Regulation of ECF Volume and Water Balance

Question 1

[…] is the major effective osmole in the ECF and determines the movement of water into/out of cells

Answer 1

NaCl

Question 2

How can you estimate the plasma osmolality (Posm) of a patient?

Answer 2

Measure serum [Na+] and mulitply by 2 to account for equal parts Cl- for each Na+ molecule

Ex: serum Na+ = 145 mEq / L then Posm = 290 mEq / L

Question 3

When a person is hyponatremic or hypernatremic, what is driving that change in [Na+]?

Answer 3

Water

Too much = hyponatremia

Too little = hypernatremia

Question 4

The driving force for fluids to shift between the body’s fluid compartments is driven by what?

Answer 4

Most important take away - WATER MOVES across the membrane, not the Na+

Question 5

What if there is isoosmotic volume change? Will there be shifts between body fluid compartments?

Answer 5

No

Question 6

IMPORTANT: Fluid shifts occur ONLY IF […] osmolality changes.

Answer 6

ECF

Question 7

Additional questions:

• Calculate TBW and ICF, ECF volumes before infusion.
• Calculate again after infusion.
• Does plasma volume (25% of ECFV) change?

Answer 7

ECF

Question 8

Answer 8

Question 9

Answer 9

Question 10

Answer 10

Question 11

Answer 11

Question 12

Answer 12

Question 13

Why does water balance change body fluid osmolality?

Answer 13

Question 14

If you were to add 1L of pure water to a person’s body (i.e. ingestion or IV infusion):

• Where is this fluid added?
• What is the effect on osmolality?
• What will be the response of the kidneys?

Answer 14

• ECF
• Decreased
• Decrease reabsorption of water to increase excretion of water to restore normal osmolality

Question 15

If you were to remove 1L of pure water from a person’s body:

• Where is this fluid removed from?
• What is the effect on osmolality?
• What will be the response of the kidneys?

Answer 15

• ECF
• Increase
• Increase reabsorption of water to restore normal fluid volume and osmolality

Question 16

Answer 16

Question 17

What will be the impact on levels of ADH and thirst in the two scenarios shown by this image?

Answer 17

Question 18

Explain how the body senses changes in osmolality.

Answer 18

Question 19

ADH is released in response to changes in what 2 things?

Answer 19

Plasma osmolality

Low blood volume / pressure

NOTE: a small increase in Posm can result in release of ADH whereas a much larger loss of volume or decrease in pressure is needed to increase ADH levels.

Question 20

Explain what this graph is showing.

Answer 20

Question 21

Explain how ADH leads to increased reabsorption of water in the kidney.

Answer 21

ADH in blood –> binds to V2 receptor on basolateral surface of cells in DCT and CD –> V2 is GPCR that stimulates AC to increase production of cAMP –> cAMP travels to nucleus and binds to cAMP response element which increases transcription of gene for aquaporin 2 channel –> AP2 loaded into membrane of vesicles and trafficked to membrane where vesicles fuse with membrane to deliver AP2 –> increased water reabsorption. This also by proxy increases Na+ reabsorption b/c Na+ travels with water. In the absence of ADH, CD does not have any aquaporins and thus does not reabsorb water unless in presence of ADH.

Question 22

Increasing ADH also increases thirst. Why is it important for the increasing ADH to preceed the increase in thirst?

Answer 22

Because collecting duct has no aquaporins. If thirst preceeded increased ADH then we’d intake all this water but there would be no increased reabsorption.

Question 23

Answer 23

Question 24

Given the case below:

• What will happen to fluid volume in her body compartments?
• What will happen to osmolality in her body compartments?
• How will the body respond?
• How would you describe her condition in one sentence?
• What will happen to her urine production?
• What will happen to levels of ADH?
• What will happen to her levels of thirst?
• What will be her urine flow rate and osmolality?

