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Kidney Development and Function in the Fetus: From Pronephros to Metanephros, Study notes of Embryology

An overview of kidney development and function in the fetus, discussing the three nephric structures (pronephros, mesonephros, and metanephros) that form during fetal development. the role of each structure in urine production, the development of associated structures such as the urinary bladder and urethra, and the significance of fetal urine production and amniotic fluid regulation.

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Kidney
Development
,
-
and
Function
in
the
Fetus
Bob
Caruthers,
CST,
PhD
The kidneys produce urine, a blood filtrate, and regulate uri-
nary volume and composition. These regulatory activities
involve balancing water and solute transport, conserving
nutrients, eliminating waste products,
and
regulating acid and
bases. The primary
purpose
of kidney function is to maintain
a
stable environment in which cellular and tissue metabolic
activity can proceed at an optimal level. The kidneys secrete
the hormone renin, erythropoietin and 1.25-dihydroxy vita-
min
D.
Renin helps regulate blood pressure. Erythropoietin
helps regulate erythrocyte production. 1,25-dihydroxy vitamin
D
plays a role in calcium metabolism. This article will discuss
the development of the kidney, and its role in the fetus."'
Since the kidneys are bilateral structures, development
involves both right and left kidneys. During fetal develop-
ment, three separate nephric structures develop in succession;
pronephros, mesonephros and metanephros (Figure
1
).
The
associated urinary bladder and urethra both develop from a
derivative of the embryonic hindgut, the urogenital sinvs,
The
pronephras forms
first,
is not active in urine production, and
rapidly undergoes camplete regression.
The
mesonephros
forms the setond kidney. The body of the mesoneghros
regresses,/but gar& of the nesonephric duct remain to form
the drainage sysrem of the male gonad. While existing, the
mesonephros
is
thaught to produce urine in the human ferns.
The third and definitive kidney, the metanephros, forms two
rudiments that make up the complete adult kidney and ureter.
The metanephras produces urine during fetal devel~pmant,~
PRONEPHROS
The pronephros is a transient structure which originates
in
the intermediate mesoderm asswiated with the cranial and
cervical somitrs. Component parts, cords of tissue or vesicles,
can
be
seen in the fourth week. The pronephros is complete1
regred by the start of the fifth week. The pronephros form
and regresses in a cranial-to-caudal sequence. No pronephric
glomeruli (cluster of capillaries) have been observed, and no
vesicles
are
associated with the pronephric duct. The
pronephros
is,
therefore, not active in urine producti0n.Y
MPSONEPHROS
The mesonephros originates in the nephrogenic cord that
is
part of the intermediate mesoderm. Early mesonephric forma-
tion is evident before the pronephros has completed
its
regre:
sion. The mesonephros also degenerates in a cranial-to-cauda
sequence. Some of the cranial structures are degenerating in
the fifth week of fetal development while the caudal structun
are still differentiating. By the eighth week of fetal develop-
ment, most of the mesonephric structures have disappeared.$
The nephrogenic cord elongates caudally.
As
it grows caudai
ly. the nephrogenic cord differentiates into mesonephric vesicle
These
vesicles
fm
from
the
first
thoracic
to
the third lumbar
wgment and quickly
increase
in number
by
the
means
of bifurc.
tion andlor subdivision. The vesicles elongate and appear
as
either pear-shaped
or
S-shaped vesicles.
These
vesicl form
rud
mentary nephrom.
The
S-shaped
vsicb develap communica-
tion with
the
mesonephric duct (Wolffian), and branches from
the
dorsal aorta
grow
toward
these
$-shaped
vesidq. The
bodit
of
the
shaped
vesicles form
a
mdlmnmry
type
Bowman's
caF
sule.
Blood
vmeb form capillary
tufts
&at push against
the
developing Bowman's capsule and connect
to
vessels
from the
donJ aorta. Portions of the $-shaped vesicle not involved in
tJ
previously described development become more convoluted
an
associate with efferent arterioles that carry blood from
the
glomeruli (capillary
tufts)
to the posterior cardinal vein!
pf3
pf4
pf5

