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Genitourinary system

The genitourinary system, also known as the urogenital system, comprises the urinary tract and the reproductive organs, which together handle the excretion of waste and the processes of reproduction in humans. It includes the paired kidneys, ureters, urinary bladder, and urethra for urinary functions, as well as sex-specific reproductive structures: in males, the testes, epididymis, vas deferens, seminal vesicles, prostate, and penis; in females, the ovaries, fallopian tubes, uterus, vagina, and external genitalia.^[1]^[2] These components are anatomically integrated, particularly in males where the urethra serves dual roles in urination and semen transport, while in females the systems are adjacent but functionally distinct.^[3] The primary functions of the genitourinary system revolve around maintaining homeostasis and enabling reproduction. The urinary tract filters approximately 180 liters of blood plasma daily through the kidneys' nephrons to produce urine, which removes metabolic wastes like urea, regulates electrolyte balance, controls blood pressure via the renin-angiotensin system, and preserves acid-base equilibrium.^[2] Urine travels via peristaltic ureters to the bladder for storage (up to about 500 mL) before voluntary expulsion through the urethra. In the reproductive domain, male structures produce spermatozoa in the seminiferous tubules of the testes (about 100-200 million daily), transport them through ductal pathways, and mix them with seminal fluid from accessory glands to form semen, which is ejaculated during intercourse; testosterone secretion from the testes also drives secondary sexual characteristics and libido.^[3] Female reproductive organs facilitate oogenesis in the ovaries, ovulation, fertilization in the fallopian tubes, embryonic implantation in the uterus, and parturition, while also producing hormones like estrogen and progesterone to regulate menstrual cycles and pregnancy.^[4] This system's integrated design underscores its vulnerability to shared pathologies, such as infections (e.g., urinary tract infections ascending to reproductive organs) or congenital anomalies affecting both urinary drainage and fertility.^[2] Disorders like kidney stones, prostate enlargement, or ovarian cysts can impair overall function, highlighting the importance of specialized medical fields like urology and gynecology for diagnosis and treatment.^[5]

Embryological Development

Urinary System Development

The urinary system originates from the intermediate mesoderm, which forms the nephrogenic cord along the posterior abdominal wall during the fourth week of gestation. This cord sequentially gives rise to three kidney structures: the pronephros, mesonephros, and metanephros. The pronephros appears first as rudimentary tubules in the cervical region around week 4 but is non-functional and regresses completely by day 25.^[6]^[7] The mesonephros follows in weeks 4 to 10, developing approximately 40 pairs of tubules with about 20 functional nephrons positioned between the L1 and L3 vertebral levels; it temporarily excretes fluid into the amniotic cavity before largely regressing.^[6]^[8] By week 5, the metanephros emerges as the definitive structure that becomes the permanent kidney, with nephrogenesis continuing until week 32 to form 1 to 3 million collecting tubules.^[6]^[7] Central to metanephric development is the ureteric bud, an outgrowth from the caudal portion of the mesonephric duct around week 5, which is induced by glial cell line-derived neurotrophic factor (GDNF) secreted from the adjacent metanephric mesenchyme, also known as the metanephric blastema.^[6]^[8] This initiates reciprocal inductive interactions: the ureteric bud branches to form the ureter, renal pelvis, major and minor calyces, and collecting ducts starting in week 6, while the metanephric mesenchyme differentiates into nephrons, including glomeruli, proximal and distal tubules, and loops of Henle, under signals such as Wnt and fibroblast growth factors.^[6]^[9] The mesonephric duct, which initially drains the mesonephros and integrates briefly with the developing urinary tract by contributing to the bladder's trigone, plays a key role in positioning the ureteric bud.^[8]^[7] The lower urinary tract develops concurrently from the cloaca, an endodermal structure that is partitioned by the urorectal septum around week 7 into the dorsal anorectal canal and the ventral urogenital sinus.^[6]^[7] The cranial portion of the urogenital sinus expands to form the bladder, incorporating the allantois as the urachus (later the median umbilical ligament) and receiving the ureters as they are absorbed into its wall; the trigone derives from the incorporated common excretory ducts of the mesonephros.^[6]^[8] The urethra arises from the caudal urogenital sinus through canalization of the urethral folds; incomplete canalization can lead to hypospadias, a congenital malformation where the urethral opening is abnormally positioned on the ventral penile surface.^[6]^[10]^[11] Following initial formation in the pelvis, the metanephric kidneys undergo ascent to their final abdominal position between weeks 6 and 9, migrating from the sacral region to the lumbar area at T12-L3.^[6]^[7] This process involves differential growth of the body caudal to the kidneys and changes in vascular supply, with initial pelvic branches of the aorta being replaced by higher origins, potentially resulting in multiple renal arteries if ascent is disrupted.^[6]^[7]

