Lecture 9 - Regulation of Extracellular Fluid Volume and Osmolarity Flashcards

1
Q

6 factors affecting sodium reabsorption?

A
  1. GFR
  2. Aldosterone
  3. Peritubular physical forces
  4. Medullary blood flow
  5. Sympathetic nerves
  6. Hormones
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2
Q

How does GFR affect sodium reabsorption? What is this called?

A

As GFR increases, Na+ filtration rate and absorption rate all go up BUT = there is a mechanism to buffer changes in GFR so that Na+ reabsorption is adequate (not matched 100% though so there is a small increase in excretion rate): glomerular-tubular balance => if the GFR increases or decreases the reabsorption will as well so that the excretion rate is not affected

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3
Q

How does aldosterone affect sodium reabsorption? Slow or fast acting?

A

Acts on cells of cortical collecting duct to bind to intracellular receptors to cause changes in transcription/translation to ultimately:

PRINCIPAL CELLS:
1. Stimulate Na+ reabsorption by increasing Na+ conductance across lumenal membrane causing the Na+/K+-ATPase to pump more Na+ out on basolateral suface => further Na+ reabsorption

  1. Stimulate K+ secretion by direct hormone effect on conductance without passing by nucleus causing the Na+/K+-ATPase to pump more K+ in and more Na+ out on basolateral suface => further Na+ reabsorption

INTERCALATED CELLS:
3. Stimulate H+ secretion via H+ ATP-ase pump insertion on lumenal membrane causing more Na+ reabsorption on the lumenal surface => causing the Na+/K+-ATPase to pump more Na+ out on basolateral suface => further Na+ reabsorption

Slow acting (hrs)

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4
Q

What 4 factors regulate aldosterone secretion? Main one?

A
  1. RAA system***
  2. Plasma K+ (rise stimulates it)
  3. ACTH (rise enhances the effects of 1 and 2)
  4. ANP (rise inhibits it)
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5
Q

What experiment was done to figure out what factors had an effect on sodium reabsorption in the kidney?

A

At the time, we thought only aldosterone and GFR regulated Na+ reabsorption, so the following experiment was done on a dog:

  1. Force the two factors to conserve Na+: drop perfusion pressure so that GFR is very low and then administer aldosterone so that the very little Na+ that is filtered is reabsorbed
  2. Infuse saline to see if the body is going to continue to accumulate Na+, which will increase the ECF and lead to pulmonary edema and death

RESULTS:
Na+ excretion actually INCREASED => proposal for natriuretic hormone that is facilitating its excretion

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6
Q

How do peritubular physical forces affect sodium reabsorption?

A

In the peritubular capillaries, net oncotic pressure is high (due to filtration of 20% of the plasma) and net hydrostatic pressure is low, which facilitates net reuptake

SO, anything that decreases oncotic pressure or increases hydrostatic pressure will decrease net reuptake in the peritubular capillaries, and vice versa AND anything that increases interstitial hydrostatic pressure will decrease net reuptake because the proximal tubule is so leaky

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7
Q

What can raise oncotic pressure in the peritubular capillary? Effect on reuptake?

A

Increase in efferent arteriole resistance => increase filtration + decrease hydrostatic pressure => increase in peritubular capillary reuptake

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8
Q

What can decrease oncotic pressure in the peritubular capillary? Effect on reuptake?

A

Decrease in efferent arteriole resistance => decrease filtration + increase hydrostatic pressure => decrease in peritubular capillary reuptake

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9
Q

How does medullary blood flow affect sodium reabsorption?

A
  1. Increase in medullary flow rate => more water exiting the vasa recta more solute reuptook and the interstitium would be diluted => less water reabsorbed in the descending limb of the loop of Henle => less solute reabsorbed in the thin ascending limb of the loop of Henle => increase in amount of solute excreted
  2. Decrease in medullary flow rate => less water exiting the vasa recta and less solute reuptook so the interstitium would be concentrated => more water reabsorbed in the descending limb of the loop of Henle => more solute reabsorbed in the thin ascending limb of the loop of Henle => decrease in amount of solute excreted
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10
Q

How do sympathetic nerves affect sodium reabsorption and ECF volume?

