Introduction

Penile erection or tumescence refers to the physiologic process during which the penis becomes engorged with blood, usually in response to sexual arousal but sometimes spontaneously. Comprehension of penile anatomy, neuro-vasculature, and the associated hormonal and molecular factors is required to understand the physiology of tumescence. Understanding the physiology of erections is important for clinicians and fertility experts to help aid patients in the therapy of erectile dysfunction. Knowledge of physiology helps derive medical intervention; thus, it is an important topic for the basis of erectile dysfunction treatment. This article will review the associated anatomy, vascular, neurologic, hormonal, and molecular factors behind the physiology of an erection.[1][2][3]

Issues of Concern

Anatomy

The penis consists of three cylindrical chambers: the paired corpora cavernosa and the corpus spongiosum. The corpora cavernosa are contained within a bilayered, collagenous sheath called the tunica albuginea and are composed of variously sized sinusoids supported by a fibrous skeleton. The fibrous skeleton provides structural support and is constructed of tunica albuginea surrounded by smooth muscle trabeculae (which regulate blood flow in and out of the sinusoids), elastic fibers, and collagen. This arrangement allows for blood to fill the sinusoids of corpora cavernosa and maintain rigidity during an erection. The tunica albuginea also helps sustain erections by restricting venous outflow by compressing the emissary veins that drain the sinusoids. The corpora cavernosa start proximally as two separate crura covered by the ischiocavernosus muscle. The contraction of this muscle forces blood distally from the cavernous space in the crura to the corpora cavernosa and provides additional rigidity during the rigid erection phase. The corpus spongiosum is the ventrally located chamber that contains the urethra and distally becomes the glans. This chamber also holds a tunica sheath that is less dense and not present in the glans. The sinusoids of the corpus spongiosum are larger than that of the corpora cavernosa. Engorgement of the corpus spongiosum constricts and pressurizes the urethral lumen to allow for forceful ejaculation. The bulbospongiosus muscle surrounds the bulb of the penis and, like the ischiocavernosus muscle, forces additional blood into the penis during the rigid erection phase. The bulbospongiosus also functions to compress the urethra to help expel semen during ejaculation.

Vascular Supply

The internal pudendal artery provides the main blood supply to the penis. This artery is a branch of the internal iliac and becomes the common penile artery distally. The common penile artery has three distinct branches, including dorsal, cavernous, and bulbourethral. The dorsal artery is responsible for supplying blood to the glans of the penis during engorgement. The bulbourethral artery supplies the corpus spongiosum and the bulb of the penis. The cavernous artery supplies the corpora cavernosa and branches into helicine arteries throughout the length of each corporal body. The helicine arteries supply the trabecular tissue and sinusoids of the erectile chambers. In the flaccid state, the helicine arteries are tortuous and constricted. In the erect state, they are straight and dilated, allowing blood to fill the corpora cavernosa. The venous drainage of the penis is mainly via the internal pudendal veins. Blood from the peripheral sinusoids travels in the trabecular network and drains via the subtunical venous plexus and eventually exits via emissary veins. The emissary veins will either drain via the internal pudendal veins or communicate with veins that converge on the deep dorsal vein and drain via the periprostatic plexus. During an erection, the emissary veins are compressed between the sinusoids and tunica albuginea to limit venous drainage from the sinusoids and maintain tumescence.

Neuroanatomy

The penis has both somatic and autonomic (i.e., sympathetic and parasympathetic) innervation. The pudendal nerve supplies the somatic innervation, which is responsible for the sensation of the penis and the contraction of the bulbospongiosus and ischiocavernosus muscles. The glans, corona, and penile skin contain numerous free nerve endings, whose fibers proximally converge to form the dorsal nerve of the penis. The penis's dorsal nerve is a distal branch of the pudendal nerve that originates from the ventral horn of S2 to S4. These nerves are responsible for receiving signals of touch, temperature, and pain. The somatomotor penile nerves originate from spinal cord segments S2 to S4 in the Onuf nucleus. These nerves travel through the sacral and pudendal nerves to innervate the ischiocavernosus and bulbospongiosus muscles. The somatomotor penile nerves are responsible for the contraction of these muscles during the rigid erection phase and ejaculation.

The chain ganglia from T11 to L2 supply the sympathetic innervation, which is responsible for vascular smooth muscle contraction of the penis. The sympathetic fibers travel through the spinal cord and exit as the superior hypogastric plexus. These nerves end terminally in the pelvic plexus and as cavernous nerves. The sympathetic innervation is responsible for the baseline tonic contraction of the helicine arteries and trabecular smooth muscle, maintaining a flaccid state—the intermediolateral nuclei of the S2 supply the parasympathetic innervation to S4 sacral spinal cord segments. The parasympathetic fibers are pro-erectogenic and responsible for vascular smooth muscle relaxation of the penis. The preganglionic fibers provided by the parasympathetic nuclei of the spinal cord pass through the pelvic nerves and join the sympathetic nerves from the superior hypogastric plexus at the pelvic plexus and cavernous nerves. The course of the autonomic nerves and its proximity to the aorta, prostate, bladder, and rectum make them vulnerable to damage during procedures. The injury could result in impaired seminal emission during ejaculation and cause iatrogenic erectile dysfunction.

