Osmolarity Regulation

Question 0

How are changes in plasma osmolarity regulated?

Answer 0

Osmoreceptors in the organum vasculosum of the laminae terminalis (OVLT) of the hypothalamus (exposed directly to the systemic circulation)

Increase osmolarity —> cell shrinks —> increased firing —> increased ADH production & release and feeling of thirst —> increased water reabsorption and increased intake of water

Question 1

Why do problems in osmolarity occur?

Answer 1

Water balance (not due sodium balance)

Question 2

Outline the production, storage, and actions of ADH.

Answer 2

Synthesised by the hypothalamus and stored in the posterior pituitary gland.

Release stimulated by an increase in osmolarity (only a 1% change required)

• Increases the permeability of the latter DCT and collecting duct to water and urea by stimulating the insertion of aquaporin II channels into the apical membrane (removal of ADH stimulates endocytosis of channels)
  note: aquaporin III & IV are always present on the basolateral membrane (always permeable to water)
• vasoconstriction at glomerulus (reduction in effective filtering area)
• increased sodium, potassium, and chloride reabsorption in the ascending limb of the loop of Henle
• increased potassium secretion (cortical collecting duct) and urea reabsorption (medullary collecting duct)

note: most important function is the recycling of urea (helps maintain the medullary concentration gradient)

Question 3

What are some conditions which involve abnormal ADH release?

Answer 3

Diabetes insipidus:
Great reduction in release of ADH from posterior pituitary gland/acquired insensitivity to ADH, causing diuresis

Give ADH injections/ADH nasal spray

Syndrome of Inappropriate ADH Secretion (SIADH):
Great increase in ADH release from the posterior pituitary gland (or from another source), causing dilutional hyponatraemia
(reduction in [Na+]plasma causes reduction in total body fluid)

Question 4

How is the sensation of thirst involved in regulating plasma osmolarity?

Answer 4

A large increase in fluid osmolarity (10%+)/large reduction in ECF volume stimulates the sensation of thirst

Sensation of thirst stops when sufficient fluid has been consumed (but before GI tract obstruction has occurred - ?mechanism)

note: salt appetite based on hedonism & regulation (deficiency drives need)

Question 5

Outline the changes in osmolarity along the nephron.

Answer 5

PCT: stable osmolarity (~35% water)

Desc. limb of loop of Henle: increase in osmolarity (~25% water) due to water reabsorption

Asc. limb of loop of Henle: decrease in osmolarity (~30% water) due to sodium reabsorption (although [water] is the same, less solute is present)

DCT: decrease in osmolarity due to further sodium reabsorption

Cortical collecting duct: decrease in osmolarity (unless ADH acts to insert aquaporin II channels -> increased water reabsorption increases the osmolarity of the lumen contents)

Medullary collecting duct: further decrease in osmolarity (less water reabsorption than cortical collecting duct)

Question 6

What factor is considered the most important by the body: volume or osmolarity?

Answer 6

Volume - great decreases in volume are more immediately life-threatening than great decreases in osmolarity

During circulatory collapse, kidneys continue to conserve water despite causing a great reduction in blood osmolarity

Question 7

How can the set point for ADH release be altered?

Answer 7

Reduction in ECF volume: set point for ADH release shifted lower, so lower osmolarity value required to stimulate ADH release (slope for ADH release is steeper)

Increase in pressure: set point for ADH release shifted higher, so higher osmolarity value required to stimulate ADH release (slope for ADH release shallower)

Question 8

How is the conc. gradient at the loop of Henle created? What does this achieve?

Answer 8

• active Na+ & Cl- reabsorption by thick ascending limb (& impermeability to water) —> increased osmolarity of renal medulla
• water flows out of descending limb into renal medulla —> increase in concentration & osmolarity of lumen contents
• fluid entering the ascending limb via the hairpin bend passively loses Na+ & Cl- (counter-current multiplication)
• recycling of urea (50% of medulla gradient)
• movement of water from descending limb of loop of Henle into ascending limb of vasa recta (blood has higher [solute] than surrounding interstitium) & diffusion of Na+, Cl-, and urea from the ascending limb of the loop of Henle into the isosmotic blood of the descending limb of the vasa recta (counter-current exchange)

Interstitial fluid in renal medulla has a gradient of increasing osmolarity with depth (hyper-osmotic) & luminal contents entering DCT has become hypo-osmotic.