Disorders of K balance

Question 1

Factors affecting K distribution

Answer 1

• Insulin and B2 adrenergic receptors induce K uptake by stimulating Na/K ATPase
• Exercise can result in hyperkalemia by A1 adrenergic receptor activation leading to increased K efflux (this is offset by the B2 activation)
• Aldo: lowers serum K by stimulating K uptake into cells and by stimulating kidneys to excrete K
• Increases plasma osmolality causes water to move to ECF, resulting in increase in ICF [K]
• The resultant feedback response is an inhibition of Na/K ATPase and this shifts net K movement to efflux, leading to hyperkalemia and normalizing the ICF [K]

Question 2

Shifting K out of cells

Answer 2

• Can be due to acidosis (H+ displaces K in cells)
• Diabetic ketoacidosis and BBs lead to inhibition of Na/K ATPase and increases net K efflux
• Hemolysis, rhabdomyolysis, tumor lysis all can lead to hyperkalemia

Question 3

Shifting K into cells

Answer 3

• Alkalosis (H+ leaves the cell, K moves in to take its place)
• Insulin and B2 increase Na/K ATPase
• Aldosterone also increases Na/K ATPase

Question 4

Renal K handling

Answer 4

• Regulated at the collecting duct (principal cells secrete, intercalated cells reabsorb)
• Secretion accounts for most of the K excretion (80% of what is filtered is reabsorbed)
• K secretion based on the activity of CCD ENaC (K secretion directly proportional to ENaC reabsorption)
• Intercalated cells actively reabsorb K thru apical H/K ATPase (antiporter)

Question 5

Regulation of K secretion

Answer 5

• In order of importance:
• Luminal flow rate
• Distal Na delivery
• Aldo
• Extracellular K
• Extracellular pH

Question 6

Luminal flow rate on K secretion

Answer 6

• Increasing luminal flow rate increases K secretion b/c it decreases the extracellular K and leads to a larger gradient for secretion
• Osmotic diuresis, increased GFR, decreased Na reabsorption before CCD, diuretics, bartter/gitelmans syndrome all will increase flow rate and can cause hypokalemia
• Decreasing flow rate (low GFR, increased PT Na/H2O reabsorption, obstruction) can decrease K secretion and lead to hyperkalemia

Question 7

K sparing diuretics

Answer 7

• Block ENaC activity and thus reduce K secretion (and H+ secretion)
• Can cause hyperkalemia, possibly acidosis
• Amiloride is ex

Question 8

Other diuretics

Answer 8

• Loop and thiazide diuretics cause K wasting and alkalosis
• Decreasing Na reabsorption before CCD leads to both increased Na delivery to CCD and increased flow
• The increased flow washes out K leading to increased secretion
• The increased Na increases ENaC activity and thus more K secretion and H+ secretion

Question 9

Aldosterone on K secretion

Answer 9

• Aldo increases Na/K ATPase activity and ENaC expression

- Both of these together lead to increase in K secretion

Question 10

Pseudohyperkalemia

Answer 10

• Hemolyzed blood, leukocytosis and thrombocyosis
• Due to ischemia from prolonged tourniquet time or exercise of the limb w/ tourniquet
• Leads to abnormally increased K

Question 11

Types of hyperkalemia (serum K > 5mEq/L)

Answer 11

• Increased K intake
• Decreased urinary K excretion
• K shift from ICF to ECF
• Excessive K ingestion will not lead to hyperkalemia unless other contributing factors are present
• Chronic hyperkalemia cannot occur unless there is decreased K excretion

Question 12

Cell shift hyperkalemia

Answer 12

• Things that move K from inside the cell to outside
• Metabolic acidosis
• Hyperglycemia (osmolarity effect)
• BBs
• Digitalis
• Hyperkalemic periodic paralysis (recurrent attacks of muscle weakness lasting over 1 hr)

Question 13

K intake

Answer 13

• Blood transfusions
• Overdose of IV KCl
• Dietary supplements plus renal failure

Question 14

Decreased K excretion

Answer 14

• Decreased tubular flow either due to renal failure or low ECFV
• Decrease in CCD K secretion rate either due to ENaC block or hypoaldosteronism
• ENaC block causes: amiloride, other K sprain diuretics
• Hypoaldosteronism: type 4 RTA, NSAIDs, ACEI/ARB, heparin, spironolactone
• Type 4 RTA: hyperkalemia that is disproportionate to level of GFR, there is mild CKD, acidosis (but normal urine acidifying ability) and hyporeninemic, hypoaldosteronism
• Underlying diseases: DM, SLE, obstruction, etc

