Pathophysiology of the Penis

Development

Normal reproductive development in male dogs and cats is dependent on exposure of the embryologic urogenital sinus and mesonephric (Wolffian) ducts to androgens during the middle third of gestation (between 20 and 40 days before birth). At this stage of development, the urogenital sinus consists of a pelvic portion that extends from the bladder to the ischial arch and from which the urethra is derived and also a phallic portion that is associated with the genital tubercle. The epithelial lining of the phallic portion expands along the genital tubercle as a solid cord called the urethral plate and hollows to form a canal. Mesenchymal proliferation on both sides of the urethral plate enlarges the urogenital folds, leading to the establishment of a median urethral groove on the ventral surface of the genital tubercle. The elongating genital tubercle develops into the penis and the urogenital folds fuse ventrally along the entire length of the genital tubercle, establishing the penile urethra. The erectile tissue of the corpus spongiosum is formed by differentiation of mesodermal tissues within the urethral folds, and it advances along the urethra as fusion of the urethral folds progresses. The scrotal swelling that arises lateral to the urogenital folds gradually moves caudomedially and the caudal parts enlarge and fuse in the midline to form the scrotum and the scrotal raphe. The prepuce develops from a separation of two layers of ectodermal cells that originate on the distal tip of the penis. In prepubertal dogs, the separation of ectodermal layers forms an incomplete ring with a ventral connection between the under surface of the glans of the penis and prepuce, known as the frenulum. In contrast to dogs, the prepuce of prepubertal cats is circumferentially adhered to the glans. In both species, this penile-preputial attachment prevents extension of the glans from the prepuce during erection. The normal preputial mucosa is composed of stratified squamous epithelium. When substitutes for preputial mucosa are needed during a surgical repair, buccal or intestinal mucosa has been successfully used as a substitute [1].

During embryonic development, the urethra is reported to arise from the fusion of paired free edges of the urethral folds, resulting in a closure of the urethral fossa after rupture of the urethral membrane [2]. However, subsequent research was unable to detect either fusion of the urethral folds or rupture of the urogenital membrane so the precise embryologic development of the urethra remains unclear [3]. What is not in dispute is that, in the absence of androgens (testosterone or dihydrotestosterone) or androgen receptors, the mesonephric ducts, penis, and penile urethra do not develop [4]. In addition, prenatal androgen exposure in female fetal dogs and cats masculinizes the urogenital sinus and allows persistence of the mesonephric ducts [5].

Anatomy and Physiology

The prepuce is a fold of skin that covers the glans penis when the penis is not erect. The prepuce consists of an external lamina and an internal lamina, which are continuous at the preputial opening. The internal lamina terminates at the fornix, where it becomes continuous with the skin of the glans, while the external lamina is the haired skin of the outer surface. The prepuce is suspended from the ventral abdomen by preputial ligaments and muscles. These modified cutaneous muscles keep the prepuce over the glans of the penis in the retracted state. The penis is attached to the ischial arch by the crura and ischiocavernosus muscles. The penis consists of the root, body, and glans. The root is not externally visible. The body of the penis is made up of cavernous tissue. The distal corpus cavernosum is ossified (os penis) and extends distally from just behind the bulb to the tip of the glans [6]. A ventral groove within the os penis accommodates the urethra, the proximal end of which is a common site of urethral obstruction with urinary calculi [4]. The glans penis of the dog is divided into two principal parts: the pars longa glandis and the bulbus glandis. Applying pressure behind the bulbus glandis results in contraction of the ischiourethralis muscle, which inserts onto a fibrous ring that encircles the common trunk of the left and right dorsal veins of the penis. Contraction of the ischiourethralis muscle occludes the dorsal vein, resulting in engorgement of the cavernous tissues within the penis. Additionally, the caudal twisting of the penis during tail-to-tail position taken during the genital lock in dogs occludes the emissary veins [7]. Transection of the ischiourethralis muscle prevents canine erection, including partial penile erection of the bulbus glandis [8]. Detumescence requires relaxation of these muscle fibers, which allows drainage through the pudendal veins.

