bleb formation and moist desquamation if the dose exceeds about 1,000 rads. People picking up a radiographer's source that gets into the general environment ...
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DIAGNOSIS AND THERAPY OF RADIATION INJURIES* NIEL WALD, M.D. Department of Radiation Health Graduate School of Public Health University of Pittsburgh Pittsburgh, Pennsylvania
IT was pointed out earlier that the main health effect of the reactor accident which provided our most real learning experience, the Three Mile Island accident, was the impact of the associated psychological stress. It appeared to me, and I can speak from some first-hand experiences in Harrisburg during the accident, that this psychological stress stemmed in part from the work of our colleagues in the media about which we belabored their representatives this morning; but that in part also it stemmed from various deficiencies in our own radiation emergency planning, related communications, and in the efficacy with which we train our own health personnel to deal with radiation problems. When people are alarmed and anxious about their health, they turn to the medical profession and to their physicians. It was apparent in the area of the Three Mile Island accident that physicians were generally little better educated to understand what was going on and what its health significance was than the rest of the population. Hence the advisors themselves in some cases recommended evacuation or pregnancy termination unnecessarily from the standpoint of actual or even likely potential radiation exposure levels. For this reason, I thought it might be useful to review some basic radiological principles and the clinical application of these principles to the problems of radiation injury. Time limitations preclude more than a brief overview of this subject, but several recent publications provide more detailed information. 1-6 In addition to increasing the degree of confidence with which we can advise an anxious patient or a concerned public, this information should also help us to deal with occasional actual radiation injuries that may occur in the kinds of accidents that we have heard described this afternoon. These generally happen in fixed radiation *Presented as part of the Symposium on the Health Aspects of Nuclear Power Plant Incidents held by the Committee on Public Health of the New York Academy of Medicine April 7 and 8, 1983.
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facilities, but may also take place in transportation accidents at our very own doorsteps. It behooves all of us, then, not only to comply with the rule book of the Joint Commission on the Accreditation of Hospitals, which says that we must be prepared to deal with radiation accidents, but also to have a little more understanding about them for the sake of our patients and for our own psychological health. Medical problems associated with radiation can be divided into those resulting from irradiation by sources external to the patient and those involving radionuclides on or in the patient. Accidents resulting in exposure to external sources of radiation may produce whole body or partial body radiation injury depending on the nature of the exposure. Those involving radionuclide contamination may present three types of medical problems, depending on whether the contaminant is externally deposited on the surface of the patient, deposited in a wound, or incorporated into body fluids and tissues. The major radiobiological impact of radiation on tissue takes place at the cell level. It is the interruption in the reproductive processes of cells primarily, along with some cell killing, that is responsible for the health impairment that may be a consequence of the exposure. This is particularly evident in high turnover cell systems, such as the gastrointestinal tract lining or hematopoietic tissue. Cessation in production of new cells, even though it may be temporary, may produce prompt health consequences in that there will be deficits in the functions ordinarily performed by those missing cells during the time their replacement is delayed. For other organs, the rate of usage of the cells is lower, and therefore the delay in the appearance of the effects is correspondingly greater. The extreme is the lens of the eye, a tissue of highly specialized cells which, even if injured at the time of exposure, may not develop resultant opacities recognizable as radiation cataracts for one or more years. Despite such variability in radiation response, recognition of this basic mechanism is useful in understanding what transpires at the clinical level. The acute radiation syndrome, which occurs when the whole body or a major portion of it is exposed to radiation, can be recognized by a characteristic pattern of signs and symptoms. There is an initial prodromal phase which occurs within minutes to a few hours after exposure, characterized by anorexia, nausea, and vomiting. This triad of symptoms is selflimited. It is a neurogenic response involving the central nervous system as well as the innervation of the end organs. It is not related to the cessation of production of cells, because the nervous system has its Bull. N.Y. Acad. Med.