Reproductive System Development

The development of the reproductive system begins during the indifferent stage of embryogenesis, up to approximately week 7, when the gonads and genitalia are bipotential and indistinguishable between sexes. Gonadal ridges form from the intermediate mesoderm starting around week 4, becoming covered by coelomic epithelium by week 5 as primordial germ cells migrate to these ridges.^[12] Concurrently, the external genitalia primordia emerge by week 6, including the genital tubercle as a ventral outgrowth, flanked by urethral folds and labioscrotal swellings.^[13] This stage reflects the shared mesodermal origin with the urinary system from intermediate mesoderm.^[12] Sex determination occurs primarily through genetic mechanisms, with the SRY gene on the Y chromosome initiating testis differentiation around weeks 6-7 in XY embryos.^[12] In the absence of SRY, as in XX embryos, ovarian development proceeds by week 12.^[13] In males, the primary sex cords thicken into testis cords by weeks 7-8, which later form seminiferous tubules, while interstitial Leydig cells differentiate by week 8 to produce testosterone starting in week 9.^[12] Testosterone stabilizes the Wolffian (mesonephric) ducts, which differentiate between weeks 9-13 into the epididymis, vas deferens, and seminal vesicles.^[13] Meanwhile, Sertoli cells within the testis cords secrete anti-Müllerian hormone (AMH) from weeks 8-10, inducing regression of the Müllerian ducts.^[12] In females, the Müllerian ducts persist and develop into the fallopian tubes, uterus, and upper vagina, with paramesonephric duct fusion completing by week 9.^[13] The Wolffian ducts regress between weeks 10-13 due to the lack of androgens.^[12] Ovarian differentiation involves the formation of secondary sex cords around weeks 10-12, enclosing primordial follicles that mature significantly after week 24.^[13] Differentiation of the external genitalia follows a default female pathway unless influenced by androgens. In males, testosterone is converted to dihydrotestosterone (DHT) by week 9, promoting elongation of the genital tubercle into the penis, fusion of the urethral folds to form the penile urethra, and fusion of the labioscrotal swellings into the scrotum by week 12.^[12] Without androgens, the genital tubercle becomes the clitoris, urethral folds form the labia minora, and labioscrotal swellings develop into the labia majora.^[13] Gonadal descent completes the positional development. Testes descend in two phases: transabdominal migration to the internal inguinal ring by week 12, guided by the gubernaculum, followed by inguinoscrotal descent between weeks 27-35, reaching the scrotum by month 7.^[12] Ovaries descend later, from the abdomen to the pelvic cavity around weeks 28-30, also facilitated by the gubernaculum.^[13]

Anatomy

Urinary Tract Structures

The urinary tract consists of the kidneys, ureters, bladder, and urethra, which collectively function to filter blood, produce urine, and facilitate its storage and excretion. The kidneys are paired, retroperitoneal organs located in the posterior abdomen, each with a bean-shaped structure measuring approximately 10-12 cm in length, 5-7 cm in width, and 2-3 cm in thickness. They are enveloped by a fibrous capsule and divided into an outer cortex and inner medulla, with the cortex containing renal columns and the medulla organized into 8-18 renal pyramids that converge into papillae draining into the renal pelvis. Each kidney houses about 1 million nephrons, the functional units responsible for urine formation. The ureters are paired, muscular tubes approximately 25-30 cm long and 3-4 mm in diameter, extending from the renal pelvis to the bladder. They feature three natural constrictions—at the ureteropelvic junction, where they cross the iliac vessels, and at the ureterovesical junction—to facilitate peristaltic waves that propel urine downward via smooth muscle contractions. The ureterovesical junction incorporates an oblique intramural course through the bladder wall, serving as a valvular mechanism to prevent vesicoureteral reflux during bladder filling or voiding. The urinary bladder is a hollow, muscular organ situated in the pelvis behind the pubic symphysis, capable of distending to hold 400-600 mL of urine in adults. Its wall comprises the detrusor muscle, a layer of interlacing smooth muscle fibers that contracts during micturition, and an inner mucosal lining of transitional epithelium that allows for expansion without rupture. The bladder's posterior-inferior region forms the trigone, a triangular area bounded by the two ureteral orifices superiorly and the urethral opening inferiorly, which remains relatively fixed and is clinically significant for its role in localizing infections. The urethra serves as the final conduit for urine expulsion, varying significantly in length and structure between sexes due to its shared distal segment with the reproductive system. In females, it measures about 4 cm and extends from the bladder neck to the external urethral orifice in the vestibule, lined by stratified squamous and transitional epithelium with mucosal folds known as rugae. In males, it is longer at approximately 20 cm, divided into prostatic, membranous, and spongy (penile) segments, surrounded by erectile tissue in the spongy portion and featuring similar mucosal rugae for flexibility. Blood supply to the urinary tract primarily derives from the renal arteries, which branch directly from the abdominal aorta at the L1-L2 level and divide into segmental arteries supplying the kidneys' cortex and medulla via interlobar, arcuate, and interlobular branches. Venous drainage follows a parallel course, with renal veins emptying into the inferior vena cava on the right and the left renal vein crossing the midline to join it. Innervation involves sympathetic fibers from T10-L2 spinal segments for vasoconstriction and parasympathetic fibers from S2-S4 for peristalsis in the ureters and detrusor contraction in the bladder, with somatic pudendal nerve input controlling the external urethral sphincter. Histologically, the urinary tract is lined by transitional epithelium from the renal pelvis through the bladder, characterized by its ability to stretch and appear cuboidal when distended or squamous-like when relaxed, providing a impermeable barrier to urine. Within the kidneys, nephrons feature a glomerular filtration barrier in Bowman's capsule, composed of fenestrated endothelial cells, a shared basement membrane, and podocyte foot processes with slit diaphragms that selectively permit water and solutes while restricting proteins and cells.

