Deterministic Effects of Radiation (Early Effects)

DETERMINISTIC EFFECTS OF RADIATION (EARLY EFFECTS)

  • Acute Radiation Syndrome (ARS)

    • Serious illness or death occurs in whole body doses of 1 Gy (100 rad) or more over a short period of time.

    • Also known as: radiation poisoning, radiation sickness, or radiation toxicity.

    • 3 Sub-categories of ARS:
      a. Hematologic Syndrome
      b. Gastrointestinal Syndrome
      c. Central Nervous System Syndrome

HEMATOLOGIC SYNDROME

  • Also known as Bone Marrow Syndrome.

  • Develops after whole-body exposure to doses ranging from 0.7 – 10 Gy (70–1000 rads) or (0.7 -10 Sv).

  • Causes a reduction in white cells, red cells, and platelets in circulating blood.

STAGES:

  1. Prodromal Stage:

    • Symptoms: Nausea, vomiting.

  2. Latent Stage:

    • Stem cells dying, patient may appear to feel well.

  3. Manifest Illness Stage:

    • Symptoms: Fever, malaise.

  4. Primary Cause of Death:

    • Destruction of bone marrow resulting from infection and hemorrhage.

GASTROINTESTINAL SYNDROME

  • Appears in humans at a threshold dose greater than 10 Gy (1000 rads) or (10 Sv).

  • Symptoms include: Nausea, diarrhea, damage to intestinal cells, infection, dehydration, and electrolyte imbalance.

STAGES:

  1. Prodromal Stage:

    • Symptoms: Severe nausea, cramps, diarrhea, vomiting.

  2. Latent Stage:

    • Stem cells in bone marrow and GI tract dying, although the patient feels well.

  3. Manifest Illness Stage:

    • Symptoms: Severe diarrhea, dehydration, fever.

    • Death occurs within 2 weeks.

CENTRAL NERVOUS SYSTEM (CNS) SYNDROME

  • Caused by doses greater than 50 Gy (5000 rads) or (50 Sv).

  • Causes a collapse of the circulatory system, increased pressure in the cranial area resulting from edema, vasculitis, and meningitis.

STAGES:

  1. Prodromal Stage:

    • Symptoms: Confusion, severe nausea, vomiting, loss of consciousness, burning sensation of skin.

  2. Latent Stage:

    • Symptoms subside for no more than a few hours.

  3. Manifest Illness Stage:

    • Symptoms: Diarrhea, convulsions, coma.

    • Death occurs within a few hours to 3 days.

STAGES OF ARS

  1. Prodromal Stage

  2. Latent Stage

  3. Manifest Illness Stage

  4. Recovery or Death Stage

PRODROMAL STAGE/LATENT STAGE OF ARS

PRODROMAL STAGE

  • Immediate response of radiation sickness.

  • Classic symptoms include: Nausea, vomiting, diarrhea occurring from minutes to days.

  • Symptoms can last up to several days.

LATENT STAGE

  • Time after exposure where there is no sign of radiation sickness.

  • Patient appears generally healthy for a few hours or a few weeks.

MANIFEST/RECOVERY STAGE OF ARS

MANIFEST ILLNESS STAGE

  • Severe symptoms include fever, severe diarrhea, dehydration, convulsions, and coma.

  • Duration: Lasts from hours to several months.

RECOVERY OR DEATH

  • Recovery process can last from several weeks to 2 years.

  • Death can occur within several months of exposure.

MEAN SURVIVAL TIME

  • Definition: Average time between exposure and death.

  • As the whole body dose increases, the time between exposure and death decreases.

EXAMPLES:

  • 200 - 1000 rads: Survival time decreases from 60 days to 4 days.

  • 1000 - 5000 rads: Survival time is approximately 4 days.

  • Above 5000 rads: Survival time ranges from 3 days to just a few hours.

LOCAL TISSUE DAMAGE

  • Resulting from irradiation doses affecting tissues or organs.

  • Possible outcomes:
    A. Reduction of organ size (atrophy).
    B. Cell death.
    C. Recovery.

FACTORS AFFECTING LOCAL DAMAGE:

A. Radiosensitivity of the tissues.
B. Rate of cell proliferation.
C. Cell maturation.

EXAMPLES OF LOCALLY AFFECTED TISSUES:

A. Skin.
B. Gonads.
C. Bone marrow.

TYPES OF LOCAL TISSUE DAMAGE:

A. Effects on skin.
B. Effects on gonads.

EFFECTS OF SKIN

  • Layers of Skin:

  1. Epidermis.

  2. Dermis.

  3. Subcutaneous tissue.

  • Accessory Structures:

  1. Sweat glands.

  2. Hair follicles.

  3. Sensory receptors.

  • All layers and accessory structures are affected by radiation exposure.

  • The epidermis comprises several layers of cells, with the lower layer consisting of basal cells (stem cells) that mature to the surface.

RADIOSENSITIVITY OF BASAL CELLS

  • Basal cells are VERY radiosensitive.

SKIN RESPONSE TO RADIATION:

  1. Erythema: Reddens skin.

  2. Desquamation: Causes ulceration of skin.

  3. Epilation: Hair loss.

EFFECTS ON GONADS

  • Human gonads are highly sensitive to radiation due to:

    • These cells produce germ cells responsible for fertility and heredity.

    • Female's ovarian stem cells: Oogonia.

    • Male's testes stem cells: Spermatogonia.

    • Maturation process of stem cells takes 3 to 5 weeks.