Cellular Level

Regulation of the smooth muscles of the penis is essential for tumescence. Cytosolic free calcium regulates the relaxation and contraction of the penile smooth muscles. Signaling from sympathetic nerves and endothelium activates the smooth muscle cells of the penis. Norepinephrine mediates sympathetic nerve signaling. Norepinephrine is released from the terminal ends of the sympathetic cavernous nerves and binds to receptors on the membrane of the smooth muscle cells. Endothelium signaling is mediated by endothelin and prostaglandin, which also activate the smooth muscle cells by binding to specific receptors located on their membranes. This activation results in the opening of calcium channels and the release of intracellular calcium stores, which leads to an increase in cytosolic free calcium ions that bind intracellular calmodulin. This calcium-calmodulin complex binds to myosin light chain kinase and triggers the phosphorylation of ATP on myosin light chains. This process creates energy for cycling of myosin cross-bridges along actin filaments resulting in smooth muscle contraction. The smooth muscles of the penis in the flaccid state contract tonically.

Inversely, a decrease in intracellular calcium ions leads to smooth muscle relaxation. Signaling from parasympathetic nerves and endothelium activates intracellular second messengers, cAMP, and cGMP. These secondary messengers activate their specific protein kinases, which leads to phosphorylation of ion channels and sarcoplasmic reticulum membrane proteins. The result of this phosphorylation is the closing of calcium channels, sequestration of calcium ions within the sarcoplasmic reticulum, and efflux of potassium ions, all of which hyperpolarize the cell. These effects reduce intracellular calcium concentrations and lead to smooth muscle relaxation.

Acetylcholine mediates the parasympathetic nerve signaling responsible for smooth muscle relaxation. Acetylcholine release is from the terminal ends of the parasympathetic cavernous nerves and binds to muscarinic receptors of the endothelium. This binding increases endothelium nitric oxide synthase (eNOS) activity, which cleaves 1-arginine into nitric oxide. Nitric oxide activates a smooth muscle cell membrane-bound enzyme called guanylyl cyclase. Guanylyl cyclase converts GTP to cGMP, the secondary messenger responsible for the activation of protein kinases. This activation results in the closing of calcium channels and sequestration of the calcium ions. Nitric oxide is also produced in the terminal ends of non-adrenergic, non-cholinergic cavernous nerves by neuronal nitric oxide synthase (nNOS). It acts similarly to the nitric oxide produced by eNOS. Thus the nitric oxide/cGMP pathway is an essential neurochemical cascade responsible for smooth muscle relaxation. Comprehension of these pathways and associated physiology helps the clinician gain further insight into the therapy for erectile dysfunction.

Mechanism

The physiology of an erection can break down into arterial dilation and venous occlusion. In most cases, tumescence occurs following sexual stimulation. This process triggers sympathetic inhibition, parasympathetic activation, and release of pro-erectogenic neurotransmitters from cavernous nerves. The activation of the parasympathetic nerves leads to reduced intracellular calcium levels, causing cavernosal and arterial smooth muscle relaxation. This effect increases blood flow by approximately 20 to 40 times the expanding sinusoids of the corpora cavernosa. As these sinusoids enlarge, the outer portions of corpora near the tunica albuginea start to occlude venous outflow. The emissary veins get compressed between the sinusoids and the inelastic portion of tunica albuginea and help maintain tumescence.

The pressure in the corpora cavernosa will rise to averages around 100 mmHg in most men. The pressure in the corpus spongiosum is approximately one-third of that found in the corpora cavernosa. This difference is because of the weaker and more elastic tunica albuginea, which produces minimal venous occlusion. Contraction of the ischiocavernosus and bulbospongiosus muscles increase pressure within all three chambers and the glans of the penis during the rigid erection phase. Intercourse and repetitive penile stimulation create a strong contraction of these muscles and force additional blood into all chambers, increasing rigidity. This process is known as the rigid erection phase, during which pressure within the erectile chambers can reach several hundred mmHg.

The intracorporeal pressure begins to decrease only in the second phase of detumescence. The first phase has a transient increase in pressure as trabecular smooth muscles within the sinusoids start to contract against an occluded venous system. During the second phase of detumescence, expansion of the emissary veins begins to drain the sinusoids, and a slow decrease in intracorporeal pressure occurs. The last phase of detumescence reveals a fast drop in pressure from fully restored venous drainage and baseline arterial flow.[4][5][6][7]

Clinical Significance

The class of drugs most commonly employed for erectile dysfunction is known as PDE5 inhibitors. Phosphodiesterases (PDE) are enzymes that degrade cGMP and cAMP. The isoform present within penile tissues is PDE5, which exclusively degrades cGMP. As levels of cGMP decrease, the intracellular concertation of calcium ions increases, and smooth muscle contraction occurs. Thus the inhibition of PDE5 results in increased levels of cGMP decreased intracellular calcium and smooth muscle relaxation. The activity of a PDE5 inhibitor, such as sildenafil, leads to prolongation of smooth muscle relaxation and vasodilation. However, they only maintain preexisting levels of cGMP and require sexual stimulation to generate cGMP in penile tissues.[8][9][10]