Early Deterministic Radiation Effects on Organ Systems.pdf

1 By Dr. Mohsen Dashti 432 Radiation Protection & Radiobiology  When living organisms experience biologic damage from exposure to radiation, the results of this exposure are classified as SOMATIC EFFECTS.  Example is cancer that occur in the exposed individual, as opposed to genetic effects, whi...

1 By Dr. Mohsen Dashti 432 Radiation Protection & Radiobiology  When living organisms experience biologic damage from exposure to radiation, the results of this exposure are classified as SOMATIC EFFECTS.  Example is cancer that occur in the exposed individual, as opposed to genetic effects, which occur in the individual's offspring.  Depending on the length of time from the moment of irradiation to the first appearance of symptoms of radiation damage, the effects are classified as either: 1. Early somatic effects 2. Late somatic effects  Late deterministic somatic effects  Late stochastic (probabilistic) effects 2 Early Deterministic Somatic Effects  Occur relatively soon after human receives high doses of ionizing radiation.  With the exception of certain lengthy high dose-rate fluoroscopic procedures, diagnostic and nuclear medicine examinations do not usually impose radiation doses sufficient to cause early deterministic effects.  Formerly called NONSTOCHASTIC somatic effects.  Have a threshold, a point at which they begin to appear and below which they are absent.  precipitated by cell death.  severity of effects are dose related.  depend on the time of exposure to ionizing radiation. They appear within:  Minutes  Hours  Days  Weeks 3 4 Early radiation effects on human from high-dose include:  Nausea  Fatigue  Erythema (diffuse redness over an area of skin after irradiation) ( Fig. 8-2 )  Epilation (loss of hair)  Blood disorders  Intestinal disorders  Fever  Dry and moist desquamation (shedding of the outer layer of skin) ( Fig. 8-3)  Depressed sperm count in the male  Temporary or permanent sterility in the male and female  Injury to the central nervous system (at extremely high radiation doses) 5 6 Organ System Response to Radiation  The characterization of an organ system as radioresistant or radiosensitive depends in large part on the radiosensitivity of cells that comprise the organ itself.  For example, intestinal disorders are caused by damage to the sensitive epithelial tissue lining the intestines. REMEMBER There is general agreement that acute doses below 100 mGy will not result in any functional impairment of tissues or organ systems. Diagnostic radiation used is below 100mGy. 7 WHOLE BODY RESPONSE TO RADIATION: THE ACUTE RADIATION SYNDROME  When the whole body (or large portion of the body) is subjected to a high acute radiation dose (2-10 GY), there are a series of characteristic clinical responses known collectively as the ACUTE RADIATION SYNDROME (ARS).  Data from epidemiologic studies of human populations exposed to doses of ionizing radiation sufficient to cause ACUTE RADIATION SYNDROME have been obtained from:  Atomic bomb survivors of Hiroshima and Nagasaki  Marshall Islanders who were inadvertently subjected to high levels of fallout during an atomic bomb test in 1954.  Nuclear radiation accident victims, such as those injured in the 1986 Chernobyl disaster  Patients who have undergone radiation therapy 8 1.Prodromal  immediate response of radiation sickness  Lasts from few minutes to hours depending on dose 2. Latent  time after exposure during which there is no outward sign of radiation sickness (healthy appearance)  Last from hours to weeks 3. Manifest illness  Toward the end of the first week of latent period, the manifest stage start.  dose-related period characterized by three separate syndromes;  a. HematologiC syndrome  b. GI syndrome  c. CNS syndrome 9 4. Recovery or death  Hematologic syndrome  Reduction in the number of white blood cells, red blood cells, and platelets in the circulating blood  Death occurs because of infection, electrolyte imbalance, and dehydration  Gastrointestinal syndrome  death occurs because of severe damage to the cells lining the intestines  uncontrolled passage of fluids across the intestinal membrane, a severe destruction of electrolyte balance, and conditions promoting infection  Measurable and severe hematologic changes accompany GI death  Central nervous system syndrome  At radiation doses sufficiently high to produce CNS effects, the outcome is always death within a few days of exposure  cause of death in CNS syndrome is apparently an elevated fluid content of the brain 10 11 LETHAL DOSE (LD) LD 50/30. 12 Lethal Dose (LD) LD 50/30  Quantitative measurement that is fairly precise when applied to experimental animals.  LD 50 for humans may require more than 30 days for its full expression.  