Answer 24

• ECF volume will decrease, which will drive decrease in ICF also
• Osmolality will increase because she’s losing more water than Na+. Although osmolality will increase relative to her starting osmolality, it will be isoosmotic across her body compartments (i.e. Osm of ECF = Osm of ICF, both will be hyperoosmotic)
• Correct osmolality and volume –> THESE ARE FIXED BY DIFFERENT MECHANISMS
• Hyperosmotic volume contraction due to excess water loss
• Decrease, need to increase volume
• ADH will be elevated
• 5% increase in plasma Osm so thirst will be elevated
• Flow rate decreased, concentrated urine so hyperosmotic urine

Question 25

[...] is what the body uses to correct osmolality. Why? [...] is what the body uses to correct volume. Why?

Answer 25

ADH increases the reabsorption of water in the collecting duct by increasing aquaporin channels present. This is essentially the same as increasing "free water". Inreasing free water will decrease osmolality since you are not changing Na+ but you are changing the volume of fluid that its dissolved in. RAAS system is used to correct volume because angiotensinogen 2 (ultimate product of RAAS) results in increased reabsorption of **BOTH** Na+ and H₂O in equal ratios. This will not change a person's osmolality since you're adding equal ratios of Na+ and water, but it will increase the total volume.

Question 26

Answer 26

Question 27

Cortical neprhons can only [...] urine while juxtamedullary nephrons can [...] urine.

Answer 27

Dilute Dilute or concentrate

Question 28

Answer 28

B

Question 29

* Where in the nephron does ADH exert its effects? * What are its effects at these locations?

Answer 29

Question 30

Describe how the suppression of ADH leads to dilute urine at the different segments of the nephron.

Answer 30

Urine in the PCT and PST is isoosmotic because there is equal reabsorption of water and Na+. In thin decending limb, Osm increases as move down limb so water will be reabsorbed and removed from urine, making urine hyperosmotic. As urine travels up thick ascending limb, Na+ is removed which results in diluted urine. The Na+ that is removed helps maintain the gradient of interstitial Osm. In the absence of ADH, this process still occurs but that explains why in the presence of ADH the interstitial Osm gradient is much higher, since ADH increases Na+ reabsorption in the TAL. Urine leaving thick ascending limb is hypoosmotic due to removal of solute. When reaches collecting duct, in absence of ADH, no water is removed but more solute is removed so it becomes even more hypoosmotic and thus we get dilute urine.

Question 31

Describe how the activation of ADH leads to concentrated urine.

Answer 31

Urine in the PCT and PST is isoosmotic because there is equal reabsorption of water and Na+. In thin decending limb, Osm increases as move down limb so water will be reabsorbed and removed from urine, making urine hyperosmotic. In the presence of ADH, the interstitial gradient is much higher due to icreased Na+ in interstitium, so even more water is removed from the urine so urine is very concentrated. Urine entering TAL is concentrated and now has a lot of Na+ removed b/c ADH is present so more solute is removed (Na+, K+, 2Cl- co transporter) leading to once again hypoosmotic urine in the DCT even in the presence of ADH which is supposed to concentrate the urine. When urine reaches the CD, ADH promotes increased aquaporins so there will be increased H2O reabsorption leading to increased Osm and thus ultimately concentrated urine.

Question 32

Where does ADH act?

Answer 32

Thick Ascending limb Collecting duct

Question 33

Describe what ADH does to the cells of the thick ascending limb.

Answer 33

Increases activity of Na+/K+/2Cl- co-transporter to further dilute urine by removing solute. This makes the interstitium have a higher osmolality so the nephron can reabsorb more water in the thin descending limb.

Question 34

How much of the filtered load of water is reabsorbed?

Answer 34

99.2%

Question 35

* Aldosterone secretion is enhanced by [...] and by [...] via increased [...]. * Aldosterone secretion is decreased by [...] and [...].

Answer 35

hyperkalemia volume contraction angiotensin II hypokalemia natriuretic peptides