Early Tissue Reactions

Early Tissue Reactions

Objectives

• Identify factors affecting early tissue reactions and time frames in which they appear.
• List/describe possible high-dose consequences of ionizing radiation on living systems.
• Describe acute radiation syndrome (ARS), and list three separate dose-related syndromes that occur with it, along with its four major stages.
• Explain why cells exposed to sublethal radiation doses recover, and discuss cumulative effects that occur after repeated radiation injuries.
• Describe local tissue damage that occurs when the human body receives high radiation exposure.
• State the doses necessary to produce skin erythema and epilation.
• Discuss the impact of high-level fluoroscopy on human skin when used for extended periods.
• Define cytogenetics, and explain how chromosome analysis can be accomplished.
• Explain karyotyping, and identify the phase of cell division in which chromosome damage from radiation can be evaluated.
• List two types of chromosomal aberrations that can result from ionizing radiation and explain them.

Key Terms

• Acute radiation syndrome (ARS)
• Biologic dosimetry
• Cytogenetics
• Desquamation
• Early tissue reactions
• Epilation
• Genetic effects
• Genetic mutations
• Grenz rays
• Karyotype
• Latent period
• Manifest illness
• Metaphase
• Pluripotential stem cell
• Prodromal stage
• Radiodermatitis
• Recovery
• Somatic effects
• Somatic tissue reactions

Somatic Effects

• Somatic effects are effects upon the body that was irradiated.
• Genetic effects are effects upon future generations due to irradiation of germ cells.
• Somatic effects are classified as early effects or late effects, depending on length of time from irradiation to appearance of symptoms.
• Somatic tissue reactions are directly related to the dose received and have consequences including cell death.
• Also known as deterministic effects.
• These effects have a threshold, a point at which the effects appear and below which they are absent, implying a "safe zone".
• The amount of biologic damage depends on the actual absorbed dose of radiation.
• Early tissue reactions have a threshold. Below that threshold, no effects are expected to appear. As the dose increases, the severity of biologic effects increases. This is known as a nonlinear, threshold dose response.

Early Tissue Reactions

• Early tissue reactions vary depending on the duration of time after exposure to ionizing radiation.
• May appear within minutes, hours, days, or weeks.
• A substantial dose is required to produce effects very soon after irradiation, and the severity of the effects is dose-dependent (more dose = more severe effects).
• Early tissue reactions are caused by cell death.
• Diagnostic imaging examinations do not use doses sufficient to cause early tissue reactions.
• High doses to the skin for long periods of time could result in skin effects (erythema).

Possible High Dose Consequences

• Possible consequences of high doses of ionizing radiation:
  • Nausea
  • Fatigue
  • Erythema (diffuse redness of the skin)
  • Epilation (hair loss)
  • Blood disorders
  • Intestinal disorders
  • Fever
  • Dry and moist desquamation (shedding of outer layer of skin)
  • Depressed sperm count in males
  • Temporary or permanent sterility in males and females
  • Injury to the central nervous system (at extremely high doses)

Acute Radiation Syndrome (ARS)

• Acute radiation syndrome (ARS) occurs in humans after large whole-body doses of ionizing radiation (6 Gyt or more) delivered over a short period of time (several hours to a few days).
• Three separate dose-related syndromes occur as part of acute radiation syndrome:
  • Hematopoietic syndrome (Hematologic or bone marrow syndrome)
  • Gastrointestinal syndrome (GI syndrome)
  • Cerebrovascular syndrome (Central nervous system or CNS syndrome)

Stages of ARS

• Prodromal period:
  • The immediate response of radiation sickness (occurs within hours after exposure).
  • At very low doses, there may not be a prodromal period.
• Latent period:
  • The time after irradiation during which there are no signs of radiation sickness.
  • A false sense of well-being that may be mistaken as recovery.
  • At very high doses, the latent period may disappear altogether.
• Manifest illness:
  • Period when signs and symptoms return.
  • Usually more severe or intense symptoms of the prodromal period, with a few additional symptoms.
• Recovery or death:
  • In high-dose exposures, the individual will die regardless of medical intervention.
  • In sublethal dose exposures (1 to 2 Gyt), the individual may recover in 3 weeks to 6 months.

