Hypo/HyperKALEMIA

which organ is the primary route of potassium elimination

which organ is the primary route of potassium elimination

the kidney

is potassium freely filtered?

yes, but almost entirely reabsorbed

where is potassium secreted and regulated in the nephron?

the collecting duct (also the loop of Henle)

how is potassium secretion regulated

via aldosterone activity

What are the prinicple cells most involved in?

potassium secretion into the urine

T/F: the serum concentration of potassium is reflective of the bodies levels

False - is mostly intracellular

what are intercalated cells mostly involved in?

potassium reabsorption from the urine back to the blood stream

what process facilitates K excretion in the urine and sodium (with water) reabsorption into the blood stream

mineralocorticoid activation with aldosterone up-regulates expression of Na/K/ATPase, ENaC, and K channels

How do the intercalated cells of the collecting duct allow for potassium reabsorption?

through the K+/H+ antiporter

what contributes to exquisite K regulation in the collecting ducts

action of principle cells (K secretion into urine) and intercalated cells (K reabsorption into blood stream)

what happens to potassium if there is a decrease in urine flow (AKI, pre-renal)

potassium goes up in the luminal fluid and decreases the ability to secrete potassium causing hyperkalemia

what happens to potassium if there is an increase in Na preload in the ultrafiltrate?

potassium secretion increases. More sodium reabsorption increases the flow through the ENaC channels and the Na/K/ATPase pump, which indirectly stimulates potassium secretion into the urine

what happens to potassium if there is blockade of ENaC channel?

Potassium reabsorption decreases. since sodium reabsorption drives potassium secretion, blocking ENaC reduces the amount of sodium available to create a gradient, leading to less potassium secretion into the urine.

what happens to potassium if there is antagonism of aldosterone?

antagonizing aldosterone reduces the activity of transporters such as ENaC and Na/K/ATPase pump. this leads to potassium retention (hyperkalemia) due to decreased sodium reabsorption and reduced potassium excretion

what happens to potassium in hypokalemia

the kidneys try to conserve potassium by increasing potassium reabsorption in intercalated cells by using the K+/H+ antiporter. potassium may also move out of cells into the extracellular soaceslightly increasing serum potassium

what happens to potassium in metabolic acidosis?

potassium is reabsorbed and the patient will pee out more H+ to decrease the acidosis which can lead to hyperkalemia

range for mild hypokalemia

3-3.5 mEq/L

range for moderate hypokalemia

2.5-3 mEq/L

range for severe hypokalemia

< 2.5 mEq/L

common causes of hypokalemia?

GI losses (vomiting, diarrhea, NG suction, Fistula), diuretics (loops), and hypomagnesemia (impairment of Na/K/ATPase pump, increased K renal wasting)

if a patient has hypomagnesemia and hypokalemia which should be treated first?

hypomagnesemia because it is a precursor to hypokalemia

factors that decrease potassium include:

decreased exogenous potassium intake, increased renal/GI potassium losses, and DRUGSw

Which drugs can cause hypokalemia

diuretics (loops), acetazolamide, amphotericin, corticosteroids and mineralocorticoids, cisplatin, penicillin’s, sorbitol, sodium polystyrene sulfonate, beta-2 agonists, and insulin and glucose

which drugs can cause hypokalemia due to renal reasons?

diuretics, acetazolamide, amphotericin, corticosteroids and mineralocorticoids, cisplatin, and penicillin’s

which drugs can cause hypokalemia due to fecal reasons?

sorbitol and sodium polystyrene sulfonate

which drugs can cause hypokalemia due to intracellular shift?

beta-2 agonists, insulin, and glucose

what are the neurological clinical presentations of hypokalemia

hyperpolarization of resting membrane potential leading to decreased muscle contraction, cramping, weakness, fatigue, and effects on the lower, and upper extremities, and respiratory muscles

what are the cardiovascular clinical presentations of hypokalemia?

arrhythmias (heart block, atrial flutter), EKG abnormalities (T-wave inversion, narrowing QRS, bradycardia, ST depression)

goals of hypokalemia treatment:

get the potassium levels to 4-4.5 mEq/L, prevent arrythmia, reverse symptoms, and correct underlying cause

treatment for hypokalemia if K = 3-3.5 mEq/L

increase potassium rich foods, and provide potassium supplementation IF underlying cardiac disease (or on digoxin)

treatment for hypokalemia if K = < 3mEq/L

give potassium supplementation

how to treat patients with asymptomatic hypokalemia?

oral supplementationh

how to treat patients with severe/symptomatic hypokalemia?

