Gynecology_Novak

Gynecology_Novak. Vagina The vagina forms in the 3rd month of embryonic life. While the uterovaginal canal is forming, the endodermal tissue of the sinusal tubercle begins to proliferate, forming a pair of sinovaginal bulbs, which become the inferior 20% of the vagina. The most inferior portion of the uterovaginal canal becomes occluded by a solid core of tissue (the vaginal plate), the origin of which is unclear. Over the subsequent 2 months, this tissue elongates and canalizes by a process of central desquamation, and the peripheral cells become the vaginal epithelium. The fibromuscular wall of the vagina originates from the mesoderm of the uterovaginal canal.


Gynecology_Novak

Gynecology_Novak. Accessory Genital Glands The female accessory genital glands develop as outgrowths from the urethra (paraurethral or Skene) and the definitive urogenital sinus (greater vestibular or Bartholin). Although the ovaries first develop in the thoracic region, they ultimately arrive in the pelvis by a complicated process of descent. This descent by differential growth is under the control of a ligamentous cord called the gubernaculum, which is attached to the ovary superiorly and to the fascia in the region of the future labia majora inferiorly. The gubernaculum becomes attached to the paramesonephric ducts at their point of superior fusion so that it becomes divided into two separate structures. As the ovary and its mesentery (the mesovarium) are brought into the superior portion of the broad ligament, the more proximal part of the gubernaculum becomes the ovarian ligament, and the distal gubernaculum becomes the round ligament.


Gynecology_Novak

Gynecology_Novak. Early in the 5th week of embryonic life, folds of tissue form on each side of the cloaca and meet anteriorly in the midline to form the genital tubercle (Fig. 5.12). With the division of the cloaca by the urorectal septum and consequent formation of the perineum, these cloacal folds are known anteriorly as the urogenital folds and posteriorly as the anal folds. The genital tubercle begins to enlarge. In the female embryo, its growth gradually slows to become the clitoris, and the urogenital folds form the labia minora. In the male embryo, the genital tubercle continues to grow to form the penis, and the urogenital folds are believed to fuse to enclose the penile urethra. Figure 5.12 The comparative development of the female and male external genitalia. A: In both sexes, the development follows a uniform pattern through the 7th week and thereafter begins to differentiate. B: The male external genitalia. C: The female external genitalia.


Gynecology_Novak

Gynecology_Novak. Lateral to the urogenital folds, another pair of swellings develops, known in the indifferent stage as labioscrotal swellings. In the absence of androgens, they remain largely unfused to become the labia majora. The definitive urogenital sinus gives rise to the vaginal vestibule, into which open the urethra, vagina, and greater vestibular glands. Clinical Correlations Developmental abnormalities of the urinary and genital systems can be explained and understood by a consideration of female and male embryologic development. Because of the intertwined development of these two systems, abnormalities in one may be associated with abnormalities in the other (25). Urinary-tract anomalies arise from defects in the ureteric bud, the metanephric blastema, or their inductive interaction with each other.


Gynecology_Novak

Gynecology_Novak. Urinary-tract anomalies arise from defects in the ureteric bud, the metanephric blastema, or their inductive interaction with each other. Renal Agenesis Renal agenesis occurs when one or both ureteric buds fail to form or degenerate, and the metanephric blastema is therefore not induced to differentiate into nephrons. Bilateral renal agenesis is incompatible with postnatal survival, but infants with only one kidney usually survive, and the single kidney undergoes compensatory hypertrophy. Unilateral renal agenesis is often associated with absence or abnormality of fallopian tubes, uterus, or vagina—the paramesonephric duct derivatives.


Gynecology_Novak

Gynecology_Novak. Abnormalities of Renal Position Abnormalities of renal position result from disturbance in the normal ascent of the kidneys. A malrotated pelvic kidney is the most common result; a horseshoe kidney, in which the kidneys are fused across the midline, occurs in about 1 in 600 individuals and has a final position lower than usual because its normal ascent is prevented by the root of the inferior mesenteric artery.


Gynecology_Novak

Gynecology_Novak. Duplication of the Upper Ureter and Renal Pelvis Duplication of the upper ureter and renal pelvis is relatively common and results from premature bifurcation of the ureteric bud. If two ureteric buds develop, there will be complete duplication of the collecting system. In this situation, one ureteric bud will open normally into the posterior bladder wall, and the second bud will be carried more distally within the mesonephric duct to form an ectopic ureteral orifice into the urethra, vagina, or vaginal vestibule; incontinence is the primary presenting symptom. Most of the aforementioned urinary abnormalities remain asymptomatic unless obstruction or infection supervenes. In that case, anomalous embryologic development must be included in the differential diagnosis.


Gynecology_Novak

Gynecology_Novak. Because the early development of the genital system is similar in both sexes, congenital defects in sexual development, usually arising from a variety of chromosomal abnormalities, tend to present clinically with ambiguous external genitalia. These conditions are known as intersex conditions or hermaphroditism and are classified according to the histologic appearance of the gonads. True Hermaphroditism Individuals with true hermaphroditism have both ovarian and testicular tissue, most commonly as composite ovotestes but occasionally with an ovary on one side and a testis on the other. In the latter case, a fallopian tube and single uterine horn may develop on the side with the ovary because of the absence of local AMH. True hermaphroditism is an extremely rare condition associated with chromosomal mosaicism, mutation, or abnormal cleavage involving the X and Y chromosomes.


Gynecology_Novak

Gynecology_Novak. Pseudohermaphroditism In individuals with pseudohermaphroditism, the genetic gender indicates one gender, whereas the external genitalia have characteristics of the other gender. Males with pseudohermaphroditism are genetic males with feminized external genitalia, most commonly manifesting as hypospadias (urethral opening on the ventral surface of the penis) or incomplete fusion of the urogenital or labioscrotal folds. Females with pseudohermaphroditism are genetic females with virilized external genitalia, including clitoral hypertrophy and some degree of fusion of the urogenital or labioscrotal folds. Both types of pseudohermaphroditism are caused either by abnormal levels of sex hormones or abnormalities in the sex hormone receptors. Another major category of genital tract abnormalities involves various types of uterovaginal malformations, which occur in 0.16% of women (Fig. 5.13) (26). These malformations are believed to result from one or more of the following situations: 1.


Gynecology_Novak

Gynecology_Novak. Improper fusion of the paramesonephric ducts. 2. Incomplete development of one paramesonephric duct. 3. Failure of part of the paramesonephric duct on one or both sides to develop. 4. Absent or incomplete canalization of the vaginal plate. Figure 5.13 Types of congenital abnormalities. A: Double uterus (uterus didelphys) and double vagina. B: Double uterus with single vagina. C: Bicornuate uterus. D: Bicornuate uterus with a rudimentary left horn. E: Septate uterus. F: Unicornuate uterus. Vagina A sagittal section of the female pelvis is presented in Fig. 5.14. The vagina is a hollow fibromuscular tube extending from the vulvar vestibule to the uterus.


Gynecology_Novak

Gynecology_Novak. Vagina A sagittal section of the female pelvis is presented in Fig. 5.14. The vagina is a hollow fibromuscular tube extending from the vulvar vestibule to the uterus. In the dorsal lithotomy position, the vagina is directed posteriorly toward the sacrum, but its axis is almost horizontal in the upright position. It is attached at its upper end to the uterus just above the cervix. The spaces between the cervix and vagina are known as the anterior, posterior, and lateral vaginal fornices. Because the vagina is attached at a higher point posteriorly than anteriorly, the posterior vaginal wall is about 3 cm longer than the anterior wall.


Gynecology_Novak

Gynecology_Novak. The posterior vaginal fornix is separated from the posterior cul-de-sac and peritoneal cavity by the vaginal wall and peritoneum. This proximity is clinically useful, both diagnostically and therapeutically. Culdocentesis, a technique in which a needle is inserted just posterior to the cervix through the vaginal wall into the peritoneal cavity, is used to evaluate intraperitoneal hemorrhage (e.g., ruptured ectopic pregnancy, hemorrhagic corpus luteum, other intraabdominal bleeding), pus (e.g., pelvic inﬂammatory disease, ruptured intra-abdominal abscess), or other intra-abdominal ﬂuid (e.g., ascites). Incision into the peritoneal cavity from this location in the vagina, known as a posterior colpotomy, can be used as an adjunct to laparoscopic excision of adnexal masses, with removal of the mass intact through the posterior vagina. Figure 5.14 The pelvic viscera. A sagittal section of the female pelvis with the pelvic viscera and their relationships.


Gynecology_Novak

Gynecology_Novak. Figure 5.14 The pelvic viscera. A sagittal section of the female pelvis with the pelvic viscera and their relationships. The vagina is attached to the lateral pelvic wall with endopelvic fascial connections to the arcus tendineus (white line), which extends from the pubic bone to the ischial spine. This connection converts the vaginal lumen into a transverse slit with the anterior and posterior walls in apposition; the lateral space where the two walls meet is the vaginal sulcus. Lateral detachments of the vagina are recognized in some cystocele formations (lateral cystoceles or paravaginal defects).


Gynecology_Novak

Gynecology_Novak. The opening of the vagina may be covered by a membrane or surrounded by a fold of connective tissue called the hymen. This tissue is usually replaced by irregular tissue tags after sexual activity and childbirth occur. The lower vagina is somewhat constricted as it passes through the urogenital hiatus in the pelvic diaphragm; the upper vagina is more spacious. The entire vagina is characterized by its distensibility, which is most evident during childbirth. The vagina is closely applied anteriorly to the urethra, bladder neck and trigonal region, and posterior bladder; posteriorly, the vagina lies in association with the perineal body, anal canal, lower rectum, and posterior cul-de-sac. It is separated from both the lower urinary and gastrointestinal tracts by their investing layers of fibromuscular elements known as the endopelvic fascia. Figure 5.15 The uterus, fallopian tubes, and ovaries. The vagina is composed of three layers: 1.


Gynecology_Novak

Gynecology_Novak. Figure 5.15 The uterus, fallopian tubes, and ovaries. The vagina is composed of three layers: 1. Mucosa—nonkeratinized stratified squamous epithelium, without glands. Vaginal lubrication occurs primarily by transudation, with contributions from cervical and Bartholin gland secretions. The mucosa has a characteristic pattern of transverse ridges and furrows known as rugae. It is hormonally sensitive, responding to stimulation by estrogen with proliferation and maturation. The mucosa is colonized by mixed bacterial ﬂora with lactobacillus predominant; normal pH is 3.5 to 4.5. 2. Muscularis—connective tissue and smooth muscle, loosely arranged in inner circular and outer longitudinal layers. 3. Adventitia—endopelvic fascia, adherent to the underlying muscularis. Blood Supply The blood supply of the vagina includes the vaginal artery and branches from the uterine, middle rectal, and internal pudendal arteries.


Gynecology_Novak

Gynecology_Novak. Blood Supply The blood supply of the vagina includes the vaginal artery and branches from the uterine, middle rectal, and internal pudendal arteries. Innervation The innervation of the vagina is as follows: the upper vagina—uterovaginal plexus; the distal vagina—pudendal nerve. Uterus The uterus is a fibromuscular organ usually divided into a lower cervix and an upper corpus or uterine body (Fig. 5.15). The portion of cervix exposed to the vagina is the exocervix or portio vaginalis. It has a convex round surface with a circular or slitlike opening (the external os) into the endocervical canal. The endocervical canal is about 2 to 3 cm in length and opens proximally into the endometrial cavity at the internal os.


