This document discusses renal embryology and kidney development. It begins by outlining the three main stages of kidney development - the pronephros, mesonephros, and metanephros. It then provides details on the development of each of these stages, including how they form from the intermediate mesoderm and their roles. The document also discusses genetic factors involved in kidney differentiation, abnormal kidney development including anomalies in number and position, and applied aspects such as hereditary polycystic kidneys.
2. • Stages of Kidney Development
• Development of Nephron
• Development of the Collecting System
• Development of Vasculature
• Molecular Biology
• Timeline of Events
• Applied Aspects
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3. • Development of the urogenital system
• Development of the metanephros
• Development of the nephron
• The nephrogenic zone
• Development of collecting system
• Development of vasculature
• Model systems to study kidney development
• Genetic analysis and applied aspects
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4. Stages of Kidney Development
•First to form is embryonic disc which gives rise to three structures ectoderm,
mesoderm and endoderm.
•Mesoderm is later divided into 1)Para axial Mesoderm
2) Intermediate Mesoderm
3) Lateral plate mesoderm
•Intermediate Mesoderm form bulging (Nephrogenic Cord) on posterior
abdominal wall
•Three slightly overlapping kidney systems are formed in a cranial to caudal
sequence during intrauterine life in humans:
1. The pronephros=(rudimentary and nonfunctional).
2. The mesonephros=(function for a short time during the early fetal period).
3. The metanephros=(forms the permanent kidney)
7. Mammalian Kidney Development
• After the folding of the embryonic disc, the intermediate
mesoderm forms a bulging on the posterior abdominal wall,
called the NEPHROGENIC CORD/ UROGENITAL RIDGE
• It extends from the cervical region to the sacral region of the
embryo.
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8. Stages of Kidney Development
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• The Human Kidney
develops in 3 successive
stages (rostral to caudal)
PRONEPHROS
MESONEPHROS
METANEPHROS
They are aligned adjacent
to the Wolfian / Nephric Duct
9. Pronephros
• Develops from the cranial most part of urogenital ridge at 22
day of gestation.
• It is transitory and regresses completely by end of the 4th
week (ie, day 28).
• At the beginning of the fourth week, the pronephros is
represented by 7 to 10 solid cell groups in the cervical region.
• These groups form vestigial excretory units, nephrotomes,
that regress before more caudal ones are formed.
• By the end of the fourth week, all indications of the
pronephric system have disappeared.
• Forms the kidney in larval stages of amphibians and fish
11. Mesonephros - in humans
• The Mesonephros first appears early in week
4
• In thoracic and lumbar segments of
intermediate mesoderm.
• Urine is produced and drains along the
mesonephric (Wolfian) duct to the
cloaca/bladder
• In week 5 the thoracic segments regress but
the mesonephric kidney continues functioning
until week 10
12. • The caudal tubules are still differentiating.
• In the male a few of the caudal tubules and
the mesonephric duct persist and participate
in formation of the genital system, but they
disappear in the female
13.
14. Fate of the Mesonephric (Wolfian)
ducts
• The development of the metanephric kidney
accompanied the changes in the reproductive
system.
• In the embryo, this egg collecting tube
(paramesonephric duct) lies parallel to the
mesonephric duct.
15. Metanephros – In Humans
• Last stage of renal development.
• Differentiation starts by 5th week of IU life.
• The metanephros forms a definitive kidney of
higher vertebrates and mammals.
• It constitutes two step for the development
of definative kidney.
16. •Kidneys arises from 2 distinct sources:
1. Excretory tubules(nephrons)=
•Derived from the lower part of nephrogenic
cord.
•Metanephros, the cells of which form the
metanephric blastema.
2. Collecting part=
•Derived from a diverticulum (ureteric bud),
arises from the lower part of the metanephric
duct.
17.
18. Evolution of the Kidneys:
Metanephros
•The ureteric buds bifurcate again and
again to form the calyces and collecting
duct system of the definitive kidney.
•The kidneys begin producing urine by
week 12, and it adds to the volume of
the amniotic fluid.
The fetus drinks this fluid in utero.
•The fetal kidneys are not responsible for
excretion as the placenta serves this function
21. • In the 6th week the kidneys begin to ascend from the sacral
region to their position in the upper abdomen.
• The metanephric ducts elongate and become the ureters.
• As the kidney ascends it receives new segmental arteries from
the aorta and loses those vessels below (“climbing a ladder”).
Thus sometimes there is more than one renal artery.
• Sometimes one kidney fails to ascend => pelvic kidney
• Sometimes the left and right kidneys become attached in the
pelvis then the horseshoe kidney can’t ascend above the
inferior mesenteric artery
22. Genes involved in differentiation of
the kidney
• WT1 expressed by the mesenchyme, it enables this
tissue to respond to induction by the ureteric bud.
• The growth factors FGF2 and BMP7 stimulate
proliferation of the mesenchyme and maintain WT1
expression.
• GDNF and HGF interact through their receptors RET
and MET, respectively, to stimulate growth of the
bud and maintain the interactions.
23. • PAX2 and WNT4, produced by the ureteric bud,
cause the mesenchyme to epithelialize in
preparation for excretory tubule differentiation.
• Laminin and type IV collagen form a basement
membrane for the epithelial cells.
24.
25. BLADDER DEVELOPMENT
•During the fourth to seventh weeks of
development the cloaca divides into the
urogenital sinus anteriorly and the anal canal
posteriorly.
• The urorectal septum is a layer of
mesoderm divides primitive anal canal
and the urogenital sinus.
26. Male and Female genital ducts
•Initially both sexes have both mesonephric and paramesonephric ducts
• In males=
The mesonephric duct becomes the ductus deferens, seminal vesicle and
parts of the prostate gland.
The paramesonephric duct degenerates completely
•In females=
The two paramesonephric ducts become the uterine tubes.
Distally the paramesonephric ducts fuse together to form the uterus and
vagina.
The mesonephric duct degenerates completely.
27.
28. Timeline of Kidney Embryology
• Week 4 : Appearance of Wolffian/mesonephric
Duct
• Day 28 : Formation of Ureteric Bud (UB)
• Week 4-8 : Initial MM induction and UB branching
• Week 8 :First nephrons are formed
• Week 6-8 : Kidneys ascend from pelvis to lumbar
location
• Week 8-15: Period of UB branching with formation
of UB ampulla and nephron units
• Week 10 : Filtration begins
• Week 32-36: End of Nephrogenesis
31. Applied Aspects
Anomalies in number-
•Renal agenesis When ureteric bud fails to
contact Metanephric Mesenchyme.
•Duplications when ureteric bud splits early
before reaching MM
•Ectopic ureters when two ureteric buds arise
from mesonephric duct.
32.
33. •Anomalous Ascent-
•When the kidney fails to ascend properly, its
location becomes ectopic.
•The inferior poles of the kidneys may also fuse,
forming a horseshoe kidney and ascent
is stopped by inferior mesenteric artery
•Kidney may fuse to the contralateral one and
ascends to the opposite side, resulting in a
cross-fused ectopy.
34.
35. •Anomalous position-
•Malrotated Kidneys - Calyces face anteriorly or
antrolaterally.
•These patients have some element of obstruction
causing inadequate drainage –leading to infection &
stone formation
•Other abnormal positions include-
• Ventral Position
• Ventromedial Position
• Dorsal Position
• Lateral Position
36. •Polycystic kidneys-
•Hereditary – autosomal dominant inheritance
• Not manifested before 30
• Kidneys enlarged, studded with cysts
• Unyeilding capsule compresses
renal parenchyma causing atrophy
• Liver,lungs and pancreas may also
be affected
