Sodium and potassium balance Flashcards
What is osmolarity?
measure of solute (particle) concentration in a solution (mOsm/L)
- the greater the number of dissolved particles, the greater the osmolarity
How does increased dietary sodium lead affect blood pressure?
- inc. dietary sodium
- inc. total body sodium
- inc. osmolarity (but this can’t happen)
- inc. water intake and retention
- inc. ECF volume
- inc. blood volume and pressure
What is the central mechanism involved in the regulation of sodium intake?
- lateral parachrachial nucleus in brainstem
- in euvolemia, serotonin and glutamate suppress basal sodium intake
- during sodium deprivation/hypovolemia?, GABA and opioids drive inc. appetite for sodium
What is the peripheral mechanism involved in the regulation of sodium intake?
TASTE
low sodium in food= appetising
high sodium= fairly unpleasant taste
Where in the nephron is most of the sodium reabsorbed?
proximal convoluted tubule- 67%
Where is the macula densa?
in the juxtaglomerular apparatus of the distal convoluted tubule (in contact w/ cells around the glomerulus)
How do the cells in the macula densa respond to increased tubular sodium?
- high sodium in tubular fluid
- inc. sodium/chloride uptake via triple transporter
- adenosine release from macula densa cells
- triggers extraglomerular mesangial cells
- promotes afferent smooth muscle cell contraction
- so reduced flow into glomerulus–> reduced renal perfusion pressure and GFR (and so less sodium coming into tubular system)
What is the best way to retain sodium?
filter less!
lower efferent arteriole pressure–> more flow through–> lower filtration pressure–> better retention of sodium and water
How does atrial natriuretic peptide (ANP) decrease sodium reabsorption?
- vasodilator
- reduces sodium reuptake in PCT, DCT and collecting ducts
- suppresses production of renin by JGA
How does beta-1 sympathetic activity increase sodium reabsorption/retention (and so inc. bp and fluid volume)?
- directly stimulates SMC of afferent arteriole (reduces GFR)
- stimulates sodium uptake in PCT
- stimulates renin production by JGA–> cleaves angiotensinogen to angiotensin 1–> cleaved by ACE to angiotensin 2–> stimulates sodium uptake in PCT and stimulates adrenal glands (zona glomerulosa) to produce aldosterone (through inc. expression aldosterone synthase, needed for last 2 steps of conversion from cholesterol)–> stimulates sodium uptake in DCT and collecting duct
What are the functions of aldosterone in the kidney?
- simulates sodium reabsorption
- increases potassium secretion
- increases H+ ion secretion
- excess aldosterone–> hypokalaemic alkalosis
What are the consequences of hypoaldosteronism?
- reduced reabsorption of sodium in distal nephron
- leads to inc. urinary loss of sodium (and so inc. loss of water)
- ECF volume falls–> inc. renin, angiotensin 2 and ADH
- low bp–> dizziness
- low salt–> salt cravings, palpitations
What are the consequences of hyperaldosteronism?
- inc. reabsorption of sodium in distal nephron
- leads to dec. urinary loss of sodium (and so dec. loss of water)
- ECF volume inc. (hypertension)–> dec. renin, angiotensin 2 and ADH
- inc. ANP and BNP production
- high bp
- muscle weakness
- thirst, polyuria
What is Liddle’s syndrome?
- inherited disease of high blood pressure
- however normal or low aldosterone levels
- mutation in the aldosterone-activated ENaC sodium channel–> always ‘on’–> inc. reabsorption of sodium (so inc. water retention and hypertension)
What is the effect of spironolactone on blood pressure?
- mineralocorticoid antagonist
- reduces effect of aldosterone
- so decreases sodium reabsorption and water retention
- leads to reduced blood pressure
What receptor does ANP bind to?
guanylyl cyclase
What are the actions of ANP?
- released in response to atrial stretch (high bp)
- causes vasodilation of renal and other blood vessels (N.B. inc. GFR by relaxing SMCs in afferent arteriole)
- inhibits sodium reabsorption in PCT and collecting ducts
- inhibits renin and aldosterone production
- -> reduces bp
How do ACE inhibitors reduce blood pressure?
reduces angiotensin 2 production
- -> leads to vasodilation (as A2 contracts vessels), so inc. vascular volume and dec. bp
- -> renal effects: dec. sodium reuptake in PCT, so dec. water reabsorption
- -> adrenal effects: dec. aldosterone production–> indirect renal effects (dec. sodium reuptake in collecting duct, so inc. sodium in distal nephron, so reduced osmotic gradient across tubular wall and dec. water reabsorption
- ——-> reduced water volume, ECF volume and bp
How do osmotic diuretics work?
put in something in PCT that doesn’t get reabsorbed, so it increases the osmolarity here–> so less water reabsorption here (region where most is reabsorbed) –> dec. bp
How do carbonic anhydrase inhibitors work as diuretics?
- block carbonic anhydrase, which is most active in PCT
- protons not produced, so sodium/proton exchange activity reduced, so dec. net reabsorption of sodium –> inc. sodium in distal nephron, and dec. water reabsorption
- N.B. also fewer protons pumped out, so reduced acidity of urine
How do loop diuretics work?
- block triple transporter (Na+/Cl-/K+) in thick ascending limb of loop of Henle
- so reduced sodium reuptake–> inc. sodium in distal nephron and reduced water reabsorption–> dec. bp
How do thiazide diuretics work?
- block sodium chloride uptake transporter in DCT
- so reduced sodium reuptake–> inc. sodium in distal nephron–> reduced water reabsorption–> dec. bp
- N.B. also inc. calcium reabsorption, as sodium-calcium anti porter on basolateral side of DCT cells–> so more calcium pumped out of cell, due to sodium gradient
How do potassium sparing diuretics work?
- e.g. spironolactone
- bind to mineralocorticoid receptor, inhibit aldosterone function–> block sodium reuptake–> inc. sodium in distal nephron–> dec. water reabsorption and dec. bp
- in collecting duct
- potassium sparing, as less potassium secreted through antiporters(?)
What is the main intracellular ion?
potassium (150mmol/L)
