SM_193a: Potassium

Question 1

In terms of K⁺ body distribution, ____ is intracellular (____ mEq/L), while ____ is extracellular (____ mEq/L)

Answer 1

In terms of K⁺ body distribution, 98% is intracellular (150 mEq/L), while 2% is extracellular (4 mEq/L)

Question 2

_____ maintains the K⁺ gradient between intracellular and extracellular

Answer 2

Na⁺/K⁺ ATPase maintains the K⁺ gradient between intracellular and extracellular

Question 3

Insulin _____ K⁺ _____ cells

Answer 3

Insulin stimulates K⁺ uptake into cells

Question 4

Epinephrine stimulates the ___ receptor leading to K⁺ uptake by cells

Answer 4

Epinephrine stimulates the beta-2 receptor leading to K⁺​ uptake by cells

(via cAMP regulation of the Na⁺/K⁺ ATPase)

(minor: epinephrine stimulates alpha receptor leading to release K⁺ from cells)

Question 5

In a patient with hyperkalemia, give _____ and _____ together to prevent the fall in glucose that would occur otherwise

Answer 5

In a patient with hyperkalemia, give insulin and glucose together to prevent the fall in glucose that would occur otherwise

(glucose prioritizes stimulation of GLUT transporter to reduce glucose in blood)

Question 6

What factors influence the distribution of K⁺?

Answer 6

• Insulin
• Epinephrine
• Acid-base balance
• Plasma osmolality
• Exercise

Question 7

Metabolic acidosis _____ plasma K⁺

Answer 7

Metabolic acidosis increases plasma K⁺

Question 8

Increased plasma osmolality _____ K⁺ release by cells

Answer 8

Increased plasma osmolality increases K⁺ release by cells

Question 9

Exercise causes _____ of K⁺ _____

Answer 9

Exercise causes release of K⁺​ from skeletal muscle

Question 10

Hyperkalemia causes the membrane to become ______

Answer 10

Hyperkalemia causes the membrane to become less negative (depolarizes)

Question 11

Hypokalemia causes the membrane to become ______

Answer 11

Hypokalemia causes the membrane to become more negative (hyperpolarizes)

Question 12

Describe EKG manifestation of hyperkalemia

Answer 12

EKG manifestation of hyperkalemia

High T wave -> prolonged PR interval, depressed ST segment, high T wave -> auricular standstill, intraventricular block, ventricular fibrillation

Question 13

Describe EKG manifestation of hypokalemia

Answer 13

EKG manifestation of hypokalemia

Low T wave -> low T wave, high U wave -> low T wave, high U wave, low ST segment

Question 14

Most K⁺ is excreted in ______

Answer 14

Most K⁺ is excreted in urine

(insulin and epinephrine are protective factors, if T1DM and take insulin more likely to develop hyperkalemia in setting of K rich diet)

Question 15

In a potassium depleted state, the renal excretion of potassium is ____

Answer 15

In a potassium depleted state, the renal excretion of potassium is low

Question 16

Renal excretion of K⁺ in settings of normal or increased K⁺ intake is _____

Answer 16

Renal excretion of K⁺ in settings of normal or increased K⁺ intake is 15-80%

Question 17

Approximately 67% of the filtered K⁺ is reabsorbed in the ______ and 20% is reabsorbed in ______

Answer 17

Approximately 67% of the filtered K⁺ is reabsorbed in the proximal tubule and 20% is reabsorbed in the loop of Henle

(reabsorption is constant fraction of the amount filtered)

Question 18

K⁺ reabsorption in the proximal tubule and loop of Henle is a constant _____ of the filtered amount

Answer 18

K⁺ reabsorption in the proximal tubule and loop of Henle is a constant fraction of the filtered amount

Question 19

Renal K⁺ secretion occurs in the ______

Answer 19

Renal K⁺​ secretion occurs in the cortical collecting tubule

(secretory pathways are heavily regulated)

Question 20

Early distal convoluted tubule is ______, while late distal convoluted tubule is ______

Answer 20

Early distal convoluted tubule is electroneutral, while late distal convoluted tubule is negative due to Na⁺ transport through ENaC (makes it favorable for K⁺ secretion)