Male Genital Structures

The male genital structures encompass the external and internal organs responsible for sperm transport and delivery, collectively forming the reproductive tract that supports male fertility. These structures include the testes, epididymis, vas deferens, accessory glands such as the seminal vesicles, prostate, and bulbourethral glands, as well as the penis and scrotum. Positioned primarily in the pelvis and perineum, they are interconnected via ducts and vascular networks to facilitate coordinated function.^[14] The testes, also known as testicles, are paired ovoid organs measuring approximately 3 to 5 cm in length and 2 to 3 cm in width, suspended within the scrotum. Each testis is enclosed by a dense fibrous capsule called the tunica albuginea, which divides the organ into lobules containing seminiferous tubules where spermatogenesis occurs, and a central mediastinum testis that serves as a structural anchor for these tubules. The testes descend from the abdominal cavity into the scrotum during fetal development to maintain an optimal environment for sperm production.^[15]^[16] Attached to the posterior surface of each testis is the epididymis, a single tightly coiled tube approximately 6 meters long when uncoiled, divided into three regions: the caput (head) at the superior pole, the corpus (body) along the lateral aspect, and the cauda (tail) at the inferior pole. This structure provides a site for sperm maturation and storage before transport.^[17] The vas deferens, or ductus deferens, is a muscular tube about 30 to 45 cm in length that originates from the cauda epididymidis, ascends through the inguinal canal as part of the spermatic cord, and descends to join the duct of the seminal vesicle, forming the ejaculatory duct near the prostate. It propels sperm via peristaltic contractions toward the urethra.^[18]^[19] The seminal vesicles are paired, convoluted sac-like glands located posterior to the bladder and superior to the prostate, each measuring about 5 to 10 cm in length. They secrete a viscous, fructose-rich fluid that constitutes approximately 60% to 70% of semen volume, providing nutrients and propulsion for sperm. The prostate is a walnut-sized (about 3 to 4 cm) glandular structure that encircles the urethra at the bladder neck, composed of fibromuscular and epithelial tissues arranged in zones. It contributes around 30% of semen volume through an alkaline secretion that neutralizes vaginal acidity and enhances sperm motility.^[20]^[21]^[22] The penis consists of three cylindrical erectile tissues: two dorsal corpora cavernosa that form the bulk of the shaft, and a ventral corpus spongiosum that surrounds the urethra and expands distally into the sensitive glans penis, covered by a retractable foreskin (prepuce) in uncircumcised individuals. Erection occurs via engorgement of these corpora with blood supplied by helicine arteries, coiled branches of the deep penile arteries that dilate during arousal. The urethra passes through the corpus spongiosum, serving both urinary and ejaculatory functions. Blood supply to the penis is primarily from the internal pudendal artery.^[23]^[24] The scrotum is a pendulous sac of skin and smooth muscle that houses the testes and epididymides, divided into two compartments by a midline septum. It features the dartos muscle, a thin layer of smooth muscle in the subcutaneous tissue that contracts to wrinkle the skin and reduce surface area for heat conservation, aiding thermoregulation by maintaining testicular temperature 2 to 3°C below core body temperature (approximately 34 to 35°C). The cremaster muscle, a striated extension of the internal oblique abdominal muscle, surrounds the spermatic cord and elevates the testes toward the body during cold exposure or arousal for additional protection and temperature control.^[25]^[26]^[27] Accessory glands include the paired bulbourethral glands (Cowper's glands), small pea-sized structures located in the urogenital diaphragm inferior to the prostate, which secrete a clear, mucus-like fluid for urethral lubrication prior to ejaculation, comprising about 1% of semen volume. Overall blood supply to the male genital structures derives from branches of the internal iliac artery, including the testicular arteries for the testes and epididymis, and the internal pudendal artery for the penis and perineal components.^[28]^[14]

