Development Flashcards
What are the 3 major stages of kidney development?
- Pronephros: formation of mesonephric duct
- Mesonephros: extends caudally, grows down
- Metanephros: ureteric bud forms & invades the metanephric mesenchyme
- UB branching occurs, molecular signals from mesenchyme
- UB makes signals to tell MM to undergo mesenchymal to epithelial transition
(retinoic acid dependent)
Mesonephric duct
Forms from epithelization of intermediate mesoderm
Also called the Wolffian duct
Individual tubes form out of this
Ureteric bud
becomes collecting tubule, collecting duct and ureters
Metanephric mesenchyme
Becomes the podocytes, epithelial cells lining Bowman’s capsule, proximal convoluted tubule, loop of Henle, distal convoluted tubule
Bladder development
From cloaca = end of terminal hindgut
Dorsal portion becomes rectum & anal canal and ventral portion becomes bladder & UG sinus (lower UG tract)
Distal ends of mesonephric ducts absorbed into wall of bladder as trigone
When does kidney ascent occur?
Weeks 6-9
CAKUT
Congenital anomalies of the kidney and urinary tract
1:500 have one
Represent 20-30% of all anomalies identified during the prenatal period
50% childhood kidney failure worldwide is attributed to CAKUT
primary insults are thought to be environmental factors & genetic mechanisms
Includes kidney hypoplasia, dysgenesis, agenesis…multicystick kidney, horseshoe kidney, duplex kidney, VUR, hydronephrosis, obstructions
Renal agenesis
Failure of UB to reach MM, often due to disruption of local molecular signalling
Usually accompanied by ipsilateral abnormalities including small or absent bladder, ureter, vas deferens, Muellerian or seminal vesicle anomalies
Unilateral: 1/1000 births, male>female
Bilateral: 1/3000-6000, perinatal lethal due to pulm hypoplasia
Duplication of the urinary tract
Gain of function in induction or differentiation
UB divides prematurely, before invading the MM –> double kidney and/or double ureter
VUR
Vesicoureteral reflux
Retrograde passage of urine from the bladder into the upper urinary tract
1% of newborns have it
Primary = most common, strongly genetic, also can be secondary
Primary VUR clinical presentation: prenatal v. postnatal
- *Prenatal**: ID’d by prenatal USG showing hydronephrosis; 10-40% of fetuses with antenatal hydro will be diagnosed with VUR postnatally
- renal hypoplasia and dysplasia (scarring)
- mostly male
- increasing grades of reflux and renal scars identify a higher risk group for subsequent renal injury & long-term effects
- *Postnatal**: generally diagnosed after febrile illness or UTI
- predominantly female
- risk of scarring increases with severity of VUR
Primary VUR pathogenesis
Most common form: anti-reflux mechanism occurs during bladder contraction by muscle compression of the intravesical ureter
incompetent closure is thought to occur due to intravesical ureter shortening: shorter submucosal tunnel permits reflux during compression
Secondary VUR Pathogenesis
Results from abnormally elevated bladder pressure
Anatomic: posterior urethral valves, 1/8000 boys, incontinence, infection, renal failure, 10-15% ESRD
Functional: neurogeneic bladder, urethral obstruction
Renal Coloboma Syndrome
Autosomal dominant
PAX2 abnormalities: affects developing eye, ear, kidney, ureteric bud, CNS
PAX2 = essential for differentiation of MM into epithelial tubules in response to inductive signals from the UB
Optho findings = from abnormal growth of periocular mesenchyme into developing eye
- severe myopia & bilateral sharply defined white excavations of optic discs
Lots of mutations/variability
Willms tumor = Nephroblastoma
Embryonic cancer of developing kidney
Most common form of childhood kidney cancer, 4th overall childhood cancer
Usual presentation: palpable abdominal mass, usually painless but may be accompanied by pain, hematuria, fever, hypertension
Usually unilateral tumor with encasing fibrous capsule; some can be bilateral & occur with other UG malformations
Cellular origin is unclear, but several genetic mutations found including tumor suppressor genes and oncogenes: WT1 (TF, tumor suppressor or oncogenic protein when overexpressed; increased risk of bilateral and recurrent dz), WTX, CTNNB1