IV supplementation with close monitoring

which foods are high in potassium :)

dried fruits, bananas, oranges, kiwi, squash, broccoli, lentils, potatoes, tomatoes, vegetable juices, peanut butter, nuts, yogurt, milk, granola, bran, and chocolate

recommended daily allowance of potassium:

50 mEq/day

what amount of potassium does JNC VII recommend people have daily?

100 mEq/day to prevent HTN and CV complications

If we are concerned about a patient developing hypokalemia and want to give them preventative medication, what can we do?

give them KCl 20 mEq/day

overall treatment dosing for hypokalemia:

Every 1 mEq/K potassium deficit give 100-400 mEq total body potassium deficit. Give 40-100 mEq KCl/day

which potassium supplement is the most common

potassium chloride (most hypokalemic patients are often hyperchloremic as well)

which potassium supplements are can be/are typically given IV?

potassium chloride and phosphate

when is it beneficial to give potassium bicarbonate?

it patient has metabolic ketoacidosis or if patient wants a potassium that comes in effervescent tablets

ADRs of oral potassium supplements:

GI-irritation and erosion

ADRs for IV potassium supplements:

thrombophlebitis, transient hyperkalemia, and pain/burning at infusion site

which forms of potassium supplements have lower GI effects?

controlled-release microencapsulated tablets and encapsulated controlled-release microencapsulated particles

which potassium supplements are easier to swallow but have more GI erosions compared to other therapies?

Wax-matrix extended-release tablets

how are IV potassium supplements prepared?

in sodium chloride solution (NS or ½ NS)

Why should IV potassium supplements not be prepared in D5W?

can worsen hypokalemia as it shifts K+ to the ICF

peripheral administration of potassium supplements:

10-20 mEq/100 mL infused over 1 hour (at the fastest)

central administration dosing of IV potassium supplements:

40 mEq/100 mL infused over 1 hour

when do patients need to receive continuous ECG monitoring?

receiving > 10 mEq/hr of potassium supplementation

when do you recheck potassium levels in patients receiving IV potassium supplementation?

Always recheck after each 40 mEq supplementation to avoid hyperkalemia

What other treatment options exist for hypokalemia besides supplementation?

remove the offending agent(s) if able (such as loops or thiazides), if a patient is on a thiazide and slightly hypokalemic you can put them on a potassium-sparing/HTCZ combo pill such as Dyazide, and supplement loop/thiazide diuretics with low dose daily KCl

What are the clinical pearls for hypokalemia?

Must correct hypomagnesemia first (get to 2 mEq/L)

10 mEq K for each 0.1 mEq/L increase in serum K.

10 mEq KCl = 10 mmol KCl = 750 mg KCl = 390 mg elemental potassium

how can you orally correct hypomagnesemia

give magnesium oxide 400-800 mg BID

how can you correct hypomagnesemia via IV treatment?

give magnesium sulfate 2-4 grams infused over 2-4 hours

Causes of hyperkalemia

increased intake of dietary potassium, decreased renal potassium excretion, renal tubular unresponsive to aldosterone, pseudohyperkalemia, rhabdomyolysis, burn injuries, drugs

what is psuedohyperkalemia?

re-distribution of K+ to the extracellular space causing labs to be elevated

why do rhabdomyolysis and burns cause hyperkalemia

cells lyse so intracellular potassium is released to the ECF

clinical presentation of hyperkalemia

frequently asymptomatic, palpitations, serum K+ > 5.5 mEq/L, and ECG changes

What is the early EKG sign/finding that tells us we need to fix the hyperkalemia quickly?

Peaked T-waves

What are examples of hyperkalemia ECG changes?

Peaked T-waves, Prolonged PR interval, Loss of P wave, Widening of QRS, and sine-wave pattern

How does acid/base imbalance affect potassium

metabolic acidosis leads to an increase in potassium concentrations - every 0.1 units decrease in pH leads to 0.6-0.8 mEq/L increase in [K]

how does hyperosmolality affect potassium

there is an increase in potassium concentration for each 10 mOsm/kg increment (transcellular shift, pulling tonicity out of the cell)

how does cell lysis / cell destruction affect potassium?

increases potassium concentrations secondary to release from intracellular stores

how does renal failure affect potassium?

increase in potassium concentrations especially if AKI or exogenous supplementation is given (kidneys can’t excrete potassium)

Which drugs can cause hyperkalemia?