Female Genital Structures

The female genital structures encompass the internal and external organs responsible for reproduction, including the ovaries, fallopian tubes, uterus, vagina, and vulva, which collectively form pathways for oocyte transport, fertilization, and gestation. These structures are situated within the pelvic cavity and supported by ligaments, with the external components visible at the body’s perineal region. The vagina connects the internal organs to the exterior, while the vulva provides protective and sensory features.^[29] The ovaries are paired, almond-shaped gonads measuring approximately 3 to 5 cm in length, located in the pelvic cavity on either side of the uterus. Each ovary consists of an outer cortex containing ovarian follicles and an inner medulla rich in blood vessels and lymphatics. The ovaries are anchored to the uterus by the ovarian ligament, which maintains their position within the broad ligament of the pelvis.^[30] The fallopian tubes, also known as uterine tubes, are bilateral muscular structures approximately 10 to 12 cm long, extending from the superior lateral aspects of the uterus to near the ovaries. They are divided into segments: the infundibulum with finger-like fimbriae that capture ovum, the ampulla for potential fertilization site, and the isthmus leading to the intramural portion within the uterine wall. The inner lining features ciliated columnar epithelium that facilitates ovum transport.^[31] The uterus is a pear-shaped, hollow muscular organ measuring about 7 to 8 cm in length, positioned in the pelvic cavity behind the bladder and anterior to the rectum. It comprises the fundus (upper dome), body (main central portion), and cervix (lower narrow segment projecting into the vagina). The uterine wall includes the outer perimetrium, thick myometrium of smooth muscle, and inner endometrium lining. Support is provided by the broad ligament enveloping the uterus and fallopian tubes, as well as lateral ligaments connecting to the pelvic sidewalls.^[32] The vagina is an elastic, muscular canal approximately 8 to 10 cm long, extending from the cervix to the external introitus. Its walls are lined with rugae—transverse folds that allow expansion—and surround the cervix to form anterior, posterior, and lateral fornices. A thin membrane, the hymen, partially covers the vaginal introitus.^[33] The vulva constitutes the external female genitalia, including the labia majora (outer fleshy folds covered with pubic hair), labia minora (inner delicate folds enclosing the vestibule), and clitoris (a small erectile structure with a glans and hood, containing dense nerve endings). The Bartholin's glands, located at the vaginal entrance within the vestibule, produce lubricating secretions. The female urethra, shared with the urinary system, is short and opens into the vulva anterior to the vaginal introitus.^[34] Blood supply to the female genital structures primarily derives from the ovarian arteries, branching directly from the abdominal aorta to nourish the ovaries and upper uterus, and the uterine arteries, arising from the anterior division of the internal iliac artery to supply the uterus, cervix, upper vagina, and fallopian tubes; anastomoses between these arteries ensure robust circulation. Innervation occurs via the pelvic plexus, incorporating sympathetic fibers from T12-L2 levels and parasympathetic fibers from S2-S4, which regulate vascular tone and sensation in the reproductive organs.^[35]

Physiology

Urinary Physiology

The urinary system maintains fluid, electrolyte, and acid-base homeostasis through the processes of filtration, reabsorption, secretion, and excretion in the nephrons of the kidneys. Urine formation begins with glomerular filtration, followed by selective modification in the renal tubules, culminating in the production of urine that is typically 1-2 L per day with an osmolality ranging from 50 to 1200 mOsm/kg, depending on hydration status.^[36]^[37] These mechanisms ensure the excretion of waste while conserving essential substances, with overall regulation influenced by hormonal signals. Glomerular filtration occurs in the Bowman's capsule, where blood plasma is filtered at a normal glomerular filtration rate (GFR) of approximately 125 mL/min in healthy adults.^[38] This process is driven by Starling forces across the glomerular capillary wall: the hydrostatic pressure in the glomerular capillaries (about 55 mmHg favoring filtration) exceeds the opposing colloid oncotic pressure (around 30 mmHg) and Bowman's space hydrostatic pressure.^[39] The filtration barrier, consisting of fenestrated endothelium, glomerular basement membrane, and podocyte slit diaphragms, exhibits selectivity based on size (restricting molecules >70 kDa) and negative charge (repelling anionic proteins like albumin), allowing water, ions, glucose, and small solutes to pass while retaining cells and large proteins.^[40] In the proximal tubule, about 65% of filtered sodium, water, and bicarbonate is reabsorbed isosmotically, along with nearly all glucose via sodium-glucose cotransporters (SGLT2 in the early segment and SGLT1 in the late segment).^[41] This reabsorption is powered by the Na+/K+-ATPase on the basolateral membrane, creating a sodium gradient that drives secondary active transport. The loop of Henle then establishes a countercurrent multiplier system for urine concentration: the descending limb is permeable to water but not solutes, allowing osmotic equilibration with the hypertonic medullary interstitium, while the thick ascending limb actively reabsorbs sodium and chloride via the Na-K-2Cl cotransporter (impermeable to water), generating a dilute tubular fluid and a medullary osmotic gradient up to 1200 mOsm/L.^[42] Secretion and final adjustments occur in the distal tubule and collecting duct, where aldosterone promotes sodium reabsorption and potassium secretion in principal cells by upregulating epithelial sodium channels (ENaC) and Na+/K+-ATPase, accounting for 5-10% of total sodium handling.^[43] Antidiuretic hormone (ADH, or vasopressin) regulates water reabsorption by inserting aquaporin-2 channels in the collecting duct principal cells, enabling concentration of urine in response to plasma osmolality. Acid-base balance is maintained through H+ secretion and HCO3- reabsorption/generation in intercalated cells, primarily via apical H+-ATPase and H+/K+-ATPase, allowing urine pH to range from 4.5 to 8.0 as needed.^[44] Micturition, or urination, involves coordinated storage and voiding: the bladder fills to 200-400 mL, stretching the detrusor smooth muscle and activating stretch receptors that trigger a parasympathetic reflex via pelvic nerves (S2-S4), causing detrusor contraction and internal urethral sphincter relaxation.^[45] Voluntary control is exerted over the external urethral sphincter by somatic pudendal nerve fibers (S2-S4), which relax to allow expulsion once the reflex is initiated. The bladder and urethra thus serve as temporary storage reservoirs during filling phases. Hormonal regulation fine-tunes these processes; the renin-angiotensin-aldosterone system (RAAS) responds to low renal perfusion by releasing renin from juxtaglomerular cells, leading to angiotensin II-mediated vasoconstriction, proximal sodium reabsorption, and aldosterone secretion to maintain blood pressure and volume.^[46] Conversely, atrial natriuretic peptide (ANP), released from atrial myocytes in response to volume expansion, promotes natriuresis by dilating afferent arterioles (increasing GFR), inhibiting RAAS, and reducing sodium reabsorption in the collecting duct.^[47]

