Patho - 4th Asessment - Environmental Diseases Iii - 2007

Environmental Diseases III Dr Issam Francis

IONIZING AND NON-IONIZING ELECTROMAGNETIC RADIATION Radiation is energy distributed across the electromagnetic spectrum as 3. Waves (long wavelengths, low frequency) 4. Particles (short wavelengths, high frequency) • 80% of radiation is derived from natural sources • 20% is derived from manufactured sources • Two Types: • Non-ionizing radiation

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Ionizing radiation

IONIZING AND NON-IONIZING ELECTROMAGNETIC RADIATION Non-ionizing radiation • • • •

Electromagnetic Long wavelengths Low frequencies Produce vibration and rotation of atoms in biologic molecules

Examples of Non-ionizing radiation 9. Electric power 10. radio waves 11. Microwaves 12. Infrared 13. Ultraviolet light

Ionizing radiation Can ionize biologic target molecules and eject electrons Two form: 1- electromagnetic waves: – x-rays – gamma rays 2- Particulate radiation: particles released by natural decay of radioisotopes or artificial acceleration of subatomic particles Classified by the type of particles emitted: – Alpha particles: 2 neutrons and 2 protons – Beta particles: electrons – – – – –

Electrons Protons Neutrons Mesons Deuterons

Beta particles weaker ionizing power but higher penetration than alpha particles

MEASURES OF RADIATION: 1- Rad (r): Radiant energy, expressed in ergs, that is absorbed by a tissue. The absorption of radiant energy is biologically more important than the total amount emitted. 2- Gray: 100 rads 3- Relative Biological Effectiveness (RBE): Term comparing the effectiveness of different forms of radiation in producing the same effect. 4- Roentgen (R): Measure of emission of radiant energy (not absorption). 5- Roentgen-equivalent Man (rem): Describes the biological effects produces by 1 rad of high-energy biological radiation.

Biologic effects of ionizing radiation Biologic effects of ionizing radiation depend on several factors: Dose rate: Cell Type: Dose Type: Cell Phase: O2 :

Single dose can cause greater injury than divided or fractionated doses Rapidly dividing cells are more radiosensitive than quiescent cells A single dose of external radiation administered to the whole body is more lethal than regional doses Cells in the G2 and mitotic phases of the cell cycle are most sensitive to ionizing radiation cell injury induced by x-rays and gamma rays is enhanced by hyperbaric oxygen (why)

Radiosensitive Cells (1) Free stem cells of hematopoietic tissue (2) Dividing cells deep in the intestinal crypts (3) Primitive spermatogonia (4) Granulosa cells of ovarian follicles (5) Basal germinal cells of the epidermis (6) Germinal cells of the gastric glands (7) Large and medium sized lymphocytes

Biologic effects of ionizing radiation The acute effects of ionizing radiation • Necrosis: doses >10 Gy • killing of proliferating cells: doses 1 to 2Gy • No histopathological effect: doses < 0.5 Gy • Subcellular damage doses < 0.5 Gy Most cells show adaptive and reparative responses Damage may be produced directly by – particulate radiation, – x-rays, or – gamma rays

Indirectly: – Oxygen-derived free radicals – Soluble products of peroxidized lipids

Biological effects of ionizing radiation Cellular Mechanisms of Radiation Injury

Acute Effects Ionizing radiation can produce a variety of lesions in DNA 6. 7. 8. 9. 10.

DNA-protein cross-links Cross-linking of DNA strands Oxidation and degradation of bases Cleavage of sugar-phosphate bonds Single stranded or double-stranded DNA breaks

Biologic effects of ionizing radiation •

Surviving cells may show delayed effects of radiation injury – Mutations – Chromosome aberrations – Genetic instability

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Genetically damaged cells may become malignant

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Tissues with rapidly proliferating cell populations are especially susceptible to the carcinogenic effects of ionizing radiation

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Most cancers induced by ionizing radiation have occurred after doses > 0.5 Gy

LATE EFFECTS OF RADIATION: •

Small arterial thickening (hyaline, collagenous), which may result in local ischemia.

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Mutation to fetuses exposed in utero

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Bone marrow hypoplasia

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Radiation dermatitis

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Radiation pneumonitis

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Induction of cancer: – – – – –

Leukemias and lymphomas Breast cancer Thyroid Lung Osteosarcoma

WHOLE BODY ACUTE RADIATION SYNDROME: 3 distinct sub-syndromes: 1- HEMATOPOIETIC: 300 rads / 200-600 rem • Intermittent nausea and vomiting • Petechiae, hemorrhage • Maximum neutrophil and platelet depression in 2 wk • Lymphocytes <1000/mm3 • Infections • May require bone marrow transplant

Gastro-intestinal: 1000 rads / 600-1000 rem destruction of GI epithelium Diarrhoea, dehydration, enteric sepsis

3- CNS: 2000 rads, >1000 rem • Endothelial injury & cerebral edema • Coma in 15 min-3 hr • Death in 14-36 hr

TUMOR RADIOSENSITIVITY: Some cell-types (and tumors) are more radiosensitive than Others HIGH SENSITIVITY: • Lymphomas • Seminoma LOW SENSITIVITY: • Osteosarcomas • Gliomas

Acute Organ Damage Bone marrow Skin Heart Lung

Atrophy Erythema -Edema, endothelial and epithelial cell death

Gastrointestinal tract Kidney Liver Urinary bladder Brain Testis Ovary Thyroid Breast Thymus, lymph nodes

Edema, mucosal ulcers Ulcers Vasodilation Veno-occlusive disease Mucosal erosion Edema, necrosis Necrosis Atresia of follicles

--Atrophy

Delayed Complications / Organ Damage Bone marrow Skin Heart

Hypoplasia, leukemia Atrophy, fibrosis, cancer Interstitial fibrosis

Lung

fibrosis; cancer

Gastrointestinal tract

Ulcers; strictures; adhesions; cancer

Kidney

Cortical atrophy, interstitial fibrosis

Liver Urinary bladder

Cirrhosis; liver tumors Submucosal fibrosis; cancer

Brain Ovary

Necrosis of white matter, gliosis; cancer Stromal fibrosis

Thyroid Breast Thymus, lymph nodes

Hypothyroidism; cancer Fibrosis; cancer Lymphoma

ACUTE AND DELAYED EFFECTS OF ULTRAVIOLET RADIATION Radiation

Wavelength /nm

Acute Effects

Delayed Effects

UVA

320-400

Erythema 8-48 hr

Tanning

Depletion of Langerhans cells

? Skin cancer

Pigment darkening Dermal inflammation UVB

290-320

Erythema 3-24 hr

Tanning

Apoptosis of keratinocytes

Solar elastosis

Depletion of Langerhans cells

Premature aging Actinic keratosis Skin cancer

UVC

200-290

? Skin cancer