Sodium Homeostasis

Question 1

sodium (Na+) homeostasis - overview

Answer 1

*sodium is the most abundant cation in blood (extracellular space)
*critical for the normal functioning of the body
*intricately connected with the balance of water in the body
*balance of sodium plays a key role in blood pressure regulation, perfusion of organs, and maintenance of cardiac output (preload)

Question 2

body fluid compartments

Answer 2

*body 50-60% water
*total body water = weight (kg) x % of H2O = intracellular fluid + extracellular fluid
*60-40-20 rule (60% total body water, intracellular fluid = 40%, extracellular fluid = 20%)

Question 3

fluid composition of intracellular fluid

Answer 3

*mainly composed of K+, Mg2+, organic phosphates (ex. ATP)

note - salty BANANA = K+ on the inside

Question 4

fluid composition of extracellular fluid

Answer 4

*mainly composed of Na+, Cl-, HCO3-, albumin

note - SALTY banana = Na+ on the outside

Question 5

sodium balance: intake vs. output

Answer 5

intake = output
*almost all of the sodium that we eat per day is excreted in the urine (very small proportions are excreted in the feces/sweat)

Question 6

sodium intake - overview

Answer 6

*need 180-500 mg of Na per day (~1/4 teaspoon per day)
*average daily sodium intake = 3500 mg of Na
*RECOMMENDED adequate intake level = 1500-2300 mg per day
*the majority of sodium comes from processed and restaurant foods

Question 7

sodium output - mechanisms for sodium excretion

Answer 7

*major trigger for Na+ excretion is changes in extracellular fluid expansion
*excretion = filtration - (reabsorption + secretion)
*amount of Na+ excreted is regulated by changes in:
-amount of sodium filtered
-amount of sodium reabsorbed
*varies from day to day, as intake varies

Question 8

mechanisms that regulate sodium excretion

Answer 8

1. GFR
2. sympathetic nervous system
3. natriuretic peptides
4. RAAS
5. blood pressure, renal perfusion pressure

Question 9

effect of GFR on sodium excretion

Answer 9

direct** relationship [IF FENa is constant along tubule]
**INCREASED GFR → INCREASED Na+ excretion
*decreased GFR → decreased Na+ excretion

Question 10

fractional excretion of sodium (FENa)

Answer 10

FENa % = (Una x Scr / Sna x Ucr) x 100

Una: urine sodium
Scr: serum creatinine
Sna: serum sodium
Ucr: urine creatine

FENa = (urine sodium x serum creatinine) / (serum sodium x urine creatinine)

Question 11

values of FENa > ? may indicate acute kidney injury

Answer 11

*values of FENa > 2% may indicate acute kidney injury

*this is because the kidneys are prone to conserve sodium:
-kidney reabsorbs 99% of filtered Na+ load
-kidney excretes < 1% of filtered Na+ load

Question 12

effect of blood pressure & renal perfusion pressure on sodium excretion

Answer 12

*INCREASED BP / renal perfusion pressure → INCREASED Na+ excretion
*this is known as “pressure natriuresis”
*nitric oxide may play a role

note - healthy people do not use pressure natriuresis to excrete excess sodium (blood pressure remains relatively stable within a wide range of sodium intakes)

Question 13

salt-sensitive vs. salt-insensitive

Answer 13

*salt-insensitivity = blood pressure does not rise with increased salt intake
*salt-sensitivity = blood pressure rises with increased salt intake

Question 14

effect of sympathetic nervous system activation on sodium excretion

Answer 14

*INVERSE relationship
*INCREASED sympathetic nervous system → DECREASED Na+ excretion (i.e. sodium retention)

Question 15

mechanisms of sympathetic nervous system on sodium excretion

Answer 15

1. increased tone of glomerular afferent arteriole via alpha-1 adrenergic receptor (vasoconstriction → decreased GFR)
2. direct stimulation of proximal sodium reabsorption (Na+/H+ exchange via alpha-1 adrenergic receptor)
3. increase renin release (beta-1 adrenergic receptor)

note - overall effect: increased sympathetic nervous system → decreased sodium excretion (i.e sodium retention)

