Disorders of Potassium Handling

Question 1

which of the following is NOT directly involved in the regulation of potassium?
a. aldosterone
b. insulin
c. angiotensin
d. catecholamines

Answer 1

aldosterone, inulin, and catecholamines (via beta2) are directly involved in regulating K+

all stimulate Na+/K+ ATPase (maintains asymmetric K+ distribution such that most is intracellular)

Question 2

how do principal cells vs intercalated cells regulating K+ in the collecting ducts?

Answer 2

principal cells: secrete K+

intercalated cells: reabsorb K+

Question 3

hypokalemia/hyperkalemia is defined by serum K+ less than/greater than…

Answer 3

serum K+ less than 2.5mmol/L = hypokalemia

serum K+ greater than 5mmol/L = hyperkalemia

Question 4

what is the cause of periodic paralysis, a rare neuromuscular disorder?

Answer 4

periodic paralysis: inherited or acquired, caused by acute transcellular shift in K+ into cells

characterized by potentially fatal episodes of muscle weakness or paralysis that can affect respiratory muscles

(recall hypokalemia often presents as weakness of respiratory muscles)

Question 5

what is the effect on hypokalemia on aquaporin expression in the nephron?

Answer 5

hypokalemia decreases aquaporin expression —> nephrogenic diabetes insipidus

Question 6

what is the effect of hypokalemia on insulin secretion?

Answer 6

hypokalemia decreases insulin secretion —> increased insulin resistance

Question 7

most common cause of measured hyperkalemia

Answer 7

pseudo-hyperkalemia due to hemolysis of the sample causing intracellular K+ to be measured in the serum

unexplained hyperkalemia should be re-checked (esp. patients with leukocytosis or thrombocytosis)

Question 8

describe 2 ways in which diabetes can cause hyperkalemia

Answer 8

1. diabetic ketoacidosis - metabolic acidosis causes shift of intracellular K+ to extracellular, in exchange for more H+ going into cells
2. severe hyperglycemia can itself cause hyperkalemia via “solvent drag”

Question 9

what is the effect of hyperkalemia on membrane potential?

Answer 9

recall membrane potential is maintained by Na+/K+ ATPase, which pumps Na+ OUT and K+ IN against their concentration gradients

hyperkalemia has depolarizing effect because it partially equalizes the K+ potential

Question 10

what is the first test that should be done on a patient with suspected hyperkalemia and why?

Answer 10

ECG because the most lethal complication of hyperkalemia is cardiac conduction abnormalities

ECG in an (otherwise normal) patient with hyperkalemia would show peaked T waves, wide QRS/prolonged PR interval, augmented R wave, and small/absent P waves

Question 11

describe how the following can be used in the treatment of hyperkalemia:
a. calcium
b. insulin/glucose
c. beta2 adrenergic agonist
d. loop/thiazide diuretic
e. GI cation exchanger
f. hemodialysis

Answer 11

a. calcium: to stabilize cardiac response to hyperkalemia (first line for K+ related arrhythmias)

b. insulin/glucose: for hyperglycemic patients, will drive K+ back into cells

c. beta2 adrenergic agonist (albuterol): drives K+ intracellularly (give at high dose)

d. loop/thiazide diuretic: enhance K+ secretion in volume overloaded patients

e. GI cation exchanger (patiromer): for patients with renal insufficiency

f. hemodialysis: for patients with ESRD

Question 12

Your patient has hyperkalemia. You’re smart so the first test you run is an ECG, which shows peaked T waves. You’re worried about K+ mediated cardiac toxicity. What is your next step?

Answer 12

calcium therapy (calcium gluconate) - first line in hyperkalemia-related arrhythmias and ECG changes

calcium will not alter serum [K+] but will stabilize cardiac response to hyperkalemia and should be initiated first when there is evidence of cardiac toxicity

Question 13

what is the effect of alpha vs beta adrenergic agonists on plasma K+?

Answer 13

alpha adrenergic agonists - shift from intra to extracellular K+ (higher plasma K+)

beta2 adrenergic agonists (ex, epinephrine) - shift from extra to intracellular K+ (lower plasma K+); same effect as aldosterone and insulin

Question 14

which of these will NOT cause an increase in extracellular potassium?
a. beta blockers
b. insulin
c. strenuous exercise
d. increased extracellular fluid osmolarity

Answer 14

move K+ OUT of cells:
a. beta blockers
c. strenuous exercise
d. increased extracellular fluid osmolarity (follows water)

insulin deficiency would also move K+ out of cells

Question 15

which of the following reduces K+ secretion?
a. acidosis
b. alkalosis

Answer 15

a. acidosis reduces K+ secretion: inhibits Na+/K+ ATPase, reducing intracellular [K+] —> therefore reduces electrochemical driving force for K+ secretion

[alkalosis increases K+ secretion]

Question 16

how are hypomagnesium and hypokalemia related?

Answer 16

hypomagnesium —> inhibition of Na+/K+/ATPase + enhanced ROMK-mediated K+ secretion (it’s probably a charge thing)

if patients are hypomagnesemic they will not respond to K+ replacement

Question 17

which of the following is NOT associated with hypokalemia?
a. Liddle Syndrome
b. Type 1 RTA (acquired)
c. Bartter Syndrome
d. Gitelman Syndrome
e. Type 2 RTA
f. SAME (licorice)

Answer 17

a. Liddle Syndrome: GOF ENaC mutation —> high BP + alkalosis

b. Type 1 RTA (acquired): urinary K+ wasting

c. Bartter Syndrome: LOF NKCC mutation —> low BP + alkalosis
d. Gitelman Syndrome: LOF NCC mutation —> low BP + alkalosis

f. SAME (licorice): aka syndrome of apparent mineralocorticoid excess —> high BP + alkalosis

Question 18

which of these will NOT present with hypomagnesium?
a. Liddle Syndrome
b. Bartter Syndrome
c. Gitelman Syndrome

Answer 18

all of these present with hypokalemia and alkalosis

b. Bartter Syndrome (LOF NKCC): HIGH Ca2+, LOW Mg2+, low ECV
c. Gitelman Syndrome (LOF NCC): LOW Ca2+, LOW Mg2+, low ECV

a. Liddle syndrome (GOF ENaC): low renin / aldosterone, HIGH ECV