Case Published: December 2018
Diagnosis: Pseudohyperkalemia due to leukocytosis and pneumatic tube transport
Case Summary: There aren’t many labs that can get a physician’s heart racing like hyperkalemia (hyperK)! The key is rapid evaluation to identify the etiology and initiation of treatment if required. For this case, we’ll focus on the etiologies of hyperK and save the treatment for another case.
Potassium stores in the body are mainly intracellular, with the intracellular concentration being 140 meq/L and the extracellular 4-5 meq/L. The Na-K ATPase is responsible for pumping 2 potassium ions into the cell and 3 sodium ions out, and maintains the resting membrane potential which is important for both muscle (including the heart!) and neural function.
We’ll review the chart below as we cover etiologies of both true and “pseudo” hyperK:
So, why does hyperK happen? After intestinal absorption (unless potassium is administered intravenously), potassium is mainly excreted by the kidney in response to increased potassium levels, increased aldosterone, and increased salt and water delivery to the distal tubule. Thus, decreased urinary excretion of potassium and hyperK can result from acute or chronic kidney injury or a disruption in one of these 3 mechanisms.
As there are significant intracellular potassium stores, increased release of potassium from these cells, transcellular shift of potassium, or efflux of potassium through channels or transporters into the extracellular space can also elevate serum and plasma potassium levels. For example, in metabolic acidosis, higher concentration of protons and need for intracellular buffering leads to subsequent potassium efflux to maintain electroneutrality. As β2-receptor agonism and insulin both promote intracellular entry of potassium, β-blockers and insulin deficiency may lead to hyperkalemia. Rigorous exercise and decreased ATP levels may lead to clinically significant hyperkalemia due to exit of potassium through channels normally inhibited by ATP.
Red blood cells (RBC) can also be the culprit – potassium can leak out of RBC during storage prior to transfusion, during episodes of hemolysis, or in the case of gastrointestinal absorption in the setting of a GI bleed. Like hemolysis, tumor lysis syndrome and crush injury (think rhabdomyolysis) also lead to cellular breakdown and the release of intracellular contents – including potassium.
Back to our patient – she did not seem to meet any of the criteria above and presented with normal kidney function – and also did not present with electrocardiogram changes (ECG) that we would expect with such a high potassium level. Her WBC is markedly elevated, suggesting a diagnosis of hematologic malignancy. Can we believe the test? In other words, is this true hyperkalemia or “pseudohyperkalemia” (pseudohyperK) : an elevation of the serum K without clinical evidence of hyperK. PsuedohyperK should be suspected in individuals with an elevated K level without risk factors for hyperK as outlined above and without ECG changes in cases of severe hyperK (i.e. peaked T-waves, prolongation of QRS, bradycardia).
Causes of pseudohyperK include release of intracellular potassium into the collection vial after collection due to high cell numbers or fragility of cell membranes (platelets, WBC), tube additives (heparin, EDTA), delayed processing, or cold sample storage. Prolonged tourniquet use or excessive fist clenching prior to sample collection can also lead to K release from skeletal muscle cells. Traumatic venipuncture may also lead to hemolysis and K release.
In patients with chronic lymphocytic leukemia (CLL) and high WBC counts, pneumatic tube transport of samples can also lead to membrane disruption of WBC – the likely culprit of pseudohyperK in this patient. In these cases, specimens can be taken to the lab without use of the pneumatic tube or analyzed with the use of a bedside blood gas analyzer that does not require transport to the lab.
The mean difference between serum and plasma K has been reported to be around 0.4 meq/L, with the serum concentration being slightly higher due to the release of potassium from platelets. In cases of thrombocytosis (usually platelets > 1,000 x 109/μl) and leukocytosis, (usually WBC > 100 x 109/μL), the serum potassium may be falsely elevated due to potassium release and a plasma potassium can be more accurate.
To complicate things a little more, plasma samples from patients with severe leukocytosis may reveal hyperK while the serum K is normal – a phenomenon known as “reverse pseudohyperK.” Heparin is used as the anticoagulant in plasma samples, and may contribute to WBC membrane destruction.
For a more in-depth look:
- Asirvatham JR, Moses V, Bjornson L: Errors in Potassium Measurement: A Laboratory Perspective for the Clinician. N Am J Med Sci 5: 255–259, 2013
- Meng QH, Wagar EA: Pseudohyperkalemia: A new twist on an old phenomenon. Critical Reviews in Clinical Laboratory Sciences 52: 45–55, 2015
- Pseudohyperkalemia and Platelet Counts. New England Journal of Medicine 325: 1107–1107, 1991