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Development of Urinary System Crissman Anatomy Block II Unit II

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From what germ layer does the urogenital system develop?
The intermediate mesoderm.
Describe the formation of the urogenital ridge.
Starts out on the dorsal aspect of the embryo and as the embryo folds the intermediate mesoderm is carried ventrally and loses its connection to somites. This forms the urogenital ridge anterior to the dorsal aorta.
What is inside the urogenital ridge?
The nephrogenic cord is inside the lateral portion of the urogenital ridge.
What part of the urogenital ridge gives rise to the genital system? What part gives rise to the urinary system?
The medial side of the ridge gives rise to the genital system and the nephrogenic cord gives rise to the urinary system.
Which develops first, the genital system or the urinary system?
The urinary system develops first.
What are the 3 kidneys developed in sequence? What germ layer do they arise from?
From the intermediate mesoderm. They are the Pronephros, the mesonephros, and the metanephros.
What are pronephros AKA? What region are they located in?
AKA Cervical nephrotomes, they are in the cervical neck region as a few cell clusters and tubules early in week 4
How developed are the pronephros? Do they persist in the adult? Are they functional?
The pronephros is rudimentary (incompletely developed). They are transitory and they are NONfunctional.
What do the pronephric ducts run to caudally? Do they persist?
These ducts run caudally to the cloaca and rapidly degenerate.
What is the mesonephros also known as? When do they appear?
AKA Thoracolumbar mesonephric system. These are a 2nd set of kidneys that appear at the end of the 4th week of development.
Are the mesonephros functional? Are they developed? What is their main purpose?
The mesonephros are functional and well developed. They act as interim kidneys until permanent kidneys form.
How many units make up the mesonephric kidney and what is their arrangement sequence.
40 units in a cranio to caudal sequence.
Where do the mesonephros form?
In the intermediate mesoderm along the thoracic somites (upper thoracic to 3rd lumbar).
What 3 transcription factors are needed to develop the mesonephros?
LIM-2
PAX-2
WT-1
What is the purpose of LIM-2
induces aggregation of mesenchyme cells into nephric duct.
What is the purpose of PAX-2? How important is this TF?
Induces conversion of intermediate mesoderm into epithelial tubules. If this is not expressed, kidney development stops.
What is the purpose of WT-1?
Also needed for mesonephric tubule formation.
After the formation of the mesonephros and mesonephric ducts what forms within the intermediate mesoderm? What do they evendually form and in what sequence?
Within the intermediate mesoderm, nephric vesicles form and elongate into nephric tubules that form in a craniocaudal sequence.
What do mesonephric tubules eventually connect to?
The mesonephric duct.
What do mesonehric tubules eventually differentiate into?
Rudimentary adult nephrons.
Describe the formation of Bowman's capsule.
The medial end of the mesonephric tubule enlarges and forms a cup-shaped sac.
What do the glomeruli form from?
Branches of ingrowing arteries coming from the dorsal aorta.
What is each renal corpuscle and nephric tubule called?
The mesonephric excretory unit.
When do the cranial mesonephric units undergo degeneration? Where do they persist?
End of 5th week. 20 pairs persist in the first 3 lumbar levels.
Describe the formation of the mesonephric duct.
Solid longitudinal rods of cells condense in the intermediate mesoderm. These are dorsolateral to the mesonephric tubules. Rds grow caudally by proliferation of the cells at their caudal tips and they grow into the ventrolateral walls of the cloaca on day 26. This region of fusion will become part of the posterior portion of the future bladder. At the region of the fusion the 2 rods undergo canalization. It continues cranially to transform the rods into mesonephric ducts. The lateral end of the mesonephric tubules fuse to the mesonephric duct to form an open passageway from the extretory unit to the cloaca.
For what period are the mesonephric excretory units functional?
6-10 weeks.
Do the mesonephric excretory units produce urine?
YES!
Does the mesonephric duct persist in both sexes? If not what does it form?
It persists in males to form part of the male genital duct system. It degenerates in females.
What are metanephros AKA? (2)
Sacral metanephric system, permanent kidneys.
When do the metanephros start forming and when do they start functioning?