Question 15

Sx of hyperkalemia

Answer 15

• Usually ASx
• Muscle weakness
• Cardiac arrhythmias
• ECG changes: wide QRS, peaked T waves, loss of P waves, short ST int, “sine wave” idioventricular rhythm

Question 16

Rx of hyperkalemia

Answer 16

• Stabilize membrane excitability: CaCl
• Increase K entry to cells (rapid and transient): glc + insulin, B2 agonist (albuterol), NaHCO3
• Removal of excess K (slow but definitive): cation exchange resin (kayexylate), diuretics, dialysis
• Dietary K restriction

Question 17

Risks of Ca

Answer 17

• Do not give in bicarb-containing solutions, chance of precipitation
• Administer only when ECG changes (loss of P waves or widening of QRS) in pts taking digitalis (can induce digitalis toxicity)
• Can cause tissue necrosis if injected SQ
• Can precipitate CaPi in tissue in pts w/ renal failure and hyperphsophatemia

Question 18

Risks of kayexylate

Answer 18

• Can cause intestinal necrosis and severe pain

- Most likely when given w/ sorbitol

Question 19

Pseudohypokalemia

Answer 19

• Serum K artificially decreases after phlebotomy

- Usually due to acute myeloblastic leukemia (blast cells take up the K in the tube)

Question 20

Hypokalemia (serum K < 3.5 mEq/L)

Answer 20

• Can 3 possible causes
• Cellular shift
• GI loss
• Urinary K wasting

Question 21

Cellular shift hypokalemia

Answer 21

• Alkalosis
• Insulin
• B2 agonist
• Hypokalemic periodic paralysis:
• Familial: precipitated by meal or exercise, repetitive episodes of acute profound hypokalemia and paralysis lasting hrs-days
• Thyrotoxic: predominantly asians, 20-40yo, mostly male, only w/ thyrotoxicosis which may be ASx

Question 22

Urinary K wasting

Answer 22

• Due to increased K secretion
• 2 possibilities: increased tubular flow or increased CCD K secretion
• Osmotic diuresis increases tubular flow and thus increases K secretion
• Decreased PT, TAL, DT Na reabsorption leads to increased K secretion
• Increased delivery of Na w/ nonreabsorbable anion to CCD increases K secretion
• Hyperaldosteronism leads to increased K secretion
• Increased membrane permeability
• All of these can cause metabolic alkalosis

Question 23

Bartter’s syndrome

Answer 23

• Due to inactivating mutations in transporters of the TAL
• Mostly NKCC, but also K channels and Cl channels
• Leads to increased Na delivery/flow to CCD and thus hypokalemia/alkalosis

Question 24

Gitelman’s syndrome

Answer 24

• Due to inactivating mutation in the NaCl cotransporter (NCC) in DT
• Leads to increased Na delivery/flow to CCD and thus hypokalemia/alkalosis

Question 25

Increased delivery of nonreabsorbable anions

Answer 25

• HCO3-, ketoanions delivery to CCD will increase K secretion (associated w/ decreased Cl delivery to CCD)
• May be due to vomiting, loss of H+
• Amphotericin can increase membrane permeability to K

Question 26

Hyperaldosteronism

Answer 26

• Can be due to activating mutations of ENaC (liddle’s)
• Can be due to high levels of transcribed/translated Aldo (GRA: glucocorticoid remediable aldosteronism)
• Can be due to LOF mutation of B-hydroxysteroid dehydrogenase, leading to excessive stimulation of Aldo receptor by cortisol, cushings
• Can also be due to high renin: renal artery stenosis, reninoma

Question 27

Sx of hypokalemia

Answer 27

• Usually ASx, muscle weakness, polyuria/polydipsia
• Rhabdomyolysis
• ECG changes: depressed ST segment, flat T wave, prolonged QT, apparent U wave
• Arrhythmias

Question 28

Rx of hypokalemia

Answer 28

• Oral KCl supplements
• IV KCl
• concaminant hypomagnesemia must be corrected
• Amiloride or spironolactone useful in pts w/ hyperaldosteronism