Gynecology_Novak

Gynecology_Novak. The cervical mucosa contains both stratified squamous epithelium, characteristic of the exocervix, and mucus-secreting columnar epithelium, characteristic of the endocervical canal. The intersection where these two epithelia meet—the squamocolumnar junction—is geographically variable and dependent on hormonal stimulation. It is this dynamic interface, the transformation zone, which is most vulnerable to the development of squamous neoplasia. In early childhood, during pregnancy, or with oral contraceptive use, columnar epithelium may extend from the endocervical canal onto the exocervix, a condition known as eversion or ectopy. After menopause, the transformation zone usually recedes entirely into the endocervical canal.


Gynecology_Novak

Gynecology_Novak. Production of cervical mucus is under hormonal inﬂuence. It varies from profuse, clear, and thin mucus around the time of ovulation to scant and thick mucus in the postovulatory phase of the cycle. Deep in the mucosa and submucosa, the cervix is composed of fibrous connective tissue and a small amount of smooth muscle in a circular arrangement. The body of the uterus varies in size and shape, depending on hormonal and childbearing status.


Gynecology_Novak

Gynecology_Novak. The body of the uterus varies in size and shape, depending on hormonal and childbearing status. At birth, the cervix and corpus are about equal in size; in adult women, the corpus has grown to two to three times the size of the cervix. The position of the uterus in relation to other pelvic structures is variable and is generally described in terms of positioning—anterior, midposition, or posterior; ﬂexion; and version. Flexion is the angle between the long axis of the uterine corpus and the cervix, whereas version is the angle of the junction of the uterus with the upper vagina. Occasionally, abnormal positioning may occur secondary to associated pelvic pathology, such as endometriosis or adhesions.


Gynecology_Novak

Gynecology_Novak. The uterine corpus is divided into several different regions. The area where the endocervical canal opens into the endometrial cavity is known as the isthmus or lower uterine segment. On each side of the upper uterine body, a funnel-shaped area receives the insertion of the fallopian tubes and is called the uterine cornu; the uterus above this area is the fundus. The endometrial cavity is triangular in shape and represents the mucosal surface of the uterine corpus. The epithelium is columnar and gland forming with a specialized stroma. It undergoes cyclic structural and functional change during the reproductive years, with regular shedding of the superficial endometrium and regeneration from the basal layer. The muscular layer of the uterus, the myometrium, consists of interlacing smooth muscle fibers and ranges in thickness from 1.5 to 2.5 cm. Some outer fibers are continuous with those of the tube and round ligament.


Gynecology_Novak

Gynecology_Novak. Peritoneum covers most of the corpus of the uterus and the posterior cervix and is known as the serosa. Laterally, the broad ligament, a double layer of peritoneum covering the neurovascular supply to the uterus, inserts into the cervix and corpus. Anteriorly, the bladder lies over the isthmic and cervical region of the uterus. Blood Supply The blood supply to the uterus is the uterine artery, which anastomoses with the ovarian and vaginal arteries. Innervation The nerve supply to the uterus is the uterovaginal plexus. Fallopian Tubes The fallopian tubes and ovaries collectively are referred to as the adnexa. The fallopian tubes are paired hollow structures representing the proximal unfused ends of the m¨ullerian duct. They vary in length from 7 to 12 cm, and their function includes ovum pickup, provision of physical environment for conception, and transport and nourishment of the fertilized ovum. The tubes are divided into several regions: 1.


Gynecology_Novak

Gynecology_Novak. The tubes are divided into several regions: 1. Interstitial—narrowest portion of the tube, lies within the uterine wall and forms the tubal ostia at the endometrial cavity. 2. Isthmus—narrow segment closest to the uterine wall. 3. Ampulla—larger diameter segment lateral to the isthmus. 4. Fimbria (infundibulum)—funnel-shaped abdominal ostia of the tubes, opening into the peritoneal cavity; this opening is fringed with numerous fingerlike projections that provide a wide surface for ovum pickup. The fimbria ovarica is a connection between the end of the tube and ovary, bringing the two closer.


Gynecology_Novak

Gynecology_Novak. The tubal mucosa is ciliated columnar epithelium, which becomes progressively more architecturally complex as the fimbriated end is approached. The muscularis consists of an inner circular and outer longitudinal layer of smooth muscle. The tube is covered by peritoneum and, through its mesentery (mesosalpinx), which is situated dorsal to the round ligament, is connected to the upper margin of the broad ligament. Blood Supply The vascular supply to the fallopian tubes is the uterine and ovarian arteries. Innervation The innervation to the fallopian tubes is the uterovaginal plexus and the ovarian plexus.


Gynecology_Novak

Gynecology_Novak. Innervation The innervation to the fallopian tubes is the uterovaginal plexus and the ovarian plexus. Ovaries The ovaries are paired gonadal structures that lie suspended between the pelvic wall and the uterus by the infundibulopelvic ligament laterally and the utero-ovarian ligament medially. Inferiorly, the hilar surface of each ovary is attached to the broad ligament by its mesentery (mesovarium), which is dorsal to the mesosalpinx and fallopian tube. Primary neurovascular structures reach the ovary through the infundibulopelvic ligament and enter through the mesovarium. The normal ovary varies in size, with measurements up to 5 × 3 × 3 cm. Variation in dimension results from endogenous hormonal production, which varies with age and with each menstrual cycle. Exogenous substances, including oral contraceptives, gonadotropin-releasing hormone agonists, or ovulation-inducing medication, may either stimulate or suppress ovarian activity and, therefore, affect size.


Gynecology_Novak

Gynecology_Novak. Each ovary consists of a cortex and medulla and is covered by a single layer of ﬂattened cuboidal to low columnar epithelium that is continuous with the peritoneum at the mesovarium. The cortex is composed of a specialized stroma and follicles in various stages of development or attrition. The medulla occupies a small portion of the ovary in its hilar region and is composed primarily of fibromuscular tissue and blood vessels. Blood Supply The blood supply to the ovary is the ovarian artery, which anastomoses with the uterine artery. Innervation The innervation to the ovary is the ovarian plexus and the uterovaginal plexus. The ureter is the urinary conduit leading from the kidney to the bladder; it measures about 25 cm in length and is totally retroperitoneal in location.


Gynecology_Novak

Gynecology_Novak. The ureter is the urinary conduit leading from the kidney to the bladder; it measures about 25 cm in length and is totally retroperitoneal in location. The lower half of each ureter traverses the pelvis after crossing the common iliac vessels at their bifurcation, just medial to the ovarian vessels. It descends into the pelvis adherent to the peritoneum of the lateral pelvic wall and the medial leaf of the broad ligament and enters the bladder base anterior to the upper vagina, traveling obliquely through the bladder wall to terminate in the bladder trigone. The ureteral mucosa is a transitional epithelium. The muscularis consists of an inner longitudinal and outer circular layer of smooth muscle. A protective connective tissue sheath, which is adherent to the peritoneum, encloses the ureter. Blood Supply The blood supply is variable, with contributions from the renal, ovarian, common iliac, internal iliac, uterine, and vesical arteries.


Gynecology_Novak

Gynecology_Novak. Blood Supply The blood supply is variable, with contributions from the renal, ovarian, common iliac, internal iliac, uterine, and vesical arteries. Innervation The innervation is through the ovarian plexus and the vesical plexus. The bladder is a hollow organ, spherically shaped when full, that stores urine. Its size varies with urine volume, normally reaching a maximum volume of at least 300 mL. The bladder is often divided into two areas, which are of physiologic significance: 1. The base of the bladder consists of the urinary trigone posteriorly and a thickened area of detrusor anteriorly. The three corners of the trigone are formed by the two ureteral orifices and the opening of the urethra into the bladder. The bladder base receives α-adrenergic sympathetic innervation and is the area responsible for maintaining continence. 2. The dome of the bladder is the remaining bladder area above the bladder base. It has parasympathetic innervation and is responsible for micturition.


Gynecology_Novak

Gynecology_Novak. 2. The dome of the bladder is the remaining bladder area above the bladder base. It has parasympathetic innervation and is responsible for micturition. The bladder is positioned posterior to the pubis and lower abdominal wall and anterior to the cervix, upper vagina, and part of the cardinal ligament. Laterally, it is bounded by the pelvic diaphragm and obturator internus muscle. The bladder mucosa is transitional cell epithelium and the muscle wall (detrusor). Rather than being arranged in layers, it is composed of intermeshing muscle fibers. Blood Supply The blood supply to the bladder is from the superior, middle, and inferior vesical arteries, with contribution from the uterine and vaginal vessels. Innervation The innervation to the bladder is from the vesical plexus, with contribution from the uterovaginal plexus.


Gynecology_Novak

Gynecology_Novak. Innervation The innervation to the bladder is from the vesical plexus, with contribution from the uterovaginal plexus. The vesical neck is the region of the bladder that receives and incorporates the urethral lumen. The female urethra is about 3 to 4 cm in length and extends from the bladder to the vestibule, traveling just anterior to the vagina. The urethra is lined by nonkeratinized squamous epithelium that is responsive to estrogen stimulation. Within the submucosa on the dorsal surface of the urethra are the paraurethral or Skene glands, which empty through ducts into the urethral lumen. Distally, these glands empty into the vestibule on either side of the external urethral orifice. Chronic infection of Skene glands, with obstruction of their ducts and cystic dilation, is believed to be an inciting factor in the development of suburethral diverticula.


Gynecology_Novak

Gynecology_Novak. The urethra contains an inner longitudinal layer of smooth muscle and outer, circularly oriented smooth muscle fibers. The inferior fascia of the urogenital diaphragm or perineal membrane begins at the junction of the middle and distal thirds of the urethra. Proximal to the middle and distal parts of the urethra, voluntary muscle fibers derived from the urogenital diaphragm intermix with the outer layer of smooth muscle, increasing urethral resistance and contributing to continence. At the level of the urogenital diaphragm, the skeletal muscle fibers leave the wall of the urethra to form the sphincter urethrae and deep transverse perineal muscles. In the coronal plane on MRI studies, the ventral urogenital diaphragm forms an interconnected complex with the compressor urethrae, vestibular bulb, and levator ani. The dorsal part connects the levator ani and vaginal sidewall via a distinct band to the ischiopubic ramus. In the sagittal plane the parallel position of urogenital diaphragm


Gynecology_Novak

Gynecology_Novak. bulb, and levator ani. The dorsal part connects the levator ani and vaginal sidewall via a distinct band to the ischiopubic ramus. In the sagittal plane the parallel position of urogenital diaphragm and levator ani can be seen (27).


Gynecology_Novak

Gynecology_Novak. Blood Supply The vascular supply to the urethra is from the vesical and vaginal arteries and the internal pudendal branches. Innervation The innervation to the urethra is from the vesical plexus and the pudendal nerve. The lower urinary and genital tracts are intimately connected anatomically and functionally. In the midline, the bladder and proximal urethra can be dissected easily from the underlying lower uterine segment, cervix, and vagina through a loose avascular plane. The distal urethra is essentially inseparable from the vagina. Of surgical significance is the location of the bladder trigone immediately over the middle third of the vagina. Unrecognized injury to the bladder during pelvic surgery may result in development of a vesicovaginal fistula. Dissection to the level of the trigone is rarely required, and damage to this critical area is unusual.


