SM 193: Potassium

Question 1

How is K distributed in the body? Where are the largest sources of K in the body? How is the concentration difference maintained?

What is the normal K concentration?

Answer 1

ICF: 98% K (biggest sources - skeletal muscle, liver, erythrocytes)
ECF: 2% (3/4 interstitium, 1/4 plasma)
Concentration maintained by 3Na-2K ATPase
Normal: 3.5-4.9mM K+ in serum

Question 2

How is the 3Na/2K ATPase regulated by Digoxin? Insulin? beta-2 agonists?

Answer 2

Digoxin: inhibits ATPase = heavy hyperkalemia (more K secretion)
Insulin: stimulates ATPase = increases K+ uptake and stimulates glucose uptake (beware hypoglycemia if you use insulin to treat hyperkalemia)
B-2 agonist: stimulates more cAMP = stimulates ATPase = increases K+ uptake

Question 3

How does Metabolic Acidosis/Alkalosis affect K distribution? Plasma Osmolality? Exercise?

Answer 3

Met. Acidosis = Increases plasma K
Met. Alkalosis = Decreases plasma K

High Plasma Osmolality = Increases Plasma K (osmotic drag)
Low Plasma Osmolality = Decrease Plasma Drag (osmotic drag)

Exercise = increases plasma K (released from skeletal muscle)

Question 4

How is K Reabsorbed in PT?

Answer 4

67% Reabsorbed here via paracellular diffusion with solvent drag (no transcellular path)

Constantly reabsorbed, no regulation

Question 5

How is K reabsorbed in the LoH (TAL)?

Answer 5

20% constant reabsorption, no regulation

1. NKCC Co-transporter on Apical Side (K into cell)
2. ROMK (K channel) on Apical Side (K out of cell)
3. K/Cl Co-transporter on basolateral side (K out of cell), and K channel on basolateral side (K out of cell)
4. Na/K ATPase on basolateral side (K into cell)

Question 6

How is K reabsorbed in DCT?

Answer 6

highly regulated area
Early DCT
Apical: Na/Cl Co-transporter into cell; K/Cl Co-transporter out of cell; ROMK K channel out of cell
Basolateral: Na/K ATPase, K Channel (out of cell)

Late DCT
Apical: ENaC (into cell), ROMK (out of cell), K/Cl co-transporter (K out)

Question 7

How is K reabsorbed in Principal Cells in Cortical CD?

Answer 7

highly regulated K
Apical: ENaC brings Na in, driving force for K secretion via ROMK and Maxi-K Channels!
Basolateral: Na/K ATPase

Increase K Secretion by increasing Na = activate ENaC = more driving force for K Secretion

Question 8

What determines K Secretion in low and high ECF volume states?

Answer 8

K Secretion is CONSTANT
Low ECF Volume:
More Aldosterone = more K secretion
Less Na delivery to Cortical CD = less ENaC = less K secretion

High ECF Volume:
Less Aldosterone = less K secretion
More Na Delivery to Cortical CD = more ENac = more K secretion

competing factors usually result in no change to K secretion

Question 9

Definition and 3 main causes of Hyperkalemia

Answer 9

plasma K > 5 mM

1. Low GFR (occurs in renal failure)
2. Aldosterone Deficiency (HyperK stimulates Aldo!!!)
3. Decreased Distal Na Delivery or blocked ENaC (amiloride)

Question 10

4 causes for a transcellular redistribution of K from ICF to ECF

Answer 10

1. Beta-blockers - inhibit Na/K ATPase
2. Digitalis Toxicity - inhibit Na/K ATPase
3. Intense Exercise - activates Katp Channel
4. Acidosis - inhibits Na/K ATPase

Question 11

Definition of Hypokalemia, and why this is a poor sign

3 broad causes

Answer 11

K plasma less than 3.5mM
Poor sign because plasma may only be slightly depleted when Substantial K depletion has occurred (ie from ICF)

1. Extrarenal Losses (GI tract)
2. Renal Losses
3. Low K Intake

Question 12

Causes of Hypokalemia associated with Metabolic Acidosis and Alkalosis

Answer 12

Metabolic Acidosis = GI losses (diarrhea) or renal tubular acidosis (renal K loss)
Metabolic Alkalosis = vomiting, non-K sparing diuretics, Barterr’s, Gitelman’s

Question 13

What is the key sign of hypokalemia associated with metabolic alkalosis due to vomiting?

Answer 13

LOW Cl in URINE!!! (lose H/Cl in vomit, kidney tries to same H+ by secreting K+)

Question 14

What is the difference between Barterr’s Syndrome and Gitelman’s Syndrome?

Answer 14

Barterr’s: urinary K wasting and metabolic acidosis, labs show high Na, K, Cl (looks like overdiuresis)
due to mutation in NKCC in TAL - volume loss triggers Aldo - saves Na at expense of more K wasting

Gitelman’s = milder phenotype of urine K wasting and metabolic acidosis; Low urine Ca
due to NCCT mutation (Na/Cl co-transporter) in DCT = low Na reabsorption = increases Ca reabsorption = low urine Ca

Question 15

Causes of hypokalemia with HTN

Answer 15

1. Primary Hyperaldosteronism: 2/2 adenoma/hyperplasia of adrenal glands
2. Cushing’s syndrome = due to cortical excess

Question 16

Causes of non-volume deplete hypokalemia

Answer 16

TRANSCELLULAR REDISTRIBUTION

1. Excess Insulin = stimulates Na/K ATPase
2. B-2 agonists (albuterol) = cAMP up = stimulates Na/K ATPase
3. Acute illness = more catecholamines = sitmulates Na/K ATPase
4. Alkalemia = stimulates Na/K ATPase (decrease serum k)