Unit 7 - Regulation of Plasma Sodium and ECF Volume

Question 1

why is maintaining plasma volume so important?

Answer 1

blood pressure drives blood flow, and blood pressure is dependent on volume
-so volume –> BP –> flow

Question 2

what are the sensors, efferent pathways, effectors, and regulated parameters of osmolarity?

Answer 2

S: hypothalamic osmoreceptors
EP: ADH and thirst
E: kidney, brain (thirst)
RP: renal free water excretion, water consumption

Question 3

what are the sensors, efferent pathways, effectors, and regulated parameters of ECF volume?

Answer 3

S: carotid sinus, aortic arch, renal afferent arteriole, and atria (actually pressure stretch receptors)
EP: renin-angiotensin-aldosterone, SNS, ADH, ANP (virtually never constant)
E: short term heart and blood vessels, but long term kidney
RP: short term blood pressure (PVR x CO), but long term renal Na excretion

Question 4

what is the renal response to abrupt increases in dietary Na (to 150 mmol)?

Answer 4

if initially in Na+ balance, and Na+ intake is increased, the kidney takes 6 days to catch up (positive balance) by retaining osmolarity by retaining 1 L water (gain 1 kg weight)

Question 5

what is the renal response to abrupt decreases in dietary Na (by 150 mmol)?

Answer 5

if initially in positive Na+ balance, and Na+ intake is decreased, the kidney takes 6 days to recover (negative balance) by retaining osmolarity by losing 1 L water (lose 1 kg weight)

Question 6

what is hemorrhage an example of and what will it cause?

Answer 6

severe ECF volume contraction

-induces decrease in GFR

Question 7

is kidney’s increase in Na+ excretion in response to an increase in ECF volume, or an increase in Na+ concentration?

Answer 7

it’s due to increase in ECF volume

-will increase excretion to retain osmolarity at 300 mmol/L (both 150 mmol Na+ and 150 mmol Cl-)

Question 8

what is effective circulating volume? what does it do?

Answer 8

functional, not anatomical, blood volume reflecting extent of tissue/organ perfusion where blood pressure is sensed

• induces regulation of Na+ excretion
• normally paralleles total ECF volume, both intra- and extra-vascular volumes

Question 9

which induces regulation of Na+ excretion: changes in effective circulating volume, or total ECF volume?

Answer 9

changes in effective circulating volume

Question 10

when is effective circulating volume less than total ECF volume?

Answer 10

in disease states that cause edema (like CHF)

Question 11

what is CHF in regards to edema?

Answer 11

increases end diastolic pressure, so increased capillary hydrostatic pressure driving fluid from intravascular to extravascular space

Question 12

what does pulmonary edema cause volume-wise?

Answer 12

if secondary to left ventricular heart failure and pulmonary HTN
-caused by increased capillary hydrostatic pressure in the lung, driving fluid from intravascular to extravascular space, that severely compromises gas exchange in lung

Question 13

what does liver disease do volume-wise?

Answer 13

caused by decrease in synthesis of albumin, so decreased plasma oncotic pressure that upsets normal Starling forces

Question 14

what does neprhotic syndrome do volume-wise?

Answer 14

disease of renal glomerulus allows inappropriate filtration of albumin = albuminuria
-decreases plasma oncotic pressure, disrupting Starling forces

Question 15

what do diuretic drugs do?

Answer 15

decrease plasma volume by “forcing” kidney to increase excretion of Na+ and water in urine
-this decreases hydrostatic pressure, and increases oncotic pressure in capilliaries, which favors absorption of edema in interstitial space back into intravascular space

Question 16

what are the 3 types of ECF volume baroreceptors?

Answer 16

1. “central” vascular sensors
   - Low pressure (very important): atria and pulmonary vasculature
   - High pressure (less important): carotid sinus, aortic arch, and juxtaglomerular apparatus (renal afferent arteriole)
2. sensors in CNS (less important)
3. sensors in liver (less important)

Question 17

what are 4 parallel effector systems that increase renal Na+ absorption and decrease renal Na+ excretion?

Answer 17

1. renin-angiotensin-aldosterone hormonal system
2. increased renal sympathetic nerve activity
3. posterior pituitary (ADH)
4. ANP

Question 18

what is the RAA hormonal system?

Answer 18

renin-angiotensin-aldosterone

• AII promotes Na+ retention by stimulating Na/H exchange in proximal tubule cells, and decreases renal plasma flow, which promotes increased Na+ resabsorption
• aldosterone induces increase in Na+ reabsorption by late distal tubule and early collecting duct

Question 19

how does increased renal SNS activity affect blood volume?

Answer 19

induces renal vasoconstriction and increased Na+ reabsorption, which reduces renal Na+ excretion

Question 20

how do ADH and ANP affect blood volume?

Answer 20

ADH - promotes water reabsorption

ANP - reduces Na+ excretion in response to reduced ECF volume

Question 21

what is angiotensinogen?

Answer 21

substrate of renin, and is alpha2-globulin made by liver and released into systemic circulation

Question 22

what is renin? what activates it?

Answer 22

made and stored in granular cells of JGA of kidney

-decreased effective circulating volume increases its release, converting angiotensinogen to AI (decapeptide)

Question 23

what is ACE?

Answer 23

angiogensin converting enzyme (decapeptide AI to octapeptide AII)
-found on luminal surface of vascular endothelium throughout body, and abundant in vasculature of lung and kidney

Question 24

what is angiotensin II’s half life?

Answer 24

2 minutes (rapid degradation by aminopeptidases)
-cleaves AII to heptapeptide AIII with less activity

Question 25

what is the most important factor controlling AII levels in plasma?