Question 16

effect of RAAS system on sodium excretion

Answer 16

*INVERSE relationship
*INCREASED RAAS activation → DECREASED Na+ excretion (i.e. sodium retention)

Question 17

RAAS system - things to know

Answer 17

*renin is the rate-limiting step
*local vs. systemic RAAS
*local RAAS systems in tissues
*counterbalance effects of RAAS:
-ACE 2 enzyme takes some angiotensin 1 and converts to angiotensin 1-7 peptides

Question 18

mechanisms of RAAS activation on sodium excretion

Answer 18

1. increases tubular Na+ REABSORPTION
   a. Ang II proximally with its effects on Na+/H+ exchanger
   b. aldosterone distally with its effects on CCD
2. Ang II vasoconstriction of both arterioles
   *vasoconstriction preferentially effects the EFFERENT arteriole → increased GFR → increased Na+ filtration (gives more substrate to be absorbed proximally & distally)
   -Ang II afferent < efferent arteriole

Question 19

regulators of RAAS activation

Answer 19

*renin is the rate-limiting step
*3 factors control renin release:
1. distal sodium delivery
2. sympathetic nervous system
3. local baroreflex

Question 20

effects of distal delivery of sodium on renin release - overview

Answer 20

*anatomy of the nephron is arranged in such a way that the distal tubule “returns” to a position adjacent to its own AFFERENT arteriole, where the JG apparatus is, including the macula densa
*macula densa informs the granular cells in the afferent arterial about NaCl concentration in the distal tubule, regulating renin secretion
*increased distal delivery of NaCl → decreased renin release

Question 21

effects of INCREASED NaCl distal delivery on renin release

Answer 21

increased NaCl delivery → macula densa reabsorbs extra Na+ via NKCC transporter → macula densa SWELLS → release of NO → modulates cAMP and intracellular calcium → INHIBITION OF RENIN RELEASE

Question 22

effects of DECREASED NaCl distal delivery on renin release

Answer 22

decreased NaCl delivery → macula densa reabsorbs less Na+ via NKCC transporter→ macula densa does NOT swell → release of PGE2 → INCREASED RENIN RELEASE

Question 23

effects of sympathetic nervous system activation on renin release

Answer 23

1. increased afferent tone via alpha-1 receptor → increased renin
2. direct stimulation of Na+/H+ exchanger via alpha-1 receptor → increased renin
3. direct stimulation of GC via beta-1 receptor → increased renin

increased SNS → INCREASED RENIN → decreased Na+ excretion

Question 24

effects of local baroreflex on renin release

Answer 24

*afferent arteriole baroreceptors sense myogenic pressure changes
*decrease in perfusion pressure → increased renin
*increase in perfusion pressure → decreased renin

Question 25

effects of RAAS activation (simple)

Answer 25

1. sodium retention
2. volume expansion
3. vasoconstriction

Question 26

effect of low salt intake on Ang II

Answer 26

increase Ang II

Question 27

effect of high salt intake on Ang II

Answer 27

decrease Ang II

Question 28

effect of volume depletion on Ang II

Answer 28

increase Ang II

Question 29

effect of volume expansion on Ang II

Answer 29

decrease Ang II

Question 30

effect of natriuretic peptides on sodium excretion

Answer 30

*ANP and other natriuretic peptides (NO, dopamine) are released in response to volume expansion (stretch) and increased salt intake
*increased natriuretic peptides → increased sodium excretion

Question 31

mechanisms of ANP release on sodium excretion

Answer 31

1. increases GFR (dilates afferent arteriole, constricts efferent arteriole)
2. decreases Na+ reabsorption
3. decreases renin release

note - ANP → increased sodium excretion (diuresis)

Question 32

mechanisms of nitric oxide release on sodium excretion

Answer 32

NO → decreased renin release & decreased Na+ reabsorption → increased sodium excretion

Question 33

mechanisms of dopamine release on sodium excretion

Answer 33

dopamine → decreased Na+ reabsorption & increased renal blood flow → increased sodium excretion