1 / 50

Acute Radiation Syndrome (A Spectrum of Disease)

Acute Radiation Syndrome (A Spectrum of Disease). Doran Christensen, DO Associate Director, REAC/TS. Acute Radiation Syndrome. Systemic Effects from Acute Radiation Exposure Multi-Faceted Spectrum of Disease Involvement of One or more Organ Systems. Ionization Process .

cadee
Télécharger la présentation

Acute Radiation Syndrome (A Spectrum of Disease)

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

  1. Acute Radiation Syndrome (A Spectrum of Disease) Doran Christensen, DO Associate Director, REAC/TS

  2. Acute Radiation Syndrome • Systemic Effects from Acute Radiation Exposure • Multi-Faceted Spectrum of Disease • Involvement of One or more Organ Systems

  3. Ionization Process • Density of Ionization Trail • Chemical Bonds • DNA Damage • Subcellular components • Mitotic Delay • Repair • Complete • Incomplete • Residual Damage? Measureable?

  4. Exposure Principles • Total vs. Partial Body Irradiation • Threshold Effect of Dose • Threshold • D50 Dose • Dose Rate • Dose Protraction or Fractionation

  5. Radiation Effects • Stochastic - “All-or-Nothing” Effect Occurrence Probability is Function of Dose • Increased Risk of Developing Cancer • Inheritable Mutations • Deterministic - Effect Severity is a Function of Dose (Commonly Associated with Threshold) • Inflammatory Response • Organ Failure • Fibrosis

  6. Deterministic Stochastic 1 1 E E 0.8 0.8 f f 0.6 0.6 f f e e 0.4 0.4 c c 0.2 0.2 t t 0 0 Dose Dose Radiation Effects

  7. Law of Bergonié and Tribondeau (1906) • More Differentiated Cells are Less Sensitive • Actively Proliferating Cells are More Sensitive • Radiosensitivity is Proportional to Mitotic and Developmental Activity Duration Rapidly Dividing Cells that Are Poorly Differentiated and Have a Long Mitotic Period Are Very Radiosensitive

  8. Exceptions: • Lymphocyte - Most Radiosensitive Cell • Oocyte - Non Mitotic Cell

  9. Radiosensitive Cells • Red Marrow • Epithelial Cells of GI System, Lung • Epithelium of Lens • Germinative Cells of Testis and Ovary • Endothelial Cells of Blood Vessels

  10. Radiosensitive Cells (cont’d) • Pluripotential Stem Cells • Rapid Mitotic Rate • Form Intermdiate Precursors and then Mature Elements. • Cells with Large Nuclei • Interphase Death • Lymphocyte, Oocyte and Salivary Gland

  11. Effects of Radiation Protraction Prodromal Component (Gy) Vomiting Diarrhea Brief Protracted Brief Protracted Exposure Exposure Exposure Exposure D50 2 5 3 6 Threshold 0.5 1.5 1 2.5 NUREG / CR 4214, Part II, p. 21

  12. GI Cellular Hierarchy IAEA – UNSCEAR 1988

  13. Skin Cellular Hierarchy IAEA – UNSCEAR 1988

  14. Exposure Prodromal Stage Latent Stage Manifest Illness Recovery Time (60 days) Phases of Acute Radiation Syndrome

  15. Acute Radiation Syndrome • Components of Radiation Effects: • Prodromal (0.5 - 3 Gy) • Hematological (1.5 - 6 Gy) • Respiratory (5 - 310 Gy) • Cutaneous (5 - 10 Gy) • Gastrointestinal (8 - 15 Gy) • Neurovascular (6 - 50 Gy) • Combined Injury

  16. Prodromal Component(0.5 - 3 Gy and higher) • Immediate Effect of Cell Membrane Damage • Mediated by Inflammatory Elements of Cell Destruction • Mediated Neurologically by Parasympathetic System

  17. TBI Dose Estimates for Prodromal Symptoms Prodromal Component (Gy) Vomiting Diarrhea Brief Protracted Brief Protracted Exposure Exposure Exposure Exposure D50 2 5 3 6 Threshold 0.5 1.5 1 2.5 NUREG / CR 4214, Part II, p. 21

  18. Hematopoietic Component(1.5 - 6 Gy and higher) • Lymphocytes • Neutrophils • Thrombocytes • Erythrocytes

  19. Hemogram3 Gy (300 Rad) TBI Exposure Source – REAC / TS Diagram – Human Irradiation 3 Gy (300 Rads)

  20. Gastrointestinal Component(8 - 15 Gy and higher) • Symptoms • Mechanisms • GI Epithelial Sterilization - 15 Gy • Veno-Occlusive Disease of Liver

