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Ninety-eight percent of body K is intracellular. Only 2% of total body potassium, about

70 mEq, is in the extracellular fluid where the normal concentration of 3.5-5 mEq/L.
I. Pathophysiology of Potassium Homeostasis

A. The normal upper limit of plasma K is 5-5.5 mEq/L, with a mean K level of

B. External Potassium Balance. Normal dietary K intake is 1-1.5 mEq/kg in

the form of vegetables and meats. The kidney is the primary organ for

preserving external K balance, excreting 90% of the daily K burden.

C. Internal potassium balance, potassium transfer to and from tissues, is

affected by insulin, acid-base status, catecholamines, aldosterone, plasma

osmolality, cellular necrosis, glucagon, and drugs.

II. Clinical Disorders of External Potassium Balance

A. Chronic Renal Failure. The kidney is able to excrete the normal dietary

intake of potassium until the glomerular filtration rate falls below 10 cc/minute

or until urine output falls below 1 L/day. Renal failure is advanced before
hyperkalemia occurs.

B. Impaired Renal Tubular Function. Renal diseases may cause

hyperkalemia, and the renal tubular acidosis caused by these conditions may

worsen hyperkalemia.

C. Primary Adrenal Insufficiency (Addison's disease) is now a rare cause of


1. Diagnosis is indicated by the combination of hyperkalemia and

hyponatremia and is confirmed by a low aldosterone and a low plasma

cortisol level that does not respond to adrenocorticotropic hormone

2. Treatment consists of glucocorticoid and mineralocorticoid agents and

volume replacement with normal saline.

D. Drugs are among the most common causes of hyperkalemia, including

nonsteroidal anti-inflammatory drugs, angiotensin-converting enzyme

inhibitors, cyclosporine, and potassium-sparing diuretics. Hyperkalemia is
especially common when these drugs are given to patients at risk for
hyperkalemia (diabetics, renal failure, hyporeninemic hypoaldosteronism,
advanced age).
E. Excessive Potassium Intake

1. Long-term potassium supplementation results in hyperkalemia most often

when an underlying impairment in renal excretion already exists.
2. Oral ingestion of 1 mEq/kg may increase the serum K level by 1 mEq/L an
hour afterward in normal individuals. Intravenous administration of 0.5

mEq/kg over 1 hour increases serum levels by 0.6 mEq/L. Hyperkalemia

often results when infusions of greater than 40 mEq/hour are given.

3. Acute K overload may result from infusion from the dependent portion of

an unmixed potassium solution or from ingestion of salt substitutes.

III. Clinical Disorders of Internal Potassium Balance

A. Diabetic patients are at particular risk for severe hyperkalemia because of

renal insufficiency and hyporeninemic hypoaldosteronism.

B. Systemic acidosis reduces the excretion of potassium and may cause


C. Endogenous potassium release from muscle injury, tumor lysis, or

chemotherapy may elevate serum potassium.

IV. Manifestations of Hyperkalemia

A. Hyperkalemia, unless severe, is usually asymptomatic. The effect of

hyperkalemia on the heart becomes significant above 6 mEq/L. As levels

increase, the initial ECG change is tall peaked T waves. The QT interval is
normal or diminished.

B. As K levels rise further, the PR interval becomes prolonged, then the P wave

amplitude decreases. The QRS complex widens into a sine wave pattern,
with subsequent cardiac standstill.
C. At serum K levels of >7 mEq/L, muscle weakness may lead to a flaccid
paralysis that spares cranial nerve function. Sensory abnormalities, impaired
speech, and respiratory arrest may follow.

V. Pseudohyperkalemia

A. Potassium may be falsely elevated by hemolysis during phlebotomy, when K

is released from ischemic muscle distal to a tourniquet, and because of
erythrocyte fragility disorders.
B. Falsely high laboratory measurement of serum potassium may occur in
normokalemic subjects who have a markedly elevated platelet (>I06
platelet/mm3) or white blood cell (>50,000/mm3) counts.
VI. Diagnostic Approach to Hyperkalemia

A. The serum K level should be repeat tested to rule out laboratory error. If
significant thrombocytosis or leukocytosis is present, a plasma potassium
level should be determined.

