This section is from the book "Research In Physiopathology As Basis Of Guided Chemotherapy With Special Application To Cancer", by Emanuel Revici. Also available from amazon: Research In Physiopathology
We noted that in all three types of shock, abnormal fatty acids can be found. A study of the role of these fatty acids permitted us to further understand the mechanism involved in these three types of shock. Since these same fatty acids have been seen to figure in abnormal metabolism of sodium chloride, the next logical step was to investigate the correlation between the latter and shock. Following this line, efforts were made to see if the differences between NaCl metabolism at different levels of organization would help explain the peculiarities of the different types of shock.
As we have noted, when abnormal fatty acids impair sodium chloride metabolism, two processes occur. First, there is abnormal fixation of chloride ions by abnormal fatty acids; then, sodium ions, freed following this chloride fixation, become bound to carbonate ions, resulting in alkaline substances. The pathological nature of chloride fixation results principally from the fact that the binding taking place at the conjugated double bonds is abnormally strong. Occurring in two steps, with a displacement of the double bond in the first, the bond between the conjugated fatty acids and chloride ions appear nonreversible. (Note 8, Chapter 6)
The great inequality in the ability of chlorides and sodium ions to pass through membranes can serve to separate, anatomically, the fixed chlorides from the free remaining cations. When this occurs, two distinct processes can be recognized, one involving the binding of chloride ions by abnormal fatty acids, the other involving the binding of carbonate ions by sodium ions and the resulting appearance of alkaline compounds. In the cells, the two processes take place separately, the sodium alkaline compound inducing the appearance of vacuoles. In tissues, the chloride fixation takes place predominantly in the cell, while the binding of carbonate occurs in the interstitial spaces. This leads to a localized intercellular alkalosis with consequent edema.
The same mechanism is involved in the changes associated with the state of shock, except that these processes occur at the systemic level. It is the part played by the sodium chloride of the blood in normal physiology, especially in the process of digestion, which explains the abnormal changes seen as characteristic of the pathological manifestations in the state of shock.
Normally, chloride ions are excreted into the stomach, where they are bound to hydrogen to form hydrochloric acid. An almost equal amount of sodium ions, bound to carbonate ions, is eliminated in a second step into the intestines via the pancreatic and intestinal secretions. The chloride and sodium ions are later liberated to form sodium chloride which is entirely reabsorbed in the distal portion of the intestinal tract, the colon. The sodium and chloride ions are not simultaneously secreted in the digestive tract. The interval between the excretion of chloride ions into the stomach and of sodium ions into the intestines accounts for the physiological "alkaline tide" associated with digestion.
When chloride ions are pathologically fixed to abnormal fatty acids in the blood, they can no longer be dissociated and secreted by the stomach in the form of hydrochloric acid. Instead, they remain bound to the fatty acids and accumulate in this form within the gastric mucosa. The multiple milliar gastric mucosal ulcerations in the state of shock results from the intervention of these abnormal fatty acids brought into the mucous membrane by the chloride ions to which they are bound. The ulcerations are caused by the catabolic action of fatty acids. Thus, the first phase of abnormal sodium chloride metabolism leads to the characteristic multiple gastric ulcerations.
The second phase is related to the metabolism of sodium. The sodium ions are secreted as carbonates by the pancreas and intestinal mucosa in the first part of the small intestine. In the state of shock, because they do not encounter the chlorides normally coming from the stomach, they remain as carbonates. As sodium carbonate is accumulated in the first portion of the small intestine, a local alkalosis occurs, leading in turn to an important local retention of water. It should be noted that this is a very different situation from achlorhydria or hypochlorhydria in which, while the chloride ions are not secreted into the stomach, no excesses of sodium ions appear in the blood or in the intestines, and consequently no local alkalosis or fluid accumulation occurs.
The difference between the systemic and tissue processes in shock lies in the localization of the abnormal sodium chloride metabolism. In tissue anomaly, the separation of sodium chloride takes place between the cells and the pericellular structures. At the systemic level, it occurs between the stomach and intestines, with the blood serving as intermediary. This mechanism explains the larger amounts of water which distend the upper parts of the intestine, as observed in autopsies of animals which have died in this form of shock.
