Kidney Development, - and Function in the Fetus
Bob Caruthers, CST, PhD
The kidneys produce urine, a blood filtrate, and regulate uri- can be seen in the fourth week. The pronephros is complete1 nary volume and composition. These regulatory activities regred by the start of the fifth week. The pronephros form involve balancing water and solute transport, conserving and regresses in a cranial-to-caudal sequence. No pronephric nutrients, eliminating waste products, and regulating acid and glomeruli (cluster of capillaries) have been observed, and no bases. The primary purpose of kidney function is to maintain a vesicles are associated with the pronephric duct. The stable environment in which cellular and tissue metabolic pronephros is, therefore, not active in urine producti0n.Y activity can proceed at an optimal level. The kidneys secrete the hormone renin, erythropoietin and 1.25-dihydroxy vita- MPSONEPHROS min D. Renin helps regulate blood pressure. Erythropoietin The mesonephros originates in the nephrogenic cord that is helps regulate erythrocyte production. 1,25-dihydroxy vitamin part of the intermediate mesoderm. Early mesonephric forma- D plays a role in calcium metabolism. This article will discuss tion is evident before the pronephros has completed its regre: the development of the kidney, and its role in the fetus."' sion. The mesonephros also degenerates in a cranial-to-cauda Since the kidneys are bilateral structures, development sequence. Some of the cranial structures are degenerating in involves both right and left kidneys. During fetal develop- the fifth week of fetal development while the caudal structun ment, three separate nephric structures develop in succession; are still differentiating. By the eighth week of fetal develop- pronephros, mesonephros and metanephros (Figure 1). The ment, most of the mesonephric structures have disappeared.$ associated urinary bladder and urethra both develop from a The nephrogenic cord elongates caudally. As it grows caudai derivative of the embryonic hindgut, the urogenital sinvs, The ly. the nephrogenic cord differentiates into mesonephric vesicle pronephras forms first, is not active in urine production, and These vesicles fmfrom the first thoracic to the third lumbar rapidly undergoes camplete regression. The mesonephros wgment and quickly increase in number by the means of bifurc. forms the setond kidney. The body of the mesoneghros tion andlor subdivision. The vesicles elongate and appear as regresses,/but gar& of the nesonephric duct remain to form either pear-shaped or S-shaped vesicles. These vesicl form rud the drainage sysrem of the male gonad. While existing, the mentary nephrom. The S-shaped vsicb develap communica- mesonephros is thaught to produce urine in the human ferns. tion with the mesonephric duct (Wolffian),and branches from The third and definitive kidney, the metanephros, forms two the dorsal aorta grow toward these $-shaped vesidq. The bodit rudiments that make up the complete adult kidney and ureter. of the shaped vesicles form a mdlmnmry type Bowman's caF The metanephras produces urine during fetal devel~pmant,~ sule. Blood vmeb form capillary tufts &at push against the developing Bowman's capsule and connect to vessels from the PRONEPHROS donJ aorta. Portions of the $-shaped vesicle not involved in tJ The pronephros is a transient structure which originates in previously described development become more convoluted an the intermediate mesoderm asswiated with the cranial and associate with efferent arterioles that carry blood from the cervical somitrs. Component parts, cords of tissue or vesicles, glomeruli (capillary tufts) to the posterior cardinal vein! Unlike thc pronephros, not all of the mesonephric smctures metanephric blastema evolves in the caudal portion of the disappear. Abut the smh week, rhe remaining mesonephros nephrogenic cord and develops into the components of the forms an ovoid mass just lateral to the midline that, with Ehe metanephric kidney associated with excretion: Bowman's cap- developinggonad, helps form the urogenital ridge. The sule, proximal convoluted tubule, loop of Henle and distal con- mwnephnc duct courscls along the lateral border of the qen~tal voluted tubule. The ureteric bud, a branch of the mesonephric ridge and comects with the urogenital sinus where it serves to duct, f~mnsthe urine collecting components: collecting tubules drain the mwnephrons. This urogeniml sinus will later develop in the kidney, papillary ducts, and major and minor calyces. into the adult urinary bladder and uret..In the male, the The ureteric bud contributes to the ureters, al~o.'