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Kidney Development , -

and Function in the Fetus

Bob Caruthers, CST, PhD The kidneys produce urine, a blood filtrate, and regulate uri- nary volume and composition. These regulatory activities involve balancing water and solute transport, conserving nutrients, eliminating waste products, and regulating acid and

bases. The primary purpose of kidney function is to maintain a

stable environment in which cellular and tissue metabolic activity can proceed at an optimal level. The kidneys secrete the hormone renin, erythropoietin and 1.25-dihydroxy vita- min D. Renin helps regulate blood pressure. Erythropoietin helps regulate erythrocyte production. 1,25-dihydroxy vitamin D plays a role in calcium metabolism. This article will discuss the development of the kidney, and its role in the fetus."' Since the kidneys are bilateral structures, development involves both right and left kidneys. During fetal develop- ment, three separate nephric structures develop in succession; pronephros, mesonephros and metanephros (Figure 1 ). The associated urinary bladder and urethra both develop from a

derivative of the embryonic hindgut, the urogenital sinvs, The

pronephras forms first, is not active in urine production, and

rapidly undergoes camplete regression. T h e mesonephros

forms the setond kidney. The body of the mesoneghros regresses,/butgar& of the nesonephric duct remain to form the drainage sysrem of the male gonad. While existing, the mesonephros is thaught to produce urine in the human ferns. The third and definitive kidney, the metanephros, forms two rudiments that make up the complete adult kidney and ureter. The metanephras produces urine during fetal devel~pmant,~ PRONEPHROS The pronephros is a transient structure which originates in the intermediate mesoderm asswiated with the cranial and cervical somitrs. Component parts, cords of tissue or vesicles, can be seen in the fourth week. The pronephros is complete r e g r e d by the start of the fifth week. The pronephros form and regresses in a cranial-to-caudal sequence. No pronephric glomeruli (cluster of capillaries) have been observed, and no vesicles are associated with the pronephric duct. The pronephros is, therefore, not active in urine producti0n.Y MPSONEPHROS The mesonephros originates in the nephrogenic cord that is part of the intermediate mesoderm. Early mesonephric forma- tion is evident before the pronephros has completed its regre: sion. The mesonephros also degenerates in a cranial-to-cauda sequence. Some of the cranial structures are degenerating in the fifth week of fetal development while the caudal structun are still differentiating. By the eighth week of fetal develop- ment, most of the mesonephric structures have disappeared.$ The nephrogenic cord elongates caudally. As it grows caudai ly. the nephrogenic cord differentiates into mesonephric vesicle

These vesicles fmfrom the first thoracic to the third lumbar

wgment and quickly increase in number by the means of bifurc. tion andlor subdivision. The vesicles elongate and appear as either pear-shaped or S-shaped vesicles. These vesicl form rud

mentary nephrom. The S-shaped v s i c b develap communica-

tion with the mesonephric duct (Wolffian),and branches from the dorsal aorta grow toward these $-shaped vesidq. The bodit of the shaped vesicles form a mdlmnmry type Bowman's caF

sule. Blood vmeb form capillary tufts &at push against the

developing Bowman's capsule and connect to vessels from the

donJ aorta. Portions of the $-shaped vesicle not involved in tJ previously described development become more convoluted an associate with efferent arterioles that carry blood from the glomeruli (capillary tufts) to the posterior cardinal vein!

Unlike thc pronephros, not all of the mesonephric smctures disappear. A b u t the smh week, rhe remaining mesonephros forms an ovoid mass just lateral to the midline that, with Ehe developing gonad, helps form the urogenital ridge. The mwnephnc duct courscls along the lateral border of the q e n ~ t a l ridge and comects with the urogenital sinus where it serves to drain the mwnephrons. This urogeniml sinus will later develop into the adult urinary bladder and u r e t.. In the male, the mesonephric tubules that lie clox to the developing gonad remain as the efferent ductules of the testis and ocher minor sauctures. The mesonephric ducts give rise to the duct of the epididyrnis, the vas deferens, the seminal vesicles and the ejaculatory duct in the male. In the female, the mesonephric ducts degenerates for the most part, while the associated paramesonephric duct (Miillerian) duct forms the uterine t u b , uterus, cervix and part of the vagina. One branch of the mesonephric duct, the ureteric bud, remains as part of the urine collection portion of the m e t a n e p k S There is evidence to support but not yet prove that the nlesonephros produces hypotonic urine? MheANEPHROS The third nephric structure to form is the metanephros, metanephric blastema evolves in the caudal portion of the nephrogenic cord and develops into the components of the metanephric kidney associated with excretion: Bowman's cap- sule, proximal convoluted tubule, loop of Henle and distal con- voluted tubule. The ureteric bud, a branch of the mesonephric duct, f~mnsthe urine collecting components: collecting tubules in the kidney, papillary ducts, and major and minor calyces. The ureteric bud contributes to the ureters, al~o.'~':~l* The nephrons are formed from the metanephric blastema. Local condensations of cells of the metanephric blastema form around dilated sections of the ureteric bud. The caps of metanephric blastema differentiate into vesicles, which evolve into S-shaped tubules. These nephrons continue to mature, and new ones are formed. As the nephrons mature there is an increase in the convolutions in the proximal and distal por- tions of the tubules and an increase in the length of the loop of Hmle?"." The metanephros forms at the level of the upper sacral seg- ment and receives its blood supply from sacral branches of the dorsal aorta. Between the sixth to

Common excreto~y bud Metanephros

FIGURE 1 -Mesonephros. gonad and metanephros during rhcir formation.

plasma. In the second trimester, the fluid production changes.

