1 Introduction

Emanuel Revici used serum potassium and total blood potassium as metrics in Research in Physiopathology as Basis of Guided Chemotherapy: With Special Application to Cancer.

Here we discuss using intracellular and extracellular potassium (and metrics computed from them) as biomarkers. These biomarkers can be used to both monitor and guide treatment. The approach discussed is based on Revici’s work, but is somewhat different.

This approach uses serum potassium and red blood cell potassium to calculate total body potassium status and estimated membrane potential using the Nernst equation for potassium.

2 Revici’s Interpretation of Potassium

Revici classified potassium as a cellular level element. As such he looked at the relative values at the cellular level (ICF) compared to the tissue level above (ECF).

The serum potassium measurement is a standard part of a blood panel. To measure the ICF Revici used a total blood potassium measurement described in Chapter 4, Note 8. Given that potassium is primarily present inside cells (~98%) the total blood value can be used as a proxy for the RBC potassium value (as measured by current lab tests). The only issue is they have different values. Here is an attempt to arrive at a conversion factor.

Assuming the influence of the serum K on the total blood K is neglible we can estimate the intracellular K from \(K_{TB} = K_{RBC} \cdot Hematocrit\) giving us \(K_{RBC} = K_{TB} \div Hematocrit\) for a typical RBC value of 90.5 corresponding to Revici’s typical total blood value of 38 (given an estimated hematocrit of 42% we compute 38 / 0.42 = 90.5). This corresponds well with the \(K_{RBC}\) normal values seen (~90).

Figure 127 from Revici’s book captures Revici’s interpretation of the blood potassium values. The serum and total blood potassium levels indicate both relative excess/deficiency and anaerobic/dysaerobic status.

Serum vs Total Blood K

3 Our Interpretation

Our interpretation retains the use of serum and total blood potassium levels to indicate both relative potassium excess/deficiency and anaerobic/dysaerobic status. The difference lies in how the status is determined.

For relative excess/deficiency we use a calculation of total body potassium based on the ICF/ECF volumes and potassium concentrations. It will be shown that this depends almost entirely on the ICF (RBC) potassium concentration.

For anaerobic/dysaerobic status we use the potassium Nernst potential. This association is speculative, but is based on the importance of the cell membrane voltage physiologically and the fact that the primary determinant of the cell membrane voltage is the potassium Nernst potential across the cell membrane.

The focus in this series of articles is on the potassium Nernst potential as an indicator of anaerobic/dysaerobic status, but both biomarkers are discussed here for completeness.

4 Total Body Potassium

Total body potassium is a straightforward calculation (28L and 14L are estimated typical intracellular and extracellular fluid volumes). \[ K_{tot} = 28L \cdot K_{ICF} + 14L \cdot K_{ECF} \] Here is a contour plot showing how total body potassium varies with the blood potassium measurements (the axes are similar to Figure 127 above).

We clearly see how total body potassium depends largely on RBC (intracellular) potassium.

The quantitative value of \(K_{tot}\) may be useful for estimating how much potassium to supplement, if deficient.

5 Potassium Nernst Potential

The Nernst potential for potassium (\(E_k\)) is calculated using the Nernst equation. \[ E_k = -V_t \cdot \ln \left( \frac{[K^+]_o}{[K^+]_i} \right) \] where \(V_t = \frac{kT}{q}\)
At body temperature (37C) this simplifies to \[ E_k = -27mV \cdot \ln \left( \frac{[K^+]_o}{[K^+]_i} \right) \]

Note that this is only an approximation of the actual resting membrane potential since it ignores the other ions (e.g. sodium and chloride). For perspective, in a neuron at rest \(E_k\) might be -86mV while the resting membrane potential was -65mV (Guyton and Hall, Textbook of Medial Physiology 9e, page 575). For further detail see the Goldman-Hodgkin-Katz Equation Calculator and notice that the resting membrane potential depends on the permeabilities and concentration gradient of each of the ions.

Using serum potassium as \([K^+]_o\) and RBC potassium as \([K^+]_i\) we create the following plot (again, the axes are similar to Figure 127 above).

We can see the correspondence between this and Revici’s Figure 127 Anaerobic and Dysaerobic quadrants. The general trend is the same from upper left (Dysaerobic, depolarized membrane) to lower right (Anaerobic, hyperpolarized membrane), but the classification of intermediate points is more precise. Individual lab test results can be plotted on this graph to indicate past and current status.

We should be able to quantify the expected variation of \(E_k\) given that RBC potassium is (believed to be, over short time durations) a relatively stable measurement. Furthermore there is literature about the variation of serum K (e.g. circadian rhythm, gender, menstrual cycle).

Note that the usual expectation is that serum K and RBC K tend to vary together. It is important to notice that the most extreme values for \(E_k\) occur when this is not the case (i.e. one is high and the other low).

6 Conclusions

Total body potassium (\(K_{tot}\)) and potassium Nernst potential (\(E_k\)) are physiologically meaningful quantitative values which are proving useful as biomarkers in clinical practice.

Part II of this series will be a case study demonstrating the use of these biomarkers to monitor and guide treatment with Revici’s Therapeutic Lipids.