~':~l* mesonephric tubules that lie clox to the developing gonad remain The nephrons are formed from the metanephric blastema. as the efferent ductules of the testis and ocher minor sauctures. Local condensations of cells of the metanephric blastema form The mesonephric ducts give rise to the duct of the epididyrnis, the around dilated sections of the ureteric bud. The caps of vas deferens, the seminal vesicles and the ejaculatory duct in the metanephric blastema differentiate into vesicles, which evolve male. In the female, the mesonephric ducts degenerates for the into S-shaped tubules. These nephrons continue to mature, most part, while the associated paramesonephric duct (Miillerian) and new ones are formed. As the nephrons mature there is an duct forms the uterine tub, uterus, cervix and part of the vagina. increase in the convolutions in the proximal and distal por- One branch of the mesonephric duct, the ureteric bud, remains as tions of the tubules and an increase in the length of the loop part of the urine collection portion of the metanepkS of Hmle?"." There is evidence to support but not yet prove that the The metanephros forms at the level of the upper sacral seg- nlesonephros produces hypotonic urine? ment and receives its blood supply from sacral branches of the dorsal aorta. Between the sixth to MheANEPHROS The third nephric structure to form is the metanephros,
Common excreto~ybud Metanephros
FIGURE 1-Mesonephros. gonad and metanephros during rhcir formation. ascending. Along with this apparent but illusionary ascension, the metanephros actually does move cephalad. The end result 1s Proximal convoluted tubule a repositioning in the lumbar area. As the metanephros ascends, it takes on a new blood supply. At the level of the sec- Bowman's capsule ond lumbar segment, the renal arteries become the definitive Glomerulus supplier of blood to rhe kidney? Collecting tubule
CONGENITAL ANOMALIES OF THE KIDNEY Oistal As with all organ development, congenital mishaps occur. convoluted tubule Renal agenesis, the failure of the kidneys to form, is related to a failure in the development of the ureteric bud or failure of the interactive mechanism between the ureteric bud and the metanephric blastema to produce nephrons. Renal agenesis may be unil~eralor bilateral. There are several types of con- loop of Henle genital cystic disease. Mile the mechanisms for each type vary, the common outcome is the production of multiple renal cysts. Congenital abnormalities of final location occur. This abnormality results from some failure during the ascent of the metanephros from the sacral to lumbar position. One variant of this is a horseshoe shaped kidney in which the two kidneys are fused at the caudal
Papillary duct FETAL URINE PRODUCTION AND AMNIOTIC RUlD REGULATION As previously mentioned, the mesonephric kidneys probably produce some urine. However, by the end of the twelfth week FIGURE &Major componenrs of the uriniferous unit in the adult kidne. of fetal development, the mesonephros is completely degener- ated, and the metanephros assumes the sole role of urine pro- able to move the fluid in and out of the lungs. Low levels of ducer. It is capable of producing large quantities of urine. This amniotic fluid during this period of fetal development are ass. fetal urine is hypotonic to fetal plasma in its sodium and chlo- ciated with pulmonary hypoplasia. Recent intrauterine them ride concentrations, The average pH is 6.0, slightly acidic. peutic techniques may reduce fetal morbidity and mortality Fetal urine has more urea and creatinine that fetal plasma but rates secondary to obstructive uropathy. During labor and it contains little protein or gluc~se.'