Male Reproductive Physiology

The male reproductive physiology encompasses the continuous production of spermatozoa, regulation by the hypothalamic-pituitary-gonadal axis, and the mechanisms of semen formation and expulsion, enabling fertility throughout adult life. Spermatogenesis, the process of sperm cell development, occurs within the seminiferous tubules of the testes and involves the transformation of diploid spermatogonia into haploid spermatozoa through mitosis, meiosis, and spermiogenesis.^[48] This process is supported by Sertoli cells, which provide structural scaffolding, nutrients, and regulatory signals to developing germ cells.^[48] The entire cycle lasts approximately 74 days in humans, culminating in the release of mature spermatozoa into the tubular lumen.^[49] A healthy adult male produces 100-200 million sperm per day, ensuring a steady supply for potential fertilization.^[50] Hormonal regulation is orchestrated by the hypothalamic-pituitary-gonadal axis, where gonadotropin-releasing hormone (GnRH) from the hypothalamus stimulates the anterior pituitary to secrete follicle-stimulating hormone (FSH) and luteinizing hormone (LH).^[51] FSH acts on Sertoli cells to promote spermatogenesis by enhancing germ cell proliferation and maturation, while LH binds to receptors on Leydig cells in the testicular interstitium, stimulating the production of testosterone at a rate of 5-10 mg per day.^[51]^[52] Testosterone, in turn, supports spermatogenesis and exerts negative feedback on the hypothalamus and pituitary to inhibit GnRH and gonadotropin release, maintaining homeostasis.^[53] Inhibin, secreted by Sertoli cells, provides additional feedback specifically targeting FSH production.^[53] Semen formation involves contributions from multiple accessory glands to create a nutrient-rich medium for sperm transport and survival. The typical ejaculate volume is 2-5 mL with a pH of 7.2-8.0, which neutralizes the acidic vaginal environment to facilitate sperm motility.^[54] Seminal vesicles contribute the majority (about 60-70%) of the fluid, including fructose as an energy source for sperm and prostaglandins that aid in cervical mucus penetration.^[55] The prostate adds further prostaglandins and enzymes that liquefy the coagulated semen post-ejaculation.^[56] During sexual arousal, parasympathetic stimulation triggers nitric oxide release from penile nerves, causing vasodilation and erection by relaxing smooth muscles in the corpora cavernosa.^[24] Ejaculation follows via sympathetic activation, which contracts the ducts of the epididymis, vas deferens, and seminal vesicles to emit semen into the urethra, expelling 400-500 million sperm in a typical event.^[57]^[58] Scrotal thermoregulation is critical for spermatogenesis, as meiosis and sperm maturation require a temperature 2-3°C below core body temperature; the scrotum achieves this through contraction of the dartos and cremaster muscles in response to thermal sensors.^[59] Elevated testicular heat impairs meiosis and reduces sperm viability.^[59] Puberty onset in males typically occurs around age 12, marked by increased GnRH pulsatility that initiates the hormonal axis and leads to Tanner stage progression: stage 1 (prepubertal), stage 2 (testicular enlargement >4 mL, initial pubic hair), stage 3 (penis growth, voice deepening), stage 4 (further genital maturation), and stage 5 (adult configuration by age 15-17).^[60]^[61]

