Hall Book Ch 8 (Acute Radiation Syndrome) Flashcards
The effect of ionizing radiation on the whole organism is discussed in this
chapter. Data on the various forms of the acute radiation syndrome (ARS)
have been drawn from many sources.
Animal experiments provide the bulk of the data and result in a significant understanding of the mechanisms of death after exposure to ( ).
At the human level, data have been drawn from experiences in radiation therapy and studies of the Japanese survivors of Hiroshima and Nagasaki, the Marshallese accidentally exposed to fallout in 1954, and the victims of the limited number of accidents at nuclear installations, including Chernobyl and the Tokaimura accident in Japan.
From these various sources, the pattern of events that follows a total body exposure to a dose of ionizing radiation has been well documented. To date, worldwide,
about ( ) humans have suffered from the ARS.
total body irradiation, 400
Early radiation lethality generally is considered to be death occurring within a
( ) that can be attributed to a specific ( ) to radiation.
Soon after irradiation, early symptoms appear, which last for a limited period; this is referred to as the ( ).
These symptoms may clear up after a few days, to be followed by a latent period before the development of the eventual life-threatening syndrome. This is illustrated in
Figure 8.1. The eventual survival time and mode of death depend on the magnitude of the dose.
few weeks, high-intensity exposure, prodromal radiation syndrome
In most mammals, three distinct modes of death in acute radiation syndrome can be identified, although in the circumstances of an actual accidental exposure, some overlap is frequently seen.
At very high doses, in excess of about ( ) Gy, death occurs ( ) hours after exposure and appears to result from ( ) breakdown; this mode of death is known as the ( ).
100, 24 to 48, neurologic and cardiovascular, cerebrovascular syndrome
At ( ) dose levels, approximately ( ) Gy, death occurs in about ( ) days and is associated with extensive bloody diarrhea and destruction of the gastrointestinal mucosa; this mode of death is known as the ( ).
intermediate, 5 to 12, 9 or 10, gastrointestinal syndrome
At ( ) dose levels, approximately ( ) Gy, death occurs several ( ) months after exposure and is caused by effects on the ( ) organs; this mode of death has come to be known as ( ) or the ( ).
lower, 2.5 to 5, weeks to 2, blood-forming, bone marrow death, hematopoietic syndrome
FIGURE 8.1 Illustrating the stages of the acute radiation syndrome. Following
total body irradiation, the ( ) develops—the intensity and length depending on the dose. There follows a ( ) period when symptoms disappear, followed by the development of manifest illness described by the cerebrovascular, gastrointestinal, or hematopoietic syndrome, depending on the dose.
prodromal syndrome, latent
The exact cause of death in the cerebrovascular syndrome is by no means
clear. In the case of both of the other modes of death—the ( )—the principal mechanisms that lead to the death of the organism are understood.
gastrointestinal and the hematopoietic syndromes
Death is caused by the depletion of the ( ) cells of a ( ) tissue: the ( ) of the gut or the ( ) cells, respectively.
The difference in the dose level at which these two forms of death occur and the difference in the time scales involved reflect variations in the ( ) of the two cell renewal systems involved and differences in the amount of the damage that can be tolerated in these different systems before death ensues.
stem, critical self-renewal, epithelium, circulating blood, population kinetics
The various symptoms making up the ( ) vary with respect to time of onset, maximum severity, and duration, depending on the size of the dose.
With doses of a few ( ) of gray, all exposed individuals can be expected to show all phases of the syndrome within 5 to 15 minutes of exposure.
Reaction might reach a maximum by about ( ) minutes and persist for a few days, gradually diminishing in intensity until the prodromal symptoms merge with the universally fatal ( ) or, after a lower dose, with the fatal ( ).
human prodromal syndrome, tens, 30, cerebrovascular syndrome, gastrointestinal syndrome
At lower doses, dose–response predictions are ( ) to make because of
the interplay of many different factors.
A severe prodromal response usually indicates a poor clinical prognosis and portends at the least a prolonged period of ( ) accompanied by potentially fatal infection: ( ).
difficult, acute hematologic aplasia, anemia and hemorrhage
The signs and symptoms of the human prodromal syndrome can be divided
into two main groups: ( ).
