Regulation of Osmolarity Flashcards
what is water regulation controlled by?
controlled by ADH (Vasopressin) = arginine vasopressin (AVP)
what is vasopressin?
Polypeptide (9aas), synthesized in the supraoptic (SO) and paraventricular (PVN) nuclei of the hypothalamus in the brain.
Posterior pituitary hormone.
what is the half life of vasopressin?
10 minutes, so can rapidly be adjusted depending on the body’s needs for H2O conservation.
what is the primary control of adh secretion?
Primary control is plasma osmolarity
how is adh secretion controlled by plasma osmolarity?
When the effective OP of the plasma ↑, the rate of discharge of ADH-secreting neurones in the SO and PVN is ↑ → ↑ release of ADH from the posterior pituitary.
what are changes in neuronal discharge mediated by?
mediated by osmoreceptors in the anterior hypothalamus, close to the SO and PVN.
what mediates thirst?
Other receptors in the lateral hypothalamus mediate thirst.
what happens to osmoreceptors when osmolarity is increased?
↑ H2O out of cell
Cell shrinks/stretch sensitive ion channel activated
↑neural discharge
↑ADH secretion
what happens to osmoreceptors when osmolarity is decreased?
H2O enters cells
Cells swell
↓neural discharge
↓ ADH secretion
what effect does changes in osmoreceptors have on osmoreceptor discharge?
Changes in the volume of the osmoreceptors → changes in osmoreceptor discharge.
what is normal plasma osmolality?
80-290mOsm/kg H2O.
It is regulated very precisely.
what do small changes in normal plasma osmolality have on adh?
Small changes in either direction results in rapid changes in ADH. System has a very high “gain” a 2.5% ↑ in osmolality can produce a 10x ↑ in ADH.
what is an ineffective osmotic pressure?
An increase in osmolarity that does not cause an increase in tonicity is ineffective in causing an ↑ in [ADH].
describe osmolality versus tonicity?
what is the concentrating ability of the human kidney limited by?
The concentrating ability of the human kidney is relatively limited and the amount of urine produced depends not only on the [ADH] but also on the amount of solute to be excreted.
what effect does drinking seawater or hypertonic solutions have on an individual?
Ingestion of hypertonic solutions, such as seawater, increase the solute load to be excreted and ∴↑urine flow → dehydration, because more H2O is required to excrete the solute load than was ingested with it.
Shipwrecked sailors die if they drink seawater.
what is the site of water regulation?
The site of water regulation is the Collecting duct, whose permeability is under the control of ADH = Anti-Diuretic Hormone (Vasopressin).
Whether or not the dilute urine delivered to the distal tubule is concentrated and to what extent depends on…
the presence or absence of the posterior pituitary hormone, ADH.
describe the mechanism of action of ADH on a collecting duct cell?
This ↑ the permeability of the collecting ducts to H2O, by incorporating H2O channels into the luminal membrane, (aquaporins).
if ADH is present what happens to H20?
If ADH is present then H2O is able to leave the collecting duct.
when H20 leaves the CD what happens?
The cortical CD becomes equilibrated with that of the cortical interstitium ie 300 mOsm/l.
The CD then passes through the hypertonic medullary interstitial gradient, created by the countercurrent multiplier of the loop of Henle
what happens if maximum ADH is present?
the contents equilibrates with that of the medullary interstitium via osmotic efflux of H2O and thus becomes highly concentrated at the tip of the medulla.
how much urine is produced with maximum ADH?
With maximal [ADH] produce a small volume of highly concentrated urine, which contains relatively less of the filtered H2O than of solute, ∴ compensating for water deficit.
Effectively adds pure H2O to the ECF.
H2O is reabsorbed by the oncotic P of vasa recta, which will be even greater then usual in the presence of the H2O deficit.
what happens in the absence of ADH?
collecting ducts are impermeable to H2O, so that the medullary interstitial gradient is ineffective in inducing H2O movements out of the CD and ∴ a large volume of dilute urine is excreted, compensating for H2O excess.
what is the effect on urine osmolality in the absence of adh?
Since further ions are reabsorbed from the CD, urine osmolarity can fall to 30-50 mOsm/l.
In a water deficit ______ water, in water excess _____ water?
conserve
lose
what is the role of urea?
Urea plays an important part in the production of concentrated urine.
what effect does the presence of adh have on urea permeability?
In the presence of ADH, movement of H2O out of the CDs greatly concentrates the urea remaining in the ducts.
CD membranes are relatively permeable to urea, particularly towards medullary tips.
in an antidiuresis with high levels of ADH what happens to urea?
urea will be reabsorbed from the CD into the interstitium, where it acts to reinforce the interstitial gradient in the region of the thin ascending loops of Henle.
In an anti-diuresis with high levels of ADH, urea is retained in order to save water and reinforce medullary gradient in region of thin ascending limb of LoH. Uraemia occurs.
why is it important that urea be reabsorbed?
because if it remained in the tubule, it would exert an osmotic effect to hold H2O in the tubule and ∴ reduce the potential for rehydration.
what also has an effect on adh secretion?
ECF volume
what effect does decreased and increased ADH have on ECF volume?
↑ ECF volume → ↓ [ADH]
↓ ECF volume → ↑ [ADH]
There is an inverse relationship between the rate of ADH secretion and the rate of discharge of stretch receptor afferents in the low and high P areas of the circulation.
where are low P receptors located?
L and R atria and great veins.
what are P receptors?
They are sometimes called “volume receptors” because they monitor the return of blood to the heart and the “fullness” of the circulation.
where are high P receptors located?
are the carotid and aortic arch baroreceptors.
what does a moderate decrease in ecf volume affect receptor wise?
atrial receptors
Normally they exert tonic inhibitory discharge of ADH secreting neurones via the vagus nerve.
↓ ECF volume → ↓ atrial receptor discharge and ∴ ↑ ADH release
when are carotid and aortic receptors affected?
However if volume changes enough to affect MBP, then carotid (and aortic) receptors will also contribute to changes in ADH secretion.
Very important in haemorrhage. Even when going from lying down to standing up, there is an↑ ADH release.
The inverse of these changes occur on volume expansion.
what are adh secreting cells?
neurones and receive multiple inputs which they integrate to determine [ADH]
what other stimulis affect adh?
↑ADH: Pain, emotion, stress, exercise, nicotine, morphine. Following traumatic surgery, inappropriate ADH secretion occurs, need to be careful about monitoring H2O intake.
↓ ADH: Alcohol, suppresses ADH release.
what would occur in the circumstances of:
osmolality greater than 250
decreased atrial stretch due to low blood volume
decreased blood pressure
what is diabetes isipidus?
ADH deficiency
what is central DI?
The hypothalamic areas synthesizing ADH may become diseased due to tumours, or in meningitis. They may be “damaged” during surgery → Central DI.
what is peripheral DI?
The Collecting duct may be insensitive to ADH → Peripheral DI.
how are patients with diabetes insipidus characterised?
Patients are characterised by the passage of very large volumes of very dilute urine, generally > 10 l/day = polyuria. They drink large volumes of H2O = polydipsia.
how is central DI treated?
by giving ADH (AVP)
how is peripheral DI treated?
For Peripheral DI, importance of the thirst mechanism for survival, can’t give ADH. Usually 2° to hypercalcaemia or hypokalaemia so resolves when ion disorders corrected.
describe the changes in filtrate volume and osmolarity along the nephron
- bowmas capsule
- end of proximal tubule
- end of loop of henle
- end of collecting duct