A
  1. Constriction of arterioles => decrease RPF and GFR + decrease of medullary blood flow => decrease Na+ excretion
  2. Stimulation of renin production => angiotensin II => decrease GFR + increase in aldosterone => decrease Na+ excretion + increase in renal vascular resistance
  3. Direct stimulation of Na+ reabsorption in the proximal tubule and thick ascending limb of the loop of Henle
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11
Q

What stimulates SNS to increase ECF volume?

A

Decrease in extracellular fluid => decrease in firing of low pressure baroreceptors => increase renal sympathetic nerve activity

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12
Q

How do hormones affect sodium reabsorption?

A

INTRARENAL HORMONES:

  1. ANP
  2. Angiotensin II
  3. Prostaglandins
  4. Kallikrein-kinins

+ EXTRARENAL

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13
Q

List the 7 actions of angiotensin II that cause Na+ retention and directly or indirectly increase BP.

A
  1. Vasoconstriction of renal vessels causing increased GFR/RPF => increased peritubular oncotic pressure => increased reuptake
  2. Stimulates aldosterone secretion by suprarenal glands to increase Na+ reabsorption in cortical collecting duct
  3. Stimulation of ADH secretion by hypo to increase water/Na+ reabsorption
  4. Decreases medullary blood flow, which stimulates Na+/H2O reabsorption in thin descending and ascending limbs of the loop of Henle
  5. DIRECTLY stimulates Na+ reabsorption in proximal tubule by directly stimulating the Na+/H+ lumenal exchanger and the Na+/K+-ATPase, in distal tubule by stimulating Na-Cl thiazide sensitive carrier, and in collecting duct by stimulating Na+ channels
  6. Stimulates sympathetic CNS outflow
  7. Stimulates general peripheral vasoconstriction
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14
Q

Describe the release and modes of action of atrial natriuretic peptide.

A

Atrial myocytes stretch and function as mechanoreceptors => release ANP (as a peptigen, which is later cleaved) in bloodstream:

  1. Increased kidney natriuresis (= excretion of Na+) and diuresis at the medullary collecting duct
  2. Vasodilation of renal arteries => increases GFR and RPF
  3. Inhibits the synthesis and release of aldosterone by the adrenal medulla
  4. Decreases renin secretion by the kidney
  5. Dilates peripheral veins => decrease in peripheral resistance => decrease in BP
  6. Opposes the effects of angiotensin on vasopressin release in the brain
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15
Q

What are the pressure sensors that allow the body to regulate the ECF volume?

A
  1. Low pressure baroreceptors in the atria
  2. Low pressure baroreceptors in the hepatic circulation
  3. High pressure baroreceptors in the juxtaglomerular apparatus
  4. High pressure baroreceptors in the aortic arch
  5. High pressure baroreceptors in the carotid sinus
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16
Q

What is pressure natriuresis? Other name?

A

Arterial pressure increases => increase in medullary blood flow (because not controlled like the rest of renal blood flow) => dilution of medullary concentration gradient + increase in renal interstitial hydrostatic pressure (causing back leak) => urinary output of NaCl and H2O increases

Other name = pressure diuresis

17
Q

Normal daily intake of fluid?

A
  1. Ingestion of food = 1 L
  2. Metabolism = 250 mL
  3. Ingestion of liquid = variable
18
Q

Normal daily output of fluid?

A
  1. Urine = variable
  2. Stool = 200 mL
  3. Skin = 100 mL
  4. Lungs = 1 L
19
Q

Osmolarity of sweat? Effect on blood osmolarity?

A

Hypotonic to blood, so the more you sweat the more your blood osmolarity increases

20
Q

Effect of rise in blood osmolarity?

A

Sensed by hypo => ADH secreted by posterior pituitary => acts on collecting duct to stimulate H2O reabsorption => decrease in urine volume + increase in urine concentration => decrease in blood osmolarity => decrease ADH secretion

21
Q

Describe in detail how ADH functions on the collecting duct cells. Fast or slow?