Answer 25

renin release from granular cells of JGA

Question 26

what are the three renal mechanisms regulating renin release?

Answer 26

1. local renal baroreceptors in afferent arterioles respond to low pressure and increase secretion of renin by granular cells
2. decreased systemic arterial blood pressure stimulates baroreceptor reflex, that causes increased sympathetic drive to JGA, increasing renin secretion
3. cells of macula densa sense tubular fluid Na+ concentration and, if low, cause increased release of renin from granular/JG cells into afferent arteriole blood supply

Question 27

what are actions of AII?

Answer 27

• induces aldosterone release from adrenal cortex
• acts on hypothalamus to increase thirst and induce release of ADH from posterior pituitary
• vasoconstricts renal and other systemic vessels:
• -in kidney: constricts efferent more than afferent arterioles to increase GFR
• -increases Starling forces favoring reabsorption of tubular fluid by peritubular capillaries
• enhances Na/H exchange in proximal tubule, which increases Na+ reabsorption
• induces hypertrophy of renal tubule cells

Question 28

what does aldosterone do?

Answer 28

mineralcorticoid secreted by adrenal cortex

• is primary long term regulator of salt balance and ECF volume, thus blood pressure
• acts on kidney tubules to increase reabsorption of Na+ and water due to increase in osmolarity from increased Na+ reabsorption
• -acts on “principal” cells in late distal tubule and early collecting duct in renal cortex
• acts on distal nephron to increase secretion and excretion of K+

Question 29

how does aldosterone increase Na+ reabsorption?

Answer 29

induced increase in Na+ transporter expression

• increased basolateral membrane Na+/K+ pumps
• increased apical membrane Na+ channels
• increased mitochondrial enzymes (ATP)

doesn’t work immediately

Question 30

why doesn’t solute reabsorption in cortical nephron participate in counter current exchange?

Answer 30

due to separate venous circulations in cortex and vasa recta of medulla; the cortical circulation is rapidly returned to renal vein

Question 31

Na+ filtration through the nephron?

Answer 31

glomerular head: 100%

• 67% reabsorbed in proximal tubule –> 33% left
• 25% reabsorbed in thick ascending LoH –> 8% left at macula densa
• 5% reabsorbed in convoluted tubule –> 3% left in collecting duct
• 3% reabsorbed in collecting duct –> 0.4% left to be excreted

Question 32

how does reabsorbion of NaCl in principal cells of cortical collecting tubule work?

Answer 32

tubular lumen (luminal side) has passive Na+ reaborbtion and K+ excretion
blood (basolateral side) has active Na/K pump (3 Na+ into blood, 2 K+ into cell) and passive K+ channel into blood

Cl- travels paracellularly, from tubular lumen to blood

Question 33

what is the transcellular/transepithelial voltage difference in the cortical collecting tubule? why is it important?

Answer 33

lumen negative; due to net efflux of positive charge from tubular fluid across epithelia

• uncoupled exchange is not stoichiometric, so it’s not electroneutral
• important b/c it’s the driving force pushing transepithelial transport of Cl- between cells (paracellularly) instead of transcellularly

Question 34

what regulates sodium reabsorption in late distal tubule and collecting duct?

Answer 34

circulating levels of aldosterone

Question 35

what are secretogogues for aldosterone?

Answer 35

• angiotensin II
• increased plasma [K+]
• ACTH (release induced by anterior pituitary)

Question 36

what is hypernatremia?

Answer 36

increase in plasma [Na+] to a level above normal range of 135-145 mEq/L

• symptoms: lethargy, weakness, and irritability
• -severe symptoms (seizure/coma) at >158 mEq/L
• caused by loss of water in excess of solutes from plasma due to inadequate water consumption in excess of solute, and/or inappropriate renal excretion of water in excess of solute
• problematic in patients who cannot ask for water or when water consumption is limited

Question 37

what are the 2 causes of hypernatremia?

Answer 37

hypovolemic - inadequate water consumption

• extreme sweating
• severe diarrhea
• polyuria
• caused by diabetes mellitus (glucosuria) or insipidus (central and/or nephrogenic)

hypervolemic - excessive hypertonic fluid consumption (seawater) or IV infusion of hypertonic saline
-hyperaldosteronism

Question 38

central VS nephrogenic diabetes insipidus

Answer 38

central: inadequate release of ADH from posterior pituitary in response to increased osmolarity
- collecting duct not sufficiently permeable to water, causing polyuria

nephrogenic: inability of collecting tubule and collecting duct to respond to ADH, even though ADH is readily available, causing polyuria

Question 39

what is hyponatremia?

Answer 39

decrease in plasma [Na+] below 135-145 mEq/L

• symptoms: nausea, vomiting, headache, lethargy, fatigue, loss of appetite, restlessness, irritability, muscle weakness, spasms, or cramps
• -severe: neurological deficits, brain swelling, seizures, coma if reabsorption by kidney

Question 40

hypervolemic VS hypovolemic hyponatremia

Answer 40

hyper: inappropriate reabsorption of water in excess of solutes from tubular fluid to plasma effectively increases plasma volume and dilutes plasma [Na+]
- occurs: CHF, kidney failure, liver failure, SIADH, psychogenic polydipsia

hypo: in clinical setting where plasma volume reduction is extreme (hemorrhage, prolonged exercise in heat, diuretic drug therapy) where consumption of water and increased “water in excess of solute” reabsorption by kidney is insufficient to correct volume depletion, but is sufficient to decrease plasma [Na]
- Addison’s disease (adrenal insufficiency - hypoaldosteronism)
- severe vomiting or diarrhea