EARLY Effects of Radiation

ACUTE RADIATION LETHALITY

*Acute Radiation Syndrome

Sequence of events following highlevel radiation exposure leading to

death within days or weeks

Acute Radiation Syndrome

Classified as: 1. HEMATOLOGIC DEATH 2. GI DEATH 3. CNS DEATH

Acute Radiation Lethality

PERIOD
APPROXIMATE

DOSE

MEAN SURVIVAL TIME

CLINICAL SIGNS/ SYMPTOMS

*Nausea, vomiting, diarrhea No visible signs

Prodromal Latent Hemato GI CNS

> 100 rad 100-10,000 rad 200-1000 rad

none none 10-60 days 4-10 days 0-3 days

*+ Anemia, leukopenia, hemorrhage, fever, infection HEMA + eimbalance, lethargy, fatigue, shock GI + ataxia, edema, vasculitis, meningitis

1000-5000 rad > 5000 rad

PRINCIPAL EARLY EFFECTS OF RADIATION

EFFECT
DEATH HEMATOLOGIC DEPRESSION SKIN ERYTHEMA EPILATION CHROMOSOME ABERRATION

ANATOMIC SITE

DT
200 rad 25 rad 200 rad 300 rad 5 rad

whole-body whole-body small field small field whole-body local tissue

GONADAL DYSFXN

10 rad

Acute Radiation Syndrome

Associated lethal periods: PRODROMAL PERIOD acute clinical symptoms that occur within hours of exposure and

continue for up to a day or two.

Acute Radiation Syndrome

Associated lethal periods: LATENT PERIOD the period after the prodromal

stage of the ARS during which

there is no visible sign of radiation

sickness

PRODROMAL PERIOD A minimum dose of 100 rad delivered to the total body, signs and symptoms may appear within a matter of minutes to hours. immediate response to radiation

However, if dose exceed to 1000 rad, symptoms may be severe

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.

MANIFEST ILLNESS
The stage of the ARS during which

signs and symptoms are apparent.

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)

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 dehydration before death caused: (infection, electrolyte imbal, dehydration)

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 2nd wave of nausea and vomiting diarrhea the irradiated person might experience: anorexia and lethargy

Gastrointestinal Syndrome
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 fluid pass across the intestinal membrane, destroyed e- bal infection

Gastrointestinal Syndrome

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)

Central Nervous System Syndrome

Latent period may last up to 12hrs Manifest illness the sx of Prodromal stage return, severely

Central Nervous System Syndrome

the irrad person experiences: Disorientation, Lose muscle coordination, Dyspnea, Seizure, Loss of equilibrium, Ataxia, Lethargy Coma

DEATH

Central Nervous System Syndrome

Characterized by: increased intracranial vasculitis, meningitis

pressure,

sufficient dose damage to all body organs

LD 50/60
is the dse f radiatin t the whle
bdy that causes 50 % f the irradiated subjects t die within 60 days.

LD 50/60
*Acute radiation lethality follows a

nonlinear, relationship.

threshold

dose-response

*350 rad acute radiation lethality for

humans (850 rad max)

Additional measures of acute lethality:

LD 10/60

LD 90/60
LD 50/30

Mean Survival Time

when the whole-body radiation

increases the average TIME between exposure and death decreases.

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

Mean Survival Time

GASTROINTESTINAL MST remains its constant (4 days) CENTRAL NERVOUS SYSTEM MST is dose-dependent (3 days to a matter of hours)

Radiation Effects on Skin

all skin layers and accessory

structures participate in the response to radiation exposure

Radiation Effects on Skin

because x-rays pass through the skin to reach the internal structures (tx), the skin is subjected to a higher radiation dose as compared to the internal structures which supposed to be the target for the tx.

