Volume Flashcards
“Volume”
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
For extraceullar fluid, how much water: Na?
1L Water + 135-145 mEq Na
“Normal Saline”
Why does Sodium remain extracellularly? Why is it important that sodium remains extracellularly?
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
What happens if you add salt alone (either via diet or via injection)?
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
What is the most specific controller of extracellular volume and why?
Sodium!
Water is not
What happens to intracellular/extracellular compartments if you drink a lot of water?
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
What is the maximum water you can drink in a day?
20L
Does diet control volume expansion/contraction?
Yes
Intake = Output
But there might be an intrinsic set point controlling Na/water content
Volume Depletion: what is it
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
Volume Depletion: Symptoms and Signs
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 does your body sense that you have a low volume?
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
What is the body’s response to volume depletion?
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
• What is the role of angiotensin II on the proximal tubule?
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
Which target genes does AII regulate?
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
• What is the importance of the Na/H exchanger, besides just Na recovery?
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
What is aldosterone? Where does it come from/what does it do?
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
ADH/vasoporins
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
How does the renin-angiotensin-aldosterone-adh system regulate volume depletion?
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
Which clinical tests can you do to diagnose volume depletion?
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**
Can the kidneys reverse volume depletion?
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
What are the “effective” volume depletion syndromes?
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
What’s stage I and stage II of effective volume depletion?
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)
What can cause volume overload?
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
How can the body sense that there is volume overload / decide to secrete sodium?
Volume expansion is sensed by baroreceptors in CV system (Hepatic sensors, Atrial sensors, JGA) –> CNS signal –> Macula densa sensing of cardiac overload –> ANF secretion
What does ANF do?
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
What are the effects of increased ANF & NE & decreased AII, aldosterone, and ADH?
- *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
ANF
Dilates afferent arteriole
Inhibits renin secretion
For increased GFR, same or less reabsorption in prox tubule
Angiotensin II
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)
Aldosterone
Enhances activity of Na chennel & K channel of principal cell of the collecting duct and H+ ATPase in intercalated cell
ADH
Enhances H2O reabsorption from the principal cells & rea reabsorption from TALH
NE
For decreased GFR, same reabsorption in proximal tubule
