Regulation of Osmolarity Flashcards
What is water regulation controlled by?
ADH (vasopressin)
ADH is also called vasopressin, but what else is it called?
Arginine vasopressin
What does AVP stand for?
Arginine vasopressin
Wha class of hormone is ADH?
Polypeptide
Where is vasopressin synthesised?
Supraoptic (SO) and paraventricular (PVN) nuclei of the hypothalamus
What does SO stand for?
Supraoptic
What does PNV stand for?
Paraventricular nuclei
Is vasopressin an anterior or posterior pituitary hormone?
Posterior pituitary
What are the 2 different ways ADH secretion is controlled?
1) Primary control is plasma osmolarity
2) ECF volume also affects ADH secretion
Explain how osmolarity controls ADH secretion?
- When the effective OP of the plasma increases, the rate of discharge of ADH-secreting neurones in the SO and PVN is increased, increasing release of ADH from posterior pituitary
- Changes in neuronal discharge is mediated by osmoreceptors in the anterior hypothalamus close to the SO and PVN
- Other receptors in the lateral hypothalamus mediate thirst
How does an increase in osmolarity impact ADH secreting cells?
Increases ADH secretion
How does a decrease in osmolarity impact ADH secreting cells?
Decrease in ADH secretion
What ion channels control secretion of ADH?
Stretch-sensitive ion channels, changes of water volume due to osmolarity activate them
What is normal plasma osmolarity?
280-290MOsm/L
How is plasma osmolarity regulated tightly?
Small changes in plasma osmolarity causes radid changes in ADH
How does a 2.5% gain in plasma osmolarity impact ADH levels?
10x increase
Does an increase in osmolarity that does not cause an increase in tonicity impact secretion of ADH?
No
What is the difference between osmolarity and tonicity?
- Osmolarity is the concentration of a solution expresses at the total number of solute particles per litre
- Tonicity is a measure of the effective osmotic pressure gradient, the water potential of two solutions separated by a semipermeable cell membrane
What is osmolarity?
- Osmolarity is the concentration of a solution expresses at the total number of solute particles per litre
What is tonicity?
- Tonicity is a measure of the effective osmotic pressure gradient, the water potential of two solutions separated by a semipermeable cell membrane
What kinds of solutes do not produce any “osmotic” drag (impact tonicity)?
Solutes that can penetrate membranes, they move together with water
Is urea an effective osmole?
No, because it can penetrate membranes
Concentrating ability of the kidney is relatively limited, what does the amount of urine produced depend on?
[ADH] and the amount of solute excreted
How does ingesting hypertonic solutions, such as seawater, impact urine?
Increases the solute load to be excreted:
- Therefore increase urine flow, causing dehydration because more water is required to excrete the solute load than was ingested with it
How does ADH impact the permeability of the collecting ducts to water?
Increases permeability by incorporating water channels into the limnal membrane (aquaporins)
How does ADH increase the permeability of the collecting ducts to water?
By incorporating water channels into the luminal membrane
What impact does ADH being present have on water in the collecting duct?
- Water is able to leave the collecting duct
- Meaning that the cortical CD becomes equilibrated with the cortical interstitium, ie 300mOsm/L
- The CD then passes through the hypertonic medullary interstitial gradient, created by the countercurrent multiplier of the loop of Henle
How is the collecting duct impacted if maximum ADH is present?
- The contents equilibrates with that of the medullary interstitium via osmotic efflux of water and thus becomes highly concentrated at the tip of the medulla
- So produces small volume of highly concentrated urine, which contains relatively less of the filtered water than of solute therefore compensating for water deficit
- Effectively adds pure water to the ECF
- Which is reabsorbed by the oncotic P of vasa recta, which will be even greater than usual in the present of water deficit
How are the collecting ducts impacted by the absence of ADH?
- Collecting ducts are impermeable to water
- So medullary interstitial gradient is ineffective in inducing water movements out of the CD and therefore a large volume of dilute urine is excreted, compensating for water excess
- Since further ions are reabsorbed from the CD, urine osmolarity can fall to 30-50 mOsm/L
What does urea play an important role in?
Production of concentrated urine
Are collecting duct membranes permeable to urea?
Yes, particularly towards medullar tips
So as urea approaches tips there is a tendency for it to move out down its concentration gradient
How does ADH impact the collecting ducts permeability to urea?
Permeability of late medullary collecting duct to urea is enhanced
Explain how urea has an important role in the production of concentrated urine?