Gynecology_Novak

Gynecology_Novak. Dissection to the level of the trigone is rarely required, and damage to this critical area is unusual. Figure 5.16 The rectosigmoid colon, its vascular supply, and muscular support. (Coronal view: peritoneum removed on right.) sigmoid wall broaden and fuse over the rectum to form a continuous longitudinal external layer of smooth muscle to the level of the anal canal.


Gynecology_Novak

Gynecology_Novak. Anal Canal The anal canal begins at the level of the sharp turn in the direction of the distal colon and is 2 to 3 cm in length. At the anorectal junction, the mucosa changes to stratified squamous epithelium (the pectinate line), which continues until the termination of the anus at the anal verge, where there is a transition to perianal skin with typical skin appendages. It is surrounded by a thickened ring of circular muscle fibers that are a continuation of the circular muscle of the rectum, the internal anal sphincter. Its lower part is surrounded by bundles of striated muscle fibers, the external anal sphincter (28).


Gynecology_Novak

Gynecology_Novak. Fecal continence is provided primarily by the puborectalis muscle and the internal and external anal sphincters. The puborectalis surrounds the anal hiatus in the pelvic diaphragm and interdigitates posterior to the rectum to form a rectal sling. The external anal sphincter surrounds the terminal anal canal below the level of the levator ani. A growing body of literature suggests that both external anal sphincter and levator ani muscles are important for fecal continence and that multiple injuries contribute to pelvic ﬂoor dysfunction (29,30) One such MRI study showed that major levator ani muscle injuries were observed in 19.1% women who delivered vaginally with external anal sphincter injuries, 3.5% who delivered vaginally without external anal sphincter injury, and none of the women who delivered by cesarean section before labor. Among women with external anal sphincter injuries, those with major levator ani muscle injuries trended more toward fecal incontinence (29). Further


Gynecology_Novak

Gynecology_Novak. who delivered by cesarean section before labor. Among women with external anal sphincter injuries, those with major levator ani muscle injuries trended more toward fecal incontinence (29). Further studies suggest that thickening of the internal anal sphincter occurs with aging, and that thinning of the external anal sphincter and a corresponding drop in squeeze pressure correlated with fecal incontinence, but not aging (31).


Gynecology_Novak

Gynecology_Novak. The anatomic proximity of the lower gastrointestinal tract to the lower genital tract is particularly important during surgery of the vulva and vagina. Lack of attention to this proximity during repair of vaginal lacerations or episiotomies can lead to damage of the rectum and fistula formation or injury to the external anal sphincter, resulting in fecal incontinence. Because of the avascular nature of the rectovaginal space, it is relatively easy to dissect the rectum from the vagina in the midline, which is routinely done in the repair of rectoceles. Blood Supply The vascular supply to the rectum and anal canal is from the superior, middle, and inferior rectal arteries. The venous drainage is a complex submucosal plexus of vessels that, under conditions of increased intra-abdominal pressure (pregnancy, pelvic mass, chronic constipation, ascites), may dilate and become symptomatic with rectal bleeding or pain as hemorrhoids.


Gynecology_Novak

Gynecology_Novak. Innervation The nerve supply to the anal canal is from the middle rectal plexus, the inferior mesenteric plexus, and the pudendal nerve. The Genital Tract and Its Relations The genital tract is situated at the bottom of the intra-abdominal cavity and is related to the intraperitoneal cavity and its contents, the retroperitoneal spaces, and the pelvic ﬂoor. Accessing it through the abdominal wall or the perineum requires a thorough knowledge of the anatomy of these areas and their relationships. Figure 5.17 The abdominal wall muscles. Table 5.7 Muscles Contributing to the Structure and Strength of the Anterolateral Abdominal Wall A. Above the arcuate line B. Below the arcuate line Ext. abdominal oblique aperneurosis Int. abdominal oblique aponeurosis Figure 5.18 A transverse section of the rectus abdominis. The aponeurosis of the external and internal oblique and the transversus abdominis from the rectus abdominis. A: Above the arcuate line. B: Below the arcuate line.


Gynecology_Novak

Gynecology_Novak. (Fig. 5.18B). The rectus is covered posteriorly by the transversalis fascia, providing access to the muscle for the inferior epigastric vessels. The transversalis fascia is a firm membranous sheet on the internal surface of the transversus abdominis muscle that extends beyond the muscle and forms a fascia lining the entire abdominopelvic cavity. Like the peritoneum, it is divided into a parietal and a visceral component. It is continuous from side to side across the linea alba and covers the posterior aspect of the rectus abdominis muscle below the arcuate line. Superiorly, it becomes the inferior fascia of the diaphragm. Inferiorly, it is attached to the iliac crest, covers the iliac fascia and the obturator internus fascia, and extends downward and medially to form the superior fascia of the pelvic diaphragm.


Gynecology_Novak

Gynecology_Novak. Characteristically, the transversalis fascia continues along blood vessels and other structures leaving and entering the abdominopelvic cavity and contributes to the formation of the visceral (endopelvic) pelvic fascia (32). The pelvic fascia invests the pelvic organs and attaches them to the pelvic sidewalls, thereby playing a critical role in pelvic support. In the inguinal region, the fascial relationships result in the development of the inguinal canal, through which the round ligament exits into the perineum. The fascia is separated from the peritoneum by a layer of preperitoneal fat. Areas of fascial weakness or congenital or posttraumatic and surgical injuries result in herniation of the underlying structures through a defective abdominal wall. The incisions least likely to result in damage to the integrity and innervation of the abdominal wall muscles include a midline incision through the linea alba and a transverse incision through the recti muscle fibers that respects the


Gynecology_Novak

Gynecology_Novak. in damage to the integrity and innervation of the abdominal wall muscles include a midline incision through the linea alba and a transverse incision through the recti muscle fibers that respects the integrity of its innervation (33).


Gynecology_Novak

Gynecology_Novak. Nerves and Vessels The tissues of the abdominal wall are innervated by the continuation of the inferior intercostal nerves T4 to T11 and the subcostal nerve T12. The inferior part of the abdominal wall is supplied by the first lumbar nerve through the iliohypogastric and the ilioinguinal nerves. Abdominal wall surgical sites below the level of the anterior superior iliac spine have the potential for ilioinguinal or iliohypogastric injury (34). The primary blood supply to the anterior lateral abdominal wall includes the following: 1. The inferior epigastric and deep circumﬂex iliac arteries, branches of the external iliac artery 2. The superior epigastric artery, a terminal branch of the internal thoracic artery


Gynecology_Novak

Gynecology_Novak. The inferior epigastric and deep circumﬂex iliac arteries, branches of the external iliac artery 2. The superior epigastric artery, a terminal branch of the internal thoracic artery The inferior epigastric artery runs superiorly in the transverse fascia to reach the arcuate line, where it enters the rectus sheath. It is vulnerable to damage by abdominal incisions in which the rectus muscle is completely or partially transected, during placement of lateral laparoscopic ports, or by excessive lateral traction on the rectus. The deep circumﬂex artery runs on the deep aspect of the anterior abdominal wall parallel to the inguinal ligament and along the iliac crest between the transverse abdominis muscle and the internal oblique muscle. The superior epigastric vessels enter the rectus sheath superiorly just below the seventh costal cartilage.


Gynecology_Novak

Gynecology_Novak. The venous system drains into the saphenous vein, and the lymphatics drain to the axillary chain above the umbilicus and to the inguinal nodes below it. The subcutaneous tissues drain to the lumbar chain. Perineum The perineum is situated at the lower end of the trunk between the buttocks. Its bony boundaries include the lower margin of the pubic symphysis anteriorly, the tip of the coccyx posteriorly, and the ischial tuberosities laterally. These landmarks correspond to the boundaries of the pelvic outlet. The diamond shape of the perineum is customarily divided by an imaginary line joining the ischial tuberosities immediately in front of the anus, at the level of the perineal body, into an anterior urogenital and a posterior anal triangle (Fig. 5.19).


Gynecology_Novak

Gynecology_Novak. Urogenital Triangle The urogenital triangle includes the external genital structures and the urethral opening (Fig. 5.19). These external structures cover the superficial and deep perineal compartments and are known as the vulva (Figs. 5.20 and 5.21). The mons pubis is a triangular eminence in front of the pubic bones that consists of adipose tissue covered by hair-bearing skin up to its junction with the abdominal wall. The labia majora are a pair of fibroadipose folds of skin that extend from the mons pubis downward and backward to meet in the midline in front of the anus at the posterior fourchette. They include the terminal extension of the round ligament and occasionally a peritoneal diverticulum, the canal of Nuck. They are covered by skin with scattered hairs laterally and are rich in sebaceous, apocrine, and eccrine glands.


Gynecology_Novak

Gynecology_Novak. The labia minora lie between the labia majora, with which they merge posteriorly, and are separated into two folds anteriorly as they approach the clitoris. The anterior folds unite to form the prepuce or hood of the clitoris. The posterior folds form the frenulum of the clitoris as they attach to its inferior surface. The labia minora are covered by hairless skin overlying a fibroelastic stroma rich in neural and vascular elements. The area between the posterior labia minora forms the vestibule of the vagina. Figure 5.19 Vulva and perineum. Figure 5.20 Superficial perineal compartment. Figure 5.21 Deep perineal compartment. The clitoris is an erectile organ that is 2 to 3 cm in length. It consists of two crura and two corpora cavernosa and is covered by a sensitive rounded tubercle (the glans).


Gynecology_Novak

Gynecology_Novak. The clitoris is an erectile organ that is 2 to 3 cm in length. It consists of two crura and two corpora cavernosa and is covered by a sensitive rounded tubercle (the glans). The vaginal orifice is surrounded by the hymen, a variable crescentic mucous membrane that is replaced by rounded caruncles after its rupture. The opening of the duct of the greater vestibular (Bartholin) glands is located on each side of the vestibule. Numerous lesser vestibular glands are also scattered posteriorly and between the urethral and vaginal orifices. The urethral orifice is immediately anterior to the vaginal orifice and about 2 to 3 cm beneath the clitoris. The Skene (paraurethral) gland duct presents an opening on its posterior surface.


