Dr Muhammad Salman Khan

Radiation has been described as a double-edged sword. On the one hand, radiation itself is a useful tool for research; medical diagnosis and therapy and on the other hand, radiation exposures, especially at high levels, can lead to increased frequencies or severities of various adverse health effects.

To produce a radiation response in humans within a few days to months, the dose must be substantial, such a response is called an early effect of radiation exposure.

Early radiation responses are described as deterministic,those that exhibit increasing severity with increasing radiation dose.

Radiosensitivity is the relative susceptibility of cells, tissues, organs, organisms, or other substances to the injurious action of radiation.

In general, it has been found that cell radiosensitivity is directly proportional to the rate of cell division and inversely proportional to the degree of cell differentiation

Highly Radiosensitive Moderately Radiosensitive Least Radiosensitive

Lymphoid tissue Skin CNS

Bone marrow Vascular endothelium Muscle

GI Epithelium Lung Bone and Cartilage

Gonads Kidney Connective tissue

Embyonic tissue Liver

Lens

The sequence of events that follow high-level radiation exposure leading to death within days or weeks is called the acute radiation syndrome.

There are, in fact, three separate syndromes

that are dose related and that follow a rather distinct course of clinical responses.

These syndromes are;

-Hematologic death

-Gastrointestinal (GI) death

-Central Nervous System (CNS) death

In addition to the three lethal syndromes, two periods are associated with acute radiation lethality;

-Prodromal Period

-Latent Period

It consists of acute clinical symptoms that appear within minutes to hours of total body exposure to the radiation doses of approximately 100 rad (1 Gy) and may last from a few hours to a couple of days

-Anorexia, Nausea, Vomiting, Diarrhea. -Easy Fatigability.-Reduction in WBCs ( Leukopenia).

Effect is dose dependent;

-Varies in time of onset

-Severity

-Duration

After the period of initial radiation sickness, a period of apparent well-being occurs, which is called the latent period.

-extends from hrs or less(5000 rad) to weeks(100 to 500 rad)

In this stage the symptoms depend on the specific syndrome and last from hours up to several months.

Most patients who do not recover will die within a few to several months of exposure. The recovery process lasts from several weeks up to two years.

Prodromal Phase symptoms i.e nausea, vomiting and diarrhea develops, with time of onset from later than 1 hour to about 24 hours after exposure and may persist for several days.

Latent phase lasts up to a month, relatively asymptomatic except for some fatigue and weakness.

Manifest Illness Phase, characterized by neutropenic fever, systemic and localized infections, sepsis, and hemorrhage.

Recovery Phase begins in 2 to 4 weeks, but as long as 6 months may be required for full recovery.

Death may occur as a result of generalized infection, electrolyte imbalance, and hemorrhage.

Mean Survival Time is 10 to 60 days.

Pathophysiology of the GI Syndrome:Depletion of the epithelial cells lining lumen of

GI tract. Intestinal bacteria gain free access to the

body.Hemorrhage through denuded areas.Loss of absorptive capacity.

Prodromal Period: Severe nausea and vomiting with watery diarrhea and cramps develops within hours after exposure and may persist for hours to as long as a day.

Latent Period of 3 to 5 days follows, during which no symptoms are present.

Manifest Illness: Return of severe diarrhea, vomiting with fever; progression to bloody diarrhea, shock and death without aggressive medical intervention may occur within 3 to 5 days.

Mean Survival Time is 4 to 10 days.

Malabsorption Malnutrition Fluid and Electrolyte Shifts Dehydration,

Acute Renal Failure, Cardiovascular collapse GI bleeding Anaemia Sepsis Paralytic Ileus Vomiting, Abdominal

distention

Prodromal Period: Nausea, vomiting and burning sensation in the skin within a few minutes of exposure.The pt become nervous and confused with loss of vision, balance and consciousness within the first hour.

Latent Period: Lasts up to 12 hours, during which earlier symptoms disappear.

Manifest Illness: Symptoms of prodromal stage return but are more severe. The person becomes disoriented;

loses muscle coordination;has difficulty breathing; may develop convulsive seizures;loss of equilibrium, ataxia and lethargy;lapses into coma; and dies.

Mean Survival Time is 0 to 3 days.

CNS syndrome is characterized by raised intracranial pressure, vasculitis and meningitis.

The LD50/60 is the doseof radiation to the wholebody that causes 50%of irradiated subjects todie within 60 days.

LD50/60 for human is approx 350 radafter whole body radiation.

As the whole body radiation dose increases, the averagetime between exposureand death decreases.

When only part of the body is irradiated, in contrast with whole-body irradiation, a higher dose is required to produce a response.

Every organ and tissue of the body can be affected by partial-body irradiation.

The effect is cell death, leading to total lack of function for that organ or tissue, or it can be followed by recovery.

