L10.1 Regulation of Kidney Development Flashcards Preview

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Flashcards in L10.1 Regulation of Kidney Development Deck (18):
1

3 pairs of organs during kidney development

From intermediate mesoderm

  1. Pronephroi (regress)
  2. Mesonephroi (may regress)
  3. Metanephroi
  • Pronephros DOESN'T become mesonephros which DOESN'T become the metanephros
    • But 1 has to occur before the other one

2

Pronephros

  • Transient organ in mammals
  • Important in amphibians and fish BUT NOT humans
  • 1 glomus draining into pronephric tubules → into pronephric duct

3

Mesonephros

  • Pronephric duct → wolffian duct → induce mesonephros → renal vesicles → proximal tubule
    • Have multiple glomeruli and mesonephric tubules → draining into mesonephric duct
  • Around 40 nephros in humans 
  • Most prominent organ region in early gestation
  • Mesonephric tubules form the efferent tubules of testis (male)

4

Metanephros

  • Begins at ~day 30 in human and finishes just before birth
  • Co-exists with mesonephros
  • ~1m nephrons in humans
    • Very Variable (even populations/ethnicity plays a role)
  • Can survive fetal without, but not post-natal

5

How is the metanephros developed

  • specification of metanephric blastema
  • From this point forms the glomerulus and tubules

6

Urerteric branching (UB) and morphogenesis

  • Outgrowth at the caudal end of Wolffian Duct
  • Invade metanephric mesechyme (MM) → induce UB
    • Reciprocal induction b/w UB and MM
  • Also forms collecting ducts/calyces/renal pelvis
    • Part of UB that does not enter MM forms ureter

7

Nephrogenesis

  • UB induce MM to condense → forms a cap mesenchyme → pretubular aggregate → undergo MET → renal vesicle

8

What does the renal vesicle develop into?

  • Comma shaped → then S shaped
    • Upper → distal convoluted tubule
    • Central → PCT, LoH, distal straight tubule
    • Lower → Renal corpuscle

9

Arcade formation

  • Tip branching only until week 15
  • After wk 15 → nephrons form on one arcade
    • 7-10 nephrons form on one arcade
      • Tip forms 1 nephron → connects to collecting duct
      • 2nd nephron induced by same tip → shift 1st and connects
    • After 20 wks → further nephrons form along length of collecting duct
  • Allows more nephrons to be formed

10

Renal Nerve development

  • Adrenergic N from 20wks in humans
    • Formed in cortex and medulla
      • Reaches adult lvls in cortex by 28wks
      • Decreases in later gestation (more important in gestation)
    • Regulate renin secretion in fetus → regulate vasodilation

11

Vascular development

  • Capillaries detected around UB after it enters MM
    • 8-10wks → vessels around S shaped bodies
    • Vasculogenesis or angiogenesis? (debate)

12

Development of kidney function in utero

  • Urine excreted into amniotic fluid but can't concentrate urine like adult
    • Produces hormones (renin/erythropoietin)
    • Contributes to amniotic fluid → important for gestation (e.g. dev of lungs)

13

Abnormalities of renal development

  • Bilateral renal agensis (Potters syndrome)
    • Don't dev kidneys → don't survive postnatally
  • Congenital abnormalities of kidney and urinary tract (CAKUT)
  • Hydronephrosis
    • Restriction of ureter
  • Polycystic kidney disease
  • Maternal drug use → leading to other deficits

14

Potter's syndrome

  • No urine produced in utero → lacks amniotic fluid → causes gross abnormalities
  • Death post natally due to lung insufficiency
  • Treatment → complete dialasis through peritoneum
  • If is a Unilateral agensis→ able to live without much complications → but more easily develop renal disease

15

CAKUT

  • 1/3 of abnormalities (genetic abnormalities underlie many cases)

16

From Maternal drug use

  • ACEi
    • Crosses placenta → inhibits fetal urine production → affects fetal renal development
  • COX1 I
    • Treats polyhydramnios
    • Inhibits fetal renal function and development
  • Social/recreational drug (alcohol/cocaine/smoking)
    • Affect nephron numbers or earlier processes

17

Significance of timing of defect

  • Earlier the deficit occurs → the more devastating the outcome

18

Programming outcomes from renal deficits

  • ↓neprhon # → impaired renal function and dysregulation of BP
  • Impaired renal development → may have additional programming outcomes other than nephron deficit