Industrial Phosgene Poisoning: A Study of Acute Pulmonary Oedema

O'Connor, James A (1948) Industrial Phosgene Poisoning: A Study of Acute Pulmonary Oedema. PhD thesis, University of Glasgow.

Abstract

The development of pulmonary oedema following the inhalation of phosgene vapour has been attributed in the past to the formation of hydrochloric acid within the alveoli, and to the action of this acid upon the alveolar walls in damaging the lung capillaries and thereby causing an exudation of plasma to take place. There are, however, both on chemical and physiological grounds, very grave objections to this conception of the pathology of phosgene poisoning. Among the more important of these objections is the fact that hydrochloric acid is known to produce rapid injury of any tissue with which it comes in contact, so that if it were formed within the alveoli it should cause immediate damage to their walls and a very rapid development of pulmonary oedema. But such a speedy onset of lung oedema does not in fact take place. Indeed, one of the most notable features of phosgene gassing is the "latent period" of many hours that must elapse between cessation of exposure to the vapour, and the onset of pulmonary oedema. The conception of alveolar damage due to a local action of hydrochloric acid is apparently an erroneous one. Consideration of the behaviour of inspired gases, and of the known physical and chemical properties of phosgene, leads to the conclusion that the inhaling of this substance must produce certain chemical changes in all the tissues of the body, and eventually to the conclusion that pulmonary oedema is a local manifestation of a generalised systemic disturbance, and not the result of a purely local damage to the lungs. Attention has been drawn to the remarkable similarity between the clinical manifestations of phosgene poisoning and of the condition known as cardiac asthma, or acute pulmonary oedema. A survey of the literature dealing with acute pulmonary oedema shows that it is no longer possible to accept the classical explanation of this condition---namely, that it is a failure on the part of the left ventricle in transferring blood from the pulmonary to the systemic circulation. Most authorities now place emphasis upon the neurogenic nature of the condition, and more recently considerable evidence has been brought forward to show that the site of the neurogenic disturbance is located in the respiratory centre. The modern conception of the causation of the acute pulmonary oedema or cardiac asthma syndrome is that it resides in "an abnormal state and an abnormal function of the respiratory centre", and that this abnormal status and functioning is due to the accumulation of acid metabolites. A great deal of indirect evidence in support of this theory has been adduced by its authors. The fundamental feature of increased tissue acidity has for the most part been based upon theoretical considerations, which show that a gradual and steady accumulation of acid metabolites must inevitably take place throughout the body tissues of those cardiac patients who are prone to develop attacks of acute pulmonary oedema. It is, however, a noteworthy fact that, in contradistinction to the classical theory, this modem concept of the pathology of cardiac asthma does explain all the well known clinical phenomena of the disease. In the present thesis evidence has been brought forward to show that inspired phosgene vapour passes practically unchanged through. the alveoli into the bloodstream and that it must then gradually enter into chemical combination with various constituents of the blood and tissues. Furthermore, no matter whether these chemical reactions take place by simple or by devious routes, they lead always to the liberation of great quantities of acid. Indeed, one molecule of phosgene entering the bloodstream will be responsible for the production of many molecules of acid and for the simultaneous and independent neutralisation of several additional molecules of base. The acid/base equilibrium of the tissues is thus very profoundly disturbed, and so there is brought about those very same conditions that had previously been postulated as the cause of the attacks of acute pulmonary oedema occurring in certain types of heart disease. The major symptoms of phosgene poisoning have been discussed in relation to increased acidity of the tissues, and all the symptoms are explainable on this basis. (Abstract shortened by ProQuest.).

• Item Type: Thesis (PhD)
• Qualification Level: Doctoral
• Keywords: Medicine, Toxicology
• Date of Award: 1948
• Depositing User: Enlighten Team
• Unique ID: glathesis:1948-79677
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 04 Mar 2020 15:41
• Last Modified: 04 Mar 2020 15:41
• URI: https://theses.gla.ac.uk/id/eprint/79677