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 saw one primary correlation between the three clinical types of shock in the fact that sometimes one type is followed by another. Super acute shock, if not lethal, may be followed by acute shock which, in turn, can change into a state of shock.
But it was the chemical analysis of blood, organs and entire bodies of animals killed by any of the three types of shock which indicated the possibility of a mechanism common to all three. A low antitryptic power of the blood, and the presence of substances resulting from protein hydrolysis were found to characterize all 3 types of shock. Additionally, an increase in the amount of free fatty acids, and the presence of abnormal members, occurred in all three types.
Fatty acids were studied from the point of view of the reciprocal position of their double bonds, through the oxidative fission method mentioned previously. The appearance of oxalic acid following oxidative fission indicates the presence of conjugated double bonds. The oxalic acid index obtained indicates the proportion of these conjugated double bonds. In normal rats, this oxalic acid index usually is zero in the total amount of fatty acids; in normal mice, values below 1 are seen. In all animals in shock, even in cases of superacute shock followed by sudden death, the oxalic acid index is invariably much higher. Furthermore, the death of an animal in acute shock or state of shock appears to be related to the presence of a critical oxalic acid index, indicating a concentration of abnormal fatty acids incompatible with life. Whether it appears in a relatively short time as in acute shock, or many days after the noxious intervention as in the state of shock, the oxalic acid index found in dying animals is between 14 and 17. Such high values are not found in superacute shock but the oxalic acid still is markedly increased. Thus, the presence of hydrolytic processes together with abnormal fatty acids appears to be a common pathogenic factor for the different forms of shock.
The three types of shock—because of the presence in all of hydrolytic processes and abnormal fatty acids—could be related to the first phase of the immediate diphasic defense phenomenon or its prolonged form. The next problem was to determine what other factors might influence the development of differing manifestations so as to make shock appear in three forms.
The study of pathological changes characterizing each of these forms was undertaken. We found cellular vacuolation a characteristic lesion in animals in superacute shock. Vacuoles are present in the parenchymal cells of the liver, to a lesser extent in the alveolar cells of the lung, and to a still lesser extent in kidney cells. Of special interest was the fact that these vacuoles are often seen in the cytoplasm and even in the nuclei of brain cells. These findings explain the predominance of the neurological symptoms in this form. In a publication in 1943, we described this vacuolation as a characteristic of the superacute shock. The fact that the characteristic pathological change encountered in superacute shock is the presence of vacuoles in different cells suggests that this form of shock occurs principally at the cellular level.
In the acute type of shock, which usually appears half an hour after noxious intervention, there may be some evidence of cellular vacuolization, but the principal changes are at the tissular level. The changes are largely localized in the immediate areas damaged by the noxious agent and are manifested by vascular and interstitial pathology such as marked edema or capillary hemorrhage. Splanchnic vasodilatation and petechiae at the surface of pleura or peritoneum appear when the noxious agent acts indirectly in the blood or is applied directly to it through intravenous injection. The degree of generalized vascular damage corresponds to the degree of direct participation of the blood. We have discussed previously, in the chapter on defense, the changes occurring in the blood which characterize hemoshock. The characteristic leucolysis, which is followed by hydrolytic digestion, explains the high degree of breakdown of blood constituents and vessels observed in this kind of shock. While the participation of the cellular level—and especially of the central nervous system—characterizes superacute shock, participation of the tissular level leads to the acute form.
We consider pathologically characteristic of the state of shock—in addition to the changes seen in blood, such as hemoconcentration, dark color, tendency to form sludges, etc.—two other specific manifestations; milliar lesions in the gastric mucosa leading to hemorrhage and ulceration, and a manifest fluid accumulation in the first portion of the small intestine. Since the various changes in the state of shock affect the blood and two organs, the stomach and duodenum, they can be considered to involve the organic and systemic levels.
This analysis has permitted us to continue to develop the hypothesis that all three forms of shock stem from the same fundamental mechanism —the appearance of abnormal fatty acids as part of the first phase of the diphasic defense reaction. The differences in manifestations between the forms of shock are due to the level at which the mechanism operates, cellular for superacute shock, tissular for acute, and organic and systemic for the state of shock.
The study of a special condition, hemoglobinuria "a frigore," or paroxystic hemoglobinuria, has helped us to understand the time factor in shock. In this condition, immersion of the hand in ice water, for instance, induces hemoglobinuria and violent chill about half an hour later. We have been able to demonstrate that in the development of such a manifestation, two or often even three hemoshocks occur, each one characterized by a diphasic phenomenon. The first shock appears within ten minutes after immersion of the hand in icy water. Usually the first sensation and chill are very slight and while a reduced hemoglobinemia is present, hemoglobinuria is almost nil. It is the second hemoshock, appearing approximately 30 minutes later, which is usually very intensive with manifest hemoglobinuria. The third shock, which appears about two hours after immersion in ice water, is usually clinically inapparent and is revealed only by blood analysis.
The study of this condition has indicated that in the appearance of the three episodes of hemoglobinuria, besides the changes in the red cells under the influence of cold, which are characteristic for the condition as seen in the Donath Landsteiner test, the important factor is the leucolysis occurring as part of the hemoshock. The subsequent hemolysis leads to free hemoglobin in the blood which, if in sufficient amount, passes into the urine. The changes induced in leucolysis will determine the degree of consequent hemolysis. The suppression of leucolysis by administration of morphine or other opium derivatives prevents any manifestation, while physical exercise undertaken following the immersion of the hand in icy water induces, in addition to a very intensive leucolysis, exceptionally intensive clinical manifestations. The time when the three hemoshocks appear also marks the time when the three forms of pathogenic shock— superacute, acute and state of shock—are seen. The intervention of three different noxious heterogenized constituents appears plausible. (Note 1)