Campbell-Walsh Urology, 11th Edition

PART V

Reproductive and Sexual Function

26

Physiology of Penile Erection and Pathophysiology of Erectile Dysfunction

Tom F. Lue

Questions

  1. Penile prosthesis tends to extrude more on the:
  2. lateral surface.
  3. ventral surface.
  4. crura.
  5. glans.
  6. dorsal surface.
  7. Accessory pudendal artery is most likely to arise from:
  8. external iliac artery.
  9. femoral artery.
  10. obturator artery.
  11. superior vesical artery.
  12. bulbourethral artery.
  13. During a rigid erection, all the following statements are true EXCEPT:
  14. dilation of the arterioles and arteries.
  15. sinusoidal relaxation.
  16. corporal pressure increase (to several hundred millimeters of mercury).
  17. subtunical venous compression reducing venous outflow.
  18. relaxation of the ischiocavernosus muscles.
  19. All of the following are neurotransmitters that promote sexual function EXCEPT:
  20. dopamine.
  21. acetylcholine.
  22. oxytocin.
  23. serotonin (5-HT).
  24. nitric oxide (NO).
  25. All of the following statements are true EXCEPT:
  26. NO stimulates the production of cyclic guanosine monophosphate (cGMP).
  27. NO released by endothelial nitric oxide synthase (eNOS) contained in the terminals of the cavernous nerve initiates the erection process, whereas nitric oxide released from neuronal nitric oxide synthase (nNOS) in the endothelium helps maintain erection.
  28. Cyclic GMP activates protein kinase G, which in turn opens the potassium channels and closes the calcium channels.
  29. Low cytosolic calcium favors smooth muscle relaxation.
  30. The smooth muscle regains its tone when cGMP is degraded by phosphodiesterase.
  31. All the following statements about testosterone are true EXCEPT:
  32. It enhances sexual interest.
  33. It increases the frequency of sexual acts.
  34. It increases the frequency of nocturnal erection.
  35. It increases visually stimulated erections.
  36. It increases bone density and lean body mass.
  37. All the following antihypertensives DO NOT negatively affect erection EXCEPT:
  38. hydrochlorothiazide.
  39. terazosin.
  40. losartan.
  41. amlodipine.
  42. captopril.
  43. All of the following are possible causes of erectile dysfunction (ED) in end-stage renal disease (ESRD) patients EXCEPT:
  44. low NO.
  45. neuropathy.
  46. low prolactin.
  47. atherosclerosis.
  48. depression.
  49. All of the following statements are true EXCEPT:
  50. NO is the principal neurotransmitter mediating penile erection.
  51. Oxytocin is a potent inducer of erection when injected into the central nervous system.
  52. Central norepinephrine transmission has a positive effect on sexual function.
  53. GABABreceptors are pro-erectile.
  54. Cannabinoid CB1 receptor activation inhibits sexual function.
  55. All the following statements about smooth muscle contraction are true EXCEPT:
  56. Myosin light chain phosphatase (MLCP) is a holoenzyme consisting of a type 1 phosphatase (PP1c), a myosin-targeting subunit (MYPT1), and a 20-kDa subunit of unknown function.
  57. MLCP inhibition may lead to enhanced smooth muscle contraction.
  58. Phosphorylation of the regulatory subunit of MLCP by Rho kinase inhibits phosphatase activity and enhances the contractile response.
  59. One of the mechanisms of increased intracellular Ca2 +is by permitting entry of extracellular Ca2 + through receptor-operated channels without a change in membrane potential.
  60. Latch state refers to a period of smooth muscle relaxation after prolonged contraction.
  61. All of the following are true statements about NO EXCEPT:
  62. Synthesis of NO is catalyzed by NOS, which converts l-arginine and oxygen to l-citrulline and NO.
  63. Upregulation of nNOS expression has been found in the corpus cavernosum of aging and diabetic rats.
  64. NOS exists as three isoforms in mammals: nNOS, inducible nitric oxide synthase (iNOS), and eNOS.
  65. Gene transfer of nNOS or eNOS to the penis has been shown to augment erectile responses in aging rats.
  66. Gene transfer of iNOS has enhanced intracavernous pressure.
  67. All the following statements are true EXCEPT:
  68. C-type natriuretic peptide (CNP) is the most potent natriuretic peptide and it relaxes the isolated cavernous smooth muscle by binding to NPR-B.
  69. Protein kinase G-I (PKGI) may induce relaxation via activation of the plasma membrane Ca2 +-ATPase pump, inhibition of IP3 generation, inhibition of Rho-kinase, stimulation of MLCP, and phosphorylation of heat shock proteins.
  70. Reduced penile adenosine levels are associated with priapism.
  71. Calcitonin gene-related peptide is a potent vasodilator released from perivascular nerve fibers.
  72. The erectogenic effects of PGE1 as a pharmaceutic agent have been extensively documented.
  73. All of the following statements about ED are true EXCEPT:
  74. Psychogenic ED is the most common form of ED.
  75. 10% to 19% of cases of ED are neurogenic.
  76. In cases of pelvic fracture, ED can be a result of cavernous nerve injury or vascular insufficiency or both.
  77. There is a decrease in penile tactile sensitivity with increasing age.
  78. In diabetics, impairment of neurogenic and endothelium-dependent relaxation results in inadequate NO release.
  79. All of the following statements about arteriogenic ED are true EXCEPT:
  80. Atherosclerotic or traumatic arterial occlusive disease can decrease the perfusion pressure and arterial flow to the sinusoidal spaces.
  81. Common risk factors associated with arterial insufficiency include hypertension, hyperlipidemia, cigarette smoking, diabetes mellitus, blunt perineal or pelvic trauma, and pelvic irradiation.
  82. Long-distance cycling is also a risk factor for vasculogenic and neurogenic ED.
  83. Lesions in the pudendal arteries are less common in men with ED than in the general population of similar age.
  84. Among men with coronary arterial disease, the prevalence of ED increases while the severity of coronary arterial lesions increases.
  85. All of the following statements are true EXCEPT:
  86. Aging is the single most important contributing factor to ED.
  87. The aging process can affect the central regulatory mechanism, hormonal and neural function, and penile structure.
  88. Diabetes mellitus and metabolic syndrome may affect multiple organ systems and cause premature aging of both central and peripheral structures and molecules that regulate erectile process.
  89. Primary ED may be due to psychogenic cause, inexperience, congenital arterial insufficiency or abnormal venous channels.
  90. Primary ED refers to a recently developed ED of unknown etiology.

