Control Of Plasma Osmolarity Flashcards
Where are the osmoreceptors located?
Hypothalamus - OVLT
How do osmoreceptors work?
Leaky endothelium exposed directly to systemic circulation (on plasma side of blood brain barrier)
Sense the changes in plasma osmolarity
Signals 2O responses responses which are mediated via two pathways leading to two pathways leading to two different complimentary outcomes
- concentration of urine
- thirst
Cells of the supraoptic nucleus lie close to OVLT with input from the baroreceptors
What happens in the brain if there is predominant water loss?
Osmoreceptors in hypothalamus increase release of ADH from posterior pituitary
An increase of 1% in osmolarity increases ADH.
Secretion of ADH to decrease water excretion
Decreased osmolarity inhibits ADH secretion.
When does the osmolarity at which ADH gets released change?
Low / high volume
A decrease in ECV means that the set point at which ADH is released is shifted to lower osmolarity values and the slope of the relationship is steeper.
In increased pressure the set point at which ADH is released is shifter higher and the slop decreases.
Volume is more important than osmolarity if volume crashes. This is why water is added despite the low osmolality values.
How does the efferent thirst pathway work?
Drinking is induced by increases in plasma osmolarity or by decreases in ECF volume.
Thirst increases intake of free water.
We stop when sufficient fluid has been consumed (but don’t know why)
Salt ingestion also makes us thirsty.
What is ADH and how does it work?
It is a small peptide (9AA) that is produced by neurosecretory cells in the hypothalamus but secreted from the posterior pituitary.
It acts on the kidney to regulate the volume and osmolarity of the urine.
ADH increases the permeability of the collecting duct to water and urea.
What is central diabetes insipidus?
This happens when plasma ADH levels are too low.
Occurs because of:
- Damage to hypothalamus or pituitary gland..
- A brain injury, particularly a fracture of the base of the skull
- A tumour
- Sarcoidosis or TB
- Aneurysm
- Encephalitis or meningitis
- Langerhan cell Histiocytosis
Keep releasing ADH so lots of urine. Managed by ADH injections or ADH nasal spray treatments.
What is nephrogenic diabetes insipidus?
This is an acquired insensitivity of the kidney to ADH
Keep releasing ADH so lots of urine. Managed by ADH injections or ADH nasal spray treatments.
What is SIADH?
Syndrome of inappropriate release of ADH.
Characterised by excessive release of ADH from the PP gland or another source. ]
Dilutional hyponatremia in which plasma sodium levels are lowered and total fluid is increased
Where is AQP 2 abundant?
Apical membrane and apical vesicles in the collecting duct.
When water low, pull AQP 2 away from apical membrane to stop water getting in.
Where are AQP 3 and AQP 4 abundant?
Collecting duct principle cells on the basolateral plasma membrane. They represent the potential exit pathway from the cell for water entering via AQP2.
What happens to AQPs if there is no ADH stimulation?
No AQP2s in the apical membrane
This means there is limited water reuptake in latter DCT and collecting duct.
Tubular fluid rich in water passes through the hyperosmotic renal pyramid with no change in water content.
Loss of large amount of hypo osmotic (dilute) urine -Diuresis.
What happens to AQPs if there is lots of ADH stimulation?
The body will need to produce hyperosmotic urine so the kidneys must reabsorb as much water as possible from the kidney tubule.
Release of ADH causes insertion of AOP2 channels into apical membrane.
So w ater moves out of collecting duct into hypoerosmotic environment as there are AQPs in both the apical an the basolateral epithelium of the tubule cells.
What broad things cause the concentration of urine?
The vertical osmotic gradient created in the loop of henle in the juxtamedullary nephrons.
Vasa recta which helps to maintain this gradient
Collecting duct changes AQP2s so changes concentration gradient to change urine.
Urea also helps in urine concentration mechanism
This makes a COUNTER-CURRENT MECHANISM.
What does the thick ascending limb of the loop of Henle do?
It has a diluting action on the filtrate.
-Removes solute without water and therefore increases osmolarity in the interstitium
-This occurs by blocking NaK2Cl transporters with a loop diuretic so the medullary insterstitium become isosmotic and copious dilute urine is produced.
Descending limb of LH
..Highly permeable to water due to AQP1 water channels which ate always open.
Descending limb is not permeable to Na+ therefore Na+ remains in the descending limb of the LoH and filtrate concentration increases.
Maximum osmolarity at the tip of LoH is 1200mOsm/Kg.
Ascending limbs of LH
Ascending limb actively transports NaCl out of tubular lumen into interstitial fluid.
It is impermeable to water.
As NaCl leaves and water remains, osmolality decreases in the ascending limb of loop of henle.
Fluid entering the DCT has ow osmolality of 100mOs/Kg
Summarise the mechanisms to get the concentration gradient
Active NaCl transport in thick ascending limb
Recycling of urea (effective osmole)
Unusual arrangement of blood vessels in the medulla descending component in close opposition to ascending component.
What is an effective osmole?
Urea - Not an effective osmole when urea transporters are present.
In kidney - they are effective osmole because they are transported like Na+
How is urea recycled?
Urea reabsorption from medullary CD
Cortical collecting duct cell are impermeable to urea
Movement into interstilitum and diffusion back in Loop
Under the influence of ADH, fractional excretion of urea decreases and urea recycling increases.
How do we preserve the concentration gradient?
Using vasa recta (counter current exchanger)
Why is the vasa recta the counter currently system?
Blood flow is always in the opposite direction to the flow of filtrate in the loop of henle, the tubule osmotic gradient is maintained as water leaving the AL will go into the vasa recta to help maintain this concentration gradient.
How does Vasa Recta work?
Water that leaves the DL of the loop of henle (due to concentration gradient created by Na+ leaving AL) diffuses into the AL of the vasa recta (blood vessles) because of the gradient that is there. This prevents where being too much water and therefore, it maintains the concentration gradient.
The Na+ and Cl- leaving the AL of the nephron will also diffuse into the DL of the vasa recta due to conc. gradient.
What is osmolality in a normal hydrated person?
500-700mOsm/Kg