Urine is eliminated into the amniotic cavity beginning about

the ninth week of development. From that point, the fetus par- ticipates in the regulation of the amniotic fluid volume by pro- ducing hypotonic urine to increase volume and swallowing it to reduce volume. The fetal kidneys produce 600-700 ml of hypotonic urine per day. The lungs produce approximately 250 ml of fluid per day. The fetus swallows approximately 590 ml of fluid per day and another 350-450 ml are reabsorbed across the chorioamnion as a result of the osmotic gradient between the amniotic fluid and maternal plasma. These fluid dynamics assist the obstetrician with evaluating fetal develop- ment. Oligohydramnios, a small volume of amniotic fluid, sug- gests renal agenesis or renal obstruction. Polyhydramnios, a large volume of amniotic fluid, suggests anencephaly because of the inability to swallow or esophageal ame~ia.""~*-'~'~~''~" Fetal nitrogenous waste is eliminated by maternal urination since the nitrogenous wastes diffuse across the placenta mem- brane into the maternal blood m up ply.^ Two kidneys, concave on the medial side, are located in the retroperitoneal space on either side of the vertebral column. In the concavity, a hilum is formed where the renal ureter exits and the blood vessels, lymphatics and nerves enter. The renal sinus is a cavity surrounded by the renal parenchyma. The renal sinus holds the renal pelvis and calyces. The parenchyma itself consists of a dark-colored cortex and lighter medulla. The cortex contains the glomeruli and some portions of the tubules. The medulla is made up of a number of renal pyramids. The pyramids contain the uriniferous tubules and blood vessels. The bases of the renal pyramids contact the cor- tex, and the apices terminate in the minor calyces. Several of the minor calyces form a major ca1yx.l.' NEPHRON AND COUECTlWG TUBULES The functional unit of the kidney, the uriniferous tubules, is composed of the nephron and collecting tubules. The nephrons produce urine, and the collecting tubules concen- trate and transport it. The proximal portion of each nephron is called the renal corpuscle. It consists of a cup-like structure called Bowman's capsule and a glomerulus. The renal corpus- cle has a vascular pole and a urinary pole. Blood vessels enter and exit the glomerulus at the vascular pole. The parietal epithelium of Bowman's capsule continues with the proximal tubule at the urinary pole. The proximal and distal portions of the tubules are convoluted. Between these convoluted sec-

tions lies the loop of Henle. The collecting tubules are ducts

that collect urine from the distal tubules and transport it to the papillary ductsag(Figure 2). SUMMARY Three separate nephric structures arise during fetal develop- ment. The second and third structures produce urine, but only the third remains as a mature and definitive organ in the fetus. The metanephros or third nephric structure plays a sig- nificant role in the regulation of amniotic fluid volume. The ' kidneys, themselves, are critical to the maintenance of a prop- er environment for cellular metabolism throughout life. A BlBUOGRAPHY

