S5 Control of Plasma osmolarity

Question 1

how does osmolarity vary ?

Answer 1

most body fluids are isotonic cells with osmolality 300 mOsm/kg except urine. urine osmolallity changes from 50-1200 mOsm/kg so must match ingestion to excretion (people ingest 600-1000 mOsm/kg and urinate 1-1/5L per day)
if water intake < excretion, plasma osmolality increases
if water intake > excretion, plasma osmolality decreases

Question 2

how are osmolality changes in ECF measured

Answer 2

by change in [Na+]

Question 3

how is plasma osmolarity changed

Answer 3

by ADH and thirst. ADH decreases renal water excretion. It is the faster, short term unconscious response.
thirst is caused by plasma osmolarity being too high, so the kidneys aren’t able to restore it themselves

Question 4

what are osmoreceptors ?

Answer 4

receptors in the hypothalamus which sense changes in osmolality. Has a fenestrated leaky endothelium which is exposed to systemic circulation on the plasma side of the BBB. has signals for pathways leading to concentrated urine and thirst
also contains cells of the supraoptic nucleus which receive input from baroreceptors so changes in BP can also induce ADH release

Question 5

what is the role of ADH ?

Answer 5

released from posterior pituitary and is sensitive to osmolality changes, has -ve feedback loops. Acts on the kidney to reduce water excretion by increasing pearmeability of collecting ducts to water and urea by inserting AQP2 channel. Low ADH causes diuresis, High ADH causes anti-diuresis

Question 6

what happens to the ADH set point for release when ECV decreases

Answer 6

the set point for ADH release is shifted to a lower osmolality changes so more ADH is released and the kidneys conserve more H20, even thought this will reduce osmolarity. when ECV increases, the set point for ADH release is shifted higher

Question 7

describe how osmoreceptors stimulate thirst ?

Answer 7

activated when you’re 10 % dehydrated. a large deficit in water/sodium is only partially compensated for by kidney, so thirst is stimulated. Drinking is induced by increases in plasma osmolarity or by decreases in ECF volume

Question 8

what are the diseases caused by ADH secretion tissues ?

Answer 8

central diabetes insipidus : plasma ADH levels are low due to damaged Hypo or pituitary gland , brain injury to skull base, tumour, aneurysm
Nephrogenic diabetes insipidus : acquired insensitivity of the kidney to ADH
effects of CDI and NDI: water inadequately reabsorbed from collecting duct causing diuresis. often managed by ADH injections
SIADH - syndrome of inappropriate ADH secretion from the posterior pituitary, leads to dilutional hyponatraemia where plasma Na+ levels are lowered and the total body fluid is increased

Question 9

what aquaporin channels are found on the kidney tubules

Answer 9

AQP1 : PT and thin DL
AQP7 : PT
AQP 3 and 4 : CD
AQP 2 : CD

Question 10

what happens when osmolality changes

Answer 10

decreases : no ADH so no AQP in CDs so limited water reuptake, loss of large amount of hypo-osmotic (dilute) urine —> diuresis
increases : kidney must reabsorb water and produce hyperosmotic urine, ADH inserts AQP into apical membrane of CD, water moves out of hyperosmotic environment

Question 11

what is counter-current multiplication

Answer 11

generation of a vertical concentration gradient in the kidney

Question 12

what structures are involved in counter-current multiplication

Answer 12

Juxtamedullary nephron with a long LoH to establish the gradient
Vasa recta to maintain the gradient
CD of all nephrons use the gradient with ADH to vary urine concentration

Question 13

how is the counter-current multiplication set up ?

Answer 13

Descending limb of LoH, mainly in juxtamedullary (long) nephrons
- AQP1 always open so permeable to water
- not permeable to Na+, so Na+ remains out and osmolarity increases
- Max osmolality in tip of LoH is 1200 Osm/kg as water moved out
Thick ascending limb of LoH - filtrate removes solute without water so increases osmolarity of the interstitium
- Active transport of NaCL —> interstitium
- osmolarity in ascending limb decreases ( as water stays but NaCl leaves, becomes hypo-osmotic)
- fluid entering the DCT has low osmolality of 100 mOsm/Kg
- The concentration of Na+ in interstitial fluid surrounding LoH (in medulla) increases. This increase in concentration is known as countercurrent multiplication as it sets up a vertical osmotic gradient

Question 14

describe what is the vertical osmotic gradient

Answer 14

Large gradient in the interstitial fluid of the medulla, isotonic at the corticomedullary border (300) but hyperosmotic at the papilla (1200)
a gradient of increasing osmolality due to : active NaCl transport in the thick ascending limb, recycling of urea, the arrangement of blood vessels in the medulla, descending components on close opposition to ascending components

Question 15

why is urea considered an effective osmole

Answer 15

ineffective osmole - when a membrane allows certain solutes to freely cross it as they dont exert an osmotic force
urea is hydrophillic so doesnt readily cross lipid barriers

Question 16

how is urea recycled ?

Answer 16

reabsorbed from medullary CD, moved into interstitium and diffusion into loop. ADH causes and urea re-cycling to increase

Question 17

what is the function of the vasa recta ?

Answer 17

maintains the CC mechanism by acting as a counter-current exchanger. Flow in VR is in the opposite direction to tubule, allowing maintenance of the osmotic gradient. Occurs by diffusion. Requires high blood flow in cortex by low in medulla.
In descending limb of VR, Na+, Cl- and urea diffuse into lumen of VR —> blood in VR increases osmolarity as reaches top of hairpin.
In ascending limb of VR, blood ascending towards cortex has higher [solute] than the surrounding interstitium so water moves in from the descending limb of LoH. Therefore the vasa recta preserves hyperosmolarity of Renal Medulla

Question 18

what are the causes of hyponatraemia

Answer 18

changes in ADH secretion
Heart failure
Kidney or Liver disease
Drugs
- thiazide diuretic, PPIs,ACEi

Approach the patient with low Na by doing a fluid assesment. treatment usually involves fluid restriction