Lecture 4: Regulation of Kidney Development 1 Flashcards
What % of CO and volume of blood does the adult kidney filter?
~25% of the CO (1.1L/min)
What do the kidneys regulate?
pH, water and salt balance, BP, renal hormones and waste removal
What is the number of nephrons you are born with and how much does this vary between people?
1,000,000
10 fold variation between people
What are the 3 pairs of excretory organs that form during development and where do they develop from?
Pronephroi, mesonephroi, metanephroi - develop from the intermediate mesoderm
What day does the pronephros form?
21-22 days gestation (human)
In what organism is the pronephros the final kidney?
Primitive organisms
What animals is the pronephros functionally important in?
Amphibians and fish
What is the position of the glomus in the pronephros?
Sits within the ceceum - blood filters and is collected by the pronephric duct
Where does the mesonephros develop?
Beneath degenerating pronephros
What does the pronephic duct give rise to and what does this structure then give rise to?
Wolffian duct
Mesonephros
When does the mesonephros develop?
Day 25
What things are not present in the mesonephros?
Juxtaglomerular apparatus and loop of henle
How many complete nephrons capable of excreting urine are present in the mesonephros?
40
When is the mesonephros at maximal size?
Day 33
What do mesonephric tubules form?
Efferent tubules of the testis in the male
When does the metanephros form?
Day 30
Why does the human kidney finish development just before birth?
Maximise nephron number and renal capacity
What is the final nephron number regulated by?
Ureteric bud branching, MET and apoptosis
What does specification of the metanephric blastema form?
Glomerulus and tubules
What is the functional kidney in mammals?
Metanephros
Where does the UB outgrowth begin?
Caudal end of Wolffian duct
What are the steps of ureteric branching and morphogenesis?
- The UB invades the metanephric mesochyme (MM)
- Metanephric mesochyme and UB produce messages to communicate and cause induction of UB to branch
What does the ureteric tree form?
Collecting ducts, calyces and renal pelvis
What does the part of the UB that does not enter the MM form?
Ureter
What are the steps of nephrogenesis?
- UB induces MM to condense
- Cap mesenchyme
- Pretubular aggregate
- Pretubular aggregate undergoes MET
- Renal vesicle
- Comma shaped
- S-shaped body
- Connects to ureteric tip to form function nephron
What does the upper, central and lower portions of the s-shaped body form?
- Upper portion of S shaped body forms distal convoluted tubules
- Central portion forms proximal tubule, loop of Henle and distal straight tubule
- Lower portion forms renal corpuscle
When do tip branching and nephron formation occur at the same time?
Up until week 15
Nephron formation continues after tip branching stops so what happens?
Arcade formation
How many nephrons per arcade?
7-10
Where do nephrons form after week 20?
Along length of collecting duct
How many nephrons would be present if no arcades formed?
50,000
When do adrenergic nerves develop and where do they form?
20 weeks - cortex (mature at 28 weeks) and medulla (reduce in later gestation)
When are capillaries detected in UB?
The day after it enters the MM
What happens to blood vessels at 8-10 weeks?
Vessels surround s-shaped bodies
What does cortisol do?
Develop lungs and throat when swallowed by baby due to secretion into amniotic fluid by kidneys
Why is urine important in utero?
Excreted by foetus into amniotic fluid - swallowed - contains important things for organ development
How is the adult kidney functioning different to the foetus?
Kidney doesn’t function like an adult kidney in utero. Fetus has GFR but it is about half of that in the adult. The fetus produces 8 fold greater urine - no worry about water conservation/loss. Despite the large production of urine in fetal life - blood flow to kidney is low - don’t need to constantly filter blood through kidneys. The amount of sodium that the fetus reabsorbs is low - functioning from mother. Water returned is not important in fetus so isn’t the same as the adult
What are the features of Potters Syndrome?
No kidneys formed, no urine formed in utero - no lung formation assistance - death soon after birth due to lung insufficiency. If babies receive glucocorticoids for lung development - they will then die of renal failure - require dialysis through peritoneum. Often get unilateral renal agenesis (live normal life) - then have half the number of nephrons - set up on a road to develop renal conditions more easily with age (less functional reserve if anything goes wrong)
What are the features of CAKUT?
- Congenital abnormalities of the kidney and urinary tract
- 1/3 of renal abnormalities
- Congenital deficits of the kidney and ureteric tract. Covers most renal deficits (accompanied by ureteric deficits)
- Often caused by congenital deficits but frequently caused by genetic abnormalities
- Quite common to have multiple malformations
What are the conditions CAKUT can lead to?
- Renal hypoplasia: small kidneys
- Dysplasia: no kidneys
- Hydroureter: large urine production - filling and dilating ureters
- Vesicouteric Reflux: urine flowing back in wrong direction from bladder to kidney
How do ACE inhibitors taken during pregnancy affect renal development?
ACE Inhibitors: used to treat hypertension, cross the placenta and inhibit fetal urine production, affect fetal renal development
How do COX-1 inhibitors affect renal development during pregnancy?
COX-1 Inhibitors: used to treat polyhydraminos, inhibit renal function and development
How do perturbations affect pregnancy?
Perturbations during pregnancy - earlier the event occurs the greater the damage. Timing of insult and gestation is important, as well as duration of insult
What populations have reduced nephron numbers?
Australian aboriginals and some African populations