Female Reproductive Physiology

The female reproductive physiology encompasses the cyclic processes that prepare the body for potential pregnancy, beginning with puberty and extending through the menstrual and ovarian cycles to fertilization and early implantation. Puberty in females typically initiates between ages 8 and 13, marked by the activation of the hypothalamic-pituitary-gonadal axis, leading to secondary sexual characteristics. Menarche, the first menstrual period, occurs on average at age 12 to 13 years, often 2 to 3 years after the onset of breast development. Breast development follows Tanner stages: stage 1 is pre-pubertal with no glandular tissue; stage 2 features breast budding under the areola around age 8-13; stage 3 shows further enlargement without areolar separation; stage 4 involves areolar projection above the breast contour; and stage 5 achieves adult configuration by age 15-18. Genital development parallels this, with pubic hair progressing from sparse (stage 2) to adult distribution (stage 5), while the internal reproductive organs mature under rising estrogen influence.^[62]^[60]^[63] The menstrual cycle, averaging 28 days with a normal range of 21 to 35 days, regulates endometrial preparation for implantation through interplay of ovarian hormones. It divides into the follicular (proliferative) phase, ovulation, and luteal (secretory) phase, with variations including anovulatory cycles more common in adolescence or perimenopause where estrogen drives endometrial growth without ovulation. During the proliferative phase (days 1-14), estrogen from developing follicles stimulates endometrial proliferation, thickening the lining from 1-2 mm to 5-7 mm with glandular elongation. The secretory phase (days 15-28) follows ovulation, where progesterone from the corpus luteum induces endometrial glands to secrete glycogen and mucus, further thickening the stroma to 10-12 mm for nutrient support. If no implantation occurs, progesterone withdrawal triggers menstruation around days 22-28, shedding the functional endometrial layer with 50-100 mL blood loss over 3-7 days.^[64]^[65]^[64] The ovarian cycle drives these changes, starting with the follicular phase where follicle-stimulating hormone (FSH) from the anterior pituitary recruits 10-20 primordial follicles, but typically one becomes dominant by day 7 due to higher FSH sensitivity and inhibin feedback. Estrogen rises progressively, peaking just before ovulation and exerting positive feedback to trigger the luteinizing hormone (LH) surge around day 14. Ovulation releases the secondary oocyte, viable for fertilization for about 24 hours, as LH induces follicular rupture 36-44 hours post-surge. The luteal phase ensues with corpus luteum formation from the ruptured follicle, peaking progesterone and estrogen levels by day 21 to maintain endometrial receptivity; without human chorionic gonadotropin (hCG) from implantation, the corpus luteum regresses by day 24, dropping hormones and initiating menses.^[64]^[65]^[66] Hormonal regulation involves pulsatile gonadotropin-releasing hormone (GnRH) from the hypothalamus, stimulating pituitary FSH and LH secretion in negative and positive feedback loops with ovarian steroids and peptides. Early follicular FSH rise is unchecked until rising inhibin B from granulosa cells provides negative feedback, selecting the dominant follicle; mid-cycle, high estrogen shifts to positive feedback, amplifying the LH surge while inhibin A later suppresses FSH. Progesterone in the luteal phase reinforces negative feedback on GnRH pulses, slowing frequency to sustain the corpus luteum until potential hCG rescue.^[64]^[65]^[67] Fertilization occurs if viable sperm meet the oocyte in the ampulla of the fallopian tube, typically within 12-24 hours post-ovulation. Sperm undergo capacitation in the female tract, involving membrane cholesterol efflux and protein phosphorylation, enabling hyperactivated motility and the acrosome reaction triggered by zona pellucida glycoproteins. The acrosome reaction exposes enzymes for zona penetration, allowing sperm-oocyte fusion and zygote formation with cortical granule release to prevent polyspermy. The zygote undergoes cleavage during tubal transport, reaching the blastocyst stage by day 5-6, followed by implantation into the receptive endometrium around day 7 post-fertilization.^[68]^[69]^[70]