Gynecology_Novak

Gynecology_Novak. The superficial perineal compartment lies between the superficial perineal fascia and the inferior fascia of the urogenital diaphragm (perineal membrane) (Fig. 5.20). The superficial perineal fascia has a superficial and deep component. The superficial layer is relatively thin and fatty and is continuous superiorly with the superficial fatty layer of the lower abdominal wall (Camper fascia). It continues laterally as the fatty layer of the thighs. The deep layer of the superficial perineal (Colles) fascia is continuous superiorly with the deep layer of the superficial abdominal fascia (Scarpa fascia), which attaches firmly to the ischiopubic rami and ischial tuberosities. The superficial perineal compartment is continuous superiorly with the superficial fascial spaces of the anterior abdominal wall, allowing spread of blood or infection along that route. Such spread is limited laterally by the ischiopubic rami, anteriorly by the transverse ligament of the perineum, and posteriorly by


Gynecology_Novak

Gynecology_Novak. wall, allowing spread of blood or infection along that route. Such spread is limited laterally by the ischiopubic rami, anteriorly by the transverse ligament of the perineum, and posteriorly by the superficial transverse perineal muscle. The superficial perineal compartment includes the following:


Gynecology_Novak

Gynecology_Novak. The vestibular bulbs are 3-cm, highly vascular structures surrounding the vestibule and located under the bulbocavernosus muscle. The body of the clitoris is attached by two crura to the internal aspect of the ischiopubic rami. The crura are covered by the ischiocavernosus muscles. The muscles of the vulva are the ischiocavernosus, the bulbocavernosus, and superficial transverse perineal. They are included in the superficial perineal compartment as follows: Action—compresses the crura and lowers the clitoris Insertion—posterior aspect of the clitoris; some fibers pass above the dorsal vein of the clitoris in a slinglike fashion Action—compresses the vestibular bulb and dorsal vein of the clitoris Action—fixes the perineal body


Gynecology_Novak

Gynecology_Novak. Action—compresses the vestibular bulb and dorsal vein of the clitoris Action—fixes the perineal body The vestibular glands are situated on either side of the vestibule under the posterior end of the vestibular bulb. They drain between the hymen and the labia minora. Their mucous secretion helps maintain adequate lubrication. Infection in these glands can result in an abscess.


Gynecology_Novak

Gynecology_Novak. The deep perineal compartment is a fascial space bound inferiorly by the perineal membrane and superiorly by a deep fascial layer that separates the urogenital diaphragm from the anterior recess of the ischiorectal fossa (Fig. 5.21). It is stretched across the anterior half of the pelvic outlet between the ischiopubic rami. The deep compartment may be directly continuous superiorly with the pelvic cavity (35). The posterior pubourethral ligaments, functioning as winglike elevations of the fascia ascending from the pelvic ﬂoor to the posterior aspect of the symphysis pubis, provide a point of fixation to the urethra and support the concept of the continuity of the deep perineal compartment with the pelvic cavity.


Gynecology_Novak

Gynecology_Novak. The anterior pubourethral ligaments represent a similar elevation of the inferior fascia of the urogenital diaphragm and are joined by the intermediate pubourethral ligament, with the junction between the two fascial structures arcing under the pubic symphysis (36). The urogenital diaphragm includes the sphincter urethrae (urogenital sphincter) and the deep transverse perineal (transversus vaginae) muscle.


Gynecology_Novak

Gynecology_Novak. The urogenital diaphragm (perineal membrane) is composed of two regions: one dorsal and one ventral. The dorsal portion consists of bilateral transverse fibrous sheets that attach the lateral wall of the vagina and perineal body to the ischiopubic ramus. This portion is devoid of striated muscle. The ventral portion is part of a solid three-dimensional tissue mass in which several structures are embedded. It is intimately associated with the compressor urethrae and the urethrovaginal sphincter muscle of the distal urethra with the urethra and its surrounding connective tissue. In this region the perineal membrane is continuous with the insertion of the arcus tendineus fascia pelvis. The levator ani muscles are connected with the cranial surface of the perineal membrane. The vestibular bulb and clitoral crus are fused with the membrane’s caudal surface (37).


Gynecology_Novak

Gynecology_Novak. Figure 5.22 The complete urogenital sphincter musculature, bladder, and vagina. (Redrawn from Haderer JM, Pannu HK, Genadry R, et al. Controversies in female urethral anatomy and their significance for understanding urinary continence: observations and literature review. Int Urogynecol J Pelvic Floor Dysfunct 2002;13:236–252, with permission.) The sphincter urethrae (Fig. 5.22) is a continuous muscle fanning out as it develops proximally and distally, including the following: 1. External urethral sphincter, which surrounds the middle third of the urethra. 2. Compressor urethrae, arcing across the ventral side of the urethra. 3. Urethrovaginal sphincter, which surrounds the ventral aspect of the urethra and terminates in the lateral vaginal wall.


Gynecology_Novak

Gynecology_Novak. 2. Compressor urethrae, arcing across the ventral side of the urethra. 3. Urethrovaginal sphincter, which surrounds the ventral aspect of the urethra and terminates in the lateral vaginal wall. The deep transverse perineal muscle originates at the internal aspect of the ischial bone, parallels the muscle compressor urethrae, and attaches to the lateral vaginal wall along the perineal membrane. Studies show that a smaller striated urogenital sphincter is associated with stress incontinence and poorer pelvic ﬂoor muscle function (38).


Gynecology_Novak

Gynecology_Novak. The urinary and genital tracts have a common reliance on several interdependent structures for support. The cardinal and uterosacral ligaments are condensations of endopelvic fascia that support the cervix and upper vagina over the levator plate. Laterally, endopelvic fascial condensations attach the midvagina to the pelvic walls at the arcus tendineus fascia pelvis anteriorly and the arcus tendineus levator ani posteriorly. The distal anterior vagina and urethra are anchored to the urogenital diaphragm and the distal posterior vagina to the perineal body.


Gynecology_Novak

Gynecology_Novak. Anteriorly, the pubourethral ligaments and pubovesical fascia and ligaments provide fixation and stabilization for the urethra and bladder. Posteriorly, they rely on the vagina and lower uterus for support. Partial resection or relaxation of the uterosacral ligaments often leads to relaxation of the genitourinary complex, resulting in the formation of a cystocele. Studies indicate that half of the observed variation in anterior compartment support may be explained by apical support (39). Various types and degrees of genital tract prolapse or relaxation are almost always associated with similar findings in the bladder, urethra, or both.


Gynecology_Novak

Gynecology_Novak. There are three levels of vaginal support as described by DeLancey (Fig. 5.23) (40). Level I support consists of paracolpium that suspends the apical portion of the vagina and is comprised of the cardinal-uterosacral ligament complex. Level II support comprises the paracolpium that is attached to the vagina laterally via the arcus tendineus fasciae pelvis and superior fascia of the levator ani. Level III support consists of the distal vaginal attachments: anteriorly, via fusion of the urethra to the vagina, laterally, to the levators, and posteriorly, with the perineal body. Figure 5.23 DeLancey levels of support. (Modified from DeLancey JOL. Anatomic aspects of vaginal eversion after hysterectomy. Am J Obstet Gynecol 1992;166:17–28, with permission.)


Gynecology_Novak

Gynecology_Novak. Figure 5.23 DeLancey levels of support. (Modified from DeLancey JOL. Anatomic aspects of vaginal eversion after hysterectomy. Am J Obstet Gynecol 1992;166:17–28, with permission.) Disruption of level I support may lead to prolapse of the uterus or vaginal vault, while damage to level II and III supports predispose to anterior and posterior vaginal prolapse. All levels of defective support should be repaired during reconstructive surgery. Blood Supply The blood supply to the vulva is as follows: 1. External pudendal artery (from femoral artery), internal pudendal artery 2. The blood supply to the superficial and deep perineal compartments is as follows: 1. Internal pudendal artery, dorsal artery of the clitoris 2. Venous drainage—internal pudendal veins, which are richly anastomotic 3. Innervation The innervation to the vulva is from branches of the following nerves: 1. 2. 3. Lateral femoral cutaneous nerve of the thigh (perineal branch) 4.


Gynecology_Novak

Gynecology_Novak. Innervation The innervation to the vulva is from branches of the following nerves: 1. 2. 3. Lateral femoral cutaneous nerve of the thigh (perineal branch) 4. Perineal nerve (branch of pudendal) 5. Superficial and deep perineal compartments, innervated by the perineal nerve


Gynecology_Novak

Gynecology_Novak. Perineal Body The perineal body or central perineal tendon is critical to the posterior support of the lower aspect of the anterior vaginal wall. It is a triangle-shaped structure separating the distal portion of the anal and vaginal canals that is formed by the convergence of the tendinous attachments of the bulbocavernosus, the external anal sphincter, and the superficial transverse perinei muscle. Its superior border represents the point of insertion of the rectovaginal (Denonvilliers) fascia, which extends to the underside of the peritoneum covering the cul-de-sac of Douglas, separating the anorectal from the urogenital compartment (41). The perineal body plays an important anchoring role in the musculofascial support of the pelvic ﬂoor. It represents the central connection between the two layers of support of the pelvic ﬂoor—the pelvic and urogenital diaphragm. It also provides a posterior connection to the anococcygeal raphe. Thus, it is central to the definition of the bilevel


Gynecology_Novak

Gynecology_Novak. two layers of support of the pelvic ﬂoor—the pelvic and urogenital diaphragm. It also provides a posterior connection to the anococcygeal raphe. Thus, it is central to the definition of the bilevel support of the ﬂoor of the pelvis.


Gynecology_Novak

Gynecology_Novak. Anal Triangle The anal triangle includes the lower end of the anal canal. The external anal sphincter surrounds the anal triangle, and the ischiorectal fossa is on each side. Posteriorly, the anococcygeal body lies between the anus and the tip of the coccyx and consists of thick fibromuscular tissue (of levator ani and external anal sphincter origin) giving support to the lower part of the rectum and the anal canal.


Gynecology_Novak

Gynecology_Novak. The external anal sphincter forms a thick band of muscular fibers arranged in three layers running from the perineal body to the anococcygeal ligament. The subcutaneous fibers are thin and surround the anus and, without bony attachment, decussate in front of it. The superficial fibers sweep forward from the anococcygeal ligament, and the tip of the coccyx around the anus inserts into the perineal body. The deep fibers arise from the perineal body to encircle the lower half of the anal canal to form a true sphincter muscle, which fuses with the puborectalis portion of the levator ani.


Gynecology_Novak

Gynecology_Novak. The ischiorectal fossa is mainly occupied by fat and separates the ischium laterally from the median structures of the anal triangle. It is a fascia-lined space located inferiorly between the perineal skin and the pelvic diaphragm superiorly; it communicates with the contralateral ischiorectal fossa over the anococcygeal ligament. Superiorly, its apex is at the origin of the levator ani muscle from the obturator fascia. It is bound medially by the levator ani and the external sphincter with their fascial covering, laterally by the obturator internus muscle with its fascia, posteriorly by the sacrotuberous ligament and the lower border of the gluteus maximus muscle, and anteriorly by the base of the urogenital diaphragm. It is widest and deepest posteriorly and weakest medially. An ischiorectal abscess should be drained without delay, or it will extend into the anal canal.


Gynecology_Novak

Gynecology_Novak. An ischiorectal abscess should be drained without delay, or it will extend into the anal canal. The cavity is filled with fat that cushions the anal canal and is traversed by many fibrous bands, vessels, and nerves, including the pudendal and the inferior rectal nerves. The perforating branch of S2 and S3 and the perineal branch of S4 also run through this space. The pudendal (Alcock) canal is a tunnel formed by a splitting of the inferior portion of the obturator fascia running anteromedially from the ischial spine to the posterior edge of the urogenital diaphragm. It contains the pudendal artery, vein, and nerve in their traverse from the pelvic cavity to the perineum. Blood Supply The blood supply to the anal triangle is from the inferior rectal (hemorrhoidal) artery and vein. Innervation The innervation to the anal triangle is from the perineal branch of the fourth sacral nerve and the inferior rectal (hemorrhoidal) nerve.