A
  1. Binds to basolateral receptor
  2. Adenyl cyclase: ATP => cAMP
  3. Stimulation of phosphokinase: ATP => AMP + PPi (phospho protein)
  4. PPi + microtubules + Ca++ => insertion of aquaporins into the lumenal membrane to facilitate water reabsorption

FAST (mins)

22
Q

Describe the pathway of excess water ingestion.

A

Excess H2O ingested => decrease in blood osmolarity => hypo osmoreceptors sense osmolarity => decrease ADH secretion => decrease plasma ADH => decrease collecting duct permeability to water => decrease in H2O reabsorbed => increase in H2O excreted by kidneys => increase in blood osmolarity

23
Q

What % decrease in osmolarity would shut off ADH secretion?

A

+3%

24
Q

Other than an increase in osmolarity, what else can regulate ADH secretion? What is ADH secretion most sensitive to?

A
  1. Atrial low pressure baroreceptors
  2. High pressure baroreceptors in aortic arch and carotid sinus
  3. Stress (e.g. pain and cytokines) (stimulates)
  4. Nausea (stimulates)
  5. Ethanol (inhibits)
  6. Hypoxia (stimulates)
  7. Hypoglycemia (stimulates)
  8. Physical activity (stimulates)
  9. Angiotensin II (stimulates)
  10. Hypercarbia (stimulates) (increase in PCO2)

Most sensitive to osmolarity: a 2% increase in osmolarity will cause the same ADH secretion as a 15% volume fall

25
Q

Normal plasma osmolarity?

A

287 mOsm/L

26
Q

Describe the basal level of plasma osmolarity.

A

Plasma osmolarity = 287 mOsm/L

Plasma ADH = 2.8 pg/mL

Urine osmolarity = 700 mOsm/L

Urine flow = 1.5 L/day

27
Q

Describe the maximal level of effective concentration of urine.

A

Plasma osmolarity = 295 mOsm/L

Plasma ADH = 4.5 pg/mL

Urine osmolarity = 1200 mOsm/L

Urine flow = 0.8 L/day

28
Q

What % decrease in TBW causes maximal concentration of urine osmolality? What is max concentration of urine?

A

2%

Max Uos > 1000 mosm/kg

29
Q

What is the plasma concentration of vasopressin at maximal antidiuresis? Can it increase beyond that?

A

5 pg/mL
Yes, but this will have no effect on reabsorption of water in kidney - BUT will have vasoconstriction effects to increase BP

30
Q

What happens to increase TBW once maximal antidiuresis has been reached?

A

THIRST!

31
Q

What is the osmotic threshold?

A

The plasma osmolality threshold before vasopressin secretion = 280 mOsm/L

32
Q

Describe the minimal level of effective concentration of urine (aka threshold for ADH secretion).

A

Plasma osmolarity = 280 mOsm/L

Plasma ADH = 0.5 pg/mL

Urine osmolarity = 50 mOsm/L

Urine flow = 20 L/day

33
Q

What is the osmotic threshold of thirst osmoreceptors? How does this compare to the osmotic threshold of vasopressin secretion? Why?

A

285-290 mosm/kg (higher than the vasopressin osmotic threshold)

Because our body can handle small changes in osmolarity, we have a whole system for that, might as well use it.

34
Q

Describe the “escape” phenomenon from the Na+ retaining effects of aldosterone.

A

If you administer aldosterone every day to a patient, it will decrease Na+ excretion on the first day, but every subsequent day the excretion will go back up (step wise manner)

This is due to the fact that on the first day, the ECF was increased, which set in motion many other factors that will counteract and override the effects of aldosterone to ensure ECF is not further increased: decrease in SNS activity, decrease in renin secretion, decrease in angiotensin II, increase in medullary blood flow, increase in ANP, increase in GFR

35
Q

If you decrease Na+ amount ingested from one day to the next, what will happen to Na+ excretion?

A

Na+ excretion will decrease little by little because the ECF is decreasing => mechanisms to increase ECF all activate which takes some time: increase in SNS activity, increase in renin secretion, increase in angiotensin II, decrease in medullary blood flow, decrease in ANP, decrease in GFR, increase in aldosterone