Clinical Aspects

Diagnostic Approaches

Diagnostic approaches to the genitourinary (GU) system encompass a range of laboratory, imaging, and invasive procedures designed to evaluate urinary tract integrity, renal function, reproductive organ health, and underlying congenital or acquired abnormalities. These methods are essential for identifying structural anomalies, functional impairments, and early signs of pathology without overlapping into therapeutic interventions. Selection of tests depends on clinical presentation, with non-invasive options prioritized initially to minimize patient risk. Urinalysis serves as a foundational, non-invasive test for assessing urinary tract health, involving physical, chemical, and microscopic examinations of a urine sample. The chemical component utilizes dipstick testing to detect parameters such as pH, protein, glucose, and ketones, providing rapid insights into metabolic and renal issues. Microscopic analysis identifies cellular elements like red and white blood cells, casts, and crystals, which can indicate inflammation, infection, or stone formation. Urine culture complements these by identifying bacterial pathogens in suspected urinary tract infections (UTIs), guiding targeted antimicrobial therapy when needed. Imaging modalities offer visualization of GU structures, with ultrasound being the preferred initial non-invasive technique for evaluating kidneys, bladder, and ureters due to its lack of ionizing radiation and real-time capabilities. It effectively detects hydronephrosis, masses, and bladder volume. For more detailed assessment, computed tomography (CT) scans provide high-resolution images of anatomy, stones, and vascular structures, while magnetic resonance imaging (MRI) excels in soft tissue delineation without radiation exposure. Cystoscopy, an endoscopic procedure, allows direct visualization and biopsy of the bladder and urethra, particularly useful for mucosal abnormalities. Blood tests are critical for gauging renal function and specific organ issues. Serum creatinine and blood urea nitrogen (BUN) levels reflect glomerular filtration and waste clearance, with elevated values signaling impaired kidney function. The estimated glomerular filtration rate (eGFR) is calculated using the 2021 CKD-EPI Creatinine Equation from serum creatinine, age, and sex (without race) to stage chronic kidney disease accurately.^[71]^[72] Prostate-specific antigen (PSA) testing measures serum levels of this prostate-derived protein to screen for prostate abnormalities, though elevations can occur in benign conditions. Functional tests evaluate dynamic aspects of GU performance. Urodynamic studies measure bladder pressure, urine flow rates, and sphincter coordination to diagnose voiding dysfunctions such as incontinence or obstruction. Semen analysis assesses male fertility by quantifying sperm count, motility, and morphology in ejaculate, alongside volume and pH, to identify reproductive barriers. Biopsy procedures provide histopathological confirmation for suspected inflammatory or neoplastic processes. Renal biopsy, obtained via percutaneous needle under imaging guidance, examines glomerular architecture in conditions like glomerulonephritis, revealing patterns of injury through light, immunofluorescence, and electron microscopy. Endometrial biopsy samples uterine lining tissue to evaluate menstrual cycle irregularities, detecting hyperplasia or secretory phase defects via office-based aspiration. Genetic screening targets congenital anomalies, particularly in disorders of sex development. Karyotyping analyzes chromosomal composition to confirm sex chromosome abnormalities. For congenital adrenal hyperplasia (CAH), primarily due to 21-hydroxylase deficiency, molecular genetic testing identifies mutations in the CYP21A2 gene. Anti-Müllerian hormone (AMH) levels assess gonadal function, with low values indicating ovarian reserve issues or dysgenetic testes in ambiguous genitalia cases. These tests apply primarily to disorders like CAH, aiding in early diagnosis and management planning.

Common Disorders

Common disorders of the genitourinary system include urinary tract infections (UTIs), affecting up to 50% of women at least once in their lifetime; kidney stones, with a lifetime risk of 10-12% in men and 6-7% in women; benign prostatic hyperplasia (BPH), impacting about 50% of men over 50; and endometriosis, occurring in approximately 10% of reproductive-age women. These conditions often share risk factors like age, hormonal changes, and lifestyle, and are detailed in subsequent subsections.^[73]^[74]^[75]^[76]

Urinary Disorders

Urinary Tract Infections (UTIs) are among the most common bacterial infections affecting the genitourinary system, primarily caused by Escherichia coli entering the urinary tract, particularly in women due to anatomical factors.^[73] Symptoms typically include dysuria (painful urination), urinary frequency, urgency, and sometimes lower abdominal pain or fever if the infection ascends to the kidneys.^[73] Basic management involves antibiotic therapy, such as nitrofurantoin or trimethoprim-sulfamethoxazole, with duration tailored to the site of infection (e.g., 3 days for uncomplicated cystitis), alongside increased fluid intake to promote clearance.^[73] Preventive measures like voiding after intercourse and avoiding irritants can reduce recurrence.^[73] Kidney stones, or nephrolithiasis, form when minerals like calcium oxalate crystallize in the urine due to factors such as dehydration, high dietary oxalate, or metabolic disorders.^[74] The most prevalent type is calcium oxalate stones, accounting for about 80% of cases.^[74] Symptoms often manifest as severe flank pain radiating to the groin, hematuria, nausea, and vomiting, especially during stone passage.^[74] Management includes pain control with analgesics, hydration to facilitate passage for small stones (<5 mm), and procedures like extracorporeal shock wave lithotripsy for larger ones obstructing the urinary tract.^[77] Chronic Kidney Disease (CKD) progresses from kidney damage over time, with primary etiologies being diabetes mellitus and hypertension, which impair glomerular filtration and lead to fibrosis.^[78] It is staged from 1 (mild) to 5 (end-stage renal disease) based on glomerular filtration rate (GFR), with stages 4-5 often requiring intervention.^[78] Common symptoms include fatigue, edema, anemia, and hypertension, emerging as GFR falls below 60 mL/min.^[78] Basic management focuses on controlling underlying causes (e.g., blood sugar and pressure optimization), with dialysis or transplantation for stage 5 to sustain life.^[78]

