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