ACEi/ARB/Direct Renin Inhibitors, Beta-blockers, digoxin, potassium containing drugs (salt substitutes and high potassium foods), aldosterone antagonists, K sparing diuretics, unfractionated heparin, cyclosporin/tacrolimus, NSAIDs

how do ACEi/ARBs/ Direct Renin Inhibitors cause hyperkalemia

due to inhibition of RAAS - hypoaldosteronism and impaired potassium excretion

Why do poor renal patients on ACEi/ARB/Direct renin inhibitors need very aggressive potassium monitoring?

there is a decrease in potassium reserves and ability to excrete potassium

how do beta-blockers cause hyperkalemia

impaired cellular uptake (transcellular potassium shift) and inhibition of renin release

how does digoxin cause hyperkalemia

via its MOA that inhibits the Na/K/ATPase channel

how do potassium containing drugs cause hyperkalemia?

via increased exogenous K load

Which electrolyte is in Penicillin G

potassium - can lead to hyperkalemia

how doe aldosterone antagonist’s cause hyperkalemia

they block aldosterone effects which can be problematic when combined with ACEi/ARBs or patients with renal insufficiency

how do potassium sparing diuretics cause hyperkalemia

they block the ENaC channel which leads to impaired potassium secretion (these drugs prevent potassium loss)

how does heparin cause hyperkalemia

it has some aldosterone production inhibition - usually from therapeutic doses and not prophylaxis

how does cyclosporine/tacrolimus cause hyperkalemia

via impaired potassium secretion

how do NSAIDs cause hyperkalemia

impaired potassium secretion

which causes hypokalemia via transcellular shift pushing serum potassium into the cell

insulin, beta-agonists, alkalosis, and alpha antagonists

which causes hyperkalemia due to transcellular shift of potassium out of the cell (in exchange for a proton)

acidosis, hyperglycemia, beta-2 antagonists, alpha agonists, increase in osmolality, and exercise

When is hyperkalemia typically present in CKD

when there is severe reduction in GFR, usually < 30 (CKD4 and 5)

how do nephrons adapt to hyperkalemia in CKD?

they excrete more potassium and maintain normokalemia - regulated by aldosterone activity

which disease state has reduced capacity for potassium excretion and patients struggle with large potassium intake (loads)

CKD

How can CKD patients remove excess potassium that the kidneys cannot excrete?

fecal potassium excretion

Which medications are used in CKD and can cause hyperkalemia

ACEi/ARBs, aldosterone antagonists (finerenone), and beta-blockers

What classifies emergent hyperkalemia?

a potassium level > 7 mEq/L or potassium levels 5.5-6.9 mEq/K WITH ECG changes

acute/emergent goals of hyperkalemia treatment

prevent arrhythmias, reversal of symptoms, K < 5.5 mEq/L within minutes

chronic hyperkalemia goals of treatment?

maintain K 4-5 mEq/L, prevent symptoms and arrhythmia, optimize underlying cause with a treatment that produces good potassium levels

what is the broad treatment algorithm for hyperkalemic emergency?

1. determine they have high potassium levels

2. determine if the ECG is normal

3. Transient therapy to quickly shift potassium into cells

4. remove excess potassium from the body

5. address underlying cause

if the ECG is abnormal for a patient with hyperkalemic emergency what should be given?

1 gram of IV calcium gluconate to stabilize cardiac myocytes

what should be done in a hyperkalemic emergency if the patient does not have an abnormal ECG?

continuous ECG monitoring (telemetry)

what are the transient therapy options for hyperkalemic emergency

regular insulin 10 units IV + 25 grams of dextrose if euglycemic, consider 50-100 mEq IV sodium bicarbonate if acidotic (pH < 7.3), consider albuterol nebulizer if unable to gain intravenous access

why is insulin + glucose most often used in hyperkalemic emergency?

has a predictable response, is safe, and relatively easy to give

T/F: IV calcium gluconate affects serum potassium concentrations

False!

what are the three ways excess potassium can be removed from the body

poopy, pee pee, and blood

What are the three examples to remove excess potassium from the body in hyperkalemic emergency

give sodium polystyrene sulfonate 15-30 grams PO, intravenous loop diuretics (if patient makes urine), or emergent hemodialysis (LAST LINE)

onset of calcium gluconate or chloride

1-2 minutes

duration of action for calcium gluconate or chloride

10-30 minutes

onset of furosemide (IV)

5-15 minutes

duration of action for furosemide (IV)

4-6 hours

which hyperkalemic treatments have an onset of 30 minutes?

regular insulin, dextrose 10%, dextrose 50%, sodium bicarbonate, and albuterol