Question 21

Describe secretion of K⁺ in cortical collecting duct

Answer 21

Secretion of K⁺ in cortical collecting duct

1. Na⁺ enters cortical collecting duct through ENaC
2. K⁺ leaves cortical collecting duct through ROMK and Maxi-K⁺

(Maxi-K⁺ responds to flow - if high flow, excretes more K⁺)

Question 22

Describe the factors that regulate K⁺ secretion

Answer 22

Factors that regulate K⁺ secretion

• Activity of Na⁺/K⁺ ATPase
• Ability of K⁺ to cross apical membrane via ROMK (potassium conductance)
• Activity of ENaC Na⁺ channels which creates favorable electrical gradient for K⁺ secretion
• Chemical gradient for K⁺ movement across apical membrane which is also influenced by urine flow (BK channel or Maxi-K)
• Aldosterone which increases activity of Na⁺/K⁺ ATPase and opens ENaC Na⁺ channel

Question 23

Aldosterone _____ the ENaC Na⁺ channel

Answer 23

Aldosterone activates the ENaC Na⁺ channel

Question 24

Main factors and hormones influencing K⁺ secretion include _____, _____, and _____

Answer 24

Main factors and hormones influencing K⁺ secretion include plasma [K⁺], aldosterone, and Na⁺ delivery and transport in the cortical collecting duct

Question 25

Describe Na⁺ channel activity in cortical collecting duct

Answer 25

Na⁺ channel activity in cortical collecting duct

• Luminal Na⁺ depends on distal Na⁺ delivery
• Na⁺ channels (ENaC) in apical membrane regulated by aldosterone
• Na⁺ channel can be blocked by amiloride (has same effect as decreasing luminal Na⁺ - reduces K⁺ secretion by reducing the electrical gradient)

Question 26

_____ and _____ are determinants of CCT secretion of K⁺

Answer 26

Aldosterone and Na⁺ delivery and transport are determinants of CCT secretion of K⁺​

Question 27

Normally mineralocorticoid and distal Na⁺ delivery go in ______ directions and K⁺ secretion ______

Answer 27

Normally mineralocorticoid and distal Na⁺ delivery go in opposite directions and K⁺​ secretion does not change much

Question 28

Normal range of plasma K⁺ is _____

Answer 28

Normal range of plasma K⁺​ is 3.5-4.0 mM

Question 29

Hyperkalemia is plasma K⁺ _____ mM

Answer 29

Hyperkalemia is plasma K⁺​ > 5.0 mM

Question 30

Describe the renal causes of hyperkalemia

Answer 30

Renal causes of hyperkalemia

• Decreased GFR: acute renal failure (oliguric), chronic renal failure (adaptations prevent hyperkalemia)
• Aldosterone deficiency
• Decreased distal Na⁺ delivery or blockade of Na⁺ channels in the cortical collecting tubule

Question 31

As GFR increases, serum K⁺ ______

Answer 31

As GFR increases, serum K⁺​ decreases

(as person ages, GFR decreases so K⁺ increases)

Question 32

Describe factors affecting adrenal aldosterone release

Answer 32

Factors affecting adrenal aldosterone release

• Angiotensin II promotes adrenal aldosterone release
• K⁺ promotes adrenal aldosterone release
• ACTH promotes adrenal aldosterone release
• ANP downregulates adrenal aldosterone release
• Dopamine down regulates adrenal aldosterone release

Question 33

In aldosterone and glucocorticoid deficiency there is _____ cortisol and _____ plasma renin activity

Answer 33

In aldosterone and glucocorticoid deficiency there is low cortisol and high plasma renin activity

Question 34

In selective aldosterone deficiency, cortisol is _____

Answer 34

In selective aldosterone deficiency, cortisol is normal

Question 35

Describe the renin-angiotensin-aldosterone system

Answer 35

Renin-angiotensin-aldosterone system

1. Renin released from kidney
2. Renin cleaves angiotensinogen released by liver to angiotensin I
3. ACE converts angiotensin I to angiotensin II in lung
4. Angiotensin II acts on brain to cause release of AVP and on kidney to cause release of aldosterone
5. AVP and aldosterone act on the kidney

Question 36

Describe iatrogenic causes of renal hyperkalemia resulting from aldosterone deficiency