Radiation Effects on Skin

ERYTHEMA 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

Radiation Effects on Skin

EPILATION grenz rays used to treat skin dse. such

as tinea capitis epilation

Potential Radiation Responses to Skin from High-Dose Fluoroscopy

Radiation Response DT Time of Onset

Early Erythema Main Erythema Tempo Epilation

200 rad 600 rad 300 rad

Hours 10 days 3 weeks

Perma Epilation
Moist Desqua

700 rad
1, 500 rad

3 weeks
4 weeks

Effects on Gonads
10 rad Gametogenesis

germ cell development from stem to

mature cells

Radiation Effects in Ovaries

irrad of ovaries atrophy thru germ cell death fetal and early childhood radiosensitive

20 to 30 years radioresistant

Radiation Effects in Ovaries

10 rad - may delay/ suppress menstrual period (mature) 200 rad temporary infertility 500 rad permanent sterility 25 to 50 rad genetic mutations the most radiosensitive cell during female germ cell development is the oocyte in the mature follicle.

Radiation Effects in Testes

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

Radiation Effects in Testes

spermatogonial stem cells are the most sensitive to radiation THE MALE SHOULD REFRAIN FROM PROCREATION FOR 2 TO 4 MONTHS UNTIL ALL CELLS THAT WERE IN THE SPERMATOGONIAL AND POSTSPERMATOGONIAL STAGES AT THE TIME OF IRRAD FROM 10 rad HAVE MATURED AND DISAPPEARED

Hematological Effects
periodic blood examination is recommended as a feature of any current radiation protection program. 25 rad whole-body dose necessary to produce hemato depression

Hemopoietic System
PLURIPOTENTIAL STEM CELL it can develop into several different types of mature cells: lymphocytes granulocytes thrombocytes erythrocytes

Hemopoietic System
Granulocytes and Erythrocytes develop at bone marrow for at least 810 days Thrombocytes have a lifetime of 5 days in bone marrow Lymphocytes are produced over varying times and have varying lifetime (some hours or others years)

Hemopoietic System
in the PERIPHERAL BLOOD, Granulocytes' lifetime days

Thrombocytes' lifetime 1 week

Erythrocytes' lifetime 4 months

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 most RADIOSENSITIVE cells in the body.

Hemopoietic Cell Survival

*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

Hemopoietic Cell Survival

- thrombocytopenia follow slowly after irrad

reach a minimum in about 30 days

recover approximately 2mos - erythrocytes are less sensitive total recovery may take 6mos to a year

Cytogenetic Effects
-nearly every type of chromosome

aberration can be radiation-induced -radiation-induced

aberrations follow a

chromosome
nonthreshold

dose-response relationship

Cytogenetic Effects
Although chromosome damage occurs at the time of irrad, it can be mos or even yrs before the damage is measured. some workers who were irrad in industrial accidents found chromosome abnormalities after 20yrs

Karyotype

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 into

a chromosome map, aligning them

form largest to smallest.

Karyotype
each cell contain and a 22 pairs pair of of

AUTOSOME

chromosomes, the X from the female and Y from the male.

Single-Hit Chromosome Aberrations

-produced by radiation during the G1 phase -the breakage of the chromatid is called chromatid deletion -in S phase, both the remaining chromosome and deleted are replicated -can also be produced by single-hit events during G2

Single-Hit Chromosome Aberrations

-ISOCHROMATIDS

= aberration visualized at M consists of

chromosome with material missing

from the ends of two sister chromatids

and two acentric fragments

Multi-Hit Chromosome Aberrations

-Ring Chromosome occur if two hits happened on the same chromosome during G1 -Dicentrics occur when adjacent chromosomes each suffer one hit and recombine chromatid joining depends on stickiness

Multi-Hit Chromosome Aberrations

-G2 phase aberrations require, 1. either the same chromosome be hit two or more times 2. adjacent chromosomes be hit and joined together However, these are RARE!

Reciprocal Translocations
-are multi-hit chromosome aberrations that require karyotypic analysis for detection

-result in no loss of genetic material, simply a rearrangement of the genes

Kinetics of Chromosome Aberration

SINGLE-HIT ABERRATIONS produced with linear-nonthreshold MULTI-HIT ABERRATIONS produced with nonlinear-nonthreshold