The gastrointestinal symptoms are ( ).
gastrointestinal and neuromuscular, anorexia, nausea, vomiting, diarrhea, intestinal cramps, salivation, fluid loss, dehydration, and weight loss
The neuromuscular symptoms include ( ).
easy fatigability, apathy or listlessness, sweating, fever, headache, and hypotension
At doses that would be fatal to ( )% of the population, the principal symptoms of the prodromal reaction are ( ).
50, anorexia, nausea, vomiting, and easy fatigability
Immediate diarrhea, fever, and hypotension frequently are associated with ( ) exposure (Table 8.1).
One of the Soviet firefighters at the Chernobyl reactor accident vividly described the onset of these symptoms as he accumulated a dose of several grays working in a high-dose-rate area.
supralethal
The prodromal phase is followed by a ( ) stage before the final radiation syndrome
develops. In the symptom-free latent stage, the patient may seem and feel
( ).
latent, relatively well for a period of hours or even weeks
The duration of the latent stage is ( ) proportional to the dose and may last a ( ) for high exposures or as long as ( ) weeks for lower exposures.
Absence of a latent phase—that is, a progressive worsening from prodromal signs and symptoms directly into the manifest illness phase—is an indicator that the dose was
probably ( ).
inversely, few hours, 2 or more, very high
The diagnosis of the ARS can also be based on laboratory data. During the
prodromal phase, evidence of ( ) can already be observed by
( ) after an exposure as low as ( ) Gy.
hematopoietic damage, a drop in the lymphocyte count, 0.5
( ) are one of the most ( ) cell lines, and a fall in the ( ) is the best and most useful laboratory test to determine the level of radiation exposure in the early phase of observation.
The circulating lymphocytes, radiosensitive, absolute lymphocyte count
Among assays for biologic dosimetry, ( ) analysis from
cultured circulating lymphocytes is the most widely accepted and reliable.
The dose–response relationships are well established in many laboratories around the
world. The lower limit of detection of a dose by using this cytogenetic method is
approximately ( ) Gy of γ- or x-rays.
chromosomal aberration, 0.2
A total body dose of about ( ) Gy of γ-rays or its equivalent of neutrons results
in death in ( ) hours. At these doses, all organ systems are also seriously
damaged; both the gastrointestinal and hematopoietic systems are, of course,
severely damaged and would fail if the person lived long enough, but ( ) brings death very quickly so that the consequences of the failure of the other systems do not have time to be expressed (i.e., death occurs before other symptoms have time to appear).
100, 24 to 48, cerebrovascular damage
The symptoms that are observed vary with the species of animal involved and also with level of radiation dose; they are summarized briefly as follows:
There is the development of severe ( ), usually within a matter of minutes. This is followed by manifestations of ( ), and finally death.
nausea and vomiting, disorientation, loss of coordination of muscular movement, respiratory distress, diarrhea, convulsive seizures, coma
Only a few instances of accidental human exposure have involved doses
high enough to produce a ( ) syndrome; two such cases are
described briefly.
In 1964, a 38-year-old man working in a uranium-235 recovery plant was
involved in an accidental nuclear excursion. He received a total body dose
estimated to be about 88 Gy made up of 22 Gy of neutrons and 66 Gy of γ-rays.
He recalled seeing a flash and was hurled backward and stunned; he did not lose
consciousness, however, and was able to run from the scene of the accident to
another building 200 yards away. Almost at once he complained of ( )
The next day, the patient was comfortable but restless. On the second day, his
condition deteriorated; he was ( ). Six hours before his death, he became
disoriented, and his blood pressure could not be maintained; he died ( ) hours
after the accident.
cerebrovascular, abdominal cramps and headache, vomited, and was incontinent of bloody diarrheal stools
restless, fatigued, apprehensive, and short of breath and had greatly impaired vision; his blood pressure could only be maintained with great difficulty
49
In a nuclear criticality accident at Los Alamos in 1958, one worker received
a total body dose of mixed neutron and γ-radiation estimated to be between ( ) Gy. Parts of his body may have received as much as ( ) Gy.