Form week 5, function week 9
Give the two sources from which the metanephric kidney is derived from. (also give any AKA names)
Metanephric diverticulum or uretic bud and the metanephric mass of intermediate mesoderm or metanephric blastema.
What do the ureteric buds form from?
The distal mesonephric duct.
What is reciprocal induction and what two structures does this apply to?
Both the ureteric bud and the metanephric blastema interact and induce each other to form the kidney.
What induces the formation of the metanephric blastema and from what source?
The ureteric bud induces the formation of the metanephric blastema from the intermediate mesoderm in the sacral level.
Fill in the blank!

Transcription factor _____ expressed by ______ and regulates synthesis of ________. This induces the growth and branching necessary for the formation of the __________.
Transcription factor WT-1 expressed by blastema and regulates synthesis of GDNF. This induces the growth and branching necessary for the formation of the ureteric bud.
What produces the growth and branching necessary for the utereric bud?
GDNF
What expresses WT-1?
The metanephric blastema.
What does c-ret do? What is it a receptor for? Where is it found?
It is a receptor for GDNF found in the ureteric bud and is necessary for bifurcation.
What happens if c-ret, WT-1 or GDNF is missing?
Renal agenesis
What signals blastema mesenchyme to aggregate? (TF)
Growth factors (FGF-2, BMP-7 and LIF)
What induce ureteric bud formation and transform cells into epithelial cells?
Transcription factors (Pax-2, BF-2, Wnt-2)
What can mutations to metanephros development cause in humans?
Anomalies in both kidneys and the genital tract or ectomic positioning of the ureter.
What eventually covers each ureteric bud?
A cap of metanephric blastema.
What forms the ureter?
The initial part of the ureteric bud.
What forms the renal pelvis?
The first branches from the ureteric bud.
WHat seperates the superior and inferior lobes during development?
Sulcus
WHat does the very first bifurcation during kidney development form?
The renal pelvis.
What does the ureteric bud form? (4)
Ureter, renal pelvis, calyces and collecting duct.
What does the metanephric blastema form? (intermediate mesoderm)
The nephron
How many bifurcations and branches are their in the 6th week? What do they fuse together to form? What do the additional 4 bifurcations form? All this bifurcating gives what appearance to the kidney?
There are 4 bifurcations that form 16 branches. They fuse together to form the major calycles. The additional bifurcations form the minor calyces. These give the kidney its lobulated appearance.
After forming the minor calyces what does further bifurcation form?
Collecting ducts.
What as at the end of each arched collecting duct and what does it differentiate into?
A cellular mass of metanephric mesoderm (blastema) that differentiates into metanephric vesicles.
What do the metanephric vesicles elongate into?
Metanephric tubules that form the nephronn.
What forms at the distal end of the elongating metanephric tubule?
The capillary glomerulus.
What do Bowman's capsule and the renal corpuscle form from?
The metanephric tubule
What forms the proximal convoluted tubule, descending and ascending limbs of the loop of HEnle and the distal convoluted tubule?
The metanephric tubule.
What is the complete nephron called with all its proximal and distal tubules as well as capsule in place?
The definitive nephron
What does the metanephric excretory unit include?
The nephron and its renal corpuscle.
WHen does the kidney reach its adult configuration?
Week 10
What forms the uriniferious tubule?
Both the ureteric bud (ureters, renal pelvis, calyces, collecting ducts) and the metanephric blastema (forms nephron)
What expresses WT-1 and what does it do?
WT-1 is expressed in blastema, and it regulates GDNF synthesis to induce ureteric bud formation.
What do Pax-2, BF-2, Wnt-2 all do?
Induce ureteric bud formation and transform mesenchymal cells into epithelial cells.
What do Mox-1, N-myc, and Hoxc-9 do?
All required for nephron differentiation and glomerulus formation.
What is c-ret and what does it do? What happens if it is lacking?
It is a receptor for GDNF it is responsible for branching and growth of the ureteric bud. Lack of the receptors causes bifid ureters and renal agenesis.
WHat expresses NGF and what does in do?
NGF is expressed in the blastema and is necessary or the formation of nephrogenic tubules.
What does GDNF do?
Needed for branching of the ureteric bud?
What will overexpression of IGF result in?
