Volume Flashcards

1
Q

“Volume”

A

Short hand for extracellular Volume

Note that total water space is 70% of body weight; 2/3 is intracellular and 1/3 is extracellular

Of extracellular, 1/3 is Vascular blood/fluid and 2/3 is interstitial fluid

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

For extraceullar fluid, how much water: Na?

A

1L Water + 135-145 mEq Na

“Normal Saline”

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

Why does Sodium remain extracellularly? Why is it important that sodium remains extracellularly?

A

If you add Sodium/water solution (normal saline), you will expand the extracellular fluid compartment because the Sodium channels are hard to open; they remain closed & the fluid stays extracellularly

This is important because when we give normal saline, the fluid stays in the extracellular compartment! This would not be true if we gave K+/water – theoretically the solution would go to intracellular compartment

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

What happens if you add salt alone (either via diet or via injection)?

A

Water flows from intracellular compartment (which shrinks) to extracellular compartment (which expands)

But you get thirsty and your hormones change = shows you how important salt is in maintaining everything in your body

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

What is the most specific controller of extracellular volume and why?

A

Sodium!

Water is not

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

What happens to intracellular/extracellular compartments if you drink a lot of water?

A

Both expand in proportion to their starting volumes

Water distributes itself among all spaces

Water is not specific for any compartment

It also decreases ADH so you pee out more water

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

What is the maximum water you can drink in a day?

A

20L

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

Does diet control volume expansion/contraction?

A

Yes

Intake = Output

But there might be an intrinsic set point controlling Na/water content

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

Volume Depletion: what is it

A

A condition where you have reduced extracellular fluid that can have many causes, but the primary event is a loss of sodium: vomiting, diarrhea, fever>sweat, exercise>sweat, not eating, hemorrhage, adrenal sufficiency, diuretics, high urine flow

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

Volume Depletion: Symptoms and Signs

A

Symptoms: light headed, weak, tired, cold extremities, thirsty

Signs: low blood pressure, orthostasis, weight loss, dry skin, no sweating, no saliva, loss of skin turgor

Kidney signs: elevated BUN/creatinine rario, low urine Na, concentrated urine, low urine volume

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

How does your body sense that you have a low volume?

A

1) Intrathoracic
- Both atria: stretch receptor –> ANP release
- Right ventricle
- Pulmonary capillaries

2) Arterial volume/baroreceptors: carotid & aortic arch
3) Renal artery baroreceptor: juxtaglomerular apparatus
4) CNS volume receptors
5) Hepatic volume receptors: process through GI system that senses sodium load & response that is greater than if it was IV

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

What is the body’s response to volume depletion?

A

Body senses volume depletion –> Signalling to CNS –>

(1) Sympathetic activation –> Renin release –> Increases Angiotensin II & Aldosterone –> recovery of urinary Na; maximizes in 2-3 days
(2) Thirst
(3) Salt appetite

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

• What is the role of angiotensin II on the proximal tubule?

A

Angiotensin II binds 2 receptors:
• (1) receptor I which signals through Gq, activates IP3 production, which increases diacyl glycerol production & Ca is released from ER/SR
• (2) voltage dependent Ca channel

• The effect of both is to cause vasoconstriction of the efferent arteriole and to regulate gene expression in the proximal tubule cell

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

Which target genes does AII regulate?

A

Na/K ATPase, Na solute cotransporter, 2Na/H exchanger
• Both increases the number of these transporters and they are placed at the correct membrane
• Encourages sodium flux into cells & is a positive regulator of sodium recovery

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

• What is the importance of the Na/H exchanger, besides just Na recovery?

A

o It has a pivotal role in turning HCO3 into CO2 using carbonic anhydrase
o This is how bicarb can cross the membrane: as CO2

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

What is aldosterone? Where does it come from/what does it do?

A

Comes from the zona glomerulosa under the influence of A II

Goes beyond the proximal tubule– at the principal cell of the nephrone (at collecting ducts, where final amount of urine is delivered)

Has a nuclear receptor (mineralocorticoid receptor), bc it’s a steroid hormone (cholesterol-derived)

Its effect is to increase ENaC receptors which reabsorb Na and K channels which secrete K in the collecting duct

17
Q

ADH/vasoporins

A

ADH stimulates the insertion of vesicles (vasoporins) into the apical membrane of the cell –> allows water to be reabsorbed in the collecting duct to the hypertonic medulla

Tight junctions seal the paracellular space allowing large Na, water, and pH gradients to form between the lumen and the blood

18
Q

How does the renin-angiotensin-aldosterone-adh system regulate volume depletion?