The close similarity between the abnormal processes that take place in sodium chloride metabolism at the tissue and systemic levels provides the basis for another working hypothesis concerning the mechanism in super acute shock. We have seen that the production of vacuoles in cells characterizes this latter form of shock. The unequal cellular permeability for chlorides and sodium in their dissociated form is known. Chloride ions can circulate much more easily between cells and the pericellular spaces than can sodium ions. An initial effect of the intervention of abnormal fatty acids in cellular pathology is the fixation of chlorides. At the same time, an increased permeability in membranes occurs. This would permit more sodium ions to pass through cell membranes and to accumulate intracellu larly, inducing a liberation of potassium, the cellular cation. As the chloride ions are bound to fatty acids in the cells, the sodium ions in the cells liberate potassium and join it to form alkaline compounds. Isolated in vacuoles, these compounds also accumulate water.
Thus, we have a concept of single pathogenesis for all three forms of shock based upon abnormal sodium chloride and water metabolism, with the abnormality taking place at different levels of the organization, cellular for superacute shock, tissular for the acute form, and systemic for the state of shock. The displacement of potassium by sodium in cellular physiology contributes to the increase in serum potassium found in all forms of shock.
The localized retention of water, prompted by the alkaline sodium compounds which result from abnormal sodium chloride metabolism, occurs in the cells, tissues or intestines in the different types of shock. Many of the differences in manifestations between the three forms of shock can be explained in terms of localization of this abnormal water metabolism. The sensitivity of the cells of the nervous system to intracellular changes explains the predominance and severity of the nervous system manifestations in superacute shock. Abnormal tissue water metabolism explains not only the predominantly local character of the manifestations seen in acute shock, but also the hemoconcentration values in these cases. As often seen in burns, important amounts of water are driven out of the blood into the damaged tissues.
The abnormal water metabolism however, appears to be the principal manifestation in the state of shock. Upper intestinal water accumulation, rather than a general unlocalized fluid loss, can be demonstrated in the pathogenesis of this form of shock. In opposition to the local lesion with a high retention of water, the general subcutaneous tissues sustain a loss of water rather than an accumulation during shock. This would not occur if there were a general increased permeability of all capillaries, allowing water to pass freely. The role of water accumulation in the first portions of the intestine due to the abnormal loss of systemic water was demonstrated in animal experiments. When the small intestinal tract had previously been removed, and a state of shock was later induced by trauma, no hemoconcentration occurred.
It is the participation of one or another of the three principal levels of the organizationócellular, tissular or systemicówhich explains why the same pathogenic process, abnormal sodium chloride and consequent abnormal water metabolism, produces such different manifestations in the various types of shock. It must not be forgotten however, that in the last analysis, the abnormalities in sodium chloride and water metabolism result from the intervention of abnormal fatty acids. Fatty acid intervention, together with the abnormal sodium chloride and water metabolism confirm the unitary pathogenesis of the three forms of shock.
Other changes associated with shock also can be related to the influence exercised by abnormal fatty acids. The appearance of rouleaux of red cells may be easily explained by fatty acid intervention. It is the replacement of the nonpolarity normally present at the surface of the red cells by a di polarity which results in the formation of the rouleaux. This can be induced by fatty acids in vitro. Sludge formation would represent a still more advanced step in this same process and would appear to result from a poly polarity at the surface of the red cells. Sludge formations have been induced in vitro by fatty acids added in larger amounts to plasma. (Note 2) They contribute to the circulatory impairment considered to be an important factor in the tissular respiratory troubles seen in shock.
We have noted that the richness in free fatty acids interferes with the ability of the red cells to keep oxygen fixed, a fact which would impair its transport. This, together with hemoconcentration and circulatory impairment, has been found to account for the black color of the blood in shock. (Note 3) The clinical manifestations are characteristic of offbalance D.