Hematopoietic Syndrome

• Hematopoietic syndrome or “bone marrow syndrome” occurs when people receive whole-body doses of ionizing radiation ranging from 1 to 10 Gyt.
• The hematopoietic system manufactures bone marrow and is the most radiosensitive vital organ system in humans.
• Bone marrow cells are being destroyed, so the body becomes more susceptible to infection and more prone to hemorrhage.
• When death occurs, it is because of excessive bone marrow destruction causing anemia and little or no resistance to infection.
• Death may occur 6 to 8 weeks post-irradiation.
• From 1 to 2 Gyt exposure, individuals can survive due to repair enzymes (may take 3 weeks to 6 months for full recovery).
• From 2 to 10 Gyt, all individuals will die and in a shorter period (as dose increases, survival time decreases).
• The individual’s general health at the time of irradiation influences the possibility of recovery.

Gastrointestinal Syndrome

• The gastrointestinal (GI) syndrome has a threshold dose of approximately 6 Gyt.
• GI syndrome does not appear at doses below 6 Gyt.
• Without medical support, individuals exposed to 6 to 10 Gyt may die 3 to 10 days post-irradiation.
• Even with medical assistance, the exposed person will only live a few days longer.
• Survival time does not change with dose in this syndrome.
• Symptoms begin to appear a few hours after exposure:
  • Nausea, vomiting, and diarrhea that persists for up to 24 hours (prodromal).
  • Symptoms will then disappear for several days (latent).
  • Nausea, vomiting, and diarrhea return (manifest).
• Death occurs due to catastrophic damage to epithelial cells lining the GI tract.
• Results in death within 3 to 5 days from infection, fluid loss, and electrolyte imbalance.
• Epithelial cells will attempt to regenerate; however, the large dose will overwhelm repair enzymes, and the individual will die before regeneration is complete.

Cerebrovascular Syndrome

• The cerebrovascular syndrome occurs at doses of 50 Gyt or more to the central nervous system and cardiovascular system.
• CNS syndrome does not appear at doses below 50 Gyt.
• Death occurs within a few hours to 2 or 3 days post-irradiation.
• Prodromal period: nervousness, confusion, severe nausea, vomiting, diarrhea, loss of vision, burning sensation of the skin, and loss of consciousness.
• Latent period: only lasts up to 12 hours.
• Manifest illness: more severe symptoms appear (shock, agitation, ataxia, edema, fatigue, lethargy, seizures, meningitis, respiratory distress, coma, etc.).
• Injured blood vessels and capillaries permit fluid to leak into the brain, increasing intracranial pressure, and causing tissue damage.
• The CNS and cardiovascular system will fail, bringing death within minutes.

Acute Radiation Syndrome Overview

Radiation Disasters

• Chernobyl:
  • On April 26th, 1986, a massive explosion destroyed reactor 4 at Chernobyl nuclear power plant in Pripyat, Ukraine.
  • Several contaminants were ejected into the atmosphere in a 3-mile high radioactive plume of intense heat.
  • Of 444 people working at the plant during the explosion, two died instantly, and 29 died within 3 months due to whole-body exposure of 6 Gyt and more.
  • 203 people were hospitalized due to acute radiation syndrome.
  • Biologic dosimetry, an analysis of tissue damage used to estimate radiation dose, was utilized.
• Hiroshima and Nagasaki:
  • The atomic bombing of Hiroshima and Nagasaki in Japan resulted in acute radiation syndrome for much of the population.
  • Those who survived demonstrated late effects (cataracts) and stochastic effects (leukemia).

Lethal Dose

• LD 50/30
  • LD 50/30 indicates the whole-body dose of radiation that is lethal to 50% of the exposed population within 30 days.
  • The LD 50/30 for adults is approximately 3.0 to 4.0 Gyt without medical support
  • Equal to 3.0-4.0 Sv
  • Whole body doses greater than 8 Gyt will cause death of the entire population in 30 days without medical support.
• LD 50/60
  • LD 50/60 indicates the whole-body dose of radiation that is lethal to 50% of the exposed population within 60 days.
  • More accurate measure for human survival due to the introduction of medical treatment for early symptoms.