~~~~~ delivery, the amniotic fluid continues to provide some protec Urine production in the fetus is related to regulation of the tion for the fetus and aid in dilatation of the cervix. In the fi amniotic fluid volume. Amniotic fluid provides some protec- trimester the fluid volume is normally between 5 and 25 mill tion from pathogenic bacteria during fetal life. The amniotic liters. At term, the volume of amniotic fluid is between 7@0 fluid compartment provides the few space to grow, move and 1000 milliliters. Abnormal amounts of amniotic fluid about and develop. Without this space, the uterus would close result from variations in fetal renal function, swallowing, lun down on the fetus and restrict development. In cases of first fluid production or transchorionic water flow. The fetus itsel, trimester amniotic fluid leakage, a fern may develop structural helps regulate these functions horrnonally. abnormalities secondary to uterine compression. By midpreg- In the first trimester, the amniotic fluid results from the nancy, the amniotic fluid plays a critical role in pulmonary transudation of fetal plasma across the fetal skm or umbilical development. Successful pulmonary development requires that cord or maternal plasma through the vascular uterine decidu the respiratory tract be filled with fluid and that the fetus bc First trimester fluid is iso-osmotic relative to fetal and maten plasma. In the second trimester, the fluid production changes. epithelium of Bowman's capsule continues with the proximal Urine is eliminated into the amniotic cavity beginning about tubule at the urinary pole. The proximal and distal portions of the ninth week of development. From that point, the fetus par- the tubules are convoluted. Between these convoluted sec- ticipates in the regulation of the amniotic fluid volume by pro- tions lies the loop of Henle. The collecting tubules are ducts ducing hypotonic urine to increase volume and swallowing it that collect urine from the distal tubules and transport it to to reduce volume. The fetal kidneys produce 600-700 ml of the papillary ductsag(Figure 2). hypotonic urine per day. The lungs produce approximately 250 ml of fluid per day. The fetus swallows approximately SUMMARY 590 ml of fluid per day and another 350-450 ml are reabsorbed Three separate nephric structures arise during fetal develop- across the chorioamnion as a result of the osmotic gradient ment. The second and third structures produce urine, but only between the amniotic fluid and maternal plasma. These fluid the third remains as a mature and definitive organ in the dynamics assist the obstetrician with evaluating fetal develop- fetus. The metanephros or third nephric structure plays a sig- ment. Oligohydramnios, a small volume of amniotic fluid, sug- nificant role in the regulation of amniotic fluid volume. The ' gests renal agenesis or renal obstruction. Polyhydramnios, a kidneys, themselves, are critical to the maintenance of a prop- large volume of amniotic fluid, suggests anencephaly because er environment for cellular metabolism throughout life. A of the inability to swallow or esophageal ame~ia.""~*-'~'~~''~" Fetal nitrogenous waste is eliminated by maternal urination BlBUOGRAPHY since the nitrogenous wastes diffuse across the placenta mem- 1. Baker LA, Gomez RA. "Embryonic development of the ureter." Sonin brane into the maternal blood m up ply.^ Nephrol, 1998, Nov; 18(6): 569-84. 2. Birnholz JC, Madana AE. "Amniotic fluid accumulation in the first mmcster."] Ultrasound Med 1995 Aug: 14(8):597-602. 3. Dura TT,da Cunha Ferreira RV.Momcal 1, Ezcurdia GM. Villa.Eliaga 1. "Zinc concentradon of amniotic fluid in the course of pregnancy and its Two kidneys, concave on the medial side, are located in the relationship to fetal weight and Imgch." GynecolObster Incest 1984; retroperitoneal space on either side of the vertebral column. 18(3):152-55. 4. Gulbis B, Gewy C, Jauniaux E. "Amniotic fluid biochemisq in xcond- In the concavity, a hilum is formed where the renal ureter trimester trisomic pregnancies: relationsh~psto fetal organ maturation and exits and the blood vessels, lymphatics and nerves enter. The dysfunction." Early Hum Deu 1998 Oct; 52(3):211-19. 5. Gulbis B, Jauniaux E, Jurkovic D. Gewy C,Ooms HA. "Biochemical renal sinus is a cavity surrounded by the renal parenchyma. investigation of fetal renal maturation in early pregnancy." Pehoic Res The renal sinus holds the renal pelvis and calyces. The 1996 Apr; 39(4 pt 1):73 1-35. 6. Heikinheimo M. Seppala M, Brock DJ. "Pregnancy specific kw I-glyco- parenchyma itself consists of a dark-colored cortex and lighter protein and human chorionic gonadotrophin levels in amniotic fluid and medulla. The cortex contains the glomeruli and some portions maternal serum in the finc half of pregnancy." Onccdiu Biol Med 1980 Aug; 1(1):71-6. of the tubules. The medulla is made up of a number of renal 7. Jauniaux E,Gulbis B, Hyett J. Nicolaides KH. "Biochemical analyses of pyramids. The pyramids contain the uriniferous tubules and mwcnchymal fluid in early pregnancy." Am J Obtet Gynecd 1998Apr; 178(4):765-69. blood vessels. The bases of the renal pyramids contact the cor- 8. Johnson KE. Human D~wlopmmralAmy.National Medical Series. tex, and the apices terminate in the minor calyces. Several of Williams & Wilkins: Baltimore, MD, 1988. 