Answers

  1. b. Ventral surface.The strength and thickness of the tunica correlate in a statistically significant fashion with location. The most vulnerable area is located on the ventral groove (between the 5 and 7 o'clock positions), where the longitudinal outer layer is absent; most prostheses tend to extrude here (Hsu et al, 1994).*
  2. c. Obturator artery.Nehra and colleagues (2008) studied 79 consecutive patients with a history of ED and noted that 35% had an accessory pudendal artery, typically arising from the obturator artery. In these men, the accessory pudendal was the dominant blood supply in 54% and the only corporal blood supply in 11%.
  3. e. Relaxation of the ischiocavernosus muscles.Sexual stimulation triggers release of neurotransmitters from the cavernous nerve terminals. This results in relaxation of these smooth muscles and the following events: (1) dilation of the arterioles and arteries by increased blood flow in both the diastolic and systolic phases; (2) trapping of the incoming blood by the expanding sinusoids; (3) compression of the subtunical venous plexuses between the tunica albuginea and the peripheral sinusoids, reducing venous outflow; (4) stretching of the tunica to its capacity, which occludes the emissary veins between the inner circular and outer longitudinal layers and further decreases venous outflow; (5) an increase in PO2 (to about 90 mm Hg) and intracavernous pressure (around 100 mm Hg), which raises the penis from the dependent position to the erect state (the full-erection phase); and (6) a further pressure increase (to several hundred millimeters of mercury) can occur with reflex contractions of the ischiocavernosus muscles (rigid-erection phase) during sexual stimulation.
  4. d. Serotonin (5-HT).General pharmacologic data indicate that 5-HT pathways inhibit copulation, but 5-HT may have both facilitory and inhibitory effects on sexual function, depending on the receptor subtype, the receptor location, and the species investigated (de Groat and Booth, 1993).
  5. b. NO released by endothelial nitric oxide synthase (eNOS) contained in the terminals of the cavernous nerve initiates the erection process, whereas nitric oxide released from neuronal nitric oxide synthase (nNOS) in the endothelium helps maintain erection. The consensus is that NO derived from nNOS in the nitrergic nerves is responsible for the initiation whereby NO from eNOS contributes to the maintenance of smooth muscle relaxation and erection (Hurt et al, 2002).
  6. d. It increases visually stimulated erections. Mulligan and Schmitt (1993) concluded that testosterone (1) enhances sexual interest; (2) increases the frequency of sexual acts; and (3) increases the frequency of nocturnal erection, but has little or no effect on fantasy-induced or visually stimulated erections.
  7. a. Hydrochlorothiazide. Data from a large U.K. trial showed that twice as many men taking thiazides for mild hypertension reported ED than those treated with propranolol or placebo.
  8. c. Low prolactin.Many of the effects of uremia can potentially contribute to the development of ED, including disturbance of the hypothalamic-pituitary-testis sex hormone axis, hyperprolactinemia, accelerated atheromatous disease, and psychologic factors (Ayub and Fletcher, 2000).
  9. d. GABABreceptors are pro-erectile. γ-Aminobutyric acid (GABA) activity in the paraventricular nucleus of the hypothalamus (PVN) provides a mechanism to balance (inhibit) proerectile signaling.
  10. e. Latch state refers to a period of smooth muscle relaxation after prolonged contraction.Smooth muscle has the ability to maintain tension for prolonged periods with minimal energy expenditure. This efficiency has been termed the latch state and is critical for sustaining the "basal" tone of the smooth muscle.
  11. b. Upregulation of nNOS expression has been found in the corpus cavernosum of aging and diabetic rats.Downregulation of nNOS expression has been found in the corpus cavernosum of aging rats (Carrier et al, 1997), castrated rats (Penson et al, 1996), and diabetic rats (Rehman et al, 1997).
  12. c. Reduced penile adenosine levels are associated with priapism.Excessive adenosine accumulation in the penis, coupled with increased A(2B)R signaling, contributes to priapism in two independent lines of mutant mice.
  13. a. Psychogenic ED is the most common form of ED.Previously, psychogenic impotence was believed to be the most common, thought to affect 90% of impotent men (Masters and Johnson, 1965). This belief has given way to the realization that ED is usually a mixed condition that may be predominantly functional or physical.
  14. d. Lesions in the pudendal arteries are less common in ED men than in the general population of similar age. Erectile dysfunction and cardiovascular disease share the same risk factors such as hypertension, diabetes mellitus, hypercholesterolemia, and smoking (Feldman et al, 1994; Martin-Morales et al, 2001). Lesions in the pudendal arteries are much more common in ED men than in the general population of similar age.Interestingly, natural remission and progression do occur in a substantial number of men with erectile dysfunction. The association of body mass index with remission and progression, as well as the association of smoking and health status with progression, offer potential avenues for facilitating remission and delaying progression using lifestyle intervention (Travison et al, 2007).
  15. e. Primary ED refers to a recently developed ED of unknown etiology.Primary ED refers to a lifelong inability to initiate and/or maintain erections beginning with the first sexual encounter. Although most cases are caused by psychologic factors, a small number of afflicted men do have a physical cause resulting from maldevelopment of the penis or the blood and nerve supply. Primary psychologic dysfunction is usually related to anxiety about sexual performance stemming from adverse childhood events, traumatic early sexual experience, or misinformation.

