Topic1-Early Rad Effects

7/29/2019 Topic1-Early Rad Effects

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EARLY Effects ofRadiation


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ACUTE RADIATION LETHALITY

*Acute Radiation Syndrome

Sequence of events following high-

level radiation exposure leading to

death within days or weeks


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Acute Radiation Syndrome

Classified as:

1. HEMATOLOGIC DEATH

2. GI DEATH

3. CNS DEATH


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Acute Radiation Lethality

PERIOD APPROXIMATEDOSE

MEANSURVIVAL

TIME

CLINICALSIGNS/

SYMPTOMS

Prodromal

> 100 rad

none

*Nausea, vomiting,diarrhea

Latent 100-10,000 rad noneNo visible signs

Hemato

200-1000 rad

10-60 days

*+ Anemia,leukopenia,

hemorrhage, fever,infection

GI 1000-5000 rad 4-10 daysHEMA + e-imbalance, lethargy,fatigue, shock

CNS > 5000 rad 0-3 days GI + ataxia, edema,vasculitis, meningitis


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PRINCIPAL EARLY

EFFECTS OF RADIATIONEFFECT ANATOMIC SITE DTDEATH whole-body 200 rad

HEMATOLOGICDEPRESSION whole-body

25 rad

SKIN ERYTHEMA small field 200 rad

EPILATION small field 300 rad

CHROMOSOMEABERRATION whole-body

5 rad

GONADAL DYSFXN local tissue 10 rad


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Associated lethal periods:

PRODROMAL PERIOD

acute clinical symptoms that occur

within hours of exposure and

continue for up to a day or two.


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Associated lethal periods:

LATENT PERIOD

the period after the prodromal

stage of the ARS during which

there is no vis ib le signof radiation

sickness


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PRODROMAL PERIOD

A minimum dose of 100 rad delivered to

the total body, signs and symptoms

may appear within a matter of minutesto hours.

immediate response to radiation

However, if dose exceed to 1000 rad,

s m toms ma be severe


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LATENT PERIOD

Period of apparent wellness after initial

radiation sickness.

Extends from hours or less (5000 rad),

to weeks (100-500 rad)

mistaken to be an indication of early

recovery from moderate radiation

sickness.


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MANIFEST ILLNESS

The stage of the ARS during which

signs and symptoms are apparent.


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Hematologic Syndrome

* 200 rad 1000 rad

person who's irradiated might

experience:

Mild sx of prodromal syndrome (few

hours-several days)

Latent period may extends for 4

weeks feeling of wellness (though

CYTOPENIA may occur)


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Hematologic Syndrome

*MANIFEST ILLNESS

vomiting, mild diarrhea, malaise,

lethargy, fever

recovery begins 2 4 weeks (dose

is not lethal) / 6 mos (full recovery)

if severely ill, hemorrhage and

dehydrat ionbefore death caused:

(infection, electrolyte imbal,

dehydration)


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Gastrointestinal Syndrome

*1000 rad 5000 rad

Prodromal Sx: vomiting and diarrhea

within hours of exposure day

Latent Period: 3 5 days (no sx)

Manifest Illness: starts at the 2

nd

waveof nausea and vomiting diarrhea

the irradiated person might

experience: anorexiaand lethargy


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Diarrhea persists (more severe)

loose, watery and bloody stools

death (after 4 10 days of irradiation)

GI death caused by damage to cell

lining in the intestines (stem cells)

intestinal cells proliferation rate:3-5days

intestinal cells denuded f lu id pass

across the intest inal membrane,

destro yed e- bal in fect ion


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Central Nervous

System Syndrome*5000 rad or >

series of ss and sx occur DEATH

within hours to days after irrad

1st : severe nausea and vomiting (few

minutes after irrad)

followed by: confusion and

nervousness, burning sensation in

skin, lose vision or even LOC (few hrs)


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Central Nervous System

Syndrome

Latent period may last up to 12hrs

Manifest illness the sx of Prodromal

stage return, severely


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Syndrome the irrad person experiences:

Disor ientat ion, Lose muscle

coordinat ion, Dyspnea, Seizure, Loss

of equ i l ibr ium , A taxia, Lethargy

Coma

DEATH


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SyndromeCharacterized by:

increased intracranial pressure,

vasculitis, meningitis

sufficient dose damage to all body

organs


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LD 50/60

is the dsef radiatin t the whle

bdy that causes 50 % fthe irradiated

subjects t die within 60 days.


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LD 50/60

*Acute radiation lethality follows a

nonl inear, threshold dose-response

relationship.

*350 rad acute radiation lethality for

humans (850 rad max)


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Additional measures of acute lethality:

LD 10/60

LD 90/60

LD 50/30


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Mean Survival Time

when the whole-body radiation

increases the average TIME between

exposure and death decreases.


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Mean Survival Time

HEMATOLOGICAL

as the radiation dose increases from

200 to 1000 rad, the MST decreases

from 60 to 4 days.

MST is dose-dependent for

hematological syndrome


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Mean Survival Time

GASTROINTESTINAL

MST remains its constant (4 days)

CENTRAL NERVOUS SYSTEM

MST is dose-dependent (3 days to amatter of hours)


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Radiation Effects on Skin

all skin layers and accessory

structures participate in the response

to radiation exposure


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because x-rays pass through the skin

to reach the internal structures (tx), the

skinis subjected to a higher radiation

dose as compared to the internal

structures which supposed to be the

target for the tx.