A

note that volume depletion can result in tissue hypoxia & damage, so the renin response is really intense

Volume depletion = low BP = underfilling of arterioles
LEADS TO:

(1) renin: converts angiotensiongen to AI to AII
AII: causes efferent constriction, more Na transports = increase in reabsorption while maintaining GFR
- also causes vasoconstriction
- also increases aldosterone, increases colelcting duct reabsorption of Na and increases excretion of H, NH4 and urea

(2) NE: last resort, bc it decreases GFR
(3) ADH: increases collecting duct reabsorption of H2O

19
Q

Which clinical tests can you do to diagnose volume depletion?

A

High BUN/creatinine
normal = 10:1
can get up to 20:1
suggests AII action on distal channel, bc one of its jobs is the increase urea reabsorption

Low FeNa & Una
FeNa = Una Pna /Ucr Pcr
normal = 1%
if lower than 1%, indicates AII and aldosterone activity bc urine is low

  • *ADH will be elevated** due to volume stimulus –> increased water recovery from collecting duct
  • *-Low Urine volume, high osmolarity**
20
Q

Can the kidneys reverse volume depletion?

A

No, bc it takes 3-4 days to maximize reabsorption

When you have a change in sodium intake/volume, it takes time to do this

In the meantime it will contribute to your volume depletion by excreting too much salt

21
Q

What are the “effective” volume depletion syndromes?

A

CHF = cardiorenal

  • stage I is volume depletion
  • stage II leads to volume retention: edema, weight gain, shortness of breath

Cirrhosis = hepatorenal

Nephrosis = prerenal

All look like volume depletion from the kidneys’ point of view, but cause a secondary increase in Na

So all the signs/symptoms are the same as volume depletion EXCEPT that you have a weight gain, because you have excess salt/volume

22
Q

What’s stage I and stage II of effective volume depletion?

A

Stage I: underfilled phenotype- bp, etc
high Bun/Cr ratio (AII on)
Low Una, low FeNa (AII, aldosterone on)
Low urine volume, high urine osmolarity (ADH on)

Stage II: normalized phenotype (BP, weight gain, edema)
Normalized BUN/Cr
Normalized Una and FeNa
Normalized urine volume, urine osmolarity
(all the hormones are turned off)

23
Q

What can cause volume overload?

A

Excess ingestion of Na + kidney failure, CHF, Cirrhosis, Nephrosis, or Mineralocorticoid excess

Na and mineralocorticoid have primary gain of Na

CHF has secondary gain of NA

Nephrosis and Cirrhosis can be either

24
Q
A
25
Q

How can the body sense that there is volume overload / decide to secrete sodium?

A

Volume expansion is sensed by baroreceptors in CV system (Hepatic sensors, Atrial sensors, JGA) –> CNS signal –> Macula densa sensing of cardiac overload –> ANF secretion

26
Q

What does ANF do?

A

Inhibits renin and angiotensin II

Increases Urine Na

Overall: increase in GFR, decrease in PiGC in both glomerulus & proximal tubule

No change in FF

You discard a higher volume of Na and Urine

27
Q

What are the effects of increased ANF & NE & decreased AII, aldosterone, and ADH?

A
  • *ANF**
  • turns off renin
  • leads to afferent vasodilation and increased GFR hence more Na filtered
  • *No renin –> no angiotensin II **
  • efferent dilation, decrease in Na transporters, decreasee in PT reabsorption while maintaining GFR
  • decrease in aldosterone –> decrease in collecting duct Na reabsorption, increase in Na, NH4, and urea excretion
  • *NE**
  • decrease in GFR
  • *No ADH**
  • decrease collecting duct H2O reabsorption
28
Q

ANF

A

Dilates afferent arteriole

Inhibits renin secretion

For increased GFR, same or less reabsorption in prox tubule

29
Q

Angiotensin II

A

Constricts efferent arteriole

Enhances activity of Na/H exchanger in proximal tubule

For same GFR, increases reabsoprtion in proximal tubule (bc Pi increases and P decreases in prox tubule –> greater diriving force for reabsorption)

30
Q

Aldosterone

A

Enhances activity of Na chennel & K channel of principal cell of the collecting duct and H+ ATPase in intercalated cell

31
Q

ADH

A

Enhances H2O reabsorption from the principal cells & rea reabsorption from TALH

32
Q

NE

A

For decreased GFR, same reabsorption in proximal tubule