FEMALE GONAD RADIATION EFFECTS:

  • 100 mGy (100 mSv) (10 rad): May suppress menstruation.

  • 2 Gy (2 Sv) (200 rad): Temporary infertility.

  • 5 Gy (5 Sv) (500 rad): Permanent sterility.

  • 250 mGy to 500 mGy (250 mSv-500mSv) (25 to 50 rad): May increase genetic mutations.

MALE GONAD RADIATION EFFECTS:

  • 100 mGy (100 mSv) (10 rads): May reduce spermatozoa.

  • 2 Gy (2 Sv) (200 rad): Temporary infertility.

  • 5 Gy (5 Sv) (500 rad): Permanent sterility.

  • 100 mGy (100 mSv) (10 rads): Should avoid procreation for 2 to 4 months due to potential genetic mutations.

HEMOPOIETIC SYSTEM

  • Consists of: Bone marrow, circulating blood, and lymphoid tissue.

  • This system is an example of a cell-renewing system.

  • Lymphoid tissue includes lymph nodes, spleen, and thymus.

  • Radiation depresses the number of blood cells.

STEM CELLS IN HEMOPOIETIC SYSTEM

  • All hemopoietic cells develop from a single type of stem cell called the pluripotential stem cell, which differentiates into many cell types.

  • Types of cells produced from the pluripotential stem cell:

    • Lymphocytes: For immune response.

    • Granulocytes: Fights bacteria.

    • Thrombocytes (platelets): Clotting of blood.

    • Erythrocytes (red blood cells): Carriers of oxygen.

HEMOPOIETIC CELL SURVIVAL

  • Following radiation exposure, there is a decrease in the numbers of all types of blood cells.

  • Order of radiosensitivity among blood cells:

    1. Lymphocytes:

    • First affected: Decrease in number (lymphopenia). Slower recovery.

    1. Granulocytes:

    • Initially increased (granulocytosis), then rapid decrease, and slower recovery (granulocytopenia). Recovery in approximately 2 months.

    1. Thrombocytes:

    • Decrease in or depletion of platelets (thrombocytopenia). Recovery in about 2 months.

    1. Erythrocytes:

    • Least sensitive; may not see injury for weeks, recovery in 6 to 12 months.

CYTOGENETIC EFFECTS

  • Study of the structure and function of the cell, especially the chromosome.

  • Radiation-induced chromosome aberrations follow a nonthreshold dose-response relationship.

NORMAL KARYOTYPE

  • Known as a chromosome map.

  • Each cell contains 22 pairs of autosomes and a pair of sex chromosomes (X for female & Y for male).

TYPES OF CHROMOSOME ABERRATIONS (DAMAGE)

  1. Single-hit aberrations.

  2. Multi-hit aberrations:
    a. Ring chromosome aberrations
    b. Dicentric chromosome aberrations
    c. Reciprocal translocation aberrations

SINGLE-HIT CHROMOSOME ABERRATIONS

  • A chromosome “hit” produces a visible derangement of the chromosome; damaging many molecular bonds and chains contained in the DNA.

MECHANISMS OF SINGLE-HIT ABERRATIONS

  1. During G1 Phase of the cell cycle (also known as chromatid deletion):

    • Both chromosomes are duplicated as deleted (broken) chromosomes during S phase.

  2. During G2 Phase:

    • Irradiation deletes (breaks) one arm of the chromosome, resulting in missing genetic material.

MULTI-HIT ABERRATIONS

  • Can occur in three ways:

  1. Ring Chromosome:

    • In G1 phase, if two hits occur on the same chromosome, a “ring” shape forms.

  2. Dicentric Chromosome:

    • Produced when adjacent chromosomes each suffer one hit and recombine with each other, leaving fragments to float.

  3. Reciprocal Translocation Chromosome:

    • Occurs during mitosis, where fragments are lost or attracted to only one daughter cell (since they are unattached to a spindle fiber); either one or both daughter cells may be missing genetic material.

    • Note: There is no loss of genetic material, only rearrangement of the genes occurs.

KINETICS OF CHROMOSOME ABERRATION

  • Very low doses of radiation cause single-hit aberrations.

  • High radiation doses exceeding 1 Gy (1 Sv) (100 rads) cause multi-hit aberrations.

GRAPHICAL REPRESENTATION:

  • Single-hit aberrations: Linear, nonthreshold.

  • Multi-hit aberrations: Nonlinear, nonthreshold; these aberrations are most significant regarding latent human damage.

SYSTEMIC RESPONSE TO RADIATION

  • When a response is directly related to dose, it is described as linear, nonthreshold.

SYSTEMIC RESPONSES INCLUDE:

  1. Hemopoietic Response:

    • Related to the formation and development of blood cells (red and white blood cells and platelets).

    • See slides 18 and 19 for details.

  2. Integumentary Response:

    • Includes skin, hair, nails, sweat glands, sebaceous glands; causing skin lesions and burns.

  3. Digestive Response:

    • Damage to the intestinal lining resulting in bloody vomiting and bloody diarrhea.

  4. Urinary Response:

    • Difficulty/painful urination leading to blood in urine and cramping.

  5. Respiratory Response:

    • Killing lung cells, inflammation of cells leading to radiation pneumonitis and radiation fibrosis.

  6. Reproductive Response:

    • Rapidly dividing cells (egg/sperm) in ovaries/testes can die, possibly causing sterility and hormone fluctuations.

  7. Muscle/Nervous Response:

    • Changes in motor function or neurological disorders.