Humans take longer time to recover than do laboratory animals.  LD 50/60, survival over a 60-day period may be a more relevant indicator of outcome for humans than is survival over a 30-day period.  LD 50/30 for adult humans is estimated to be 3.0 to 4.0 Gy without medical support.  For x-rays and gamma rays, this is equal to an equivalent dose of 3.0 to 4.0 Sv.  Whole-body doses greater than 6 Gy may cause the death of the entire population in 30 days without medical support. With medical support, human beings have tolerated doses as high as 8.5 Gy. 13  Other measures of lethality also are quoted, such as LD 10/30, LD 50/60, and LD 100/60.  The values reported in the literature vary widely based on the following:  The role played by radiation in fatalities in which other factors (e.g., fire at Chernobyl, physical effects of a large explosion at Hiroshima and Nagasaki, chemical contamination in a few nuclear accidents) were present.  The medical treatment that the patient may receive during the prodromal and latent stages, before many of the symptoms of ARS appear.  Regardless of treatment, whole-body equivalent doses of greater than 12 Gy t are considered fatal. 14 Repair and Recovery cells contain a repair mechanism inherent in their biochemistry (repair enzymes). Mechanisms of repair are not well understood however there are three outcomes of damage to mammalian cells 1. Lethal damage - irreversible, irreparable and results in cell death. 2. Sublethal damage - under normal circumstances can be repaired in a few hours. 3. Potentially lethal damage - damage which can be modified by post irradiation conditions i.e.; normally would result in cell death but post irradiation conditions are modified to reduce cell death.  Physical factor affecting the repair and recovery  Dose rate  Presence of oxygen 15 Schematic diagram of organ system response to radiation. 16  protracted; dose delivered continuously but at a lower dose rate.  lower dose rate, allows time for intracellular repair and tissue recovery.  e.g., total of 600 rad delivered in 3 min (200 rad/min) is lethal for a mouse but survive for 600 rad is delivered at the rate of 1 rad/hr for a total of 600 hours  fractionation, dose delivered at the same dose rate but with equal fractions of dose each separated by time.  less effect because intracellular repair and recovery occur between doses  used routinely in radiationtherapy 17  Cell survival curves illustrating the effect of dose rate for low LET radiation. Lethality is reduced because repair of sublethal damage is enhanced when a given dose of radiation is delivered at a low versus a high dose rate. 18  oxygenated cells, which receive more nutrients, have a better prospect for recovery than do hypoxic (poorly oxygenated) cells.  the oxygenated cells are more severely damaged by radiation, but those that survive repair themselves and recover from the injury. 19 Some local tissues suffer immediate consequences from high radiation doses.  Examples of such tissues include the following:  Skin  Male and female reproductive organs  Eye (Ocular)effect 20 EFFECT ON SKIN 1. Erythema: sunburn like reddening of hair. 2. Epilation (also called alopecia): loss of hair 3. Desquamation: ulceration and denudation of skin  Skin reactions to radiation exposure are deterministic and have a threshold of approximately 1 Gy below which no effects are seen. Longer fluoroscopy times required for cardiovascular and interventional procedure are of great concern  Injuries have been reported Potential radiation response Approximate Approximate ly threshold ly time of dose (Gy) Oneset Early transient erythema 2 Hours Main erythema 6 10 days Temporary epilation 3 3 weeks Permanent epilation 7 3 weeks Moist desquamatio n 1.5 4 weeks 21 22 During cardiovascular or therapeutic interventional procedures that use high-level fluoroscopy for extended periods of time, the effects of ionizing radiation on the skin are significant. Patient exposure rates have been estimated to range from 100 to 200 mGy a /min and sometimes even greater. A list of radiation-induced skin injuries may be found in Table 11-2 . 23  Gonads are very radiosensitive  Females  Ova within ovarian follicles are sensitive  Temporary sterility: 1.5 Gy acute dose  Permanent sterility: 6.0 Gy acute dose*  reported for doses as low as 3.2 Gy  Males  Testes contain radiosensitive (spermatogonia) radioresistance (mature spermatozoa)  Temporary sterility: 2.5 Gy acute dose*  reported for doses as low as 1.5 Gy  Permanent sterility: 5.0 Gy acute dose  Reduced fertility 20-50 mGy/wk when total dose > 2.5 Gy 24 EYE (OCULAR)EFFECT Lens of the eye contains sensitive population of radiosensitive cells can accumulate and cause cataract (blurred vision).  Latent period at least one year  > 7 Gy cause cataract  < 2 Gy may cause cataract 25 26