernosal pressure. Smooth muscle relaxation is mediated by intracellular generation of cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP) via activation of guanylate cyclase by nitric oxide. Treatment modalities for ED (shown in blue) include oral phosphodiesterase type 5 (PDE-5) inhibitors, which inhibit the breakdown of cGMP, and local vasoactive agents. A link between testosterone and nitric oxide synthase has been demonstrated experimentally, but the significance of this observation in humans has not been established (indicated by the dashed line and question mark). Psychotherapy (not shown) may also be effective in selected individuals with ED. (From Ref. 4.)

FIGURE 51-1. Mechanism of erection and sites of action of various treatment modalities for erectile dysfunction (ED). Penile erection is achieved through relaxation of smooth muscle cells lining arterial vessels and sinusoidal spaces in the corpora cavernosa, which leads to increased arterial inflow and pressure, decreased venous outflow, and increased intracavernosal pressure. Smooth muscle relaxation is mediated by intracellular generation of cyclic guanosine monophosphate (cGMP) from guanosine triphosphate (GTP) via activation of guanylate cyclase by nitric oxide. Treatment modalities for ED (shown in blue) include oral phosphodiesterase type 5 (PDE-5) inhibitors, which inhibit the breakdown of cGMP, and local vasoactive agents. A link between testosterone and nitric oxide synthase has been demonstrated experimentally, but the significance of this observation in humans has not been established (indicated by the dashed line and question mark). Psychotherapy (not shown) may also be effective in selected individuals with ED. (From Ref. 4.)

Detumescence occurs with sympathetic discharge after ejaculation. Sympathetic activity induces smooth muscle contraction of arterioles and vascular spaces leading to a reduction in blood inflow, decompression of the sinusoidal spaces, and enhanced outflow.

Testosterone also plays a significant albeit complex role in erectile function. Testosterone is responsible for much of a man's libido. With low serum concentrations, libido declines. Additionally, testosterone helps with stabilization of intracav-ernosal levels of NO synthase, the enzyme responsible for triggering the NO cascade. Interestingly, some patients with low or borderline low serum concentrations of testosterone will have normal erectile function, while some with normal levels will have dysfunction.

Normal penile erections are complex events that require the full function of the vascular, neurologic, and hormonal systems. Anything that affects the function of these systems may lead to ED. ED can be classified as organic, psychogenic, or a mixture of these. Organic dysfunction includes abnormalities in the three systems responsible for a normal erection or may be medication-induced (Tables 51-1 and 51-2). Note that many of the risk factors for ED are the same as risk factors for cardiovascular (CV) disease. In many patients, ED is the first indication of the endothelial dysfunction associated with cardiovascular disease. The presence of ED risk factors leads to the assumption that the patient has organic dysfunction. Most commonly, medical conditions that impair arterial flow into or out of the erectile tissue or affect the innervation will be strongly associated with ED. Patients with diabetes mellitus have exceptionally high rates of ED as a result of vascular disease and neuropathy. Additionally, a relationship has been found between low testosterone levels and an increased incidence of metabolic syndrome and type 2 diabetes.8

Psychogenic dysfunction occurs if a patient does not respond to psychological arousal. It occurs in up to 30% of all cases of ED. Common causes include performance anxiety, strained relationships, lack of sexual arousability, and overt psychiatric disorders such as depression and schizophrenia.9 Many patients may initially have organic dysfunction, but develop a psychogenic component as they try to cope with their inability to achieve an erection. It has been estimated that up to 80% of ED cases have an organic cause, with many having a psychogenic component as well.1

Table 51-1 Factors Associated With ED

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