This relationship, which is also critical for the understanding of the pharmacology of the elements, can be summarized in the following table:

Amount of Element at the Proper Level

Amount of Element at the Higher Level

Interpretation: Occurrence at the Proper Level

high

high

quantitative excess

low

high

qualitative insufficiency

high

low

qualitative excessive

utilization

low

low

quantitative deficiency

From a practical point of view, we must have information on the amount of the element both at the proper level and at a higher level. We found that for the elements proper to the cellular level, such information can be obtained by comparing the amounts in plasma and red cells (or total blood). It is not the ratio between these values—as often supposed— which is important, but rather the values themselves. For changes at the systemic level, the comparison can be made between blood and urine, the latter corresponding to the level above the systemic.

The importance of this concept can be seen in the following examples. Potassium is a cellular level element. In cancer, in offbalance type A, potassium is present in abnormally high quantity in proliferating cells. It is also found in high amounts in blood red cells. In these cases, potassium is found in low values in the hierarchically higher level in the blood plasma or serum. The abnormality does not reside in a simple hypokaliemia, but in excessive utilization of potassium at the cellular level, a low amount of potassium in red cells also would indicate a potassium deficiency. A high amount of potassium in serum and red cells can be interpreted, as mentioned above, as corresponding to a quantitative excess. The reduction in the quantity of potassium in red cells, together with an excess in the serum, indicates a qualitative deficiency at the proper level.

We have the true picture of the situation if we consider that "qualitative" excess or deficiency is determined by the ability to form the proper compounds. While it is the element as such which has to be administered in order to correct a quantitative deficiency, other factors must be changed to overcome qualitatively deficient utilization, excessive utilization, and quantitative excess. (Fig. 127)

The relationship between the amount of potassium in serum

Fig. 127. The relationship between the amount of potassium in serum and in total blood permits to indicate the existing condition as being in normal limits, in quantitative deficiency or excess, or in an offbalance type A or D.

Although these relationships represent the most important aspect of the pharmacodynamy of the elements, still others must be considered. An excess or deficiency of an element at a superior level, even if it serves as a biological defense means to combat an abnormality at a lower level, represents a problem by itself for the superior level. The fact that the element does not belong to this level gives a noxious character to its influence. The influence exerted upon sensitive organs often induces important abnormal manifestations. Hyperkalemia, even originated by an abnormally low utilization of potassium at the cellular level, can lead to serious troubles in the function of the nervous system or of the heart.

Another important aspect of the reactivity of an element is its influence upon levels below its proper level. An element acting at a lower level usually has a biologically opposite effect to what it has at the proper level and therefore is a noxious influence. At the lower level, the A or D type of activity of the element is reversed.

Sodium, for instance, which is an agent of the A type of the metazoic compartment, produces an offbalance of type D at the cellular level, which is hierarchically inferior to its own. Similarly, Mg, which is a D agent at its own metazoic level, has an A inducing activity at the cellular level.

Analysis of the pharmacology of elements in terms of their A or D inducing activity, the level at which they belong and the compounds through which they act, is still only in its early stages although it represents a program of great promise. In the presentation which follows, we will try to interpret the data concerning the elements in terms of A and D inducing activity. We start with Hm elements having a D inducing activity. They parallel in their action the lipoids, with a negative polar group. Table XVII lists Hm elements or the D series and relates them through their periods to the organizational compartments.

Table XVII. Hm Elements

Compartments

Metals

Non Metals

Organic

Be

C O

Metazoic

Mg

Si S

Cellular

Ca Sc

V

Mn

Co

Cu

Ge

Se

Nuclear

Sr Y

Nb

Tc

Rh

Ag

Sn

Te

Submorphol.

Ba

Ta

Re

Ir

Au

Pb

Primary Biol.

Ce

Nd

Sm

Gd

Dy

Er

Yb

Submolecular

Ra Th

U

Pu

Cm

Cf

We have already discussed the pharmacological activity of sulphur and selenium through the compounds in which they enter and will not discuss them again here. Before analyzing the other elements, it is of interest to emphasize again a principal character of their activity. As most of the elements act through specific compounds, the factors which determine the entry of elements into specific biological combinations appear to be of capital importance. Availability of the element alone is only one factor in its pharmacodynamy. With this in mind, we have investigated some of the elements of this Hm group.

We know little about any influence of berryllium as a metal upon the organism as an entity. Its toxic effects are due to abnormal amounts active at lower levels. In the same period of the chart of elements, we have two nonmetals, C and O, for which the organism represents the proper level. The general pharmacological nature of oxygen is indicated by the role of oxidation in metabolic changes. Oxidation represents the first step toward catabolic, homotropic changes. The respiratory phase in the metabolism of carbohydrates, the oxidative fission of fatty acids, and the oxidative des amination of amino acids represent examples of the fundamental homo tropic intervention of oxygen.

Acting at the systemic level, immediately inferior to its own level, oxygen has a different action. According to the rule mentioned above, oxygen, a D agent at its proper level, will have an A activity for the blood, which we will study below together with the other A agents. The homo tropic relationship of oxygen to fatty acids was discussed above with the study of the biological role of these substances.

The relationship between CO2 and fatty acids also is interesting. Large amounts of free fatty acids in the blood were seen to allow better fixation of CO2 to hemoglobin, just as large amounts of sterols do for oxygen. We have investigated this correlation between CO2 and fatty acids by keeping a fatty acid, such as linoleic acid, in an atmosphere of CO2 connected to a manometer. A manifest negative pressure results. The venous blood, rich in CO2, which also shows a predominance of fatty acids, loses CO2 and fatty acids during passage through the lungs.