  21. Respiratory Component(5 - 310 Gy and higher) • Sensitive from Highly Vascular Tissue • Endothelial Cells • Type II Alveolar Cell • Effect is Dose-Rate Related • Pneumonitis • Fibrosis

  22. Pulmonary Lethality Syndrome Dose Rate (Gy/hr) Threshold (Gy) • 0.05 310 • 0.1 160 • 0.5 40 • 1 20 • 10 7 • 100 5 NUREG / CR-4214, Part II, p. 55

  23. Neurovascular Component(8 - 50 Gy and higher) • Brain Cells are Fixed, Post-Mitotic Cells • Weak Link -- Stromal Cells • Endothelial Cells Turnover • 2 Months to 3 Years (3 Days) • EEG Changes Doses as Low as 1 Gy

  24. Neurovascular Component (continued) • 1 - 6 Gy - Glial Cell Damage • 10 Gy - Morphologic Changes • 10 - 20 Gy - Vascular Lesions • 40 Gy - White Matter Necrosis • 60 Gy - Demyelinization

  25. Ovarian Function Ovarian Dose (Gy) Results 0.6 - No Deleterious Effect 1.5 - Some Risk for Ovulatory Suppression in Women over 40 2.5 - 5.0 - 60% Women Aged 15-40 Have Permanent Suppression Remainder have Temporary Amennorrhea 100% Women Over 40 have Permanent Suppression 5.0 - 8.0 - 60-70% Women Aged 15-40 Have Permanent Suppression Remainder have Temporary Amennorrhea >8.0 - 100% Permanent Ovulatory Suppression NUREG / CR-4214, p II-70

  26. Sperm Production Testicular Dose (Gy) Results 0.1 - 0.3 - Temporary Oligospermia 0.3 - 0.5 - 100% Temporary Aspermia from 4 - 12 mo Post-Irradiation Full Recovery by 48 mo 0.5 - 1.0 - 100% Temporary Aspermia from 3 - 17 mo Full Recovery Beginning at 8 - 38 mo 1 - 2 - 100% Temporary Aspermia from 2 - 15 mo Recovery Beginning at 11 - 20 mo 2 - 3 - 100% Aspermia Beginning at 1 - 2 mo No Recovery Observed after 40 mo NUREG / CR-4214, p II-73

  27. Radiation Skin Injury • Effects • Time Frame • Injury Course

  28. Radiation Skin Injury • .75 Gy - Hair Follicles Change • 3 Gy - Epilation • 6 Gy - Erythema • 10 Gy - Dry Desquamation • 20 Gy - Wet Desquamation (Transepithelial Injury)

  29. Skin Effects Effect Parameter Brief Protracted Exposure Exposure Erythema Threshold 3 6 D50 6 20 Transepithelial Threshold 10 40 Injury D50 20 80 NUREG / CR-4214, p II-68

  30. Skin Effects Effect Single Onset Dose (Gy) Time Epilation 3 - 7 ~18 days Erythema 10 - 20 12 - 17 days Pigmentation 10 - 20 Dry Desquamation 10 - 20 30 - 70 days Moist Desquamation 20 - 24 30 - 50 days That Heals Telangiectasia 17 - 24 6 mo - years Nonhealing Necrosis > 60 months, years NUREG / CR-4214, p II-68

  31. El Salvador Patient + 32 Days Hyperpigmentation ( Bronzing )

  32. El Salvador Patient + 32 Days Dry Desquamation

  33. El Salvador Patient + 32 Days Transition to Wet Desquamation

  34. El Salvador Patient + 32 Days Wet Desquamation

  35. Triage • By Conventional Injuries • Trauma • Burns • By Radiation Injury • Prodromal Symptoms • Hematologic Picture

  36. Modified USSR Classification (1986) • Class 1 Class 2 • Prodrome>3 hrs *1 - 3 hrs* • Lymphs (3-6 days)600 - 1000300 - 500 • TBI Dose1 - 2 Gy2 - 4 Gy • Survival EstimateProbable w / o txPossible w / o tx • Class 3 Class 4 • Prodrome.5 - 1 hr < .5 hr • Lymphs (3-6 days)100 - 200 <100 • TBI Dose4.2 - 6.3 Gy6 - 12, 16 Gy • Survival EstimateProbable w / txNot Likely Mettler FA, Kelsey CA, Ricks RC Eds. Medical Management of Radiation Accidents. Boca Raton: CRC Press, 1990, p. 72. *Barabanova A. REAC/TS Newsletter. Winter 1992, Oak Ridge, TN, p 1-2.