1. Baker LA, Gomez RA. "Embryonic development of the ureter." Sonin Nephrol, 1998, Nov; 18(6): 569-84.

  1. Birnholz JC, Madana AE. "Amniotic fluid accumulation in the first mmcster."] Ultrasound Med 1995 Aug: 14(8):597-602.
  2. 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 relationship to fetal weight and Imgch." Gynecol Obster Incest 1984; 18(3):152-55.
  3. Gulbis B, Gewy C, Jauniaux E. "Amniotic fluid biochemisq in xcond- trimester trisomic pregnancies: relationsh~psto fetal organ maturation and dysfunction." Early Hum Deu 1998 Oct; 52(3):211-19. 5. Gulbis B, Jauniaux E, Jurkovic D. Gewy C, Ooms HA. "Biochemical investigation of fetal renal maturation in early pregnancy." Pehoic Res 1996 Apr; 39(4 pt 1):73 1-35.
  4. Heikinheimo M. Seppala M, Brock DJ. "Pregnancy specific k w I-glyco- protein and human chorionic gonadotrophin levels in amniotic fluid and maternal serum in the finc half of pregnancy." Onccdiu Biol Med 1980 Aug; 1(1):71-6.
  5. Jauniaux E, Gulbis B, Hyett J. Nicolaides KH. "Biochemical analyses of mwcnchymal fluid in early pregnancy." Am J Obtet Gynecd 1998 Apr; 178(4):765-69.
  6. Johnson KE. Human D~wlopmmralA m y. National Medical Series. Williams & Wilkins: Baltimore, MD, 1988.
  7. McCance KL, Huether SE. Pathophysiology: Tk Bwfogic Bask for Disarsc in Ad& and Children. The CV Mosby Co: St Louis, MO, 1990.
  8. Puohkka J. Ylosralo P. Tuimala R, Haapalahti J, Jarvinen PA. "Amniotic fluid beta-2-microglohlin in normal and Complicated pregnancies. Correlation with guswtional age, cnatinine concentrarion and US ratio." G>necol Ohnt Invest 1982; 13(3):129-34. I I. Snyder JM, Kwun JE, O'Brien JA, Rosenfeld CR, Odom MJ. "The con- centntion of the 35-kDa surfactant apoprocein in amniotic fluid from normal and diabetic pregnancies." Pedion Res 1988 Dec, 24(6):72&34.
  9. Stuarc RO, Nigam SK. "Development of the mhular nephron." Smin Nephrol 1995 Jul; 15(3):315.!6.
  10. Szaflik K, Kozarzewski M, Adamceqski D. "Fecal bladder catheterization in severe obstructive uropathy before the 24th weak of pregnancy." Feral D q n Thcr 1998 May-Jun; 13(3):133-35.
  11. Wallner El, Carone FA, Ahrahamson DR. Kumar A, Kanwar YS. "Diverse aspects of metanephric dovclopmonr." Minosc Res Tech 1997 Nov 1; 39(3): 261.84.

EARN ca c-rr AT n m 161

You will be awarded one continuing education (CE) credit for recertification after reading the designated article and completing the exam with a score of 70% or better. If you are a current AST member and are certified, credit eamed through completion of the CE exam will auto- matically be recorded in your file-you do not have to submit a CE reporring

form. A printout of all the CE credits

you have eamed, including Journal CE credits, will be mailed to you in the first quarter following the end of the calendar year. You may check the status of your CE record with A S r at any time. If you are not an AST member or not certified, you will be notified by mail when Joumrrl credits are submitted, but your credits will not be recorded in ASTs files. Detach or photocopy the answer block, include your check or money ' (^) order ($6 for members or $10 for non- Which of the following is not one of the three nephric structures to arise during fetal development: a. metanephros b. polyhydramnios c. mesonephros J d. pronephros J Which nephric structure forms the two rudiments that make up the complete kidney and ureter? a. metanephros b. polyhydramnios c. mesonephros d. pronephros Which structure's component parts (cords of tissue or vesicles) can be seen in the fourth week of pregnancy a. metanephros b. polyhydramnios c. mesonephros d. pronephros ' Which structure is not active in urine production? a. metanephros b. polyhydramnios c. mesonephros d. pronephros Continuing Education Examination (January 1999) Kidney Development and Function in the Fetus Category 3 0 Certified Member Ll^ Certified Nonmember Certification No. Name Address City State ZIP Chapter or At-Large Region Telephone Mark one box next to each number. Only one correct or best answer can be selected for each question. A B C D A B C D 1 ' i C 1 O Q 6. C I P ' i P

2. a a 0 0 7. C I Q O Q

  1. 3 P O D 8. 3 P O 3
  2. D P P Q 9 L i C I Q Q
    1. P O 0 0 1 P 0 'i

members) made payable to AST and AST, 7108-C S Alton Way, Suite 1 K

send it to the Accounting Department, Englewood, CO 80112-2106.

5. Which structure's vesicles form 9. Amniotic fluid nephrons? a. protects the fetus a. metanephros b. allows space for development b. mesonephros c. assists in pulmonary c. pronephros development d. a and b d. all of the above 6. The urogenital sinus will later 10. By the ninth week, the fetus develop into the participates in regulating amniotic a. urinary bladder and urethra fluid by b. testes a. producing hypotonic urine c. vagina b. swallowing hypotonic urine d. ureteric bud c. producing fluid in the lungs d. all of the above 7. The originates from the metanephric blastema and uteric bud. a. metanephros b. mesonephros c. bladder d. uterus 8. Congenital anomalies of kidney development are due to a failure in: a. the development of the uteric bud b. the production of nephrons c. (^) the ascent to the lumbar position d. all of the above