B. Measure 24 hour urine output, urinary K excretion, blood urea nitrogen, and

serum creatinine. Renal K retention is diagnosed when urinary K excretion

is less than 20 mEq/day.

C. High urinary K and K excretion >20 mEq/day is indicative of excessive K

intake as the cause.

VII. Renal Hyperkalemia

A. If urinary K excretion is low and urine output is in the oliguric range and

creatinine clearance is lower than 20 cc/minute, renal failure is the probable

cause. Prerenal azotemia resulting from volume depletion must be ruled out
because the hyperkalemia will respond to volume restoration.

B. When urinary K excretion is low, yet blood urea nitrogen and creatinine levels

are not elevated and urine volume is at least 1 L daily and renal sodium

excretion is adequate (about 20 mEq/day), then either a defect in the

secretion of renin or aldosterone or tubular resistance to aldosterone is likely.

Low plasma renin and aldosterone levels, will confirm the diagnosis of

hyporeninemic hypoaldosteronism. If plasma aldosterone is low despite high

renin values, the use of heparin should be suspected. Addison's disease is

diagnosed by a low serum aldosterone.
C. When inadequate K excretion is not caused by hypoaldosteronism, a tubular

defect in K clearance is suggested. Urinary tract obstruction, renal transplant,

lupus, or a medication should be considered.
VIII. Extrarenal Hyperkalemia

A. When hyperkalemia occurs along with high urinary K excretion of >20

mEq/day, excessive intake of K is the cause. Potassium excess in IV fluids,
diet, or medication should be sought. A concomitant underlying renal defect
in K excretion is also likely to be present.
B. Blood sugar should be measured to rule out insulin deficiency; blood pH and
serum bicarbonate should be measured to rule out acidosis.
C. Endogenous sources of K, such as tissue necrosis, hypercatabolism,
hematoma, gastrointestinal bleeding, or intravascular hemolysis should be
IX. Management of Hyperkalemia

A. Acute Treatment of Hyperkalemia

1. Calcium Chloride

a. If the electrocardiogram shows loss of P waves or widening of QRS

complexes, calcium chloride should be given IV; calcium reduces the

cell membrane threshold potential but will not lower the potassium


b. Calcium gluconate 10% should be given as 2-3 ampules over 5

minutes. In patients with circulatory compromise, 1 ampule of calcium

chloride IV should be given over 3 minutes.

c. If the serum K level is greater than 7 mEq/L, calcium should be given

because of imminent cardiac toxicity. If digitalis intoxication is

suspected, calcium must be given cautiously. Coexisting hyponatremia

should be treated with hypertonic saline.

2. Insulin

a. If the only ECG abnormalities are peaked T waves and the serum level

is under 7 mEq/L, treatment should begin with insulin (regular insulin,

5-10 U by IV push) with 50% dextrose water (D50W) 50 mLs IV push

(unless the blood sugar is already substantially elevated).

b. Repeated insulin doses of 10 U and glucose can be given every 15

minutes for maximal effect.

3. Sodium Bicarbonate

a. Bicarbonate promotes cellular uptake of K, and it should be given as

two 50-mEq ampules IV push.

b. Bicarbonate should be avoided if severe heart failure or hypernatremia.
If the serum calcium is low (as in uremic acidosis), calcium should also

be given in a separate IV line to avoid hypocalcemic tetany during alkali

4. Potassium Elimination Measures

a. Furosemide (Lasix) 100 mg IV should be given immediately to promote

kaliuresis; normal saline may be added to avoid volume depletion.
b. Sodium polystyrene sulfonate (Kayexalate) is a cation exchange resin
that binds stool K. Dosage is 30-60 gm with 50 cc of 20% sorbitol
orally. A retention enema of 50-60 gm in 200 cc of 20% sorbitol has a
more rapid effect.

c. Emergent hemodialysis for hyperkalemia is not usually necessary, even

in renal failure. §