On the glans of the adult intact cat penis is a band about 4 mm wide, consisting of 120 to 150 backward-pointing keratinized spines encircling the glans and forming 6 to 8 circular rows [9]. These spines are androgen-sensitive and an indirect indicator of the presence of male hormones in cats [9]. The spines completely regress 13 to 24 weeks after castration [9]. The spines are an adaptation to provide additional stimulation during breeding to induce ovulation [9]. However, the smooth penis of the castrated male will still cause ovulation [9]. The urethral epithelium is also androgen-sensitive in male cats and is significantly higher with a lower fibrocyte density than in castrates [4]. The presence of penile spines can be used to identify incompletely castrated males [10]. Additional endocrine stimulation testing can be used to confirm a diagnosis of incomplete castration beginning with a venous blood sample collected for baseline testosterone concentration. Post-stimulation blood samples are collected 30 and 120 minutes after intravenous (500 IU/cat) administration of human chorionic gonadotropin (HCG) [10]. Testosterone concentrations increase by 5- and 10-fold in 30 and 120 minutes, respectively [10]. HCG administration by intravenous injection produces a more consistent stimulation than intramuscular or subcutaneous administration.

The vascular supply of the prepuce is through the dorsal artery and vein of the penis and a branch of the external pudendal vessels. The lymphatic drainage is to the preputial and superficial inguinal lymph nodes. The blood supply to the corpus cavernosum penis is by the deep and dorsal penile arteries. Erection occurs when an increase in cavernosal arterial blood flow is coupled with a decrease in venous outflow from the corpora via the dorsal penile vein, resulting in sinusoidal relaxation and filling of the corpora cavernosum.

The corpus cavernosum is a conglomeration of venous sinusoids that functions as erectile tissue. The caudal epigastric artery can serve as a donor vessel to increase blood flow to the corpus cavernosa when flow has been reduced to the dorsal penile artery [11]. In the dog, the rapid engorgement of the bulb also depends on dilation of helicine arteries in the erectile tissue along with venous blood from the pars longa glandis. An elaborate venous drainage system connects the corpora to the iliac veins, and leakage in this system is an important cause of impotence in man. The circumflex vein drains into the deep dorsal vein and provides additional drainage to the distal two thirds of the cavernous bodies. Minor cavernous vein leakage in the presence of normal arterial flow has minimal effect on the development of erection [12]. However, penile rigidity can be prevented by excessive cavernous vein outflow resulting from pathologic changes in the cavernous smooth muscles, abnormal local venous drainage, insufficient neurotransmitter release, and alteration of the cavernous endothelium []. The corporal bodies are easily accessible to percutaneous needle punctures and can be used as an emergency vascular access in dogs with severe hypovolemia [14].

The spinal nuclei for control of erection are located in the intermediolateral gray matter at the S1-S3 and T12-L3 in dogs [15]. The sacral nuclei axons fuse to form the pelvic nerve (nervus erigens), whose visceral parasympathetic efferent fibers (cavernous nerves) are located on the lateral aspect of the urethra [15]. The cavernous nerves penetrate the tunica albuginea of the corpora cavernosa alone and enter with the deep penile artery and cavernous vein [15]. These nerves can be damaged easily during urogenital surgery. Desensitization of the glans penis results in genital disorientation during mating and also intromission failure in cats [16] but not in dogs [17]. In the dog, thoracolumbar sympathectomy results in reduced mating frequency, but when copulation does occur, the genital lock, which is highly dependent on vasomotor changes in the penis, remains unaltered [18]. Erection can be induced via electrostimulation of the cavernous nerves along the posterolateral aspect of the prostate [11]. Erection can also be induced in castrated males, but a higher threshold level of energy is needed. The minimum voltage required to induce erection in intact dogs (0.2 - 4.0 V) was half of that of castrates (0.6 - 12 V) [19].

The hypogastric nerve is a peripheral sympathetic nerve that plays a crucial role in the transport of sperm through the vas deferens, secretion of accessory gland fluid, and bladder neck closure. Pressure receptors for ejaculation are located in the body of the penis beneath the surface of the epithelium. Ejaculation failure occurs when sympathetic pathways from the lumbar splanchnic nerve are injured bilaterally in the retroperitoneum or within the pelvis, resulting in impaired bladder neck closure but unimpaired seminal emission [20]. Bilateral transection of the hypogastric nerves in dogs results in retrograde ejaculation, as the hypogastric nerves are the sole pathway of efferent signals for active bladder neck contraction at ejaculation [20]. The function of the hypogastric nerve can be returned after hypogastric nerve-hypogastric nerve reattachment [20].