Male Reproductive Disorders

Benign Prostatic Hyperplasia (BPH) involves nonmalignant enlargement of the prostate gland, common in men over age 50 due to hormonal changes like increased dihydrotestosterone.^[75] It affects urinary outflow by compressing the urethra, leading to symptoms such as nocturia, weak stream, hesitancy, and incomplete emptying.^[75] Initial management includes alpha-blockers like tamsulosin to relax prostate smooth muscle and improve flow, with 5-alpha reductase inhibitors for larger prostates; transurethral resection is reserved for refractory cases.^[75] Prostate Cancer arises from uncontrolled prostate cell growth, with risk factors including age, family history, and African ancestry; nearly all cases link to androgen signaling.^[79] Screening often uses prostate-specific antigen (PSA) levels, with elevated values prompting biopsy; the Gleason score (6-10) grades aggressiveness based on histological patterns.^[79] Symptoms may include urinary obstruction or hematuria in advanced stages, though early disease is often asymptomatic.^[79] Treatment varies by stage and grade, ranging from active surveillance for low-risk (Gleason ≤6) to radical prostatectomy, radiation, or androgen deprivation for higher-risk cases.^[79] Erectile Dysfunction (ED) results from impaired penile blood flow or nerve function, with vascular causes (e.g., atherosclerosis) predominant in older men and neurologic factors (e.g., diabetes) contributing across ages.^[80] Symptoms involve difficulty achieving or maintaining an erection sufficient for intercourse, often with reduced libido.^[80] First-line management includes phosphodiesterase-5 (PDE5) inhibitors like sildenafil, which enhance nitric oxide-mediated vasodilation; lifestyle modifications and addressing comorbidities are adjuncts.^[80]

Female Reproductive Disorders

Endometriosis occurs when endometrial-like tissue implants ectopically, possibly due to retrograde menstruation or immune dysregulation, affecting 10% of reproductive-age women.^[76] It causes chronic pelvic pain, dysmenorrhea, dyspareunia, and infertility through inflammation and adhesions.^[76] Diagnosis often requires laparoscopy for visualization; management includes nonsteroidal anti-inflammatory drugs for pain, hormonal therapies (e.g., combined oral contraceptives) to suppress cycles, and laparoscopic excision for severe lesions.^[81] Polycystic Ovary Syndrome (PCOS) stems from hyperandrogenism and insulin resistance, leading to ovarian cyst formation and disrupted ovulation in 5-10% of women.^[82] Key symptoms encompass irregular menses, hirsutism, acne, and anovulation-related infertility, alongside metabolic risks like obesity.^[82] Management prioritizes lifestyle changes (weight loss improves 50% of cases), metformin for insulin sensitization, and oral contraceptive therapy (OCT) for cycle regulation and androgen suppression; ovulation induction aids fertility.^[83] Cervical Cancer is predominantly caused by persistent high-risk human papillomavirus (HPV) infection, particularly types 16 and 18, accounting for over 90% of cases.^[84] Early symptoms are often absent, progressing to abnormal vaginal bleeding or discharge; advanced disease may involve pelvic pain.^[84] Prevention relies on HPV vaccination (e.g., Gardasil) starting at age 11-12 and Pap smear screening every 3-5 years from age 21 to detect precancerous changes.^[85] Treatment for invasive cancer includes hysterectomy, radiation, or chemotherapy based on stage.^[84]

Shared Disorders

Urinary Incontinence affects both sexes, with stress type triggered by increased abdominal pressure (e.g., coughing) due to weak pelvic floor muscles, and urge type from bladder overactivity causing sudden urgency.^[86] Prevalence rises with age, impacting up to 50% of older adults, with symptoms of involuntary leakage disrupting daily life.^[86] First-line treatment involves pelvic floor exercises (Kegels) to strengthen muscles, effective in 50-70% of mild cases, alongside behavioral therapies like bladder training.^[87] Anticholinergics manage urge incontinence, while surgery addresses severe stress cases.^[88] Infertility impacts 10-15% of couples worldwide, defined as failure to conceive after 12 months of unprotected intercourse, with causes split evenly between female (e.g., ovulatory dysfunction), male (e.g., low sperm count), and combined factors.^[89] Symptoms manifest as delayed or absent pregnancy despite attempts, often linked to underlying conditions like PCOS or varicocele.^[90] Evaluation includes semen analysis and ovulation tracking; for severe cases, in vitro fertilization (IVF) achieves 30-40% live birth rates per cycle in women under 35.^[90]

Congenital Disorders

Hypospadias is a birth defect where the urethral opening is located on the underside of the penis due to incomplete fusion during fetal development, occurring in about 1 in 200-300 male births.^[10] It may cause urinary stream deviation, chordee (penile curvature), and future fertility issues if untreated.^[10] Surgical correction (urethroplasty) is recommended between 6-18 months to reconstruct the urethra and achieve normal function and cosmesis, with success rates over 90% in specialized centers.^[10] Cryptorchidism, or undescended testes, affects 3% of full-term male infants, resulting from failure of testicular descent into the scrotum, potentially due to hormonal or anatomical issues.^[91] It increases risks of infertility and testicular cancer if persistent beyond infancy.^[91] Management involves orchiopexy surgery by age 1 (ideally 6-12 months) to relocate the testis, preserving fertility potential in 80-90% of unilateral cases.^[91]

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