Session 6

Question 1

What causes osmolality changes in the ECF?

Answer 1

Problems with water balance - not sodium (which changes volume)

Question 2

Describe what happens when hypothalamic osmoreceptors detect a high osmolality

Answer 2

1% increase in osmolality -> ADH -> kidney -> changes renal water excretion

<10% change in osmolality or reduced volume -> thirst -> increased fluid intake

Question 3

Where is ADH made and stored?

Answer 3

Made in hypothalamus, stored in posterior pituitary gland

Question 4

How does decreased blood volume or pressure have an effect on ADH release?

Answer 4

The set point is shifted to a lower osmolality value (more ADH released). The kidneys preserve H2O even though this will reduce osmolality of body fluids - volume is more important that osmolality.
The set point increases if the blood volume/pressure increases

Question 5

What is the ultimate compensation for fluid/salt deficit?

Answer 5

Ingestion

Question 6

What are central and nephrogenic diabetes insipidus?

Answer 6

Central - low plasma ADH levels due to damage to hypothalamus/pituitary, brain injury, tumour or sarcoidosis
Nephrogenic - an acquired insensitivity of the kidney to ADH

Question 7

How can diabetes insipidus be managed?

Answer 7

ADH injections/nasal spray

Question 8

What syndrome is characterised by excessive ADH release from pp gland or other source and what does it result in?

Answer 8

Syndrome of inappropriate ADH secretion (SIADH) - results in dilutional hyponatraemia

Question 9

Describe the distribution of different aquaporin channels in the nephron

Answer 9

AQP1&7 are on both sides of the membrane in PCT

In the CD: AQP2 on apical (target for ADH) and AQP3/4 on basolateral

Question 10

Describe the affect of ADH on aquaporin channels

Answer 10

No ADH -> no AQP2 in apical membrane -> limited water reuptake in late DT and early CD -> loss of hyposmotic urine

If AQP2 is present, there needs to be a hyperosmotic interstitium for water to move out

Question 11

What allows the production of concentrated urine (as well as ADH and urea)?

Answer 11

Medullary counter current mechanism:
-juxtamedullary nephron creates the vertical osmotic gradient
-vasa recta helps preserve this gradient
Allows water to move out as it passes down the collecting duct

Question 12

Describe how osmolality changes around the loop of Henle

Answer 12

The descending limb of the long LoH is highly permeable to water (AQP1) but not permeable to Na+, so osmolality increases to a maximum 1200mOsm/L at the tip.
The ascending limb is impermeable to H2O but actively transports NaCl into the interstitium. Fluid leaving the DCT has an osmolality of 100 mOsm/L

Question 13

What are the essential mechanisms for the production of the medullary concentration gradient?

Answer 13

Active NaCl transport in thick ascending limb
Recycling of urea (effective osmole)
Arrangement of blood vessels in medulla

Question 14

How does urea help maintain the medullary concentration gradient?

Answer 14

Medullary aquaporin channels allow the passage of urea into the interstitium where it collects in the deeper portions. As its concentration rises it diffuses back into the ascending LoH. The recycling of urea is proportional the the amount of ADH. It is an effective osmole.

Question 15

How do the vasa recta maintain the medullary concentration gradient?

Answer 15

It acts as a counter current exchanger. Water goes straight from the descending limb of the LoH to the ascending limb of the vasa recta so it does not wash out the interstitial gradient.

Question 16

Describe how osmolality changes around the vasa recta

Answer 16

Descending limb - blood osmolality increases as Na+, Cl- and urea diffuse into it
Ascending limb - osmolality decreases as water diffuses in

Question 17

What is a diuretic?

Answer 17

A substance that promotes diuresis by increasing the renal excretion of water and sodium

Question 18

List the different classes of diuretics, where they act and give examples

Answer 18

Loop - inhibit Na/K/2Cl symport in LoH. Furosemide
Thiazide - inhibit Na/Cl symport in DCT. metolazone
Potassium sparing - inhibit ENaC in CCT. Amiloride
Aldosterone antagonists - also K+ sparing. Spironolactone
Osmotic - freely filtered but not reabsorbed. Mannitol

Question 19

Why do diuretics that block ENaC have a K+ sparing effect? (Hyperkalaemia).

Answer 19

Na reabsorption favours K secretion due to a negative lumen potential. Hyperkalaemia especially if used with ACEi, K supplements or in renal failure.

Question 20

When are loop diuretics used?

Answer 20

Very potent. Used in heart failure to reduce preload and afterload, nephrotic syndrome to treat oedema, renal failure, hypercalcaemia and liver cirrhosis (spironolactone preferred)

Question 21

What diuretics increase/decrease Ca2+ reabsorption?

Answer 21

Loop diuretics - impairs reabsorption

Thiazides - increase reabsorption

Question 22

When are thiazides used?

Answer 22

Less potent. Used widely in hypertension

Question 23

When are aldosterone agonists used?

Answer 23

Hypertension due to Conn’s syndrome

Ascites and oedema due to liver cirrhosis

Question 24

Describe how loop and thiazide diuretics can lead to hupokalaemia

Answer 24

Block Na&H2O reabsorption in LoH or early DT -> increased delivery of Na&H2O to late DT and CD ->

• > increased Na reabsorption in principle cells -> favourable electrical gradient for K secretion
• > faster flow rate, more secreted K washed away -> favourable gradient

Question 25

How is hypokalaemia resulting from thiazide and loop diuretics limited?

Answer 25

Used in combination with K+ sparing diuretics or K+ supplements