Session 6 Flashcards
What causes osmolality changes in the ECF?
Problems with water balance - not sodium (which changes volume)
Describe what happens when hypothalamic osmoreceptors detect a high osmolality
1% increase in osmolality -> ADH -> kidney -> changes renal water excretion
<10% change in osmolality or reduced volume -> thirst -> increased fluid intake
Where is ADH made and stored?
Made in hypothalamus, stored in posterior pituitary gland
How does decreased blood volume or pressure have an effect on ADH release?
The set point is shifted to a lower osmolality value (more ADH released). The kidneys preserve H2O even though this will reduce osmolality of body fluids - volume is more important that osmolality.
The set point increases if the blood volume/pressure increases
What is the ultimate compensation for fluid/salt deficit?
Ingestion
What are central and nephrogenic diabetes insipidus?
Central - low plasma ADH levels due to damage to hypothalamus/pituitary, brain injury, tumour or sarcoidosis
Nephrogenic - an acquired insensitivity of the kidney to ADH
How can diabetes insipidus be managed?
ADH injections/nasal spray
What syndrome is characterised by excessive ADH release from pp gland or other source and what does it result in?
Syndrome of inappropriate ADH secretion (SIADH) - results in dilutional hyponatraemia
Describe the distribution of different aquaporin channels in the nephron
AQP1&7 are on both sides of the membrane in PCT
In the CD: AQP2 on apical (target for ADH) and AQP3/4 on basolateral
Describe the affect of ADH on aquaporin channels
No ADH -> no AQP2 in apical membrane -> limited water reuptake in late DT and early CD -> loss of hyposmotic urine
If AQP2 is present, there needs to be a hyperosmotic interstitium for water to move out
What allows the production of concentrated urine (as well as ADH and urea)?
Medullary counter current mechanism:
-juxtamedullary nephron creates the vertical osmotic gradient
-vasa recta helps preserve this gradient
Allows water to move out as it passes down the collecting duct
Describe how osmolality changes around the loop of Henle
The descending limb of the long LoH is highly permeable to water (AQP1) but not permeable to Na+, so osmolality increases to a maximum 1200mOsm/L at the tip.
The ascending limb is impermeable to H2O but actively transports NaCl into the interstitium. Fluid leaving the DCT has an osmolality of 100 mOsm/L
What are the essential mechanisms for the production of the medullary concentration gradient?
Active NaCl transport in thick ascending limb
Recycling of urea (effective osmole)
Arrangement of blood vessels in medulla
How does urea help maintain the medullary concentration gradient?
Medullary aquaporin channels allow the passage of urea into the interstitium where it collects in the deeper portions. As its concentration rises it diffuses back into the ascending LoH. The recycling of urea is proportional the the amount of ADH. It is an effective osmole.
How do the vasa recta maintain the medullary concentration gradient?
It acts as a counter current exchanger. Water goes straight from the descending limb of the LoH to the ascending limb of the vasa recta so it does not wash out the interstitial gradient.
Describe how osmolality changes around the vasa recta
Descending limb - blood osmolality increases as Na+, Cl- and urea diffuse into it
Ascending limb - osmolality decreases as water diffuses in
What is a diuretic?
A substance that promotes diuresis by increasing the renal excretion of water and sodium
List the different classes of diuretics, where they act and give examples
Loop - inhibit Na/K/2Cl symport in LoH. Furosemide
Thiazide - inhibit Na/Cl symport in DCT. metolazone
Potassium sparing - inhibit ENaC in CCT. Amiloride
Aldosterone antagonists - also K+ sparing. Spironolactone
Osmotic - freely filtered but not reabsorbed. Mannitol
Why do diuretics that block ENaC have a K+ sparing effect? (Hyperkalaemia).
Na reabsorption favours K secretion due to a negative lumen potential. Hyperkalaemia especially if used with ACEi, K supplements or in renal failure.
When are loop diuretics used?
Very potent. Used in heart failure to reduce preload and afterload, nephrotic syndrome to treat oedema, renal failure, hypercalcaemia and liver cirrhosis (spironolactone preferred)
What diuretics increase/decrease Ca2+ reabsorption?
Loop diuretics - impairs reabsorption
Thiazides - increase reabsorption
When are thiazides used?
Less potent. Used widely in hypertension
When are aldosterone agonists used?
Hypertension due to Conn’s syndrome
Ascites and oedema due to liver cirrhosis
Describe how loop and thiazide diuretics can lead to hupokalaemia
Block Na&H2O reabsorption in LoH or early DT -> increased delivery of Na&H2O to late DT and CD ->
- > increased Na reabsorption in principle cells -> favourable electrical gradient for K secretion
- > faster flow rate, more secreted K washed away -> favourable gradient
How is hypokalaemia resulting from thiazide and loop diuretics limited?
Used in combination with K+ sparing diuretics or K+ supplements