In presence of ADH, movement of water out of CD greatly concentrates urea remaining in the ducts:
- CD membranes are relatively permeable to urea, particular towards medullary tips
- So as urea approaches tip, there is increasing tendency for it to move out down its concentration gradient
- Permeability of late medullary CD to urea is enhanced by ADH
- So in an antidiuresis with high levels of ADH urea will be reabsorbed from CD into interstitium where it acts to reinforce the interstitial gradient in the region of the thin ascending loops of Henle
What is the medical term for raised level of urea in the blood?
Uraemia
When can uraemia occur?
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 (raised level in the blood of urea) occurs
Why is it important that urea is reabsorbed?
If it remained in tubule would exert an osmotic effect to hold water in the tibule and therefore reduce the potential for rehydration
How does ECF volume impact ADH secretion?
- Increase in ECF volume causes decrease in [ADH]
- Decrease in ECF volume causes increase in [ADH]
Is the relationship between the rate of ADH secretion and the rate of discharge of stretch receptors proportional or inverse?
Inverse
What are the two classes of stretch receptors that impact ADH secretion?
Low pressure receptors
High pressure receptors
Where are low pressure stretch receptors for ADH release found?
Left and right atrium
Great veins
What are low pressure stretch receptors also called?
- Sometimes called volume receptors because they monitor the return of blood to the heart and the “fullness” of circulation
Where are high pressure stetch receptors found?
Carotic and aortic arch baroreceptors
What receptors are primarily affected by moderate decreases in ECF volume?
Atrial receptors
How does a moderate decrease in ECF volume impact atrial receptors?
- Normally they exert tonic inhibitory discharge of ADH secreting neurons via the vagus nerve
- Decrease ECF volume -> decreased atrial receptor discharge -> increased ADH release
What happens if ECF goes from a moderate change to a small enough amount to impact mean blood pressure (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 increase in ADH release
- The inverse of these changes occur on volume expansion
ADH secreting cells are neurons and receive multiple inputs that they integrate to determine [ADH], other than ECF volume what other stimuli impacts ADH secretion?
- Increases ADH
- Pain, emotion, stress, exercise, nicotine, morphine
- Following traumatic surgery inappropriate ADH secretion occurs, so need to be careful about monitoring water intake
- Decreases ADH
- Alcohol, suppresses ADH release
Other than ECF volume, what other stimuli increase ADH?
- Pain, emotion, stress, exercise, nicotine, morphine
- Following traumatic surgery inappropriate ADH secretion occurs, so need to be careful about monitoring water intake
Other than ECF volume, what other stimuli decreases ADH secretion?
- Alcohol, suppresses ADH release
What is a decrease in blood pressure detected by?
Carotid and aortic baroreceptors
What is low blood volume detected by?
Atrial stretch receptor
What is a change in osmolarity detected by?
Hypothalamic osmoreceptors
What is diabetes insipidus?
ADH deficiency
What are some causes of diabetes insipidus?
Hypothalamic areas synthesising ADH may become diseases due to tumours or meningitis, or can be damaged during surgery causing central DI (diabetes insipidus)
What are the different kinds of diabetes insipidus?
Central diabetes insipidus
Peripheral diabetes insipidus
What does DI stand for?
Diabetes insipidus
What are patients with DI characterised by?
- Very large volumes of very dilute urine, generally >10L/day – polyuria
- Drink large volumes of water – polydipsia
What is the medical term for excess urination?
Polyuria
What is the medical term for excess thirst?
Polydipsia
What can central DI be treated by?
Giving ADH (AVP)
Why can peripheral DI not be treated by giving ADH, but central DI can be?
Peripheral DI, due to importance of thirst mechanism for survival cannot give ADH, it is usually secondary to hypercalcaemia or hyperkalaemia so resolved when ion disorders are corrected:
- May arise due to genetic defect in the V2 (ADH) receptor or in gene for aquaporins (H2O channel)
What is peripheral DI usually secondary to?
Hypercalaemia or hyperkalaemia
What genetic deficit may peripheral DI arise due to?
- May arise due to genetic defect in the V2 (ADH) receptor or in gene for aquaporins (H2O channel)
What is the osmolarity of the fluid in the Bowman’s capulse?
300mOsM
What is the osmolarity of the fluid at the end of the proximal tubule?
300mOsM
What is the volume of the fluid at the end of the loop of Henle?
100mOsM
What is the osmolarity of the fluid at the end of the collecting duct?
50-1200mOsM
