General physiopathology of blood proteins; establishment and discussion of its fundamental law

Abstract

A synthesis of the general Physiopathology of the plasma proteins has been stablished, by General Physiopathology of plasma proteins being understood as a study of modificactions of the fractions considered as a whole without taking into account those which present a specific function (Fibrinogen, prothrombin, esterases, iodoproteins, etc.). After studying the experimental and clinical disproteinemias a general law is stablished and discussed.

In the experimental disproteinemias are separetely considered the hyperproteinemias and the hypoproteinemias and amongst the latter the hypoproteinemias by plasmapheresis, by diets low in protein, combincd (plasmaphereres and diets low in protein) and finally the toxic hypoproteinemias (In this group are those obtained by the functional disturbance of an organ or System the result of surgical intervention or by the injection of substances or Chemical producís of various kinds).

From the study of the bibliography and from personal experiment it can be shown that in the hypoproteinemias by plasmapheresis: In the acute plasmapheresis an hypoproteinemia is obtained in which the relative proportion between the fractions is not modified. In the subacute plasmapheresis an hypoproteinemia is obtained in which a greater proportion of albumin than globulin is mantained within the circulation. If when this are producen the animal presents and State of shock followed bv a bad regeneration in the next 24 hours, an hypoproteinemia is obtained with greater proportion of globulin. In the chronic plasmapheresis, in the stage of exhaustion of reserve or compensatory mechanism, is obtained and hypoproteinemia with grea­ ter proportion of globulin.

Studying the regeneration of the fractions in this different kinds of hypoproteinemia is shown that following and acute plasmapheresis the rate of regeneration is rapid in the first 24 hours and the first fraction to be regenerated is the albumin. After a subacute plasma­ pheresis without shock the regeneration is also rapid at 24 hours and the first fraction to be regenerated is the albumin. In the subacute

plasmapheresis with shock the regeneration is small and a great in­ crease of globulin over albumin is observed. The regenerative stage following a chronic plasmapheresis is caractherized by a more or less rapid return of tire albninin fraction to normality.

In thc hypoproteinemias by diets low in protein is seen in the no regenerative stage that the globulin is practically without variation and the albninin is clcarly lower, and on the other hand thc inverse phenomenon is tipical of the regenerative stage, that is to say the coinparatively rapid recovery of the normal valué of the albumin fraction.

In the hypoproteinemias by plasmapheresis and diets low in pro­ tein is shown too and unbalanced condition due to a diminution in the albumin. A previous stage is presented in which it is necessary to cxtract by plasmapheresis a greater amouut of protein than in thc stage of stablished hypoproteincmia. In this early stage there is ex- tiacted a greater quantity of albumin than of globulin. When this reserve capacity is exhausted an hypoproteincmia is stablished with a great diminution in the albumin and without variation in the glo­ bulin. A study of the factors regulating thc regeneration of this hypoproteinemias shows that the capacity of albumin production is more sensitive to the noxious factors than the capacitv to produce globulin and that all the factors that stimulate the regeneration of the proteinemia stimulate the production of albumin.

In the toxic hypoproteinemias similar results are shown and after discussing the value of some exceptions one rcaches the conclusion that whenever an experimental hypoproteincmia is produced be it through plasmapheresis, diets low in protein, combined (plasmaphe­ resis and diets low in protein) or toxic, a desequilibrium in stablished between the albumin and thc globulin with a fall in the former and a state of no change or an increase in the latter.

A study of what has written about the hyperproteinemias shows the same desequilibrium with a fall in the albumin and a rise in the globulin.

Caractheristic examples are shown in the processes uf human pathology which present an hypoprotcinemia or hyperproteinemia more pronounced, and after discussing certain exceptions, some of this inust be considered as seudo-disproteinemias, it is evident that as occurs ir. experimental pathology, the desequilibrium is produced between the fractions and always in the same manner, i. e., with a fall in the albumin and no change or increase in the globulin.

There must be noted the recent observations of several authors who insist upon the importance ot this iact and the personal observations made obtaining the fractioning curve with sociium sulfite or thiosulphate. In this are shown the caracteristic fact in all the pathological serums the drop of the curve in the globulin zone to arrive at the albumin below normal values.

After this synthesis of bibliographic and personal study there can be deduced from the results of hypoproteincmia by plasmapheresis, diets low in protein or combined, that the organism is inclined to maintain the normal equilibrium between the fractions of plasma proteins and as long as the compcnsatory mechanisms do not break down or reserve capacity be not reduced, a larger proportion of albumin is kept in the circulation and it is only when such compcnsatory

mechanism breaks down that disproteinemia is produced. Once disproteinemia has been stablished of whatever type it may be, wether experimental or clinical, the desequilibrium between the fractions is at the expense of the albumin.

It is for all this tliat we believe it posible to arrive at formulating a general law for the phisiopathology of the plasma proteins, as follows: whenever there be frroduced an unconipensated disturbance of the plasma proteins metabolism a dcsequuíˆibrium of its fractions is stablished in the sense of a deficit in the albuniin jraction.

The hypothesis in explanation of this general fact are discussed on a besis of two fundamental posibilities, a) that the fractions ofplasma proteins are of independent origin, and b) that they are gene- tically interdependent.

a) If the fractions are genetically independent, this general fact could be cxnlaincd in three ways, Ist) that every pathogenic cause able to produce a disproteinemia weakens the organ or mechanism which produce the albumin and, on the other hand, stimulate or do not affect the globulin producen 2nd) that in the last instance, all pathogenic cause produccr of a disproteinemia actuate tlirough only one mechanism. 3rd) that it be the resultant of a body regulatory mechanism. After a critical study of this three hypothesis one finds them hard to accept and, therefore, the explanation of this general fact oí the phisiopathology of the plasma proteins cannot be looked for in genetic independence between the fractions, but rather on a basis of their genetic interdependence.

b) In this interdependence of the fractions two hypothesis may be suggested. Irst) that the genetic dependence may exist in the cell or organ of their origin or 2nd) that it occur later in another organic territory. Within this hypothesis two possibilities presents themselves, namely, that the change from one on the other be produced in the circulating plasma itself or in an special organ amongst whose activities may be this particular function.

This hypothesis are discussed it may be considered that it is better explained the general Phisiopathology of the plasma proteins that which suposes the change from one to the other in the circu­ lating plasma itself, it is not possible to accept or refute one or other of them, but to explain this fundamental law the genetic in­ terdependence amongst the fractions must to be acceptea.

Finally it is clear that this fundamental law must be taken hito account in the discussion of the problems related to the origin and metabolism of the plasma proteins and this is of great importance in its solution.