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)
What stimulates potassium uptake into tissue?
- insulin (also aldosterone and adrenaline)
- insulin stimulates sodium-proton exchanger, increasing sodium coming into tissue cells, so inc. activity of Na+/K+ ATPase, to get rid of the sodium
Where is potassium secreted if there is normal or inc. potassium intake?
DCT and collecting ducts
Where is potassium reabsorbed in the kidney under normal conditions?
- 67% in PCT
- 20% in thick ascending limb of loop of Henle
- Na+/K+/Cl- transporter
What factors stimulate potassium secretion?
- inc. plasma K+
- inc. aldosterone
- inc. tubular flow rate
- inc. plasma pH
How does increased tubular flow lead to increased potassium secretion?
w/ inc. flow, primary cilia on distal cells stimulate PDK1
–> inc. calcium conc. in cell–> stimulates openness of K+ channels, so more moves out
What are the causes of hypokalaemia?
- inadequate dietary intake (too much processed food)
- diuretics (due to inc. tubular flow rate)
- surreptitious vomiting
- diarrhoea
- genetics (Gitelman’s syndrome- mutation in Na/Cl transporter in distal nephron)
What are the causes of hyperkalaemia?
- in response to K+ sparing diuretics
- ACE inhibitors
- elderly
- severe diabetes
- kidney disease