  37. Andrews LymphocyteNomogram • Confirms suspected radiation exposure • Determines significant hematological involvement • Serial CBCs every 6 h From Andrews GA, Auxier JA, Lushbaugh CC: The Importance of Dosimetry to the Medical Management of Persons Exposed to High Levels of Radiation. In Personal Dosimetry for Radiation Accidents. Vienna, International Atomic Energy Agency, 1965, pp 3- 16

  38. Goans Nomogram – The Next Advance Goans, RE, “Clinical Care of the Radiation-Accident Patient: Patient Presentation, Assessment, and Initial Diagnosis” in Ricks RC, Berger ME, O’Hara FM, The Medical Basis for Radiation Accident Preparedness – The Clinical Care of Victims, p18.

  39. Combined-Injury Triage whenRadiation Doses are Known* Conventional Triage Changes in Expected Triage Category Categories if Injuries are following Only Trauma Whole-Body Radiation Dose (Gy) No Radiation Exists < 1.5 (150 rad) 1.5-4.5 (150-450 rad) > 4.5 (450 rad) Prodrome Onset < 3 h 1 – 3 h < 1 h Immediate Immediate Immediate Expectant Delayed Delayed Expectant Expectant Minimal Minimal Expectant Expectant Expectant Expectant Expectant Expectant *Decision based on whole-body radiation dose, assuming all casualties are wearing personal dosimeters Source: Medical Consequences of Nuclear Warfare, 1989, p. 39

  40. Combined Injury

  41. Combined Injury -Total Body Irradiation + Burns Rat Model AFRRI Medical Effects of Nuclear Weapons Course “Triage and Treatnent of Radiation Casualties” Lecture, slide 35

  42. Treatment Overview • Supportive Care • Surgical Recommendations • Selective Gut Decontamination • Bone Marrow Transplants (not as successful) • Biological Response Modifiers • Cytokines (more successful) • Complications of Acute Radiation Syndrome

  43. Supportive Care • Fluid and Electrolyte Replacement • Reverse Isolation • Total Parenteral Nutrition • Empiric Antibiotics for Documented Infection

  44. Supportive Care (cont’d) • Irradiated Blood Products • Enteral Feedings • Intravenous Glutamine • Sucralfate

  45. Surgical Recommendations • Based on Immunocompetence Status (neutropenia immunocompetence) • Life-Saving / Major Surgery within 36 - 48 h • Elective Procedures until 45 - 60 days Following Hematopoietic Recovery Browne D, Weiss JF, MacVittie TJ, Pillai MV (eds) Treatment of Radiation Injuries, 1990, Plenum Press, New York, p. 229

  46. Selective Gut Decontamination • Historical Background • Non-Systemic Abx vs. Systemic Abx • Fluoroquinolones • Ciprofloxacin, Ofloxacin • Norfloxacin

  47. Cytokine Combinations • IL-3/G-CSF • IL-3/GM-CSF

  48. Acute Radiation Syndrome Complications • Hematologic/Gastrointestinal • Interstitial Pulmonary Fibrosis • Veno-occlusive Disease of the Liver • Herpes Simplex (HSV) Reactivation • Cytomegalovirus (CMV) Reactivation • Combined Injuries

  49. Any Questions? uncleofdisaster@cdc.gov

  50. References • NUREG / CR-4214, Health Effects Models for Nuclear Power Plant • Accident Consequence Analysis: Low LET Radiation, Part II: Scientific Bases • for Health Effects Models, US Nuclear Regulatory Commission, 1989. • Browne D, Weiss JF, MacVittie TJ, Pillai MV (eds)Treatment of Radiation Injuries, • 1990, Plenum Press, New York, p. 229 • AFRRI Medical Effects of Nuclear Weapons Course “Triage and Treatnent of • Radiation Casualties” Lecture, slide 35 • IAEA, The Radiological Accident in San Salvador, 1989 • Ricks RC, Berger ME, O’Hara FM, The Medical Basis for Radiation-Accident • Preparedness – The Clinical Care of Victims, Parthenon Publishing Group, Inc: • New York:2002. • Saenger EL, Andrews GA, Linnemann RE, Wald N: Radiation Accident Preparedness • Medical and Managerial Aspects. Science-Thru-Media: New York 1981, p 15. Revision 6.1 – 17 Apr 2004

More Related