Potassium

Hypokalemia (low potassium) has been found in >90% of hypertensive patients with primary aldosteronism (Conn syndrome). This uncommon entity is a curable cause of hypertension. Low potassium occurs with endogenous or exogenous increase in other corticosteoids, including that in Cushing syndrome, as well as with dietary or parenteral deprivation of potassium (e.g., parenteral therapy without adequate potassium replacement). Hypokalemia occurs with vomiting, diarrhea, fistulas, laxatives, diuretics, burns, excessive perspiration, Bartter syndrome, some cases of alcoholism and folic acid deficiency, in alkalosis and in renal tubular acidosis, as well as in other entities. Low potassium is much more significant with a low pH than with a high pH. When pH increases by 0.1, potassium decreases approximately 0.6 mmol/L. With low pH, as in ketoacidosis, as therapeutic adjustment towards normal is made, plasma/serum K(+) levels will decrease. Phosphorous levels tend to follow potassium levels downwards during therapy of diabetic ketoacidosis; both are largely intracellular. With insulin therapy (and increased utilization of carbohydrates), potassium moves into cells and serum/plasma level falls. Hyperalimentation may have a similar effect. Hypokalemia has been reported in slightly more than one-half of a series of 32 patients with acute myelogenous leukemia,¹ but thrombocytosis can increase serum potassium levels, vide supra. Thiazide/chlorthalidone therapy may cause hyperuricemia and hypercalcemia as well as hypokalemia. The watery diarrhea-hypokalemia-achlorhydria (WDHA) syndrome most often is related to vasoactive intestinal polypeptide (VIP).

Hyperkalemia (high potassium) reflects generally inadequate renal excretion, mobilization of potassium from the tissues or excessive intake or administration. Hyperkalemia occurs with hemolysis, trauma, with administration of potassium salts of some drugs, Addison disease, acidosis, insulin lack, with increased osmolality (e.g., glucose, mannitol), and in other entities as well as with renal diseases. Increased potassium can occur with potassium sparing diuretics, nonsteroidal anti-inflammatory drugs, especially in the presence of other factors. 

A discussion of the relation between lactic acidosis and ketoacidosis and elevated serum potassium levels is provided in a paper by Fulop.² Drug effects are summarized.³

Pseudo hyperkalemia (PHK), or falsely elevated potassium, occurs due to a wide range of pre-analytical factors, include specimen collection, processing and handling, and certain physiological factors.^4,5 Any one or a combination of the following may result in a falsely elevated potassium:

Collection^4,5

• fist clenching—causes local release of potassium during contraction of forearm muscles
• prolonged tourniquet application—causes hemoconcentration and possible hematoma affecting water balance of cells and cell lysis that can lead to elevated potassium
• traumatic collection (mechanical factors)—cell lysis due to mechanical factors such as the use of smaller gauge needles (e.g., use of butterfly needle), excessive force with syringe draws and vigorous mixing may increase the risk of cell lysis
• incorrect order of collection or draw—collection of K+EDTA sample immediately prior to drawing an SST can cause carryover of the additive into serum tubes causing artificially elevated potassium
• contamination at blood draw—collection/draw above intravenous infusion site may potentially contaminate the sample with IV fluids containing potassium, use of potassium containing antiseptic at the draw site

Processing and handling^4,5

• prolonged exposure of serum or plasma to cells—blood cells continue glycolysis in vitro in the collection tube. As the glucose is consumed, the Na+K+ATPase that maintains intracellular electrolyte concentration ceases to function
• allowing serum samples to clot refrigerated—cold temperatures inhibit the function of Na+K+ATPase that maintains intracellular electrolyte concentration. Since cells contain a high concentration of potassium, it leaks out, causing in vitro elevation of potassium
• re-centrifugation—causes potassium rich RBCs to release potassium during the re-spinning process
• inappropriate centrifugation or improperly spun sample—RBCs can contaminate the separated serum and release potassium into the sample

Physiological factors that may cause in vitro potassium elevation

• Hematologic disorders^7-9
  • Thrombocytosis—platelets release potassium during the clotting process. With marked thrombocytosis, the potassium contribution from platelets can significantly increases serum potassium in vitro. A platelet count of >500*10³ cells/µl has been shown to significantly alter measured serum potassium. Plasma potassium is not impacted
• Leukocytosis—leukemic white blood cells are abnormally fragile and susceptible to lysis during sample handling. Markedly elevated leukocytes may cause an in vitro elevation in potassium from white blood cell lysis. Both serum and plasma samples may be impacted with plasma sample being more vulnerable. The risk of PHK increases as leukocyte count increases in which CLL and AML patients are particularly susceptible due to WBC fragility
• Familial pseudo hyperkalemia⁶—This is a rare hereditary condition that results in "leaky" red cells in which RBCs show a temperature-dependent leakage of potassium when stored at room temperature

Employing appropriate draw techniques and handling is imperative in maintaining physiological potassium level representative of the patients' value at the time of draw.