Skin Effects

• Many early radiologists and dentists developed radiodermatitis, a significant reddening of the skin caused by excessive exposure to low-energy ionizing radiation that eventually caused cancerous lesions on the hands and fingers.
• Three layers of skin:
  • Epidermis (outer layer)
  • Dermis (middle layer)
  • Hypodermis (subcutaneous fat layer)
• Skin is continuously regenerating, making it relatively radiosensitive.
• A single dose of 2 Gyt can cause radiation-induced skin erythema within 24-48 hours.
• Desquamation, shedding of the outer layer of skin, occurs at higher doses (moist then dry).
• Epilation, hair loss, can be caused by exposure to radiation due to growing tissue of hair follicles (moderate doses produce temporary hair loss, and large doses can produce permanent hair loss).
• Skin diseases such as ringworm were historically treated and cured by irradiating the affected area with Grenz rays (x-rays with energies of 10 to 20 kVp).
  • If the ringworm was located on the scalp, the irradiation could result in temporary epilation.
  • If the dose was sufficient, permanent hair loss could result.

Reproductive System Effects

• Human germ cells are relatively radiosensitive.
• Doses as low as 0.1 Gyt can result in depressed sperm count and potential genetic mutations in future generations for males, and delayed or suppressed menstruation in females.
• Radiation therapy patients, radiation accident victims, and volunteer convicts have provided data regarding radiation effects on the gonads.
• The cells of the testes and ovaries respond differently to radiation due to differences in progression from stem cells to mature cells.
  • The spermatogonia stem cells of the testes continually reproduce (time from stem cell to mature cell = 3 to 5 weeks).
  • The oogonia ovarian stem cells multiply only during fetal development, before birth, and steadily decline throughout life.
    • Follicles rupture and eject ova (mature cells) every 28 days.
    • Small follicles = least radiosensitive, intermediate-sized follicles = most radiosensitive, large follicles = moderately radiosensitive (somewhere in the middle).

Hematologic Effects

• Hematopoietic system consists of:
  • Bone marrow
  • Circulating blood
  • Lymphoid organs (lymph nodes, spleen, and thymus gland)
• Cells in this system develop from a single pluripotential stem cell that determines what type of cell will develop and what its function will be.
• Types of cells that develop:
  • Lymphocytes
  • Granulocytes
  • Thrombocytes (platelets)
  • Erythrocytes
• Life span of each type of blood cell differs (EX: lymphocytes = only a few hours, erythrocytes = almost 120 days).
• Blood counts were used to monitor occupational radiation exposure in the 1920s and 1930s. Hematologic depression was found to have occurred after whole-body exposure of 0.25 Gyt

Cytogenetic Effects

• Cytogenetics is the study of cell genetics with an emphasis on chromosomes.
• Cytogenetic analysis of chromosomes may be accomplished through the use of a chromosome map called a karyotype.
• A karyotype is a photograph of the human cell nucleus during metaphase.
• Metaphase is the phase of mitosis in which chromosome damage from radiation exposure can be evaluated.
• Chromosome aberrations (deviation from normal development of growth of structures containing genetic material) and chromatid aberrations have been observed during metaphase.

Summary

• Early effects are biologic effects that occur soon after high doses of ionizing radiation.
• Early tissue reactions are not common in diagnostic radiology.
• Somatic effects occur on the body irradiated, whereas genetic effects occur in future generations.
• Acute radiation syndrome (ARS) occurs after large whole-body doses of ionizing radiation in a short period of time.
• ARS has three syndromes: hematopoietic, gastrointestinal, and cerebrovascular.
• ARS has four periods: prodromal, latent period, manifest illness, and recovery/death.
• LD 50/60 is the whole-body dose of ionizing radiation that will result in death to 50% of the exposed population within 30 days (more accurate for humans than LD 50/30).
• High radiation doses can result in local tissue damage (i.e., erythema or epilation).
• Human germ cells are relatively radiosensitive (0.1 Gyt can cause effects).
• Karyotyping is the process of pausing mitosis during metaphase to create a map of chromosomes to assess damage.