Sodium Homeostasis Flashcards
sodium (Na+) homeostasis - overview
*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)
body fluid compartments
*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%)
fluid composition of intracellular fluid
*mainly composed of K+, Mg2+, organic phosphates (ex. ATP)
note - salty BANANA = K+ on the inside
fluid composition of extracellular fluid
*mainly composed of Na+, Cl-, HCO3-, albumin
note - SALTY banana = Na+ on the outside
sodium balance: intake vs. output
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)
sodium intake - overview
*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
sodium output - mechanisms for sodium excretion
*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
mechanisms that regulate sodium excretion
- GFR
- sympathetic nervous system
- natriuretic peptides
- RAAS
- blood pressure, renal perfusion pressure
effect of GFR on sodium excretion
DIRECT relationship [IF FENa is constant along tubule]
*INCREASED GFR → INCREASED Na+ excretion
*decreased GFR → decreased Na+ excretion
fractional excretion of sodium (FENa)
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)
values of FENa > ? may indicate acute kidney injury
*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
effect of blood pressure & renal perfusion pressure on sodium excretion
*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)
salt-sensitive vs. salt-insensitive
*salt-insensitivity = blood pressure does not rise with increased salt intake
*salt-sensitivity = blood pressure rises with increased salt intake
effect of sympathetic nervous system activation on sodium excretion
*INVERSE relationship
*INCREASED sympathetic nervous system → DECREASED Na+ excretion (i.e. sodium retention)
mechanisms of sympathetic nervous system on sodium excretion
- increased tone of glomerular afferent arteriole via alpha-1 adrenergic receptor (vasoconstriction → decreased GFR)
- direct stimulation of proximal sodium reabsorption (Na+/H+ exchange via alpha-1 adrenergic receptor)
- increase renin release (beta-1 adrenergic receptor)
note - overall effect: increased sympathetic nervous system → decreased sodium excretion (i.e sodium retention)
effect of RAAS system on sodium excretion
*INVERSE relationship
*INCREASED RAAS activation → DECREASED Na+ excretion (i.e. sodium retention)
RAAS system - things to know
*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
mechanisms of RAAS activation on sodium excretion
-
increases tubular Na+ REABSORPTION
a. Ang II proximally with its effects on Na+/H+ exchanger
b. aldosterone distally with its effects on CCD -
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
regulators of RAAS activation
*renin is the rate-limiting step
*3 factors control renin release:
1. distal sodium delivery
2. sympathetic nervous system
3. local baroreflex
effects of distal delivery of sodium on renin release - overview
*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
effects of INCREASED NaCl distal delivery on renin release
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
effects of DECREASED NaCl distal delivery on renin release
decreased NaCl delivery → macula densa reabsorbs less Na+ via NKCC transporter→ macula densa does NOT swell → release of PGE2 → INCREASED RENIN RELEASE
effects of sympathetic nervous system activation on renin release
- increased afferent tone via alpha-1 receptor → increased renin
- direct stimulation of Na+/H+ exchanger via alpha-1 receptor → increased renin
- direct stimulation of GC via beta-1 receptor → increased renin
increased SNS → INCREASED RENIN → decreased Na+ excretion
effects of local baroreflex on renin release
*afferent arteriole baroreceptors sense myogenic pressure changes
*decrease in perfusion pressure → increased renin
*increase in perfusion pressure → decreased renin
effects of RAAS activation (simple)
- sodium retention
- volume expansion
- vasoconstriction
effect of low salt intake on Ang II
increase Ang II
effect of high salt intake on Ang II
decrease Ang II
effect of volume depletion on Ang II
increase Ang II
effect of volume expansion on Ang II
decrease Ang II
effect of natriuretic peptides on sodium excretion
*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
mechanisms of ANP release on sodium excretion
- increases GFR (dilates afferent arteriole, constricts efferent arteriole)
- decreases Na+ reabsorption
- decreases renin release
note - ANP → increased sodium excretion (diuresis)
mechanisms of nitric oxide release on sodium excretion
NO → decreased renin release & decreased Na+ reabsorption → increased sodium excretion
mechanisms of dopamine release on sodium excretion
dopamine → decreased Na+ reabsorption & increased renal blood flow → increased sodium excretion