Chapter review

  1. Intracorporal smooth muscle is contracted in the flaccid state due to intrinsic myogenic activity, adrenergic neurotransmission, and endothelium-derived contracting factors.
  2. Sexual stimulation triggers release of neurotransmitters from the cavernous nerve terminals. This results in relaxation of the smooth muscles and (a) dilation of arteries; (b) trapping of incoming blood by the expanding sinusoids; (c) compression of the subtunical venous plexuses between the tunica albuginea and the peripheral sinusoids reducing venous outflow; (d) stretching of the tunica to capacity, which occludes the emissary veins; (e) an increase in PO2; and (f) further pressure increases with contraction of the ischiocavernosus muscles.
  3. The sympathetic system causes detumescence (norepinephrine is the neural transmitter).
  4. Thiazide diuretics may be responsible for impotence. Drugs most commonly associated with ED are antiandrogens, antidepressants, and antihypertensives.
  5. Luteinizing hormone-releasing hormone agonists result in the reduction of sexual desire in 70% of patients.
  6. Sexual dysfunction is a common event after the induction of antiretroviral therapy.
  7. The prevalence of ED is three times higher in diabetic men, occurs at an earlier age, and increases with the duration of the disease.
  8. The metabolic syndrome consisting of glucose intolerance, insulin resistance, obesity, dyslipidemia, and hypertension increases the risk of ED.
  9. About half of people with chronic renal failure have significant sexual dysfunction. Moreover, following transplantation about half continue to have ED.
  10. Primary ED is a lifelong inability to initiate or maintain an erection. In most cases it is psychogenic, but in a small number it is due to maldevelopment of the penis and/or blood and nerve supply.
  11. Aging is the single most important contributing factory to ED.
  12. Endothelial dysfunction is the final common pathway to ED in patients with hyperlipidemia, diabetes mellitus, hypertension, and chronic renal failure.
  13. The strength and thickness of the tunica are correlated in a statistically significant fashion with location. The most vulnerable area is located on the ventral groove (between the 5 and 7 o'clock positions), where the longitudinal outer layer is absent; most prostheses tend to extrude here.
  14. Testosterone (1) enhances sexual interest; (2) increases the frequency of sexual acts; and (3) increases the frequency of nocturnal erection, but has little or no effect on fantasy-induced or visually stimulated erections.
  15. ED is usually a mixed condition that may be predominantly functional or physical.

* Sources referenced can be found in Campbell-Walsh Urology, 11th Edition, on the Expert Consult website.