Examples of local tissues that can be affected immediately are;

-Skin-Gonads-Bone Marrow

The most commonly affected tissue is the skin.

Damage to the basal cells results in the earliest manifestation of radiation injury to the skin.

Early Transient Erythema: Within a few hours after single doses in excess of about 200 rad/2 Gy, an early transient erythema might occur in a well-defined area matching the entrance site of the X-ray beam.

The area may look much like sunburn.

This reaction peaks at about 24 hrs and subsides after approximately 48 hrs.

It is thought to represent an early phase of inflammation, with hyperemia and increased permeability of the capillaries resulting from the release of proteolytic histamine-like

enzymes. The intensity of the erythema increases with

the dose.

Main Erythema:A second hyperemic phase, the main erythematous reaction (main

erythema), begins about 10 days after a dose of about 600 rad and earlier when doses are very high.

Its intensity, which is also dose-dependent, reaches a peak around the 14th day.

The skin becomes warm and edematous.

The patient may complain of burning,

tenderness, and itching. The main erythema represents a secondary

inflammatory reaction to damage to the proliferating cells at the basal cell layer of the epidermis.

If the dose is not much greater than the threshold, the erythema fades after 4 weeks.

Temporary Epilation (hair loss): Epilation (hair loss) results from depletion of the germinal

layers of hair follicles. Single doses of 300-600 rad might result in

temporary loss of hair after about 3 weeks. Re growth occurs after approximately 8-12

weeks.

Permanent Epilation: Doses in excess of 700 rad may irreversibly damage the hair follicle, and permanent epilation of the affected

follicles ensues.

Dry Desquamation: If the radiation dose exceeds about 800-1200 rad, the main erythema may progress to dry desquamation of the skin within 25-30 days.

The erythematous skin is then covered with scales and flakes of corneum, similar to the aftereffects of a sunburn.

Moist Desquamation:If the radiation dose is even higher i.e 1500-2000 rad, blistering and sloughing of the superficial skin (moist desquamation) occurs within 20-28 days.

Blister Formation: At radiation doses in excess of about 1500-2500 rad, blister formation occurs in about 15-25 days.

Ulceration (within skin): At radiation dose above 2000 rad ulceration within the skin may occur in 2-3 weeks.

Necrosis (deeper penetration): At radiation dose of about 2500 rad, necrosis develops in 3 weeks.

As an example of local tissue effects, human gonads are particularly sensitive to radiation.

Because these organs control fertility and heredity, their response to radiation has been studied extensively.

Testicular Dose (rad)

Effect

10-30 Temporary Oligospermia

30-50 100% temporary aspermia from 4-12 months post-exposure. Full recovery by 48 months.

50-100 100% temporary aspermia from 3-17 months post-exposure.Full recovery beginning 8-38 months

100-200 100% temporary aspermia from 2-15 months post-exposure. Full recovery biginning 11-20 months

200-300 100% aspermia beginning at 1-2 months post-exposure. No recovery observed up to 40 months

Ovarian Dose (rad)

Effect

60 No effect

150 Some risk for ovulatory suppression in women > 40 years of age.

250-500 In women aged 15-40, 60% may suffer permanent ovulatory suppression; remainder may suffer temporary amenorrhea. In women > 40 years of age, 100% may have permanent ovulation suppression. Menopause may be artificially produced.

500-800 In women aged 15-40, 60-70% may suffer permanent ovulatory suppression; remainder may experience temporary amenorrhea.

>800 100% ovulation suppression.

Haematopoietic system consists mainly of;-Lymphocytes-Granulocytes-Thrombocytes-Erythrocytes

Cytogenetics is the study of the genetics of the cells, particularly cell chromosomes.

• Single hit effects produced by radiation during G1 phase are breakage of a chromatid called chromatid deletion.

• During S phase both the remaining chromosome and the deletion are replicated.

• The chromosome aberration visualised at metaphase consists of a normal looking chromosome with material missing from the ends of two sister chromatids and two accentric fragments without centromere (isochromatids)

A single chromosome can sustain more than one hit

In the G1 phase of the cycle ,ring chromosomes are produced if the two hits occur on the same chromosome

Dicentrics are produced when adjacent chromosomes each suffer one hit and recombine

These are multihit aberations These result in no loss of genetic

material,simply rearrangement of genes Require karyotypic analysis for detection

Formation Of Dicentric Chromosome

Formation Of RingChromosome

Procedure Amount of Radiation (mrem)

X-Ray extremity (arm,hand,foot,leg) 1 mrem

X-Ray dental 1 mrem

X-Ray chest 6 mrem

X-Ray pelvis/hip 65 mrem

X-Ray skull/neck 20 mrem

X-Ray barium enema 405 mrem

X-Ray upper GI 245 mrem

CT-head 200 mrem

CT-abdomen 800 mrem

Nuclear medicine (e.g. thyroid scan) 14 mrem