This person went into a state of shock immediately and was unconscious within a few
minutes. After ( ) hours, no lymphocytes were found in the circulating blood, and
there was virtually a complete ( ) despite the administration of large amounts of fluids. The patient died ( ) hours after the accident.
39 and 49, 120
8
urinary shutdown
35
The exact and immediate cause of death in what is known as the cerebrovascular syndrome is not fully understood. Although death is usually attributed to events taking place within the ( ), much higher doses are required to produce death if the head alone is irradiated rather than the ( ) body; this would suggest that effects on the rest of the body are by no means ( ).
It has been suggested that the immediate cause of death is damage to the ( ), which results in an increase in the fluid content of the brain owing to leakage from small vessels, resulting in a buildup of pressure within the ( ).
central nervous system, entire, negligible, microvasculature, bony confines of the skull
A total body exposure of more than ( ) Gy of γ-rays or its equivalent of neutrons
commonly leads in most mammals to symptoms characteristic of the
( ), culminating in death some days later (usually between ( ) days). The characteristic symptoms are ( ).
10, gastrointestinal syndrome, 3 and 10, nausea, vomiting, and prolonged diarrhea
People with the gastrointestinal syndrome lose their ( ) and appear ( ).
( ), extending for several days, usually is regarded as a bad sign because it indicates that the dose received was more than ( ) Gy, which is inevitably fatal.
The person with this syndrome shows signs of ( ); death usually occurs in a few days.
There is no instance on record of a human having survived a dose in excess of 10 Gy.
appetite, sluggish and lethargic, Prolonged diarrhea, 10
dehydration, loss of weight, emaciation, and complete exhaustion
The symptoms (of gastrointestinal syndrome) that appear and the death that follows are attributable principally to the ( ) by the radiation. The normal lining of the intestine is a classic example of a ( ) tissue; Figure 8.2 shows the general characteristics of such a tissue. It is composed of a ( ).
depopulation of the epithelial lining of the gastrointestinal tract
self-renewing
stem cell compartment, a differentiating compartment, and mature functioning cells
FIGURE 8.2 The classic self-renewal tissue. The stem cell compartment
contains the dividing cells. Of the new cells produced, some maintain the pool,
and some go on to differentiate and produce mature functioning cells.
If the tissue is exposed to radiation, the ( ) is the stem cell compartment.
Huge doses of radiation are needed to destroy differentiated cells and prevent
them from functioning, but modest doses kill some or all of the stem cells in the
sense that they lose their ( ) integrity.
“Achilles heel”
reproductive
Irradiation does not produce an ( ) effect on the tissue because it does not affect the ( ) cells. The delay between the time of irradiation and the onset of the subsequent radiation syndrome is dictated by the ( ) of the mature functioning cells.
immediate, functioning, normal life span
The structure of the intestinal epithelium is illustrated in Figure 8.3. Dividing
cells are confined to the ( ), which provide a continuous supply of new cells;
these cells move up the villi, differentiate, and become the functioning cells.
The cells at ( ) are sloughed off slowly but continuously in the normal course of events, and the villi are continuously replaced by cells that originate from mitoses in the crypts.
( ) barrier separates the blood vessels in the villi from the contents of the intestine.
crypts, the top of the folds of villi, A single-cell-thick
FIGURE 8.3 The gastrointestinal epithelium is an example of a classic ( ) tissue. Stem cells in the crypts divide rapidly and provide cells that differentiate to form the lining of the ( ). A single cell layer separates the blood supply within the villus from the contents of the gastrointestinal (GI) tract.
self-renewal, villi
An exposure to radiation kills cells in the crypts, cutting off a supply of cells to
cover the villi. As a consequence, the villi shrink and, eventually, the barrier
between ( ) is compromised, leading to a loss of fluids and massive infections. (Courtesy of Dr. Jack Little.)
A dose of radiation of about ( ) Gy sterilizes a large proportion of the dividing cells in the crypts; a dose of this order of magnitude does not seriously affect the ( ) cells.
blood supply and the contents of the GI tract, 10, differentiated and functioning
