Flashcards in One Deck (21):
From where are the genital and urinary systems derived? What are the 3 units?
The urinary and genital systems arise from the intermediate mesoderm, a longitudinal ridge of mesenchymal cells (urogenital ridge) along the dorsal wall of the amniotic cavity (Fig. 1.1). The intermediate mesoderm (nephrogenic cord) gives rise to a cranial-to-caudal excretory unit that is roughly divisible into three units (Fig. 1.2):
• Metanephros (definitive kidney)
Describe the pronephros and its development.
The pronephros is vestigial, transitory, and nonfunctional. It is analogous to kidneys in primitive fish, consisting of a few clusters of cells (also known as nephrotomes) in the cervical region. These excretory units regress by the end of the fourth week as more caudal regions of the nephrogenic cord develop.
Describe the development and eventual fate of the mesonephros.
In the human embryo, at 22 days gestation, committed mesenchymal cells in the anterior intermediate mesoderm proliferate to form the urogenital ridge. In this area segmentally arranged sets of nephrogenic tissue appear in cephalo-caudal sequence. In each urogenital ridge, a solid longitudinal rod, the mesonephric duct, develops and opens into the cloaca. The mesonephric tissue gives rise to an S-shaped loop (excretory tubule) that acquires a tuft of capillaries also known as the glomerulus (Fig. 1.3). Collectively, these structures comprise a renal corpuscle. Approximately thirty segmentally arranged sets of renal corpuscles drain into the mesonephric duct. Urine formation begins as the excretory units of the mesonephros develop. As caudal mesonephric units differentiate, cranial units degenerate. In males, some of the caudal mesonephric segmented tubules persist to become efferent ductules of the testes; while the mesonephric ducts become the epididymis and vas deferens. By the second trimester, the mesonephros is no longer functional.
Describe the function and importance of the metanephros.
The metanephros, or permanent kidney, begins to develop in the fifth week and is functional by the ninth week. Although elimination of metabolic wastes is primarily handled by the placenta, the metanephros produces urine. Urine derived from the metanephros is essential for amniotic fluid accumulation which, in turn, is crucial for normal growth and development of the fetus. Any condition that interferes with the production of urine or prevents its draining into the amniotic cavity leads to a condition referred to as oligohydramnios.
Describe the development of the collecting system of the definitive kidney. Describe the development of the tubules and glomerulus.
The collecting system of the definitive kidney develops from an epithelial metanephric diverticulum or ureteric bud that sprouts from the mesonephric duct near its entrance into the cloaca (Fig. 1.4). The ureteric bud penetrates the metanephric tissue (metanephric blastema) and subdivides up to 15 times to form the definitive collecting system including the ureter, renal pelvis, the major and minor calyces, and 1-3 million collecting tubules.
The metanephric blastema (also known as the metanephric mass of intermediate mesoderm or metanephrogenic blastema) is comprised of mesoderm from the caudal portion of the nephrogenic cord. It condenses in a cap-like formation around the distal most end of the ureteric bud (Fig. 1.5). The ureteric bud induces mesenchymal cells in the metanephric mass to generate metanephric vesicles (renal vesicles), which elongate and give rise to S-shaped tubules. One end of the S-tubule fuses with the distal end of the ureteric bud to establish continuity of the urinary pathway. The tubule lengthens and differentiates into the proximal convoluted tubule, loop of Henle, distal convoluted tubule and connecting tubule. Endothelial cells migrate to the opposite end of the S-shaped tubule and differentiate into a capillary tuft, or glomerulus. The glomerular capillary tuft receives blood from an afferent arteriole (derived from branches of the dorsal aorta) and drains blood into a muscular efferent arteriole. The efferent arteriole envelops the tubules, thus serving as the principal blood supply for the renal tubules. The tubules and glomeruli comprise the basic functional unit of the kidney, i.e., the nephron. After nephrogenesis is complete, at about 32 weeks gestation, the kidneys increase in size by hypertrophy of the existing nephrons.
Describe the function of the different factors and receptors involved in kidney development.