Gynecology_Novak

Gynecology_Novak. Innervation The innervation to the anal triangle is from the perineal branch of the fourth sacral nerve and the inferior rectal (hemorrhoidal) nerve. Retroperitoneum and The subperitoneal area of the true pelvis is partitioned into potential spaces by the var- Retroperitoneal Spaces ious organs and their respective fascial coverings and by the selective thickenings of the endopelvic fascia into ligaments and septa (Fig. 5.24). It is imperative that surgeons operating in the pelvis be familiar with these spaces, as discussed below. Prevesical Space The prevesical (Retzius) space is a fat-filled potential space bound anteriorly by the pubic bone, covered by the transversalis fascia, and extending to the umbilicus between the medial umbilical ligaments (obliterated umbilical arteries); posteriorly, the space extends to the


Gynecology_Novak

Gynecology_Novak. Figure 5.24 Schematic sectional drawing of the pelvis shows the firm connective tissue covering. The bladder, cervix, and rectum are surrounded by a connective tissue covering. The Mackenrodt ligament extends from the lateral cervix to the lateral abdominal pelvic wall. The vesicouterine ligament originating from the anterior edge of the Mackenrodt ligament leads to the covering of the bladder on the posterior side. The sagittal rectum column spreads both to the connective tissue of the rectum and the sacral vertebrae closely nestled against the back of the Mackenrodt ligament and lateral pelvic wall. Between the firm connective tissue bundles is loose connective tissue (paraspaces). (From Von Peham H, Amreich JA. Gynaekologische Operationslehre. Berlin, Germany: S Karger, 1930, with permission.) anterior wall of the bladder. It is separated from the paravesical space by the ascending bladder septum (bladder pillars).


Gynecology_Novak

Gynecology_Novak. Upon entering the prevesical space, the pubourethral ligaments may be seen inserting into the posterior aspect of the symphysis pubis as a thickened prolongation of the arcus tendineus fascia. With combined abdominal and vaginal bladder neck suspensory procedures, the point of entry is usually the Retzius space between the arcus tendineus and the pubourethral ligaments.


Gynecology_Novak

Gynecology_Novak. Rectovaginal Space The rectovaginal space extends between the vagina and the rectum from the superior border of the perineal body to the underside of the rectouterine Douglas pouch. It is bound anteriorly by the rectovaginal septum (firmly adherent to the posterior aspect of the vagina), posteriorly by the anterior rectal wall, and laterally by the descending rectal septa separating the rectovaginal space from the pararectal space on each side. The rectovaginal septum represents a firm membranous transverse septum dividing the pelvis into rectal and urogenital compartments, allowing the independent function of the vagina and rectum and providing support for the rectum. It is fixed laterally to the pelvic sidewall by rectovaginal fascia (part of the endopelvic fascia) along a line extending from the posterior fourchette to the arcus tendineus fasciae pelvis, midway between the pubis and the ischial spine (42). An anterior rectocele often results from a defective septum or an avulsion


Gynecology_Novak

Gynecology_Novak. from the posterior fourchette to the arcus tendineus fasciae pelvis, midway between the pubis and the ischial spine (42). An anterior rectocele often results from a defective septum or an avulsion of the septum from the perineal body. Reconstruction of the perineum is critical for the restoration of this important compartmental separation and for the support of the anterior vaginal wall (43). Lateral detachment of the rectovaginal fascia from the pelvic sidewall may constitute a “pararectal” defect analogous to anterior paravaginal defects.


Gynecology_Novak

Gynecology_Novak. Presacral Space The presacral space is the superior extension of the retrorectal space and is limited by the deep parietal peritoneum anteriorly and the anterior aspect of the sacrum posteriorly. It harbors the middle sacral vessels and the hypogastric plexi between the bifurcation of the aorta invested by loose areolar tissue. Presacral neurectomy requires familiarity with and working knowledge of this space. Abdominal sacrocolpopexy involves dissection in the presacral space down to the anterior longitudinal ligament, which is the point of fixation for the tail of the Y-shaped mesh graft. The surgical space is bound superiorly by the bifurcation of the great vessels and laterally by the ureter on the right and the mesentery of the sigmoid colon and the left common iliac vein on the left. The left iliac vein lies medial to the left iliac artery bounding this space and is more prone to injury during laparoscopic entry or presacral dissection.


Gynecology_Novak

Gynecology_Novak. Peritoneal Cavity The female pelvic organs lie at the bottom of the abdominopelvic cavity covered superiorly and posteriorly by the small and large bowel. Anteriorly, the uterine wall is in contact with the posterosuperior aspect of the bladder. The uterus is held in position by the following structures: 1. The round ligaments coursing inferolaterally toward the internal inguinal ring 2. The uterosacral ligaments, which provide support to the cervix and upper vagina and interdigitate with fibers from the cardinal ligament near the cervix 3. The cardinal ligaments, which provide support to the cervix and upper vagina and contribute to the support of the bladder


Gynecology_Novak

Gynecology_Novak. The cardinal ligaments, which provide support to the cervix and upper vagina and contribute to the support of the bladder Anteriorly, the uterus is separated from the bladder by the vesicouterine pouch and from the rectum posteriorly by the rectouterine pouch or Douglas cul-de-sac. Laterally, the bilateral broad ligaments carry the neurovascular pedicles and their respective fascial coverings, attaching the uterus to the lateral pelvic sidewall. The broad ligament is in contact inferiorly with the paravesical space, the obturator fossa, and the pelvic extension of the iliac fossa, to which it provides a peritoneal covering, and with the uterosacral ligament. Superiorly, it extends into the infundibulopelvic ligament. Ureter In its pelvic path in the retroperitoneum, several relationships are of significance and identify areas of greatest vulnerability to injury of the ureter (Fig. 5.25): 1.


Gynecology_Novak

Gynecology_Novak. Ureter In its pelvic path in the retroperitoneum, several relationships are of significance and identify areas of greatest vulnerability to injury of the ureter (Fig. 5.25): 1. The ovarian vessels cross over the ureter as it approaches the pelvic brim and lie in lateral proximity to the ureter as it enters the pelvis. 2. As the ureter descends into the pelvis, it runs within the broad ligament just lateral to the uterosacral ligament, separating the uterosacral ligament from the mesosalpinx, mesovarium, and ovarian fossa. Figure 5.25 The course of the ureter and its relationship to the sites of greatest vulnerability. Pubovesical lig. Bladder Obturator a. Uterine a. Ureter Sup. vesical a. Vagina Uterosacral lig. Ureter Ovarian a. (infundibulopelvic lig.) 3.


Gynecology_Novak

Gynecology_Novak. Pubovesical lig. Bladder Obturator a. Uterine a. Ureter Sup. vesical a. Vagina Uterosacral lig. Ureter Ovarian a. (infundibulopelvic lig.) 3. At about the level of the ischial spine, the ureter crosses under the uterine artery in its course through the cardinal ligament; the ureter divides this area into the supraureteric parametrium surrounding the uterine vessels and the infraureteric paracervix molded around the vaginal vessels and extending posteriorly into the uterosacral ligament. In this location, the ureter lies 2 to 3 cm lateral to the cervix and in proximity to the insertion of the uterosacral ligament at the cervix. This proximity warrants caution when using the uterosacral ligament for vaginal vault suspension (44,45). 4. The ureter then turns medially to cross the anterior upper vagina as it traverses the bladder wall.


Gynecology_Novak

Gynecology_Novak. 4. The ureter then turns medially to cross the anterior upper vagina as it traverses the bladder wall. About 75% of all iatrogenic injuries to the ureter result from gynecologic procedures, most commonly abdominal hysterectomy (46). Distortions of pelvic anatomy, including adnexal masses, endometriosis, other pelvic adhesive disease, or fibroids, may increase susceptibility to injury by displacement or alteration of usual anatomy. Careful identification of the course of the ureter before securing the infundibulopelvic ligament and uterine artery is the best protection against ureteric injury during hysterectomy or adnexectomy. Even with severe intraperitoneal disease, the ureter can always be identified using a retroperitoneal approach and noting fundamental landmarks and relationships.


Gynecology_Novak

Gynecology_Novak. Pelvic Floor The pelvic ﬂoor includes all of the structures closing the pelvic outlet from the skin inferiorly to the peritoneum superiorly. It is commonly divided by the pelvic diaphragm into a pelvic and a perineal portion (47). The pelvic diaphragm is spread transversely in a hammocklike fashion across the true pelvis, with a central hiatus for the urethra, vagina, and rectum. Anatomically and physiologically, the pelvic diaphragm can be divided into two components: the internal and external components. The external component originates from the arcus tendineus, extending from the pubic bone to the ischial spine. It gives rise to fibers of differing directions, including the pubococcygeus, the iliococcygeus, and the coccygeus. Figure 5.26 The fascial components of the pelvic diaphragm.


Gynecology_Novak

Gynecology_Novak. Figure 5.26 The fascial components of the pelvic diaphragm. The internal component originates from the pubic bone above and medial to the origin of the pubococcygeus and is smaller but thicker and stronger (47). Its fibers run in a sagittal direction and are divided into the following two portions: 1. Pubovaginalis fibers run in a perpendicular direction to the urethra, crossing the lateral vaginal wall at the junction of its lower one-third and upper two-thirds to insert into the perineal body. The intervening anterior interlevator space is covered by the urogenital diaphragm. 2. Puborectalis superior fibers sling around the rectum to the symphysis pubis; its inferior fibers insert into the lateral rectal wall between the internal and external sphincter.


Gynecology_Novak

Gynecology_Novak. 2. Puborectalis superior fibers sling around the rectum to the symphysis pubis; its inferior fibers insert into the lateral rectal wall between the internal and external sphincter. The pelvic diaphragm is covered superiorly by fascia, which includes a parietal and a visceral component and is a continuation of the transversalis fascia (Fig. 5.26). The parietal fascia has areas of thickening (ligaments, septae) that provide reinforcement and fixation for the pelvic ﬂoor. The visceral (endopelvic) fascia extends medially to invest the pelvic viscera, resulting in a fascial covering to the bladder, vagina, uterus, and rectum. It becomes attenuated where the peritoneal covering is well defined and continues laterally with the pelvic cellular tissue and neurovascular pedicles.


Gynecology_Novak

Gynecology_Novak. Musculofascial elements (the hypogastric sheath) extend along the vessels originating from the internal iliac artery. Following these vessels to their respective organs, the hypogastric sheath extends perivascular investments that contribute to the formation of the endopelvic fascia so critical for the support of the pelvic organs. Thus, the parietal fascia anchors the visceral fascia, which defines the relationship of the various viscera and provides them with significant fixation (uterosacral and cardinal ligaments), septation (vesicovaginal and rectovaginal), and definition of pelvic spaces (prevesical, vesicovaginal, rectovaginal, paravesical, pararectal, and retrorectal). For its support, the pelvic ﬂoor relies on the complementary role of the pelvic diaphragm and its fascia resting on the perineal fibromuscular complex. It is composed of the perineal Figure 5.27 The double-layered muscular support of the pelvic diaphragm.