9. McCance KL,Huether SE. Pathophysiology: Tk Bwfogic Bask for Disarsc in the minor calyces form a major ca1yx.l.' Ad& and Children. The CV Mosby Co: St Louis, MO, 1990. 10. Puohkka J. Ylosralo P. Tuimala R, Haapalahti J, Jarvinen PA. "Amniotic fluid beta-2-microglohlin in normal and Complicated pregnancies. NEPHRON AND COUECTlWG TUBULES Correlation with guswtional age, cnatinine concentrarion and US ratio." The functional unit of the kidney, the uriniferous tubules, is G>necolOhnt Invest 1982; 13(3):129-34. I I. Snyder JM,Kwun JE, O'Brien JA, Rosenfeld CR,Odom MJ."The con- composed of the nephron and collecting tubules. The centntion of the 35-kDa surfactant apoprocein in amniotic fluid from nephrons produce urine, and the collecting tubules concen- normal and diabetic pregnancies." Pedion Res 1988Dec, 24(6):72&34. 12. Stuarc RO, Nigam SK. "Development of the mhular nephron." Smin trate and transport it. The proximal portion of each nephron Nephrol 1995 Jul; 15(3):315.!6. is called the renal corpuscle. It consists of a cup-like structure 13. Szaflik K, Kozarzewski M, Adamceqski D. "Fecal bladder catheterization in severe obstructive uropathy before the 24th weak of pregnancy." Feral called Bowman's capsule and a glomerulus. The renal corpus- Dqn Thcr 1998 May-Jun; 13(3):133-35. cle has a vascular pole and a urinary pole. Blood vessels enter 14. Wallner El, Carone FA, Ahrahamson DR. Kumar A, Kanwar YS. "Diverse aspects of metanephric dovclopmonr." Minosc Res Tech 1997 Nov 1; and exit the glomerulus at the vascular pole. The parietal 39(3): 261.84. EARN AT ca c-rr nm Continuing Education Examination (January 1999) 161 You will be awarded one continuing Kidney Development and Function in the Fetus Category 3 education (CE) credit for recertification after reading the designated article and 0 Certified Member Ll Certified Nonmember completing the exam with a score of 70% or better. If you are a current AST member and Certification No. are certified, credit eamed through Name completion of the CE exam will auto- matically be recorded in your file-you Address do not have to submit a CE reporring form. A printout of all the CE credits City State ZIP you have eamed, including Journal CE Chapter or At-Large Region Telephone credits, will be mailed to you in the first quarter following the end of the Mark one box next to each number. Only one correct or best answer can be calendar year. You may check the status selected for each question. of your CE record with ASr at any time. ABCD A B C D If you are not an AST member or not 1 'iC1OQ 6.CIP'iP certified, you will be notified by mail 2. aa00 7.CIQOQ when Joumrrl credits are submitted, but 3. 3P O D 8.3PO3 your credits will not be recorded in 4. DPPQ 9LiCIQQ ASTs files. 5. 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Which of the following is not one of 5. Which structure's vesicles form 9. Amniotic fluid the three nephric structures to arise nephrons? a. protects the fetus during fetal development: a. metanephros b. allows space for development a. metanephros b. mesonephros c. assists in pulmonary b. polyhydramnios c. pronephros development c. mesonephros J d. a and b d. all of the above d. pronephros J 6. The urogenital sinus will later 10. By the ninth week, the fetus Which nephric structure forms the develop into the participates in regulating amniotic two rudiments that make up the a. urinary bladder and urethra fluid by complete kidney and ureter? b. testes a. producing hypotonic urine a. metanephros c. vagina b. swallowing hypotonic urine b. polyhydramnios d. ureteric bud c. producing fluid in the lungs c. mesonephros d. all of the above d. pronephros 7. The originates from the metanephric blastema and uteric Which structure's component parts bud. (cords of tissue or vesicles) can be a. metanephros seen in the fourth week of b. mesonephros pregnancy7 c. bladder a. metanephros d. uterus b. polyhydramnios c. mesonephros 8. Congenital anomalies of kidney d. pronephros ' development are due to a failure in: a. the development of the uteric Which structure is not active in bud urine production? b. the production of nephrons a. metanephros c. the ascent to the lumbar b. polyhydramnios position c. mesonephros d. all of the above d. pronephros