Answer 36

Iatrogenic causes of renal hyperkalemia resulting from aldosterone deficiency

• Converting enzykme inhibitors: block angiotensin II formation -> block aldosterone release
• Angiotensin II blockers: block angiotensin II receptor -> block aldosterone release
• Chronic heparin therapy: impairs aldosterone synthesis
• Cyclosporin A and Tacrolimus (FK506): decrease secretion of responsiveness to aldosterone
• Spironolactone: inhibits mineralocorticoid receptor
• NSAIDs: release renin secretion normally mediated by prostaglandins

Question 37

Name the Na⁺ channel blockers that cause decreased distal Na⁺ delivery or blockade of Na⁺ channels in the cortical collecting duct

Answer 37

Na⁺ channel blockers that cause decreased distal Na⁺ delivery or blockade of Na⁺ channels in the cortical collecting duct

• Amiloride
• Triamterene
• Trimethoprin
• Pentamidine

Question 38

Acquired defects in potassium excretion include _____, _____, and _____

Answer 38

Acquired defects in potassium excretion include chronic obstructive nephropathy (damage to collecting duct cells impairs both H⁺ and K⁺ secretion), sickle cell disease, and systemic lupus erythematosus

Question 39

Hypokalemia is plasma K⁺ _____

Answer 39

Hypokalemia is plasma K⁺ < 3.5 mM

(symptomatic hypokalemia at 2.5 mM, plasma K⁺ may only be slightly reduced even with substantial body K⁺ depletion)

Question 40

Causes of depletional hypokalemia (low body K⁺) include _____, _____, and _____

Answer 40

Causes of depletional hypokalemia (low body K⁺) include extra-renal losses, renal losses, and low intake

• Extra-renal losses: GI tract losses - vomiting, diarrhea, intestinal fistulas, tube drainage, villous adenoma, laxative abuse
• Renal losses: mineralocorticoid excess, diuretics, Bartter syndrome, Gitelman syndrome, renal tubular acidosis

Question 41

Nondepletional hypokalemia (normal body potassium) results from ______

Answer 41

Nondepletional hypokalemia (normal body potassium) results from transcellular redistribution

Question 42

Causes of hypokalemia associated with metabolic acidosis are _____ and _____

Answer 42

Causes of hypokalemia associated with metabolic acidosis are diarrhea and renal tubular acidosis type I and II

Question 43

Causes of hypokalemia associated with metabolic alklalosis include _____, _____, _____, and _____

Answer 43

Causes of hypokalemia associated with metabolic alklalosis include vomiting, diuretics (thiazide and loop diuretics), Bartter syndrome, Gitleman syndrome

Question 44

Describe hypokalemia associated with HTN

Answer 44

Hypokalemia associated with HTN (BP indicates there is another cause)

• Primary hyperaldosteronism: secondary to adenoma, hyperplasia of adrenal glands
• Cushing’s syndrome: cortisol excess

Question 45

Describe Bartter syndrome

Answer 45

Bartter syndrome: loss of function mutation of Na⁺/K⁺/2Cl^- co-transporter in thick ascending limb

• Hypokalemia (urinary K⁺ wastage)
• Metabolic alkalosis
• Normal or low BP
• Increased plasma renin activity, plasma aldosterone, and urinary prostaglandins
• Resistance to exogenous angiotensin II infusion
• Urinary Ca²⁺ excretion normal or increased
• Plasma Mg²⁺ normal or low

Question 46

Describe Gitelman syndrome

Answer 46

Gitelman syndrome: loss of function mutation of Na⁺/Cl^- symporter

• Milder phenotype than Bartter
• Hypokalemia (urinary K⁺ wasting)
• Metabolic alkalosis
• Normal or low BP
• Increased plasma renin activity and plasma aldosterone
• Low serum Mg²⁺
• Low urinary Ca²⁺ excretion

Question 47

Describe differential diagnosis of metabolic alkalosis with hypokalemia

Answer 47

Differential diagnosis of metabolic alkalosis with hypokalemia

• Cl^- low in vomiting (Cl^- not secreted by kidneys in vomiting)

Question 48

Describe causes of hypokalemia related to transcellular distribution of potassium

Answer 48

Causes of hypokalemia related to transcellular distribution of potassium