Early Tissue Reactions Notes

Early Tissue Reactions

Objectives

• Identify factors affecting early tissue reactions and the time frames in which they appear.
• List and describe possible high-dose consequences of ionizing radiation on living systems.
• Describe acute radiation syndrome (ARS), listing the three dose-related syndromes and the four major stages.
• Explain why cells exposed to sublethal radiation doses recover and discuss cumulative effects after repeated radiation injuries.
• Describe local tissue damage from 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 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 or late effects, depending on the time from irradiation to symptom appearance.
• 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.
• They have a “safe zone”.
• The amount of biologic damage depends on the actual absorbed dose of radiation.
• The graph demonstrates the threshold of early tissue reactions. 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. (The graph does not increase in a straight line, nonlinear, and has a “safe zone”.)

Early Tissue Reactions

• Early tissue reactions vary depending on duration of time after exposure to ionizing radiation.
• May appear within minutes, hours, days, or weeks.
• A substantial dose is required to produce effects 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.
• Should still be mindful of dose, as 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).
  • More on stochastic effects in the next chapter.

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.
  • First appears as moist skin peeling, then develops into dry skin flaking.
• 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 Effects Cont.

• 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).
• The low-energy photons were able to cure the disease, but 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).
• Fun fact: 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. The lethal dose that will result in death to 50% of the population within 60 days.