Gynecology_Novak

Gynecology_Novak. Figure 5.27 The double-layered muscular support of the pelvic diaphragm. membrane (urogenital diaphragm) anteriorly and the perineal body joined to the anococcygeal raphe by the external anal sphincter posteriorly. This double-layered arrangement, when intact, provides optimal support for the pelvic organs and counterbalances the forces pushing them downward with gravity and with any increase in intra-abdominal pressure (Fig. 5.27). Dynamic imaging techniques, such as MRI, CT, and ultrasonography, increasingly are used to provide additional information in the evaluation of pelvic ﬂoor problems by visualizing anatomic landmarks during different functional phases.


Gynecology_Novak

Gynecology_Novak. Endopelvic Fascia Controversy exists surrounding the use of the term “fascia” as it applies to the pelvis. Histologic studies reveal that the linings of the levator ani, piriformis, and obturator internus are genuine examples of pelvic fascia. One example in which the term “fascia” is incorrectly used is in reference to the tissue that is plicated in an anterior colporrhaphy. Histologically, it is the muscular lining of the vagina that is plicated. There are no discrete capsules of fascia that separate the bladder and vagina from each other.


Gynecology_Novak

Gynecology_Novak. The endopelvic fascia is a sheet of fibroareolar tissue following the blood supply to the visceral organs and acts as a retroperitoneal mesentery. The fascia divides the retroperitoneal space into avascular planes. The endopelvic or pubocervical fascia attaches the cervix and vagina to the lateral pelvic sidewall. It is composed of two parts: the parametrium, which is that part connected to the uterus (i.e., the uterosacral and cardinal ligaments), and the paracolpium, which is that part connected to the vagina. The parametrium and cardinal ligaments continue to the vaginal introitus and fuse directly to the supporting tissues associated with the vagina. The uterine and vaginal arteries travel in these structures. The uterosacral ligaments are the posterior components of the cardinal ligaments, extending from the cervix and upper vagina to the lateral sacrum. Lateral pelvic support is provided by linear condensations of obturator and levator ani fascia termed the arcus tendineus


Gynecology_Novak

Gynecology_Novak. ligaments, extending from the cervix and upper vagina to the lateral sacrum. Lateral pelvic support is provided by linear condensations of obturator and levator ani fascia termed the arcus tendineus fascia pelvis and the arcus tendineus levator ani, respectively. The arcus tendineus levator ani serves as a point of attachment for the pubococcygeus and iliococcygeus muscles and lies on the fascia of the obturator internus muscle. It runs from the posterolateral pubic ramus to the ischial spine. The arcus tendineus fascia pelvis runs from the anterior pubis to the ischial spine as it joins with the arcus tendineus levator ani. It provides lateral (paravaginal) support to the anterior vagina.


Gynecology_Novak

Gynecology_Novak. Obturator Space The obturator membrane is a fibrous sheath that spans the obturator foramen through which the obturator neurovascular bundle penetrates via the obturator canal. The obturator internus muscle lies on the superior (intrapelvic) side of the obturator membrane. The origin of the obturator internus is on the inferior margin of the superior pubic ramus and the pelvic surface of the obturator membrane. Its tendon passes through the lesser sciatic foramen to insert onto the greater trochanter of the femur to laterally rotate the thigh. The obturator artery and vein originate as branches of the internal iliac vessels. As they emerge from the cranial side of the obturator membrane via the obturator canal and enter the obturator space, they divide into many small branches, supplying blood to the muscles of the adductor compartment of the thigh. Cadaver work contradicted previous reports that the obturator vessels bifurcate into medial and lateral branches (48). Rather, the


Gynecology_Novak

Gynecology_Novak. blood to the muscles of the adductor compartment of the thigh. Cadaver work contradicted previous reports that the obturator vessels bifurcate into medial and lateral branches (48). Rather, the vessels are predominantly small (<5 mm in diameter) and splinter into variable courses. The muscles of the medial thigh and adductor compartment are (from superficial to deep) the gracilis, adductor longus, adductor brevis, adductor magnus, obturator externus, and obturator internus. In contrast to the vessels, the obturator nerve emerges from the obturator membrane and bifurcates into anterior and posterior divisions, traveling distally down the thigh to supply the muscles of the adductor compartment. With the patient in the dorsal lithotomy position, the nerves and vessels follow the thigh and course laterally away from the ischiopubic ramus. Transobturator incontinence slings and anterior trocar-based mesh prolapse kits are often placed beneath the adductor longus tendon and just lateral to


Gynecology_Novak

Gynecology_Novak. laterally away from the ischiopubic ramus. Transobturator incontinence slings and anterior trocar-based mesh prolapse kits are often placed beneath the adductor longus tendon and just lateral to the descending ischiopubic ramus in order to avoid the obturator neurovascular bundle, which lies lateral and superior to this relatively safe point of entry through the obturator membrane.


Gynecology_Novak

Gynecology_Novak. New surgical approaches are being developed to solve old problems and often require surgeons to revisit familiar anatomy from an unfamiliar perspective or with a different understanding of complex anatomic relationships. Examples of innovative surgical approaches that require renewed understanding of anatomic relationships include laparoscopic or robotic surgery, midurethral incontinence slings that traverse the obturator or retropubic spaces, and prolapse kits that traverse pararectal and paravesical spaces. Anatomic alterations secondary to disease, congenital variation, or intraoperative complications may make familiar surgical territory suddenly seem foreign. All of these situations require surgeons to be perpetual students of anatomy, regardless of their breadth or depth of experience. Several strategies for continuing education in anatomy are suggested: 1. Review relevant anatomy before each surgical procedure. 2.


Gynecology_Novak

Gynecology_Novak. Several strategies for continuing education in anatomy are suggested: 1. Review relevant anatomy before each surgical procedure. 2. Study the gynecologic literature on an ongoing basis—numerous publications document the evolution of newer concepts regarding anatomic issues such as pelvic support. 3. Operate with more experienced pelvic surgeons, particularly when incorporating new surgical procedures into practice. 4. Periodically dissect fresh or fixed cadaveric specimens; this practice may be arranged through local or regional anatomy boards or medical schools or by special arrangement at the time of autopsy. 5. Take advantage of newer computer-generated three-dimensional pelvic models and virtual reality interactive anatomic and surgical simulators, when available, to better understand functional anatomy and to help plan complicated surgical procedures (49,50). 1.


Gynecology_Novak

Gynecology_Novak. 1. International Anatomical Nomenclature Committee. Nomina 3. Handa VL, Pannu HK, Siddique S, et al. Architectural differences anatomica. 6th ed. Edinburgh, Scotland: Churchill Livingstone, in the bony pelvis of women with and without pelvic ﬂoor disorders. 1989. Obstet Gynecol 2003;102:1283–1290. 2. Sze EH, Kohli N, Miklos JR, et al. Computed tomography compari-4. Mattox TF, Lucente V, McIntyre P, et al. Abnormal spinal curvason of bony pelvis dimensions between women with and without genital ture and its relationship to pelvic organ prolapse. Am J Obstet Gynecol prolapse. Obstet Gynecol 1999;93:229–232. 2000;183:1381–1384. 5. Nguyen JK, Lind LR, Choe JY, et al. Lumbosacral spine and pelvic inlet changes associated with pelvic organ prolapse. Obstet Gynecol 2000;95:332–336. 6. Stein TA, Kaur G, Summers A, et al. Comparison of bony dimensions at the level of the pelvic ﬂoor in women with and without pelvic organ prolapse. Am J Obstet Gynecol 2009;200:241.e1–5. 7.


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Gynecology_Novak. 6. Stein TA, Kaur G, Summers A, et al. Comparison of bony dimensions at the level of the pelvic ﬂoor in women with and without pelvic organ prolapse. Am J Obstet Gynecol 2009;200:241.e1–5. 7. Thompson JR, Gibbs JS, Genadry R, et al. Anatomy of pelvic arteries adjacent to the sacrospinous ligament: importance of the coccygeal branch of the inferior gluteal artery. Obstet Gynecol 1999;94:973–977. 8. DeLancey JOL, Kearney R, Chou Q, et al. The appearance of levator ani muscle abnormalities in magnetic resonance imaging after vaginal delivery. Obstet Gynecol 2003;101:46–53. 9. Singh K, Jakub M, Reid WM, et al. Three dimensional assessment of levator ani morphologic features in different grades of prolapse. Am J Obstet Gynecol 2003;189:910–915. 10. Barber MD, Bremer RE, Thor Kb, et al. Innervation of the female levator ani muscles. Am J Obstet Gynecol 2002;187:64–71. 11. Snooks SJ, Swash M. the innervation of the muscles of continence. Ann R Coll Surg Engl 1986;68:45–49. 12.


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Gynecology_Novak. 11. Snooks SJ, Swash M. the innervation of the muscles of continence. Ann R Coll Surg Engl 1986;68:45–49. 12. Percy JP, Neill ME, Swash M, et al. Electrophysiological study of motor nerve supply of pelvic ﬂoor. Lancet 1981;1:16–17. 13. Pierce LM, Reyes M, Thor KB, et al. Innervation of the levator ani muscles in the female squirrel monkey. Am J Obstet Gynecol 2003;188:1141–1147. 14. Bremer RE, Barber MD, Coates KW, et al. Innervation of the levator ani and coccygeus muscles of the female rat. Anat Rec 2003;275:1031– 1041. 15. Vanderhorst VG, Holstege G. Organization of lumbosacral motoneuronal cell groups innervating hindlimb, pelvic ﬂoor, and axial muscles in the cat. J Comp Neurol 1997;382:46–47. 16. Uhlenhuth E, Day EC, Smith RD, et al. The visceral endopelvic fascia and the hypogastric sheath. Surg Gynecol Obstet 1948;86:9–28. 17.


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Gynecology_Novak. 16. Uhlenhuth E, Day EC, Smith RD, et al. The visceral endopelvic fascia and the hypogastric sheath. Surg Gynecol Obstet 1948;86:9–28. 17. Thompson JD, Rock WA, Wiskind A. Control of pelvic hemorrhage: blood component therapy and hemorrhagic shock. In: Thompson JD, Rock JA, eds. TeLinde’s operative gynecology. 7th ed. Philadelphia, PA: Lippincott, 1991:151. 18. Lee RB, Stone K, Magelssen D, et al. Presacral neurectomy for chronic pelvic pain. Obstet Gynecol 1986;68:517–521. 19. Polan ML, DeCherney A. Presacral neurectomy for pelvic pain in infertility. Fertil Steril 1980;34:557–560. 20. Cilento GB, Bauer BS, Retik BA, et al. Urachal anomalies: defining the best diagnostic modality. Urology 1998;52:120–122. 21. Vaughan ED Jr, Middleton GW. Pertinent genitourinary embryology: review for the practicing urologist. Urology 1975;6:139–149. 22.


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Gynecology_Novak. 21. Vaughan ED Jr, Middleton GW. Pertinent genitourinary embryology: review for the practicing urologist. Urology 1975;6:139–149. 22. Byskov AG, Hoyer PE. Embryology of mammalian gonads and ducts. In: Knobil E, Neill JD, eds. The physiology of reproduction. 2nd ed. New York: Raven, 1994:487. 23. Cilento GB, Bauer BS, Retik BA, et al. Urachal anomalies: defining the best diagnostic modality. Urology 1998;52:120–122. 24. Arey LB. The genital system. In: Arey LB, ed. Developmental anatomy. 7th ed. Philadelphia, PA: Saunders, 1974:315. 25. Moore KL. The urogenital system. In: Moore KL, ed. The developing human: clinically oriented embryology. 3rd ed. Philadelphia, PA: Saunders, 1982:255. 26. Semmens JP. Congenital anomalies of female genital tract: functional classification based on review of 56 personal cases and 500 reported cases. Obstet Gynecol 1962;19:328–350. 27.