If the ureteric bud fails to form or is abnormal the metanephric blastema does not develop. Conversely if the metanephric blastema is defective, orderly branching and growth of the ureteric bud do not occur. Several hours of contact with the ureteric bud ampulla and metanephric blastema are required to induce the formation of the epithelial vesicle and subsequent development of the nephron. Prior to induction, Wilm tumor suppressor 1 (WT1) is expressed in the metanephric mass, and is believed to induce competence (responsiveness to molecular signals) in the ureteric bud (Fig. 1.6). WT1 also regulates the synthesis of glial-derived neurotropic factor (GDNF) and hepatocyte growth factor (HGF) in the mesenchyme. These factors stimulate branching in the ureteric bud. The tyrosine kinase receptors, RET and MET, serve as receptors for GDNF and HGF, respectively. RET and MET are initially expressed in the mesonephric duct and later localized to the tip of the ureteric bud. Fibroblast growth factor 2 (FGF-2) and bone morphogenetic protein 7 (BMP7) are expressed by the ureteric bud. These signaling molecules prevent apoptosis in the metanephric blastema and signal the mesenchyme to grow and aggregate. They also appear to induce the expression of WT1. Subsequently, WNT9B and WNT6 are expressed in the ureteric bud, which, in turn, induce the expression of PAX2 and WNT4 in the metanephric mesenchyme. PAX2 induces the aggregation of the metanephric mesenchyme, while WNT4 induces the development of renal tubular epithelium in the aggregated mesenchyme (mesenchymal-epithelial transformation).
Describe the process of the ascent of the kidney.
The kidneys initially develop in the pelvic region on either side of the aorta. Relative growth and straightening of the body raise the kidneys into the abdomen (approximately to the T12-L3 level). During ascent, the kidneys are displaced laterally and their associated hila, which are situated ventrally, shift medially. This shift is partly due to overgrowth of the lips of the hilum and partly due to rotation. In their pelvic position, the kidneys are perfused by branches of the common iliac arteries. As they ascend at each level, new renal arteries arise from the cephalic segment of the aorta and the inferior branches degenerate. The permanent renal arteries are the most cranial branches supplying the kidneys. The ascent of the kidneys is terminated when they contact the adrenal gland. Because of the process of sequential appearance and degeneration of branches of the aorta supplying the kidneys, 25% of the population may possess two or more supernumerary (accessory) renal arteries (Fig. 1.7).
Describe the development of the urinary bladder and urethra
During the sixth week of gestation the cloaca divides into the posterior rectum and urogenital sinus by the urorectal septum (Fig. 1.8). The urogenital sinus is continuous with the allantois, which has a dilated base. The urogenital sinus is divided into a cephalic dilated vesical segment, middle narrow pelvic segment and caudal phallic segment. The vesical segment forms the urinary bladder. The middle pelvic segment, in the female, forms most of the urethra and, in the male, forms the membranous and prostatic urethra. The caudal phallic segment (also known as the definitive urogenital sinus) is covered by the urogenital membrane. In females the definitive urogenital sinus gives rise to a small portion of the urethra and vestibule and in males it forms the penile urethra.
What is renal agenesis? What causes it? Describe potters syndrome? What are some other clinical manifestations? What happens in unilateral renal agenesis?
Renal agenesis results when the ureteric bud fails to induce the metanephric blastema. Possible explanations include failure of the ureteric bud to penetrate and make contact with the metanephric blastema, early degeneration or regression of the ureteric bud, absence of the blastema or failure of the blastema to produce or respond to inducing substances (see reciprocal induction in kidney development). Renal agenesis was first described by Potter in 1946 and was characterized by a fetus with a flattened nose, prominent epicanthic folds and low set and posteriorly rotated ears.
Absence of both kidneys occurs in about 1:6000 live births. Agenesis is more frequent in males (3:1). In approximately half of the affected fetuses, there are no other malformations except those associated with Potter syndrome. Oligohydramnios results from failure of urine production. Fetuses with renal agenesis may also have reduced circumference of the chest associated with pulmonary hypoplasia. The majority of female fetuses with bilateral renal agenesis also have abnormalities in the reproductive system; whereas the majority of males have normal reproductive anatomy. In some cases anomalies of the gastrointestinal tract, cardiovascular system and musculoskeletal system are found. Since the placenta is the major excretory organ, this condition is compatible with prenatal life but not with postnatal life.
Unilateral renal agenesis is an incidental finding. The contralateral kidney undergoes compensatory hyperplasia, i.e., the number of nephrons and their size is increased. Fetal urine production and postnatal renal function are not compromised in unilateral renal agenesis.
What is renal hypoplasia and what is the result?
These kidneys have fewer nephrons than expected for the developmental age. They may also have diminished number of papillae and calyces. If severe, this condition may cause renal insufficiency in infancy.
44 CLINICAL CORRELATION
Recent evidence suggests that reduced numbers of nephrons may be a precursor for a variety of chronic kidney diseases that occur in the setting of systemic disease (eg, diabetes) or after environmental exposure to nephrotoxins (eg, lead). It is conceivable that reduced numbers of nephrons are a proxy for a decrease in renal reserve. Accordingly, a decrease in renal reserve may heighten the risk for clinical renal disease, as fewer nephrons cannot adequately compensate for the loss of injured nephrons.
What is renal ectopia? What are some variations of it? What are some possible results?