The male dog has two ejaculatory reflexes that are mainly controlled by somatic signals via the pudendal nerve from which the dorsal nerve of the penis arises. The first ejaculatory reflex occurs following intromission, lasts for 15 to 30 seconds, and is characterized by intense pelvic movement, alternate stepping of the back legs, rapid engorgement of the glans penis, contraction of the bulbospongiosus muscle, and expulsion of the sperm-rich fraction of the ejaculate. The second ejaculatory reflex occurs during the genital lock, lasts for 10 to 30 minutes, and is characterized by rhythmic contraction of the urethral muscles, bulbospongiosus muscle, and ischiocavernosus muscle, and expulsion of prostatic fluid.

Congenital Penile and Preputial Abnormalities

Hypospadias

Hypospadias is an uncommon congenital abnormality of male external genitalia in dogs and cats [21]. The exact frequency is unknown because severe cases result in neonatal death and mild cases may go undiagnosed [21]. Few reports have been published of this condition in cats and a review of 2.2 million canine medical records from 17 veterinary teaching hospitals yielded only 66 cases [21]. Hypospadias occurs when development of the urethra is incomplete. Hypospadias is defined by the location of the urethral orifice: glandular, penile, penoscrotal, scrotal, and perineal [1]. Hypospadias may result from fetal androgen deficiency, 5-α-reductase deficiency, or tissue resistance to androgens [22]. Hypospadias also occurs frequently with intersex conditions. Affected individuals are genetically male (XY) with abnormally formed external genitalia and bilateral cryptorchidism. In addition, a familial genetic component to hypospadias in dogs may exist as the Boston terrier breed is overrepresented with this condition [21]. Developmental preputial defects, such as those occurring with hypospadias, can be surgically corrected by manipulation of the preputial muscles to provide cranial advancement of the prepuce over the penis. A caudal superficial epigastric arterial pedicle flap has been suggested as a source of skin for preputial reconstruction [23]. Blood supply to the flap site, skin availability, type and size of defect, and restoration of function following reconstruction all must be considered before surgery.

Persistent Frenulum

Persistence of the penile frenulum occurs infrequently in dogs and cats. Common clinical signs of a persistent frenulum include pain during erection, intromission failure, balanoposthitis, and dysuria [24]. In non-breeding animals, no clinical signs may be associated with the condition. Surgical ligation and sectioning of the frenulum are curative and the prognosis is excellent [24].

Phimosis

Phimosis, a rare disorder in dogs and cats, is the inability to extend the glans penis beyond the preputial orifice and is characterized by a narrow preputial opening [25]. Few published reports exist on abnormally small preputial openings in dogs. Clinical signs of phimosis vary from an asymptomatic narrowing of the preputial orifice, to preputial urine retention with posthitis, to complete occlusion of the preputial orifice with signs of urinary obstruction. Surgical repair of phimosis includes resection of a small wedge of the dorsal preputial margin followed by apposition of the ipsilateral preputial skin and mucosal edges [26]. Care must be taken that the new preputial opening is not made too large so as to allow continual protrusion of the penis.

Acquired Penile and Preputial Abnormalities

Paraphimosis

Paraphimosis is an inability to completely withdraw the penis into the prepuce [27]. It is most commonly seen in young intact males and may occur secondary to trauma, masturbation, sexual hyperactivity or the presence of a female in estrus, constriction of preputial hair around the penis, inability of the preputial muscles to pull the prepuce back over glans penis after erection, pseudohermaphroditism, neurologic deficits in dogs with posterior paresis, or as an idiopathic event. Prolonged exposure of the glans penis causes vascular engorgement, epithelial drying, edema, and inflammation, thus exacerbating the paraphimosis [27]. The condition becomes worse with time and may progress to corporal thrombosis.

