Changes In Plasma Osmolarity

Question 0

How much do we urinate a day?

Answer 0

1-1.5L/day

Question 1

If water intake is less than water excretion, what happens to the osmolarity?

Answer 1

Osmolarity increases

Question 2

What is urinary osmolarity?

Answer 2

500-700mOsm/L

Question 3

What senses changes in plasma osmolarity?

Answer 3

Hypothalamic osmoreceptors in the OVLT

Question 4

What are the two efferent pathways for regulation of osmolarity? What is the effector and what is changed?

Answer 4

ADH - effector is kidney, affects renal water excretion

Thirst - effector is brain and drinking behaviour, water intake is affected

Question 5

How are changes in osmolarity detected?

Answer 5

Fenestrated leaky endothelium exposed directly to systemic circulation
Senses changes in plasma osmolarity - osmoreceptors expand when more dilute and shrink with higher osmolarity
Responses mediated by the two efferent pathways

Question 6

Where is ADH released from?

Answer 6

Posterior pituitary

Question 7

How is the ADH pathway initiated?

Answer 7

When osmolarity increases, osmoreceptors shrink
Stimulate secretion of ADH
More water is retained
Decreased osmolarity inhibits ADH secretion

Question 8

What is ADH?

Answer 8

A small peptide - about 8 amino acids long

Hormone

Question 9

What does ADH do?

Answer 9

Addition of aquaporin 2 in the apical membrane of the collecting duct.
Increased reabsorption of water

Increases permeability of collecting duct to urea causing its reabsorption, which water also follows

Question 10

How is aquaporin 2 removed from the membrane?

Answer 10

Endocytosis

Question 11

What aquaporin does the basolateral membrane always contain and why?

Answer 11

Aquaporins 3 and 4
So that it is constantly permeable to water
Any water that enters across the apical membrane can pass into the peritubular blood

Question 12

Why does increased urea reabsorption in the collecting duct increase water reabsorption?

Answer 12

Water follows it out
Urea also moves down its conc gradient into the ascending limb which is permeable to urea but not water
Can then pass back into the CD where it is reabsorbed in the medullary portion and recycled again

Question 13

Where is ADH secreted from?

Answer 13

Posterior pituitary

Question 14

What is secretion of inappropriate ADH (SIADH)?

Answer 14

Excessive release of ADH from posterior pituitary gland or other source

Question 15

What happens in SIADH?

Answer 15

Dilution all hyponatraemia in which plasma sodium levels are lowered and total body fluid increases

Question 16

Symptoms of SIADH?

Answer 16

Nausea
Vomiting
Headache
Confusion
Lethargy
Fatigue
Appetite loss
Restlessness
Irritability
Muscle weakness
Spasms
Cramps
Seizures
Decreased consciousness
Coma

Question 17

How is SIADH treated?

Answer 17

ADH antagonists

Question 18

What is diabetes insipidus?

Answer 18

When the posterior pituitary gland doesn’t produce enough ADH or acquired insensitivity of kidney to ADH
Water is inadequately reabsorbed from CD and lots of urine is produced

Question 19

How is diabetes insipidus treated?

Answer 19

ADH injections

ADH nasal spray

Question 20

What happens to the osmolarity of the kidney as you descend deeper into it?

Answer 20

It increases

Question 21

How is the medullary gradient generated?

Answer 21

Active NaCl transport in thick ascending limb and recycling of urea sets up the osmotic gradient

Question 22

How does the thick ascending limb have a diluting effect on the ultrafiltrate?

Answer 22

Removes solute/ions without water following

Question 23

What happens to the medullary gradient when loop diuretics are used?

Answer 23

Blocks NaKCC transporters
Medullary interstitium becomes isotonic
Large amounts of dilute urine are produced

Question 24

What maintains the osmotic gradient of the medulla?

Answer 24

Flow in the vasa recta in the opposite direction to the tubule
(Vasa recta acts as a countercurrent exchanger, conc gradient produced by LoH acts as a counter current multiplier)

Question 25

What happens to the blood as it passes through the vasa recta?

Answer 25

Begins as isosmotic
Enters hyper osmotic tissue of medulla
Na and Cl diffuse into the vasa recta
Osmolarity of blood increases
At tip of loop it is isosmotic with medullary interstitium
Blood ascending towards cortex is now hyper osmotic compared to interstitium
Water moves in from descending limb of loop of Henle

Question 26

So what is the overall effect of the vasa recta?

Answer 26

Prevent the medullary hyper osmolarity from being dissipated

Question 27

What happens to ADH and urine osmolarity of plasma osmolarity decreases?

Answer 27

No ADH stimulation
No aquaporin in later DCT and CD
Less water reabsorption
Tubular fluid with lots of H2O passes through
Urine is hypo-osmotic

Question 28

What happens to ADH and urine osmolarity of plasma osmolarity increases?

Answer 28

ADH is released so aquaporin channels are inserted onto the apical membrane
Cell becomes more permeable to water
More hyperosmotic urine

Question 29

How does ADH cause insertion of aquaporin 2 on the apical membrane?

Answer 29

Binds to GPCR on the basolateral membrane
ATP -> cAMP
PKA produced
Aquaporin 2 produced

Question 30

So what are the overall effects of ADH?

Answer 30

Vasoconstriction
Increases Na, K, Cl reabsorption in ascending limb
Increases water reabsorption in late DT and CD
Increases K+ secretion in cortical CD
Increases urea reabsorption in CD