IP2: Renal Regulation of Potassium Secretion, and Diuretics

Question 1

ECF K+ is tightly regulated at _____ meq/L

Answer 1

4.2

Question 2

What is high K+ ECF called? What about low?

Answer 2

➢ High [K+]ECF: Hyperkalemia
➢ Low [K+]ECF: Hypokalemia

Question 3

What factors shift K+ into the cells causing a hypokalemia?

Answer 3

insulin
aldosterone
B2-adrenergic stimulation
alkalosis
decreased ECF osmolarity
hyperkalemia
increase Na/K ATPase activity

Question 4

What factors shift K+ out the cells causing a hyperkalemia?

Answer 4

insulin deficiency (diabetes)
aldosterone deficiency (addison’s)
B2-adrenergic antagonsists
acidosis
increased ECF osmolarity
exercise
hypokalemia
decreased Na/K ATPase activity

Question 5

Does hyperkalemia have acidosis or alkalosis?

Answer 5

❖ Acidosis → Hyperkalemia
❖ Alkalosis → Hypokalemia

Question 6

What are the three factors in tubular processing of K+?

Answer 6

Filtration; Reabsorption; Secretion

Question 7

Day to Day regulation of [K+]
ECF is the function of which parts of the nephron?

Answer 7

late Distal Tubule/Collecting Duct

Question 8

If you have high K+ intake then you have increased K+ secretion in what cell?

Answer 8

principal cell

Question 9

If you have low K+ intake then you have increased K+ reabsorption in which cell?

Answer 9

alpha intercalated cell

Question 10

What are the factors that determine the rate of K+ secretion by prinicpal cells?

Answer 10

1. Na+/K+ ATPase Activity
2. Transepithelial potential difference (TEPD) between blood and lumen
3. Permeability of apical membrane for K+

Question 11

What are the factors that control the principal cells K+ secretion?

Answer 11

Increased K+ secretion
- increased K+ conc
- increased aldosterone
- increased distal tubule flow rate
- alkalosis

Question 12

Without what hormone would you lose the ability to regulate the K+ levels?

Answer 12

aldosterone

Question 13

What causes an increased in distal tubule flow rate which also causes K+ secretion?

Answer 13

• increased ECF volume
• Na+ loading
• some diuretics

Question 14

What are some causes of hyperkalemia?

Answer 14

➢ 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)

Question 15

What are some causes of hypokalemia?

Answer 15

➢ 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

Question 16

What is a diuretic?

Answer 16

drugs that increase urine volume output

Question 17

What is the most common reason why people take diuretics?

Answer 17

• reduce ECFV (extracellular fluid volume)
  – Reduces edema
  – Reduces MAP (mean arterial pressure)

Question 18

How do diuretics work?

Answer 18

1. Act by decreasing Na+ reabsorption from some part of the nephron.
   ⁻ Most common type
   ⁻ Natriuresis causes diuresis by an osmotic mechanism.
2. Act by decreasing H2O reabsorption
   ⁻ Increases H2O excretion (Aquaresis)

Question 19

What are the diuretics that modify salt excretion?

Answer 19

• loop diuretics (furosemide)
• K+ sparing (spironolactone)
• thiazides
• carbonic anhydrase inhibitors
• osmotic diuretics

Question 20

What are the diuretics that modify water excretion?

Answer 20

• ADH agonists
• ADH antagonists
• osmotic diuretics

Question 21

What is a major target for many diuretics?

Answer 21

Na+ Transport

Question 22

What is the target of osmotic diuretics?

Answer 22

Inhibits H2O reabsorption all along nephron

Question 23

What are the results of osmotic diuretics?

Answer 23

⁻ due to Aquaresis
⁻ To a lesser extent it increases Na+ and K+ excretion

Question 24

What is the target of carbonic anhydrase inhibitors?

Answer 24

Proximal tubule (PT)
➢ Inhibits Na+reabsorption by indirectly inhibiting Na+/H+ 2⁰ active symporter

Question 25

What is the result of carbonic anhydrase inhibitors?

Answer 25

⁻ Natriuresis
⁻ Aquaresis
⁻ Acidosis (side effect)

Question 26

What is the target of loop diuretics?

Answer 26

Thick ascending limb (TAL)
➢ Inhibit Na+-K+-2Cl- - 2⁰ Active
Symporter

Question 27

What are the results of loop diuretics?

Answer 27

⁻ Natriuresis
⁻ Aquaresis
⁻ Most powerful diuretics available
(30% of GFR may appear in urine!).
⁻ Overwhelm downstream absorptive capacity (DCT and CD).
⁻ Disrupt countercurrent multiplier

Question 28

What is the target of thiazide diuretics?

Answer 28

early Distal Convoluted Tubule (DCT)
➢ Inhibit Na+-Cl- - 2⁰ Active
Symporter

Question 29

What are results of the thiazide diuretics?

Answer 29

⁻ Natriuresis
⁻ Aquaresis
⁻ Overwhelm downstream
absorptive capacity (late DCT
and CD).

Question 30

What are K+ sparing diuretics?

Answer 30

aldosterone antagonists
Na channel blocker

Question 31

Why do many diuretics cause K+ loss (hypokalemia)?

Answer 31

➢ Increasing flow rate of filtrate through distal nephron increases K+ secretion.
➢ Keeps luminal K+ concentration low supporting secretion
➢ Hypokalemia may result

Question 32

What is the target for K
+ Sparing Diuretics?

Answer 32

Collecting duct (CCT or CD)

1. Aldosterone antagonists
   ⁻ decrease activity of Na+/K+ ATPase, ENaC, K+ channel
2. ENaC blockers
   ⁻ decreased Na+ uptake, Na+/K+ activity, K+ secretion

Question 33

What are the results of the K
+ Sparing Diuretics?

Answer 33

➢ Natriuresis
➢ Aquaresis
➢ without hypokalemia