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complete complement of neurons at birth and does not replace them. The period between the cessation of these prodromal symptoms and the onset of health impairment is known as the latent period, which for radiation exposures in the midlethal range lasts about two to three weeks. At this exposure level, the hematopoietic system is the most important one involved. Cessation of production of new blood cells begins at the time of exposure, but, depending on the size and life span of the various cell populations, cells may continue to mature and function for several weeks. Lymphocytes decrease within hours while the erythrocytes may not reach their nadir for six weeks. A period is reached about 30 days after the exposure, at which time the leukocyte and platelet populations in circulation are at their low point. Disappearance of platelets leads to purpura and hemorrhage; disappearance of both lymphoid cells with their immunologic functions and granulocytes with their phagocytic capabilities leads to infection. This is the period of manifest or overt illness stemming from radiation exposure which occurred several weeks before. An understanding of this underlying pathophysiology will facilitate accurate prediction of clinical effects and therefore provide time for better preparation to manage them. Managed successfully, clinical manifestations may disappear within a matter of one or two weeks, and normal health is restored as far as the acute effects of the radiation exposure are concerned. At higher levels of exposure, the time period of the clinical response is shifted to days rather than weeks. The same sequence occurs: a prodromal phase, which may be a little more dramatic-with diarrhea added to the triad of symptoms we mentioned before; a latent period, which may last only a few days; and the development of overt clinical illness. At this level of exposure, cells lining the gastrointestinal tract are at particular risk, especially in combination with hematopoietic and vascular damage. As the cells are lost and not replaced, the consequences of loss of blood, fluids, and electrolytes; inadequate absorption of nutrients; entry of bacteria-all of these lead to an acute fulminating enterocolitis which is likely to be fatal, because clinical management has thus far been unsuccessful. At still higher levels of whole body exposure, one sees a combination of cardiovascular and central nervous system damage which develops within hours rather than days or weeks. Prodromal symptoms merge with alterations in the state of consciousness, from depression with somnolence and lethargy to hyperexcitability, convulsions, tremors, and ataxia. The massive irradiation of these vital systems results in the inability to mainVol. 59, No. 10, December 1983
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tain the normal blood pressure level, heart rate, and respiratory rate, leading to irreversible shock, cardiovascular collapse, and death in a few hours to a day or two. The evidence that the pathologist subsequently may see of radiation injury in the brain may be quite limited-some aggregations of granulocytes along the cerebral blood vessels and meninges, cerebral edema, and some localized changes in certain cells, such as the granular cell layer of the cerebellum. But it is functional impairment rather than a cell population deficit that is the basis for this kind of acute radiation injury. Some generalizations concerning the magnitude of exposure associated with the acute radiation syndrome may be useful. Neurovascular damage is seen after several thousands of rads, gastrointestinal damage with the low thousands of rads, and hematopoietic damage after exposures below a thousand rads down to about 100 rads. Therapeutic effort is directed primarily at the hematologically injured patient because this is where therapy makes the difference between survival and death. In this connection, it should be noted that an absorbed dose of radiation of about 350 to 400 rads is generally expected to result in the death of 50% of a hypothetical untreated population of humans by about 60 days. This is based on the Japanese A-bomb experience and some other situations where treatment was very limited, as well as on radiobiological animal research and theory. On the other hand, with adequate conservative supportive treatment, the LD50 can be moved up to about 500 rads, based on some accidentpatient experience. Bone marrow transplantation offers more intensive therapy. From its growing use in leukemia patients, we know that a preparatory whole-body exposure of 1,000 rads is tolerated well when bone marrow transplantation is performed promptly thereafter. We can therefore increase the LD50 estimate to somewhere above 1,000 rads when that form of intensive therapy is available. In the clinical care of radiation injury it is reassuring to have an estimate of the magnitude of the exposure from an independent source of information, such as physical dosimetry, but as physicians it is important for us to recognize that without the physical dosimetry we can also recognize the nature and severity of radiation injury by some time-honored methods of clinical diagnosis. These are summarized in Table I. The information in Table I is meant to be self-explanatory and a much simplified reminder of useful clinical points in the diagnosis of radiation injury. Note that they are all nonspecific, and that any one of them alone Bull. N.Y. Acad. Med.
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TABLE I. RADIATION INJURY EVALUATION PROCEDURES AND THEIR RESULTS IN RELATION TO TIME AND MAGNITUDE OF RADIATION EXPOSURE Minimum exposure
required
Procedure
Finding
Time of onset
History Physical examination Blood count and differential Chromosome analysis Sperm count
Nausea, vomiting Erythema Epilation Lymphocytes
