Where is ADH produced?
supraoptic (SO) and paraventricular (PVN) nuclei of the hypothalamus in the brain.
Posterior pituitary hormone.
What is the half life of ADH?
Half-life » 10 minutes, so can rapidly be adjusted depending on the body’s needs for H2O conservation.
What is the primary control of plasma osmolarity?
Plasma osmolarity - increase means increase in ADH prouction by the supraoptic and paraventricular nuclei
What causes the change in neuronal discharge in the SO and PVN?
Osmoreceptors in the anterior hypothalamus close to the SO and the PVN
Where are the receptors that mediate thirst?
What happens to osmoreceptors when the osmolarity is high?
H2O moves out of the cell
Cell shrinks / stretch sensitive ion channel is activated
Increase in neural discharge
Increase in ADH secretion
What happens to osmoreceptors when osmolarity is decreased?
H2O enters cells
↓ ADH secretion
What is normal plasma osmolarity?
Describe the 'gain' in the ADH system
Small changes in either direction results in rapid changes in ADH. System has a very high “gain” a 2.5% increase in osmolality can produce a 10x increase in ADH.
What must the increase in osmolarity include in order to create an increase in ADH concentration?
Must also have an increase in tonicity
(Tonicity is the term used to encompass solutes that are non-penetrating and therefore produce an osmotic drag)
Does urea affect tonicity?
No! It is permeable
Why do shipwrecked sailors die of they drink sea water?
Seawater increases the solute load to be excreted
More water is required to excrete the solute than was ingested with it
The maximum concentration of urine is 1200-1400 mOsmoles/l
What happens after vasopressin binds to the membrane receptor on the kidney tubule?
Receptor activates cAMP second messenger system
Cell inserts AQP2 water pores into apical membrane (increases the permeability of the collecting ducts to H2O)
Water is absorbed by osmosis into the blood
If ADH is present and water is able to leave the collecting duct - what does the cortical collecting duct become equilibrated with?
The cortical interstitium (300 mOsmoles/l)
CD then passes through the hypertonic medullary interstitial gradient created by the countercurent multiplier of the loop of henle
What does the contents of the collecting duct equilibrate with if maximum ADH is present?
Equilibrates with that of the medullary interstitium - via osmotic efflux of H2O and thus becomes highly concentrated at the tip of the medulla
Describe the volume and concentration of urine when there is maximal ADH
Small volume of highly concentrated urine
This in essence adds pure H2O to the ECF
How is water reabsorbed in the presence of high ADH?
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 collecting duct in the absence of water?
Collecting ducts are impermeable to water (medullary interstitial gradient is ineffective in inducing H2O movements out of the collecting duct)
Large volume of dilute urine is excreted - compensating for H2O excess
What is the role of urea in anti-diuresis (high levels of ADH)
The permeability of the late medullary collecting duct to urea is enhanced by ADH
Urea is reabsorbed from the collecting duct into the interstitium, where it acts to reinforce the interstitial gradient in the region of the thin ascending loops of henle
Besides reinforcing the interstitial gradient - what is the other effect of the urea being reabsorbed?
If it remained in the tubule it would exert an osmotic effect to hold H2O in the tubule - therefore reduce potential rehydration
What is the effect of ECF volume on ADH?
Increased ECF volume = decreased ADH
Decreased ECF volume = increase in ADH
Where are the low pressure receptors and the high pressure receptors?
Low pressure: Located in the left and right atria and great veins
High pressure: Carotid and aortic arch baroreceptors
What is the action of the low volume receptors in the atria / great veins when there is low ECF volume?
Primarily affects the atrial receptors
Normally (when ECF volume is within normal limits) there is an inhibatory effect on ADH production via the vagus nerve
(The atrial receptors constantly send signals saying 'we don't need any ADH')
So when there is a decrease in the ECF volume there is a decrease in atrial receptor discharge
(The lecture also says that if the change in volume is enough to affect mean blood pressure then the carotid and aortic receptors will also contribute to changes in ADH secretion)
What happens to ADH secretion when you stand up?
There is an increase in ADH secretion
What are ADH secreting cells?
Neurones - they receive multiple inputs which they integrate to determine ADH
What other stimuli increase ADH production?
Pain, emotion, stress, exercise, nicotine, morphine. Following traumatic surgery, inappropriate ADH secretion occurs, need to be careful about monitoring H2O intake
What other stimuli redeuce ADH secretion?
What is diabetes insipidus?
When hypothalamic areas become damaged and cannot produce sufficient ADH - central
The collecting duct may become impermeable to ADH - peripheral ADH
How is 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
How is peripheral DI treated?
Usually 2° to hypercalcaemia or hypokalaemia so resolves when ion disorders corrected.
(May arise as a genetic defect in the V2 (ADH) receptor or in gene for aquaporins (H2O channels).
Which part of the nephron can you find osmolarity of 300 mosmoles/l?
End of proximal tubule
Where in the nephron can you find fluid with the osmolarity of 100 mosmoles/l?
End of loop of henle (100 mOsmoles/L)
End of collecting duct (50 - 1200 mOsmoles/L)