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Gynecology_Novak. 26. Semmens JP. Congenital anomalies of female genital tract: functional classification based on review of 56 personal cases and 500 reported cases. Obstet Gynecol 1962;19:328–350. 27. Brandon CJ, Lewicky-Gaupp C, Larson KA, et al. Anatomy of the perineal membrane as seen in magnetic resonance images of nulliparous women. Am J Obstet Gynecol 2009;200:583.e1–6. 28. Lawson JO. Pelvic anatomy. II. Anal canal and associated sphincters. Ann R Coll Surg Engl 1974;54:288–300. 29. Terra MP, Beets-Tan RG, Vervoorn I, et al. Pelvic ﬂoor muscle lesions at endoanal MR imaging in female patients with faecal incontinence. Eur Radiol 2008;18:1892–1901. 30. Heilbrun ME, Nygaard IE, Lockhart ME, et al. Correlation between levator ani muscle injuries on magnetic resonance imaging and fecal incontinence, pelvic organ prolapse, and urinary incontinence in primiparous women. Am J Obstet Gynecol 2010;202:488.e1–6. 31.


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Gynecology_Novak. 31. Lewicky-Gaupp C, Hamilton Q, Ashton-Miller J, et al. Anal sphincter structure and function relationships in aging and fecal incontinence. Am J Obstet Gynecol 2009;200:559.e1–5. 32. Curtis AH. A textbook of gynecology. 4th ed. Philadelphia, PA: Saunders, 1943. 33. Moore KL. Clinically oriented anatomy. 2nd ed. Baltimore, MD: Williams & Wilkins, 1985. 34. Whiteside JL, Barber MD, Walters MD, et al. Anatomy of ilioinguinal and iliohypogastric nerves in relation to trocar placement and low transverse incisions. Am J Obstet Gynecol 2003;189:1574– 1578. 35. Oelrich TM. The striated urogenital sphincter muscle in the female. Anat Rec 1983;205:223–232. 36. Milley PS, Nichols DH. The relationship between the pubo-urethral ligaments and the urogenital diaphragm in the human female. Anat Rec 1971;170:281. 37. Stein TA, DeLancey JO. Structure of the perineal membrane in females: gross and microscopic anatomy. Obstet Gynecol 2008;111: 686–693. 38.


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Gynecology_Novak. 37. Stein TA, DeLancey JO. Structure of the perineal membrane in females: gross and microscopic anatomy. Obstet Gynecol 2008;111: 686–693. 38. Morgan DM, Umek W, Guire K, et al. Urethral sphincter morphology and function with and without stress incontinence. JUrol 2009; 182:203–209. 39. Summers A, Winkel LA, Hussain HK, et al. The relationship between anterior and apical compartment support. Am J Obstet Gynecol 2006;194:1438–1443. 40. DeLancey JOL. Anatomic aspects of vaginal eversion after hysterectomy. Am J Obstet Gynecol 1992;166:17–28. 41. Uhlenhuth E, Wolfe WM, Smith EM, et al. The rectovaginal septum. Surg Gynecol Obstet 1948;86:148–163. 42. Lefﬂer KS, Thompson JR, Cundiff GW, et al. Attachment of the rectovaginal septum to the pelvic sidewall. Am J Obstet Gynecol 2001; 185:41–43. 43. Nichols DH, Randall CL. Clinical pelvic anatomy of the living. In: Nichols DH, Randall CL, eds. Vaginal surgery. Baltimore, MD: Williams & Wilkins, 1976:1. 44.


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Gynecology_Novak. 43. Nichols DH, Randall CL. Clinical pelvic anatomy of the living. In: Nichols DH, Randall CL, eds. Vaginal surgery. Baltimore, MD: Williams & Wilkins, 1976:1. 44. Barber MD, Visco AG, Weidner AC, et al. Bilateral uterosacral ligament vaginal vault suspension with site specific endopelvic facial defect repair for treatment of pelvic organs. Am J Obstet Gynecol 2000; 183:1410–1411. 45. Buller JL, Thompson JR, Cundiff GW, et al. Uterosacral ligament: description of anatomic relationships to optimize surgical safety. Obstet Gynecol 2001;97:873–879. 46. Symmonds RE. Urologic injuries: ureter. In: Schaefer G, Graber EA, eds. Complications in obstetric and gynecologic surgery. Philadelphia, PA: Harper & Row, 1981:412. 47. Lawson JO. Pelvic anatomy. I. Pelvic ﬂoor muscles. Ann R Coll Surg Engl 1974;54:244–252. 48. Whiteside JL, Walters MD. Anatomy of the obturator region: relations to a transobturator sling. Int Urogynecol J 2004;15:223–226. 49.


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Gynecology_Novak. 48. Whiteside JL, Walters MD. Anatomy of the obturator region: relations to a transobturator sling. Int Urogynecol J 2004;15:223–226. 49. Parikh M, Rasmussen M, Brubaker L, et al. Three dimensional virtual reality model of the normal female pelvic ﬂoor. Ann Biomed Eng 2004;32:292–296. 50. Bajka M, Manestar M, Hug J, et al. Detailed anatomy of the abdomen and pelvis of the visible human female. Clin Anat 2004;17:252– 260. Oliver Dorigo Otoniel Mart´ez-Maza Jonathan S. Berek The regulation and maintenance of normal tissue requires a balance between cell proliferation and programmed cell death, or apoptosis. The regulation of ovarian function occurs through autocrine, paracrine, and endocrine mechanisms. Disruption of these autocrine and paracrine intraovarian pathways may be the basis of polycystic ovarian disease, disorders of ovulation, and ovarian neoplastic disease.


Gynecology_Novak

Gynecology_Novak. Among the genes that participate in control of cell growth and function, protooncogenes and tumor suppressor genes are particularly important. Growth factors trigger intracellular biochemical signals by binding to cell membrane receptors. In general, these membrane-bound receptors are protein kinases that convert an extracellular signal into an intracellular signal. Many of the proteins that participate in the intracellular signal transduction system are encoded by proto-oncogenes that are divided into subgroups based on their cellular location or enzymatic function. Oncogenes comprise a family of genes that result from gain of function mutations of their normal counterparts, proto-oncogenes. The normal function of proto-oncogenes is to stimulate proliferation in a controlled context. Activation of oncogenes can lead to stimulation of cell proliferation and development of a malignant phenotype.


Gynecology_Novak

Gynecology_Novak. Tumor suppressor genes are involved in the development of most cancers and are usually inactivated in a two-step process in which both copies of the tumor suppressor gene are mutated or inactivated by epigenetic mechanisms like methylation. The most commonly mutated tumor suppressor gene in human cancers is p53. T lymphocytes have a central role in the generation of immune responses by acting as helper cells in both humoral and cellular immune responses and by acting as effector cells in cellular responses. T cells can be distinguished from other types of Figure 6.1 External stimuli affect the cell, which has a specific coordinated response. lymphocytes by their cell surface phenotype, based on the pattern of expression of various molecules, as well as by differences in their biologic functions.


Gynecology_Novak

Gynecology_Novak. lymphocytes by their cell surface phenotype, based on the pattern of expression of various molecules, as well as by differences in their biologic functions. ● There are two major subsets of mature T cells that are phenotypically and functionally distinct: T-helper/inducer cells, which express the CD4 cell surface marker, and the T-suppressor/cytotoxic cells, which express the CD8 marker. TH1 and TH2 are two helper T-cell subpopulations that control the nature of an immune response by secreting a characteristic and mutually antagonistic set of cytokines: Clones of TH1 produce interleukin-2 (IL-2) and interferon-γ (IFN-γ), whereas TH2 clones produce IL-4, IL-5, IL-6, and IL-10.


Gynecology_Novak

Gynecology_Novak. Advances in molecular biology and genetics have improved our understanding of basic biologic concepts and disease development. The knowledge acquired with the completion of the human genome project, the data available through The Cancer Genome Atlas (TCGA), the development of novel diagnostic modalities, such as the microarray technology for the analysis of DNA and proteins, and the emergence of treatment strategies that target specific disease mechanisms all have an increasing impact on the specialty of obstetrics and gynecology.


Gynecology_Novak

Gynecology_Novak. Normal cells are characterized by discrete metabolic, biochemical, and physiologic mechanisms. Specific cell types differ with respect to their mainly genetically determined responses to external inﬂuences (Fig. 6.1). An external stimulus is converted to an intracellular signal, for example, via a cell membrane receptor. The intracellular signal is transferred to the nucleus and generates certain genetic responses that lead to changes in cellular function, differentiation, and proliferation. Although specific cell types and tissues exhibit unique functions and responses, many basic aspects of cell biology and genetics are common to all eukaryotic cells.


Gynecology_Novak

Gynecology_Novak. Normal Cell Cycle Adult eukaryotic cells possess a well-balanced system of continuous production of DNA (transcription) and proteins (translation). Proteins are constantly degraded and replaced depending on the specific cellular requirements. Cells proceed through a sequence of phases called the cell cycle, during which the DNA is distributed to two daughter cells (mitosis) and subsequently duplicated (synthesis phase). This process is controlled at key checkpoints that monitor the status of a cell, for example, the amount of DNA present. The cell cycle is regulated by a small number of heterodimeric protein kinases that consist of a regulatory subunit (cyclin) and a catalytic subunit (cyclin-dependent kinase). Association of a cyclin with a cyclindependent kinase (CdkC) determines which proteins will be phosphorylated at a specific point during the cell cycle. Figure 6.2 The cell cycle.


Gynecology_Novak

Gynecology_Novak. Figure 6.2 The cell cycle. The cell cycle is divided into four major phases: M phase (mitosis), G1 phase (period between mitosis and initiation of DNA replication), S phase (DNA synthesis), and G2 phase (period between completion of DNA synthesis and mitosis) (Fig. 6.2). Postmitotic cells can “exit” the cell cycle into the so-called G0 phase and remain for days, weeks, or even a lifetime without further proliferation. The duration of the cell cycle may be highly variable, although most human cells complete the cell cycle within approximately 24 hours. During a typical cell cycle, mitosis lasts about 30 to 60 minutes, the G1 phase 7 to 10 hours, S phase 10 hours, and G2 phase 5 hours. With respect to the cell cycle, there are three subpopulations of cells: 1. Terminally differentiated cells cannot re-enter the cell cycle. 2. Quiescent (G0) cells can enter the cell cycle if appropriately stimulated. 3. Dividing cells are currently in the cell cycle.


Gynecology_Novak

Gynecology_Novak. Terminally differentiated cells cannot re-enter the cell cycle. 2. Quiescent (G0) cells can enter the cell cycle if appropriately stimulated. 3. Dividing cells are currently in the cell cycle. Red blood cells, striated muscle cells, uterine smooth muscle cells, and nerve cells are terminally differentiated. Other cells, such as fibroblasts, exit from the G1 phase into the G0 phase and are considered to be out of the cell cycle. These cells enter the cell cycle following exposure to specific stimuli, such as growth factors and steroid hormones. Dividing cells are found in the gastrointestinal tract, the skin, and the cervix.