Renal ectopia occurs when a kidney is located outside its normal position. The pelvis is the most common location of an ectopic kidney. In crossed renal ectopia both kidneys are located on one side of the body. Frequently they are fused and are thought to arise from a common metanephric blastema. Hydronephros, hydroureter, or dysplastic changes often develop in these kidneys.
What is horseshoe kidney? What causes it? What happens in it? What are the clinical manifestations?
A horseshoe kidney is seen in 1 in 500 live births and may also be seen in up to 7% of infants with Turner syndrome. It results from fusion of the lower poles of the kidney before their ascent. The fused area consists of connective tissue and a superficial cortical bridge. The renal mass thus formed is displaced to the pelvic brim (Fig. 1.9). Two separate ureters course ventrally and drain into the bladder. The ascent of the renal mass is hindered by the inferior mesenteric artery. A plausible hypothesis to explain this condition is medial displacement of the metanephros by the umbilical arteries, convergence of ureteric buds, or medial migration of nephrogenic tissue. Although horseshoe kidneys are often asymptomatic, pelvic kidneys in general are subject to an increased incidence of infection and obstruction.
Describe renal dysplasia? What are the results? What causes it? What are the clinical results?
Renal dysplasia is the most common cause of kidney cysts. In these kidneys the architecture of the cortex and medulla is disorganized, the glomeruli are small and immature and the tubules are simple and atrophic. Cyst formation is variable and can involve any part of the kidney. Dysplastic kidneys are usually large but dysfunctional. It is believed that this anomaly results from injury to the ureteric bud and interferes with normal mesenchymal-epithelial transformation. In addition, urethral obstruction may cause damage to the collecting duct ampulla. Urinary tract obstruction is a frequent occurrence in renal dysplasia.
What is PKD? What are the two different types of PKD? Describe their inheritance. Describe their pathologic and clinical manifestations?
PKD encompasses at least two modes of inheritance. One is autosomal recessive, or infantile PKD, and the other is autosomal dominant, or adult PKD (ADPKD). The kidneys in the autosomal recessive type are greatly enlarged and contain numerous elongated radially oriented cysts.
The autosomal dominant type of PKD may remain asymptomatic. In many patients with ADPKD, clinical symptoms occur between ages 40 and 50 years. However, the kidneys in the fetus are sometimes enlarged and may reveal early cyst formation. The cysts are small initially and are not radially oriented. At least two abnormal genes have been identified in ADPKD using linkage analysis. The most common pedigree is associated with an abnormal gene on the short arm of chromosome 16.
Describe duplex ureter and the anatomical and clinical consequences.
A duplex ureter results from branching of the ureteric bud before it enters the metanephric blastema. Frequently two separate pelves and two proximal ureters are present. Usually the ureters merge and a single ureter enters the bladder. If both ureters remain separated the upper pole ureter is often ectopic and enters the bladder inferiorly. In the male the ureter may open into the prostatic urethra, the seminal vesicle or any other part of the urethra. In females it may open into the urethra, the vestibule or the vagina. Hydronephrotic and dysplastic changes can develop with these anomalies.
What is ureteral obstruction? When and where and how is it seen? What causes it?
Ureterovesical junction obstruction with hydronephrosis a frequent anomaly identified by ultrasonographic examination of the fetal urinary tract. The obstruction is caused by aplasia or hypoplasia of the ureteric lumen at its entry into the bladder.
What are absent or small bladders associated with?
Absent or small bladders are associated with renal agenesis or dysplasia.
What is exstrophy of the bladder? What causes it? What occurs in it? What is it associated with?
Exstrophy of the bladder arises from a defect in the lower abdominal wall musculature exposing the mucosal surface of the bladder. The mucosa of the bladder is continuous with the margins of the abdominal wall. The pubic bones are widely separated. Incomplete closure of the abdominal wall is caused by failure of the mesoderm to invade the central lower abdominal region, where a large wedge of cloacal membrane persists. When the cloacal membrane disintegrates the epithelia of the urogenital sinus and hindgut are exposed. The extent of exstrophy depends on the extent of impaired mesodermal migration and the extent of cloacal membrane rupture. It has been suggested that an overdeveloped cloacal membrane may delay or hinder mesenchymal movement and fusion. This disorder is often accompanied by epispadias.
What is epispadias? What causes it?
Epispadias is an opening of the urethra on the dorsum of the penis. Urinary incontinence is a common symptom. It is believed to occur as a result of rupture of the urogenital sinus dorsally.
What are posterior urethral valves? What do they cause?
Posterior urethral valves are epithelial folds that project from the mucosa of the urethra near the base of the bladder. These are the most common cause of lower urinary tract obstruction. When completely obstructed, oligohydramnios will develop.