Wilm's tumors
What causes Wilm's tumors?
Overexpression of IGF
What is the purpose of cadherins in kidney formation?
They make tight junctions in forming epithelial tubes.
What are laminin and integrin necessary for?
Diapedesis to occur as cells migrate.
What is the starting positions of the kidneys? How do they end up in their adult positions?
Close to each other in the pelvis. The abdomen and pelvis grow "away" from them.
Describe the rotation of the hilum.
Rotates medially 90 degrees.
Describe the changing blood supply of the kidneys.
1st comes from common iliac arteries. Then it is derived from segmental branches off the aorta as the kidney ascends. The caudal branches degenrate.
Describe the normal blood supply to the kidney.
1 renal artery for each kidney coming from the aorta.
What is polar accessory renal arteries?
When accessory renal arteries pass inferior or superior to the renal artery.
How can obstruction of the ureter occur do the persistance polar accessory renal arteries? What is the named pathology associated with this? Describe what happens.
Inferior polar crosses anterior to the ureter. This results in hydronephrosis or dilatation of the pelvis and calyces due to backup of urine.
What does unilateral renal agenesis result from? What side does it usually occur on? What are its symptoms?
Unilateral renal agenesis is due to a lack of ureteric bud. There are usually no symptoms due to compensatory hypertrophy of the remaining kidney.
What causes bilateral renal agenesis?
Failure of metanephric blastema or failure of the ureteric bud to form
What is bilateral renal agenesis associated with?
Potter's syndrome
What is pelvic kidney?
Failure of the kidney to ascend
What structure does a divided kidney with a bifid ureter have two of?
Two renal pelves
What causes a divided kidney with bifid ureter?
Incomplete division of ureteric bud.
What causes a discoid kidney?
Both kidneys fail to ascend and fuse together in pelvis.
What fuses in a horseshoe kidney?
Iferior poles.
What causes a horseshoe kidney?
Kidney gets held up by inferior mesenteric artery as it ascends.
What causes supernumerary kidney?
2 ureteric buds in stead of one.
What is malrotation associated with? What is it?
Kidneys rotate laterally with hilum going laterally. Usually associated with ectopic kidney.
What is a supernumary kidney with bifid ureters caused by?
Complete division of ureteric bud
What causes unilateral fused kidney?
Kidneys fuse together in pelvis prior to ascending.
Where is the PDK gene located
Chromosome 16
Which presents in childhood dominant or recessive Polycystic kidney disease?
Recessive.
What regulates proliferation of epithelial cells in the kidney?
Sensing of flow by cilium of kidney epithelial cells.
What is nonfunctional in PCKD?
Cilium of epithelium of kidneys.
What is the urogenital sinus and rectum formed by?
Partitioning of the cloaca by the urorectal septum.
What covers the inferior opening of the urogenital sinus?
Urogenital membrane.
What are the 3 parts of the urogenital sinus? Which is continuous with the allantois?
Vesical part (continous with allantois) -superior
Pelvic part -middle
Phallic part -inferior
What does the vesical portion of the urogenital sinus form in males?
Most of the bladder
What does the pelvic portion of the urogenital sinus form in males?
Membranous and prostatic urethra
What does the phallic portion of the urogenital sinus form in males?
Proximal penile urethra
What is the distal poriton of the penile urethra formed by? What is the origin of this tissue?
It is formed by the glandular urethral plate. It is ectodermal in origin.
What does the vesical portion of the urogenital sinus form in females?
Most of the bladder
What does the pelvic portion of the urogenital sinus form in females?
Complete urethra
What does the phallic portion of the urogenital sinus form in females?
Vestibule of the vagina
What does the allantois degenerate into?
Urachus or median umbilical ligament
What is a urachal sinus?
Where the urachus drains out the umbilicus.
What is a urachal fistula?
Where the urachus remains open and urine can dribble out of the umbilicus.
What is the process where the mesonephric ducts are ncoporated into the posterior wall of the forming bladder?
Exstrophy.
When can exstrophy of the bladder occur?
When the anterior abdominal wall and anterior wall of bladder fail to close.
What is the result of exstrophy of the bladder?
Eversion of the urinary bladder on the surface.

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