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Radiation Effects on

SkinERYTHEMA

sunburn-like reddening of the skin

300-1000 rad (initial mild erythema

may occur within the first/second day

2 weeks).

DESQUAMATION

ulceration and denudation of the skin


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EPILATION

grenz raysused to treat skin dse. such

as tineacapitis epilation


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Radiation Response DT Time of Onset

Early Erythema 200 rad HoursMain Erythema 600 rad 10 days

Tempo Epilation 300 rad 3 weeks

Perma Epilation 700 rad 3 weeks

Moist Desqua 1, 500 rad 4 weeks

Potential Radiation Responses to Skin

from High-Dose Fluoroscopy


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Effects on Gonads

10 rad

Gametogenesis

germ cell development from stem to

mature cells


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Rad iat ion Effec ts in Ovaries

irrad of ovaries atrophy thru germ cell

death

fetal and early childhood

radiosensitive

20 to 30 years radioresistant


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Rad iat ion Effec ts in Ovaries

10 rad - may delay/ suppress menstrual

period (mature)

200 rad temporary infertility500 rad permanent sterility

25 to 50 rad genetic mutations

the most radiosensitive cell during

female germ cell development is the

oocytein the mature follicle.


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Rad iat ion Effects in Tes tes

50 to 300 rad normal birth to babies

10 rad reduced spermatozoa

200 rad temporary infertility

(2-12 months after irrad)

500 rad permanent sterility


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Rad iat ion Effects in Testes

spermatogonial stem cells are the

most sensitive to radiation

THE MALE SHOULD REFRAIN FROM

PROCREATIONFOR 2 TO 4 MONTHS

UNTIL ALL CELLS THAT WERE IN THE

SPERMATOGONIAL ANDPOSTSPERMATOGONIAL STAGES AT

THE TIME OF IRRAD FROM 10 rad

HAVE MATURED AND DISAPPEARED


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Hematological Effects

periodic blood examination is

recommended as a feature of anycurrent radiation protection program.

25 rad whole-body dose necessary toproduce hemato depression


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Hemopoietic System

PLURIPOTENTIAL STEM CELL

it can develop into several different

types of mature cells:

lymphocytes

granulocytes

thrombocytes

erythrocytes


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Hemopoietic System

Granulocytes and Erythrocytes

develop at bone marrow for at least 8-

10 days

Thrombocytes have a lifetime of5 days

in bone marrow

Lymphocytes are produced overvary ing t imesand have varying l i fet ime

(some hoursor others years)


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Hemopoietic System

in the PERIPHERAL BLOOD,

Granulocytes' lifetime days

Thrombocytes' lifetime 1 week

Erythrocytes' lifetime 4 months


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Hemopoietic Cell Survival

the principal response of the system

to radiation is a decrease in number of

all cell types

the LYMPHOCYTES and

SPERMATOGONIA are the mostRADIOSENSITIVE cells in the body.


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*After irrad, these might occur:

- lymphocytopenia

- granulocytosis granulocytopenia if rad dose is moderate, abortive

granulocytosis count may occur 15-20 days

ff irrad. minimum granulocyte levels are reached

approximately 30 days

recovery takes approximately 2mos


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- thrombocytopenia follow slowly after irrad

reach a minimum in about 30 days

recover approximately 2mos

- erythrocytes are less sensi t ive

total recovery may take 6mos to a year


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Cytogenetic Effects

-nearly every type of chromosome

aberration can be radiation-induced

-radiation-induced chromosome

aberrations follow a nonthreshold

dose-response relationship


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Cytogenetic Effects

Although chromosome damage occurs

at the time of irrad, it can be mos or

even yrs before the damage ismeasured.

some workers who were ir rad inindustr ia l accidents found

chromosome abnormal it ies af ter 20yrs


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Karyotype


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Karyotype

-photographs of chromosomes are

taken and enlarged so that each

chromosome can be cut out like a

paper doll and paired with its sister intoa chromosome map, aligning them

form largest to smallest.


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Karyotype

each cell contain 22 pairs of

AUTOSOME and a pair of

chromosomes, the X from the female

and Y from the male.


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Single-Hit Chromosome

Aberrations

-produced by radiation during the G1

phase

-the breakage of the chromatid is calledchromatid deletion

-in S phase, both the remaining

chromosome and deleted are replicated

-can also be produced by single-hit

events during G2


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Single-Hit Chromosome

Aberrations

-ISOCHROMATIDS

= aberration visualized at M consists of

chromosome with material missing

from the ends of two sister chromatidsand two acentric fragments


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Multi-Hit Chromosome

Aberrations

-Ring Chromosome occur if two hits

happened on the same chromosome

during G1-Dicentr ics occur when adjacent

chromosomes each suffer one hit and

recombinechromatid joining depends on

stickiness


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Multi-Hit Chromosome

Aberrations

-G2 phase aberrations require,

1. either the same chromosome be hit

two or more times

2. adjacent chromosomes be hit andjoined together

However, these are RARE!


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Rec iprocal Translocat ions

-are multi-hit chromosome aberrations

that require karyotypic analysis for

detection

-resul t in no loss of genet ic mater ia l ,

s imply a rearrangement o f the genes


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Kinetics of Chromosome

AberrationSINGLE-HIT ABERRATIONS

produced with l inear-nonthreshold

MULTI-HIT ABERRATIONS

produced with nonl inear-nonthreshold

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Topic1-Early Rad Effects