The conservative treatment is to replace the penis in the prepuce as soon as possible with the aid of regional anesthesia. Penile edema can be relieved by massage. A preputiotomy may be necessary to accommodate replacement of the penis. If a preputiotomy is performed, the tissues should be carefully closed to the original state. In cases where nonsurgical management has failed, preputial lengthening (preputioplasty), preputial muscle myorrhaphy (shortening of the preputial muscles), and penile amputation with concurrent urethrostomy have been reported to correct the paraphimosis [28]. To amputate the penis, the prepuce is reflected caudally following excision of the suspensory structures and ligation of the preputial blood supply. The dorsal and deep arteries of the penis, both branches of the perineal artery, are ligated when the penis is amputated from the ischial attachments [29]. A segment of the urethra should be retained for urethrostomy.

Phallopexy is another method for treatment of paraphimosis that results from the creation of a permanent adhesion between the dorsal surface of the penis and the preputial mucosa [27]. Phallopexy should be performed on the dorsal surface of the penile shaft to avoid the urethra and the looser preputial tissues present on the ventral side [27]. During this procedure, care must be taken to avoid incising into the underlying cavernous tissue [27]. Urine pooling and balanoposthitis may result if this procedure is performed too far caudally in the prepuce [27]. The penile tip should be retained inside the preputial orifice 5 to 10 mm when the penis is in the non-erect state [25].

Priapism

Priapism, an uncommon disorder in cats and dogs, is a persistent penile erection in the absence of sexual excitation that results in pain and dysuria. Priapism is most likely to develop secondary to trauma during mating or during castration, genitourinary infection or inflammation, or constipation resulting in persistent pelvic nerve stimulation, neurologic dysfunction (e.g., distemper-associated inflammatory lesions within the spinal cord), or from decreased venous outflow resulting from an occlusive thromboembolism or mass.30 This form of priapism (low-flow priapism) is associated with a poorer prognosis as the damage from the ischemia is more severe.31 In low-flow priapism, the danger is not in the priapism itself, but in the reduction of oxygen and an elevation of carbon dioxide partial pressure resulting from the hemostasis within the cavernous tissues.32 High-flow priapism results from a persistent increase in blood flow from a neuro-arterial disturbance or the development of arteriovenous fistulae.31

Arteriovenous fistulae are reported infrequently dogs and cats. Occasionally, arteriovenous fistulae develop on the prepuce.33 Clinically, a preputial arteriovenous fistula manifests as a network of large tortuous pulsating blood vessels that enlarge gradually over several months.33 Diagnosis can be made using angiography. Angiography is the optimal technique for planning treatment of arteriovenous communications. Characteristic angiographic findings of arteriovenous fistulae include premature venous filling, absence of the normal capillary phase, and reduced distal arterial flow.34 Conservative surgical treatment for arteriovenous fistulae involves ligating the proximal supplying vessels to reduce blood flow through the fistula.33 The prognosis for dogs with arteriovenous fistulae depends on the size and site of the fistula and the degree of cardiovascular failure at the time of diagnosis.34

A penile cavernogram can be used to identify thromboemboli or masses resulting in decreased venous outflow as well as the extent of venous outflow impairment.35 Dynamic cavernosography consists of infusing heparinized saline at increasing rates (3-25 ml/minute) until the intracavernous pressure plateaus at 80 mm Hg (full erection pressure) followed by infusion of 60% Hypaquetm meglumine contrast medium to opacify abnormally draining veins.13 Butterfly needles (21-gauge) can be inserted into the corpora cavernosa and connected to a pressure transducer. Dynamic cavernosometry should be performed following erection induction with administration of intracavernous papaverine (2-10 mg).11,36 Papaverine decreases arterial resistance and increases venous resistance. Intracavernosal injection of epinephrine, norepinephrine, or phenylephrine prevents penile erection.37

Regardless of the primary cause, stagnation of blood containing a decreased concentration of oxygen and an increased concentration of carbon dioxide in the cavernous tissues results in edema formation with further venous occlusion and eventual irreversible fibrosis in the main venous outflow tracts of the penis. Histologically, severe cavernosal congestion with large hemoglobin crystals and organizing fibrin thrombi develop.30 Conservative treatment consists of various combinations of cold water compresses, penile lubrication, corticosteroids, antibiotics and diuretics. Because the penis cannot be manually reduced into the prepuce, it becomes congested, dry, and eventually necrotic. Medical treatment with intravenous benzotropine mesylate (0.015 mg/kg), an anticholinergic and antihistaminergic drug, has been used successfully in horses but must be administered within 6 hours after the onset of priapism.38 Increasing venous outflow via drainage and flushing of the cavernous tissues with heparinized saline (0.9% NaCl) solution in combination with infusion of phenylephrine39 or epinephrine40 has also been reported for the treatment of low-flow priapism. However, the penis may be irreparably damaged at the time of initial presentation, necessitating amputation and urethrostomy.

