Lecture 3: Developmental Origins of Renal Disease Flashcards
What environmental things may reduce nephron number?
Poor diet, disease
Why do diseases present an increased risk for CVD?
Mutated sodium channels or changes in number of sodium channels
When is nephrogenesis complete in humans?
37 weeks
When is nephrogenesis complete in rats?
After birth
What is reduced nephron endowment associated with?
Increased BP
How does reduced nephron number lead to increased BP?
Placental insufficiency decreases nephron number - increased blood flow to each nephron - increased GFR relative to nephron ratio. Increased glomerular volume damages glomerulus - don’t act as a proper filter, increasing amount of sodium coming through and into blood - increased BP
What organ do glucocorticoids develop?
Lungs
If leptin is reduced what happens to mammary glands?
Altered development - low quality milk
What happens to small males that stay with the nutrient deficient mother?
At 6 months - low nephron number, glomerular hypertrophy, increased BP
What is unique about spragdorli rats?
Increased propensity to obesity
What secretes leptin?
Adipocytes
What is leptin critical for?
Nephrogenesis and organogenesis
What is the primary role of leptin?
Appetite suppression and increased energy expenditure
How does leptin act?
Acts via leptin signalling pathway – leptin binds to receptor to activate intracellular signalling cascade - binds to receptor and activates proteins via phosphorylation
What is wrong with leptin in obesity?
In obesity leptin is not signalling as well in the hypothalamus and is not signalling fullness – overeating
