Integrative Physiology II- Renal Regulation of Potassium Secretion and Diuretics Flashcards
what is the [K+]ECF
4.2 meq/L
what are the mechanisms controlling K+ homeostasis
-control of K+ distribution between ECF and ICF
- to keep [K]+ ECF constant, rate of K+ excretion=rate of K+ input
what are factors that shift K+ into cells thereby decreasing [K+]ECF
-insulin
-aldosterone
- beta2 adrenergic stimulation
- alkalosis
- low ECF Osm
- increased Na+/K+ ATPase activity
-dilute ICF
- low EC gradient for diffusion of K+ out of cell
what are factors that shift K+ out of cells thereby increasing [K+]ECF
-increased insulin deficiency in DM
- aldosterone deficiency in Addisons disease
-Beta2 adrenergic antagonists
-acidosis
-increased ECF Osm
-strenuous exercise
-Cell lysis
-decreased Na+/K+ ATPase activity
-concentrated ICF
- high EC gradient for diffusion out of cell
does acidosis cause hyperkalemia or hypokalemia
hyperkalemia
how does acidosis cause hyperkalemia
H+ inhibits Na+ K+ ATPase causing K+ to build up in the cell
what are the three factors in the tubular processing of K+
filtration, reabsorption and secretion
where is most K+ absorbed
in the PT
where is most K+ secreted
CD
what are the substances that go through all 3 processes in renal processing
urea and K+
what is day to day regulation of [K+] ECF a function of
late distal tubule/collecting duct
what does a high K+ intake cause
increased K+ secretion by principal cells
what does a low K+ intake cause
increased K+ reabsorption by alpha intercalated cells
what are the factors that determine rate of K+ secretion by principal cells
- Na+/K+ ATPase activity
- transepithelial potential difference (TEPD) between blood and lumen
- permeability of apical membrane for K+
what are factors that control prinicpal cell K+ secretion
- high [K+]ECF
- high aldosterone
-high distal tubule flow rate - acid/base status: if alkalosis: high K+ secretion and if acidosis: low K+ secretion
what are the mechanisms of how increased [K+]ECF increases K+ secretion
-increased Na+/K+ ATPase activity
-TEPD is more lumen negative due to increased Na+ reabsorption which favors K+ secretion
- increased number K+ channels in apical membrane
- stimulates aldosterone secretion
how does aldosterone increase K+ secretion
-increased K+ intake -> increased plasma K+ -> increased aldosterone secretion at the renal cortex -> increased plasma aldosterone -> increased K+ secretion at the CCD
-> K+ excretion
what causes increased distal tubule flow rate to increase K+ secretion
- increased ECF volume
-Na+ loading
-some diuretics
what are the mechanisms of increased distal tubule flow rate increasing K+ secretion
-increased tubule flow rate keeps luminal K+ lower, maintaining chemical gradient for secretion
- increases #BK channels in apical membrane
what are the causes of hyperkalemia
- renal failure
- decreased distal nephron flow (CHF, NSAID)
- decreased aldosterone or decreased effect of aldosterone (adrenal insufficiency, resistance to aldosterone, K+ sparing diuretics)
-metabolic acidosis - diabetes
what are the causes of hypokalemia
- very low intake of K+
- GI loss of K+ from diarrhea
- metabolic alkalosis
- excess insulin
- increased distal tubular flow: salt wasting nephropathies, osmotic diuretics, loop diuretics
- excess aldosterone
what are diuretics
drugs that increase urine volume output
what is the most common reason for diuretics
to reduce ECFV which reduces edema and MAP
what are the 2 mechanisms of action of diuretics and which is more common
-act by decreasing Na+ reabsorption from some part of the nephron - more common
- act by decreasing water reabsorption
how do diuretics decrease Na+ reabsorption
natriuresis causes diuresis by an osmotic mechanism and affects reabsorption of Cl-, K+, and other ions
how do diuretics decrease water reabsorption
by increasing water excretion through aquaresis
what are drugs that modify salt excretion
-carbonic anhydrase inhibitors at the PCT
- loop diuretics at the TAL
- thiazides at the DCT
- K+ sparing diuretics at the CCT
-osmotic diuretics
what are drugs that modify water excretion
- osmotic diuretics
-ADH agonists - ADH antagonists
what do osmotic diuretics target
inhibits water reabsorption all along the nephron
what is the result of osmotic diuretics
- diuresis due to aquaresis
- to lesser extent it increases Na+ and K+ excretion
what do osmotic diuretics do
nonabsorbable substance is filtered
what are osmotic diuretic effects similar to
effects of endogenous substances like glucose - diuresis caused by hyperglycemia
what are the targets of carbonic anhydrase inhibitors and what does it do
-proximal tubule
- inhibits Na+ reabsorption by indirectly inhibiting Na+/H+ secondary active symporter
what is an example of a carbonic anhydrase inhibitor
acetazolamine
where does more than 80% of HCO3- reabsorption and H+ secretion occur
in the proximal tubule
what do carbonic anhydrase inhibitors do
block Na+ reabsorption indirectly
what are the results in diuresis by carbonic anhydrase inhibitors
-natriuresis
- aquaresis
- acidosis
what are the targets of loop diuretics and what do they do
-TAL
- inhibits Na+ K+ 2Cl- secondary active symporter
what are examples of loop diuretics
-furosemide, ethancrynic acid, bumetanide
what are the results in diuresis of loop diuretics
- natriuresis
- aquaresis
- overwhelm downstream absorptive capacity of DCT and CD
-disrupt countercurrent multiplier
what are the most powerful diuretics available
loop diuretics
what is the target of thiazide diuretics and what do they do
-early DCT
- inhibit Na+ Cl- secondary active symporter
-block Na+ Cl- cotransport mechanism in early distal tubule
what are examples of thiazide diuretics
hydrochlorothiazide, chlorthalidone
what are the results in diuresis of thiazide diuretics
-natriuresis
- aquaresis
-overwhelm downstream absorptive capacity
what are the K+ sparing diuretics
aldosterone antagonists and Na channel blockers
what is the mechanism and site of action of aldosterone antagonists
-decreased Na+ absorption and K+ secretion
- late distal and collecting tubule
what is the mechanism and site of action of ENaC blockers
- block ENaC and decrease K+ secretion
- late distal and collecting tubule
how do some diuretics cause K+ loss/hypokalemia
-increasing flow rate of filtrate through distal nephron increases K+ secretion
- keeps luminal K+ concentration low supporting secretion
what are examples of aldosterone antagonists
spironolactone and eplerenone
what are examples of ENaC blockers
amiloride and triamterene
what are the results in diuresis of K+ sparing diuretics
- natriuresis
-aquaresis
-without hypokalemia
