Renal Embryology Flashcards
renal development - general concepts
*developing fetus has an intermediate mesoderm (IM) which develops craniocaudally from the cervical to lumbar regions of the fetus
*mammals develop 3 pairs of embryonic kidneys sequentially: 1) pronephros; 2) mesonephros; 3) metanephros
renal development - tissues
*at 5 weeks gestation, reciprocal signaling induces the outgrowth of the ureteric bud from the caudal mesonephric duct
*metanephric mesenchyme condenses around the ureteric bud to become metanephric blastema
renal development - timeline
*4 wks gestation: kidneys start developing
*9wks: first glomeruli, bladder
*20-36 wks: nephrogenesis occurs
*~36 wks: nephrogenesis is complete
*at birth, kidney growth is due to enlargement of the glomerular diameter & significant increase in tubular volume and length
nephrogenesis
- vesical differentiates and elongates, forming a comma-shaped, then S-shaped body
- the lower limb of the S-shaped body forms the glomerular podocytes
- endothelial cells migrate into the cleft of the S-shaped body
- the distal end of the S-shaped body elongated and differentiates to from nephron tubules from the proximal tubule to the DCT
- DCT connects to the collecting system
ureteric bud/mesonephric duct differentiate into
COLLECTING SYSTEM:
*ureter
*renal pelvis
*major and minor calyces
*collecting tubules & ducts
*Trigone of bladder
metanephric blastema differentiates into
NEPHRONS:
*podocytes
*epithelial cells lining Bowman’s Capsule
*proximal convoluted tubules
*loop of Henle
*distal convoluted tubules
effects of prematurity on renal development
*human nephrogenesis stops at birth
*therefore, premature infants have REDUCED NEPHRON MASS
*leads to increased risk of hypertension, chronic kidney disease
congenital anomalies of the urinary system (overview)
*renal anomalies are common, 3-20% of live births
*many asymptomatic
*may not manifest until later in life
*causes include: environmental factors (maternal medication exposure, high glucose, folate deficiency) or genetically based
*more than 500 syndromes with genetic basis that involve malformations of the urinary tract
renal duplications
*embryonic anomaly = bifurcation or duplicated ureteric bud
*results in extra ureter
*ectopic expression of GDNF by metanephric mesenchyme more proximally along mesonephric duct
renal agenesis - overview
*embryonic anomaly = faulty interaction between ureteric bud and metanephric mesenchyme
*attributed to mutations of glial cell line-derived neurotrophic factor (GDNF), which plays a role in induction of the ureteric bud
unilateral renal agenesis
*solitary kidney; remaining kidney undergoes compensatory enlargement, such that most patients are asymptomatic
*occurs in 0.1% of adults
*high rate of coexisting urogenital abnormalities
bilateral renal agenesis
*incompatible with extra-uterine life
*results in oligohydramnios, no kidneys, and non-visualized bladder on prenatal ultrasound
*one of the causes of Potter Sequence
Potter Sequence - pathogenesis
*oligohydramnios → compression of developing fetus → limb deformities, facial anomalies (low-set ears and retrognathia, flattened nose), compression of chest and lack of amniotic fluid aspiration into fetal lungs → pulmonary hypoplasia (cause of death)
Potter Sequence - etiology
*caused by chronic placental insufficiency or reduced fetal urine output (oligohydramnios), including:
-ARPKD
-obstructive uropathy (ex. posterior urethral valves)
-bilateral renal agenesis
Potter Sequence - clinical presentation
P - pulmonary hypoplasia
O - oligohydramnios
T - twisted face
T - twisted skin
E - extremity defects
R - renal defects
renal hypoplasia
*unilateral OR bilateral
*SMALL size, non-dysplastic, less than normal number of nephrons
*can lead to chronic kidney disease if bilateral
*genetic causes, maternal factors
renal aplasia
*rudimentary kidney
renal dysplasia
*embryonic anomaly = abnormal metanephric differentiation
*unilateral or bilateral
*kidney(s) often contain ectopic tissue (cartilage, muscle)
*kidneys may have cysts
*reduced renal function, more likely to develop chronic kidney disease
*can occur with renal hypoplasia
multicystic dysplastic kidney (MCDK)
*embryonic anomaly = abnormal metanephric differentiation
*MOST COMMON CAUSE OF CONGENITAL SOLITARY KIDNEY
*60% involute by age 10 yrs
*second most common cause of flank mass in newborn
*usually UNILATERAL (bilateral not compatible with life)
*2x more common in MALES
*kidney is not functional
*atretic ureter
*detected during antenatal ultrasound
congenital polycystic disease
*hundreds to thousands of cysts within kidney parenchyma
*cysts form from variety of locations along nephron
*other organs (pancreas, liver) can be involved
*includes ADPKD, ARPKD, and medullary cystic kidney disease
effects of fetal exposure to RAAS blockade (ACEi or ARB)
*few infants survive
*results in oligohydramnios
*after neonatal period: polyuria, polydipsia
*salt-losing nephrogenic diabetes insipidus
*inability to concentrate urine due to impaired osmotic gradient in renal medulla
*reduced glomerular filtration rate
hydronephrosis - overview
*most common cause of ABDOMINAL MASS IN NEWBORN
