Session 5 - Changes in Plasma Osmolarity

Question 1

How does the balance of water intake and water excretion change plasma osmolarity?

Answer 1

If water intake < water excretion = plasma osmolarity increases If water intake > water excretion = plasma osmolarity decreases

Question 2

How is plasma osmolarity regulated? What senses it?

Answer 2

• Hypothalamic osmoreceptors in the OVLT (organum vasculoum of the laminae terminalis) sense changes in plasma osmolality
• A fenestrated leaky endothelium is exposed directly to systemic circulation, which senses changes in plasma osmolarity
• These osmoreceptors shrink and reduce nerve firing when plasma osmolarity is high, releasing ADH to conserve water
• Osmoreceptors can signal secondary responses which alter urine concentration and thirst levels.

Question 3

How does ADH affect osmolarity? Where is it released from?

Answer 3

• Increase in osmolarity, i.e. loss of water, stimulates ADH release from posterior pituitary
• Low ADH = lots of urine produced
• ADH increases permeability of the collecting duct to water also increases permeability to urea

Question 4

If plasma osmolarity is low, how does the kidney ensure it is brought back up?

Answer 4

If plasma osmolarity decreases (high circulating volume):

• Results in hypo-osmotic urine
• No ADH stimulation = absence of aquaporin in latter DCT and CD = fluid stays in the tubule and is not reabsorbed.
• Loss of large amount of dilute urine.

Question 5

Give the pathway through which aquaporin 2 is inserted into the apical membrane of the latter DCT and CD

Answer 5

• ADH attaches to GPCR on basolateral membrane of duct cell
• Activates G protein which activates AC
• AC converts ATP to cAMP which activates PKA
• PKA activates insertion of AQP2 into the apical membrane.

Question 6

What is the pathology behind Diabetes insipidus? How is it managed?

Answer 6

o Pituitary gland doesn’t secrete enough ADH

o Water inadequately reabsorbed so large quantity of urine produced

o Managed with ADH injections or nasal sprays

Question 7

What is the pathology behind inappropriate ADH secretion?

Answer 7

o Excessive release of ADH from posterior pituitary gland or another source

o Results in hyponatremia, which is lowered plasma sodium levels and total body fluid is increased.

Question 8

What are the features of the Juxtamedullary nephrons?

Answer 8

JM nephrons contain the Vasa Recta, which is a counter current series of blood vessels which serves to generate an osmotic gradient

Question 9

How is the medullary gradient generated?

Answer 9

• Thick ascending limb of the loop of Henle is crucial. It removes the solute without water and therefore increases the osmolarity of the interstitial fluid (blocking NaKCC transporters therefore results in copious dilute urine production)
• Urea is reabsorbed from the CD and moves through the interstitium and diffuses back into the loop. Urea when in the interstitium acts as an osmole and attracts more water from tubules. Urea recycling increases under ADH.
• In the ascending limb:

o Impermeable to H2O but permeable to NaCl and urea

o Urea high in interstitial fluid and low in tubular fluid, therefore moves into tubular fluid.

Ions are actively transported into the interstitial fluid, generating a concentration gradient. Vasa recta capillary passively absorbs the ions in the interstitial fluid as it descends, concentrating the blood and making it hypertonic. This hypertonicity is then used to passively absorb water from the interstitial fluid and prevent the concentration gradient in the interstitial fluid from becoming isotonic with the tubular fluid.

The reason that not all the ions in the interstitial fluid are passively absorbed is due to the urea gradient and the oncotic pressure of the capillary contributing to the reabsorption.