Gynecology_Novak

Gynecology_Novak. G1 Phase In response to specific external stimuli, cells enter the cell cycle by moving from the G0 phase into the G1 phase. The processes during G1 phase lead to the synthesis of enzymes and regulatory proteins necessary for DNA synthesis during S phase and are mainly regulated by G1 cyclindependent kinase–cyclin complexes (G1CdkC). Complexes of G1CdkC induce degradation of the S phase inhibitors in late G1. Release of the S phase CdkC complex subsequently stimulates entry into the S phase. Variations in the duration of the G1 phase of the cell cycle, ranging from less than 8 hours to longer than 100 hours, account for the different generation times exhibited by different types of cells.


Gynecology_Novak

Gynecology_Novak. S Phase The nuclear DNA content of the cell is duplicated during the S phase of the cell cycle. The S phase CdkC complex activates proteins of the DNA prereplication complexes that assemble on DNA replication origins during G1. The prereplication complex activates initiation of DNA replication and inhibits the assembly of new prereplication complexes. This inhibition ascertains that each chromosome is replicated only once during the S phase.


Gynecology_Novak

Gynecology_Novak. G2 Phase RNA and protein synthesis occurs during the G2 phase of the cell cycle. The burst of biosynthetic activity provides the substrates and enzymes to meet the metabolic requirements of the two daughter cells. Another important event that occurs during the G2 phase of the cell cycle is the repair of errors of DNA replication that may have occurred during the S phase. Failure to detect and correct these genetic errors can result in a broad spectrum of adverse consequences for the organism and the individual cell (1). Defects in the DNA repair mechanism are associated with an increased incidence of cancer (2). Mitotic CdkC complexes are synthesized during the S and G2 phases, but are inactive until DNA synthesis is completed.


Gynecology_Novak

Gynecology_Novak. M Phase Nuclear–chromosomal division occurs during the mitosis or M phase. During this phase, the cellular DNA is equally distributed to each of the daughter cells. Mitosis provides a diploid (2n) DNA complement to each somatic daughter cell. Following mitosis, eukaryotic mammalian cells contain diploid DNA, reﬂecting a karyotype that includes 44 somatic chromosomes and an XX or XY sex chromosome complement. Exceptions to the diploid cellular content include hepatocytes (4n) and the functional syncytium of the placenta.


Gynecology_Novak

Gynecology_Novak. Mitosis is divided into prophase, metaphase, anaphase, and telophase. Mitotic CdkC complexes induce chromosome condensation during the prophase, assembly of the mitotic spindle apparatus, and alignment of the chromosomes during the metaphase. Activation of the anaphase promoting complex (APC) leads to inactivation of the protein complexes that connect sister chromatids during metaphase, permitting the onset of anaphase. During anaphase, sister chromatids segregate to opposite spindle poles. The nuclear envelope breaks down into multiple small vesicles early in mitosis and reforms around the segregated chromosomes as they decondense during telophase. Cytokinesis is the process of division of the cytoplasm that segregates the endoplasmic reticulum and the Golgi apparatus during mitosis. After completion of mitosis, cells enter the G1 phase and either re-enter the cell cycle or remain in G0.


Gynecology_Novak

Gynecology_Novak. Ploidy After meiosis, germ cells contain a haploid (1n) genetic complement. After fertilization, a 46,XX or 46,XY diploid DNA complement is restored. Restoration of the normal cellular DNA content is crucial to normal function. Abnormalities of cellular DNA content cause distinct phenotypic abnormalities, as exemplified by hydatidiform molar pregnancy (see Chapter 39). In a complete hydatidiform mole, an oocyte without any nuclear genetic material (e.g., an empty ovum) is fertilized by one sperm. The haploid genetic content of the fertilized ovum is then duplicated, and the diploid cellular DNA content is restored, resulting in a homozygous 46,XX gamete. Less often, a complete hydatidiform mole results from the fertilization of an empty ovum by two sperm, resulting in a heterozygous 46,XX or 46,XY gamete. In complete molar pregnancies, the nuclear DNA is usually paternally derived, embryonic structures do not develop, and trophoblast hyperplasia occurs. Rarely, complete moles are


Gynecology_Novak

Gynecology_Novak. or 46,XY gamete. In complete molar pregnancies, the nuclear DNA is usually paternally derived, embryonic structures do not develop, and trophoblast hyperplasia occurs. Rarely, complete moles are biparental. This karyotype seems to be found in patients with recurrent hydatiform moles and is associated with a higher risk of persistent trophoblastic disease.


Gynecology_Novak

Gynecology_Novak. A partial hydatiform mole follows the fertilization of a haploid ovum by two sperm, resulting in a 69,XXX, 69,XXY, or 69,XYY karyotype. A partial mole contains paternal and maternal DNA, and both embryonic and placental development occur. Both the 69,YYY karyotype and the 46,YY karyotype are incompatible with embryonic and placental development. These observations demonstrate the importance of maternal genetic material, in particular the X chromosome, in normal embryonic and placental development. In addition to total cellular DNA content, the chromosome number is an important determinant of cellular function. Abnormalities of chromosome number, which often are caused by nondisjunction during meiosis, result in well-characterized clinical syndromes such as trisomy 21 (Down syndrome), trisomy 18, and trisomy 13. Genetic Control of the Cell Cycle


Gynecology_Novak

Gynecology_Novak. Genetic Control of the Cell Cycle Cellular proliferation must occur to balance normal cell loss and maintain tissue and organ integrity. This process requires the coordinated expression of many genes at discrete times during the cell cycle (3). In the absence of growth factors, cultured mammalian cells are arrested in the G0 phase. With the addition of growth factors, these quiescent cells pass through the so-called restriction point 14 to 16 hours later and enter the S phase 6 to 8 hours thereafter. The restriction point or G1/S boundary marks the point at which a cell commits to proliferation. A second checkpoint is the G2/M boundary, which marks the point at which repair of any DNA damage must be completed (4–7). To successfully complete the cell cycle, a number of cell division cycle (cdc) genes are activated.


Gynecology_Novak

Gynecology_Novak. Cell Division Cycle Genes Among the factors that regulate the cell cycle checkpoints, proteins encoded by the cdc2 family of genes and the cyclin proteins appear to play particularly important roles (8,9). Growth factor–stimulated mammalian cells express early-response or delayed-response genes, depending on the chronological sequence of the appearance of specific RNAs. The early-and delayed-response genes act as nuclear transcription factors and stimulate the expression of a cascade of other genes. Early-response genes such as c-Jun and c-Fos enhance the transcription of delayed-response genes such as E2Fs. E2F transcription factors are required for the expression of various cell cycle genes and are functionally regulated by the retinoblastoma (Rb) protein. Binding of Rb to E2F converts E2F from a transcriptional activator to a repressor of transcription. Phosphorylation of Rb inhibits its repressing function and permits E2F-mediated activation of genes required for entry into the S


Gynecology_Novak

Gynecology_Novak. E2F from a transcriptional activator to a repressor of transcription. Phosphorylation of Rb inhibits its repressing function and permits E2F-mediated activation of genes required for entry into the S phase. Cdk4-cyclin D, Cdk6-cyclin D, and Cdk2-cyclin E complexes cause phosphorylation of Rb, which remains phosphorylated throughout the S, G2, and M phases of the cell cycle. After completion of mitosis, a decline of the level of Cdk-cyclins leads to dephosphorylation of Rb by phosphatases and, consequently, an inhibition of E2F in the early G1 phase.


Gynecology_Novak

Gynecology_Novak. Cdks are being evaluated as targets for cancer treatments because they are frequently overactive in cancer disease and Cdk-inhibiting proteins are dysfunctional. The Cdk4 inhibitor P1446A-05, for example, specifically inhibits Cdk4-mediated G1-S phase transition, arresting cell cycling and inhibiting cancer cell growth (10). SNS-032 selectively binds to Cdk2, -7, and -9, preventing their phosphorylation and activation and subsequently preventing cell proliferation.


Gynecology_Novak

Gynecology_Novak. As cells approach the G1-S phase transition, synthesis of cyclin A is initiated. The Cdk2-cyclin A complex can trigger initiation of DNA synthesis by supporting the prereplication complex. The p34 cdc2 protein and specific cyclins form a complex heterodimer referred to as mitosis-promoting factor (MPF), which catalyzes protein phosphorylation and drives the cell into mitosis. Cdk1 assembles with cyclin A and cyclin B in the G2 phase and promotes the activity of the MPF. Mitosis is initiated by activation of the cdc gene at the G2-M checkpoint (11,12). Once the G2-M checkpoint is passed, the cell undergoes mitosis. In the presence of abnormally replicated chromosomes, progression past the G2-M checkpoint does not occur.


Gynecology_Novak

Gynecology_Novak. The p53 tumor suppressor gene participates in cell cycle control. Cells exposed to radiation therapy exhibit an S-phase arrest that is accompanied by increased expression of p53. This delay permits the repair of radiation-induced DNA damage. In the presence of p53 mutations, the S-phase arrest that normally follows radiation therapy does not occur (13,14). The wild type p53 gene can be inactivated by the human papillomavirus E6 protein, preventing S-phase arrest in response to DNA damage (15).


Gynecology_Novak

Gynecology_Novak. Apoptosis The regulation and maintenance of normal tissue requires a balance between cell proliferation and programmed cell death, or apoptosis. When proliferation exceeds programmed cell death, the result is hyperplasia. When programmed cell death exceeds proliferation, the result is atrophy. Programmed cell death is a crucial concomitant of normal embryologic development. This mechanism accounts for deletion of the interdigital webs, palatal fusion, and development of the intestinal mucosa (16–18). Programmed cell death is also an important phenomenon in normal physiology (19). The reduction in the number of endometrial cells following alterations in steroid hormone levels during the menstrual cycle is, in part, a consequence of programmed cell death (20,21). In response to androgens, granulosa cells undergo programmed cell death (e.g., follicular atresia) (22).


Gynecology_Novak

Gynecology_Novak. Programmed cell death, or apoptosis, is an energy-dependent, active process that is initiated by the expression of specific genes. This process is distinct from cell necrosis, although both mechanisms result in a reduction in total cell number. In programmed cell death, cells shrink and undergo phagocytosis. Conversely, groups of cells expand and lyse when undergoing cell necrosis. The process is energy independent and results from noxious stimuli. Programmed cell death is triggered by a variety of factors, including intracellular signals and exogenous stimuli such as radiation exposure, chemotherapy, and hormones. Cells undergoing programmed cell death may be identified on the basis of histologic, biochemical, and molecular biologic changes. Histologically, apoptotic cells exhibit cellular condensation and fragmentation of the nucleus. Biochemical correlates of impending programmed cell death include an increase in transglutaminase expression and ﬂuxes in intracellular calcium


Gynecology_Novak

Gynecology_Novak. cellular condensation and fragmentation of the nucleus. Biochemical correlates of impending programmed cell death include an increase in transglutaminase expression and ﬂuxes in intracellular calcium concentration (23).