*dilation of renal pelvis & collecting system
*diagnosed on antenatal ultrasound or incidental finding post-natally
*dilation of renal pelvis and between renal calyces
*can be unilateral or bilateral
Alport Syndrome
*inherited disorder, due to mutation of genes encoding alpha-3, -4, or -5 type IV collagen chains (most commonly X-linked), resulting in abnormal basement membrane (basket-weave appearance)
*clinical manifestations:
-hematuria
-proteinuria
-progressive CKD → renal failure
-sensorineural hearing loss
-ocular abnormalities (lens displacement anterior lenticonus)
hydronephrosis - causes
- vesicoureteral reflux
- obstruction (UPJO, PUV, or ureterovesical junction obstruction)
- transient/physiological
- neurogenic bladder
ureteropelvic junction obstruction (UPJO)
*complete or partial obstruction of the ureter where it exits the kidney (between the renal pelvis and the ureter)
*mostly arises from a congenital stenosis of the ureter
*detected antenatally
*common cause of hydronephrosis (bear paw pattern)
*presenting symptoms: flank mass, UTI, pain, hematuria
vesicoureteral reflux (VUR) - overview / epidemiology
*retrograde flow of urine from bladder toward upper urinary tract
*most common pediatric urologic condition
*affects up to 30% of children with a febrile UTI
*common cause of hydronephrosis, but does not always present with hydronephrosis
*often self-resolves as child grows
*can be a secondary VUR due to high bladder pressure (neurogenic bladder, posterior urethral valves)
*complications include chronic UTIs, pyelonephritis, renal scarring, HTN, chronic kidney disease
vesicoureteral reflux (VUR) - defined
*retrograde flow of urine from the bladder back into the ureters, and sometimes all the way up to the kidneys
primary vesicoureteral reflux (VUR) - pathogenesis
*malformation of the ureter as it passes through the bladder wall, preventing normal closure of the ureter at the ureteric opening into the bladder
*usually corrects itself or improves with aging
secondary vesicoureteral reflux (VUR) - pathogenesis
*urine flow distal to the ureters is obstructed, usually either in the bladder neck or in the urethra
*commonly caused by posterior urethra valves in males
vesicoureteral reflux (VUR) - complications
*increased risk of urinary tract infections, including pyelonephritis
*scarring, HTN
*increased risk of CKD
*reflux nephropathy due to chronic urine reflux back into the kidney
lower urinary tract development
*the cloaca gives rise to the bladder and the lower GI tract (rectum & anus)
*at 4-5 weeks gestation, the cloaca divides into the anterior urogenital sinus and the posterior anal canal
*superior portion of urogenital sinus → urinary bladder
*middle portion of urogenital sinus → prostatic & membranous portions of the urethra
bladder exstrophy
*embryonic anomaly = failure of abdominal wall to close during fetal development
*results in protrusion of posterior bladder wall through the lower abdominal wall
*symphysis pubis diastasis
*multiple abnormalities in pelvis, bladder, urethra, and external genitalia
*common in males
*associated abnormalities: vesicoureteral reflux, incontinence, recurrent UTIs, hernia
posterior urethral valve (PUV) - overview
*most common cause of URINARY OBSTRUCTION IN MALE children
*congenital valve in the posterior (prostatic) urethra due to persistent urogenital membrane
*important b/c they can obstruct urine flow
*associated with renal dysplasia
*spectrum of severity
*risk of perinatal mortality & HIGH risk of chronic kidney disease
posterior urethral valves (PUVs) - pathogenesis
*a congenital malformation of the prostatic urethra caused by persistence of urogenital membrane (only present in males)
posterior urethral valve (PUV) - postnatal presentations
*pulmonary hypoplasia
*weak urine stream
*frequent UTI
*voiding dysfunction, enuresis (incontinence)
*trouble toilet training
Prune Belly Syndrome / Triad Syndrome
*triad of:
1. deficiency or absence of anterior abdominal wall musculature
2. bilateral cryptorchidism (undescended testicles)
3. bilateral ureter, bladder, & urethral abnormalities
ectopic kidney
- pelvic kidney (most common):
-failure of kidney to ascend during embryogenesis, resulting in kidney remaining in pelvis - cross-fused ectopia:
-one kidney and its ureter are on the same side of the body as the other kidney
-may be fused with normal kidney
*associated anomalies: VUR most common
horseshoe kidney - overview
*fusion abnormality in which the kidneys are fused together, typically at the lower poles
*isthmus of horseshoe kidney lies at the level of L4-L5 (gets trapped on inferior mesenteric artery during ascent)
*more susceptible to trauma due to blockage of inferior mesenteric artery
*more common in: males, Turner Syndrome, Trisomy 18
*complications: 50% associated with VUR; increased risk of ureter obstruction
horseshoe kidney - pathogenesis
*the two kidneys fuse (usually the lower poles) during development
*when the poles migrate upward during growth, the fused midline portion becomes trapped at the inferior mesenteric artery, placing the fused kidneys lower in the abdomen and less protected than usual
