IP2: Renal Regulation of Potassium Secretion, and Diuretics Flashcards
ECF K+ is tightly regulated at _____ meq/L
4.2
What is high K+ ECF called? What about low?
➢ High [K+]ECF: Hyperkalemia
➢ Low [K+]ECF: Hypokalemia
What factors shift K+ into the cells causing a hypokalemia?
insulin
aldosterone
B2-adrenergic stimulation
alkalosis
decreased ECF osmolarity
hyperkalemia
increase Na/K ATPase activity
What factors shift K+ out the cells causing a hyperkalemia?
insulin deficiency (diabetes)
aldosterone deficiency (addison’s)
B2-adrenergic antagonsists
acidosis
increased ECF osmolarity
exercise
hypokalemia
decreased Na/K ATPase activity
Does hyperkalemia have acidosis or alkalosis?
❖ Acidosis → Hyperkalemia
❖ Alkalosis → Hypokalemia
What are the three factors in tubular processing of K+?
Filtration; Reabsorption; Secretion
Day to Day regulation of [K+]
ECF is the function of which parts of the nephron?
late Distal Tubule/Collecting Duct
If you have high K+ intake then you have increased K+ secretion in what cell?
principal cell
If you have low K+ intake then you have increased K+ reabsorption in which cell?
alpha intercalated cell
What are the factors that determine the rate of K+ secretion by prinicpal cells?
- Na+/K+ ATPase Activity
- Transepithelial potential difference (TEPD) between blood and lumen
- Permeability of apical membrane for K+
What are the factors that control the principal cells K+ secretion?
Increased K+ secretion
- increased K+ conc
- increased aldosterone
- increased distal tubule flow rate
- alkalosis
Without what hormone would you lose the ability to regulate the K+ levels?
aldosterone
What causes an increased in distal tubule flow rate which also causes K+ secretion?
- increased ECF volume
- Na+ loading
- some diuretics
What are some causes of hyperkalemia?
➢ Renal failure
➢ Decreased distal nephron flow (heart failure, severe volume depletion, NSAID, etc.)
➢ Decreased aldosterone or decreased effect of aldosterone
- adrenal insufficiency
- resistance to aldosterone
- K+ sparing diuretics (spironolactone)
➢ Metabolic acidosis
➢ Diabetes (kidney disease, acidosis, decreased insulin)
What are some causes of hypokalemia?
➢ Very low intake of K +
➢ GI loss of K+ (diarrhea)
➢ Metabolic alkalosis
➢ Excess insulin
➢Increased distal tubular flow
-salt wasting nephropathies
- osmotic diuretics
- loop diuretics
➢Excess aldosterone
What is a diuretic?
drugs that increase urine volume output
What is the most common reason why people take diuretics?
- reduce ECFV (extracellular fluid volume)
– Reduces edema
– Reduces MAP (mean arterial pressure)
How do diuretics work?
- Act by decreasing Na+ reabsorption from some part of the nephron.
⁻ Most common type
⁻ Natriuresis causes diuresis by an osmotic mechanism. - Act by decreasing H2O reabsorption
⁻ Increases H2O excretion (Aquaresis)
What are the diuretics that modify salt excretion?
- loop diuretics (furosemide)
- K+ sparing (spironolactone)
- thiazides
- carbonic anhydrase inhibitors
- osmotic diuretics
What are the diuretics that modify water excretion?
- ADH agonists
- ADH antagonists
- osmotic diuretics
What is a major target for many diuretics?
Na+ Transport
What is the target of osmotic diuretics?
Inhibits H2O reabsorption all along nephron
What are the results of osmotic diuretics?
⁻ due to Aquaresis
⁻ To a lesser extent it increases Na+ and K+ excretion
What is the target of carbonic anhydrase inhibitors?
Proximal tubule (PT)
➢ Inhibits Na+reabsorption by indirectly inhibiting Na+/H+ 2⁰ active symporter
What is the result of carbonic anhydrase inhibitors?
⁻ Natriuresis
⁻ Aquaresis
⁻ Acidosis (side effect)
What is the target of loop diuretics?
Thick ascending limb (TAL)
➢ Inhibit Na+-K+-2Cl- - 2⁰ Active
Symporter
What are the results of loop diuretics?
⁻ Natriuresis
⁻ Aquaresis
⁻ Most powerful diuretics available
(30% of GFR may appear in urine!).
⁻ Overwhelm downstream absorptive capacity (DCT and CD).
⁻ Disrupt countercurrent multiplier
What is the target of thiazide diuretics?
early Distal Convoluted Tubule (DCT)
➢ Inhibit Na+-Cl- - 2⁰ Active
Symporter
What are results of the thiazide diuretics?
⁻ Natriuresis
⁻ Aquaresis
⁻ Overwhelm downstream
absorptive capacity (late DCT
and CD).
What are K+ sparing diuretics?
aldosterone antagonists
Na channel blocker
Why do many diuretics cause K+ loss (hypokalemia)?
➢ Increasing flow rate of filtrate through distal nephron increases K+ secretion.
➢ Keeps luminal K+ concentration low supporting secretion
➢ Hypokalemia may result
What is the target for K
+ Sparing Diuretics?
Collecting duct (CCT or CD)
- Aldosterone antagonists
⁻ decrease activity of Na+/K+ ATPase, ENaC, K+ channel - ENaC blockers
⁻ decreased Na+ uptake, Na+/K+ activity, K+ secretion
What are the results of the K
+ Sparing Diuretics?
➢ Natriuresis
➢ Aquaresis
➢ without hypokalemia