Trauma

Traumatic lesions of the penis and prepuce may result from bite wounds or automobile accidents, in association with a pelvic injury or during sexual activity while the penis is erect. Treatment of traumatic lesions of the penis varies depending on the damage. Emergency therapy should be directed at controlling hemorrhage and maintaining patency of the urethra. If the tip of the penis is lacerated, it can be debrided and sutured. A tourniquet around the proximal penis will decrease the amount of blood in the field and improve the precision with which sutures are placed. If damage is extensive, it may be necessary to amputate larger parts of the traumatized penis. A wedge-shaped incision should be made through the corpora tissues, and the os penis distal to the lesion is removed with a rongeur [29]. The cavernous body of the penis is sutured and the urethral orifice is re-established on the ventral body of the penis. Following preputial reconstruction, daily penile extrusion should be carried out to prevent adhesions between the penis and the prepuce.

The os penis can be fractured as a result of trauma; however, this injury is rare [41]. Fracture of the os penis may result in occlusion or disruption of the penile urethra. Presenting clinical signs include dysuria, stranguria, pollakiuria, and hematuria. In acute cases, pain can be elicited over the fracture site. Urethral catheterization may also indicate an obstruction at the level of the os penis. If a urinary catheter can be passed and the os penis fragments are well aligned, the fracture may heal satisfactorily with placement of an indwelling catheter for 5 to 21 days after the injury [42]. Distraction of the fracture fragments or swelling-associated trauma can result in urethral occlusion, which necessitates a urethrostomy to re-establish urine flow. A prescrotal urethrotomy will allow catheterization of the bladder if a urethral catheter will not pass through the penile urethra and will preserve the male's reproductive function [29]. The retractor penis muscle should be reflected to one side because splitting the retractor penis muscle will result in muscle contraction and premature closure of the urethrostomy site [29].

Radiography is necessary for definitive diagnosis of an os penis fracture [43]. Surgical repair of the fracture is indicated if urethral obstruction is occurring. A rubber tourniquet is placed caudal to the os penis to minimize bleeding during surgery and a longitudinal incision is made through the epithelium on the lateral aspect of the penis [43]. A small periosteal elevator should be passed along the urethral groove in order to separate the corporal bodies from the os penis. Ventral ridges of the os penis can be debrided using bone-cutting forceps to allow expansion of the urethra within the urethral groove during healing of the fracture to prevent urethral narrowing. A finger plate [41] and Kirschner wires [44] have been used in the surgical repair of os penis fractures. Dorsal positioning of the screws through the os penis will prevent occlusion of the urethra [43]. In chronic cases of os penis fractures, palpation of the penis may reveal slight thickening over the fracture site [41]. Chronic dysuria or complete urethral obstruction following bone callus formation along the fracture site impinging the urethra may occur within 2 years of the trauma [41,43,45]. A retrograde urethrogram using a contrast agent will confirm location of urethral narrowing [43]. Surgical repair is accomplished by removing excess bone and fibrous tissue [43]. The effect of a fracture of the os penis on breeding ability has not been reported.

Neoplasia

Neoplasms of the glans penis and penis are not common.28 Neoplasia common to skin will occur on the penis and prepuce; this includes papilloma, hemangioma, melanoma, and histiocytoma [28]. The transmissible venereal tumor can be found on the glans penis and prepuce. It is a contagious, neoplastic disease, transmitted by transplantation of viable tumor cells during mating [46]. Malignant neoplasms include mast cell sarcoma, reticulum cell sarcoma, melanoma, hemangiosarcoma, squamous cell carcinoma, and venereal sarcoma. Squamous carcinoma may be seen on the epithelium of the glans; a hemangiosarcoma of the cavernous tissues may occur [28]. Clinical signs include persistent or intermittent preputial discharge with the presence of solitary or multiple cauliflower-like, papillary, multilobulated or pedunculated masses. Any of these lesions should be widely excised and identified, and chemotherapy and/or radiation therapy should be instituted if indicated based on tumor identification.