radiation biology

RADIATION BIOLOGY

A.KUMAR

PG STUDENT

ORAL MEDICINE AND RADIOLOGY

CONTENTS

INTRODUCTION

RADIATION MEASUREMENTS

RADIATION INJURY

Terminologies TYPES OF RADIATION EFFECTS

Stochastic effects

Deterministic (non-stochastic) effects

Short term effects (acute)

Long term effects (chronic)

Somatic effects (late)

Genetic effects

In-Utero Effects

Factors determine biological effects of radiation

BIOLOGICAL EFFECTSEFFECT ON CELLS

1.DNA

2.CYTOPLASM

3.NUCLEUS

4.CHROMOSOMES

5.PROTEINS

6.CELL DIVISION

7.CELL DEATH

RADIATION EFFECT ON CRITICAL ORGANS

1.SKIN

2.BONE MARROW

3.THYROID

4.GONADAL

5.EYE

EFFECT ON ORAL TISSUES

1.ORAL MUCOSA-MUCOSITIS

2.TASTE BUDS

3.SALVARY GLANDS-XEROSTOMIA

4.TEETH- RADIATION CARIES

5.BONES-OSTEORADIO NECROSIS

EFFECT ON WHOLE BODY

1.ACUTE RADIATION SYNDROME

2.HEMATOPOITIC SYNDROME

3.GASTROINTESTINAL SYNDROME

4.CARDIOVASCULAR SYNDROME

5.CENTRAL NERVOUS SYNDROME

RADIATION BIOLOGY

Radiation biology is the study of the effects of ionizing radiation on living systems.

RADIATION

• Radiation, as defined as the emission and propagation of energy through space or a substance in the form of waves or particles.

• IONIZING RADIATION

• NON-IONIZING RADIATION

Ionizing Radiation

• Ionizing radiation can be defined as radiation that is capable of producing ions by removing or adding an electron to an atom.

• Ionizing radiation can be classified into two groups:

• (1) particulate radiation

• (2) electromagnetic radiation.

ELECTROMAGNETIC RADIATION

• Electromagnetic radiation can be defined as the propagation of wave like energy (without mass) through space or matter.

CONTENTS

INTRODUCTION


RADIATION INJURY


Stochastic effects





Genetic effects

In-Utero Effects



• Radiation can be measured in the same manner as other physical concepts such as time, distance, and weight.

• International Commission on Radiation Units and Measurement (ICRU) has established special units for the measurement of radiation.

• Such units are used to define four quantities of radiation:

(1) exposure.

(2) dose.

(3) dose equivalent.

(4)Radioactivity

• At present, two systems are used to define radiation measurements:

(1) The older system is referred to as the traditional system, or standard system.

(2) the newer system is the metric equivalent known as the SI system.

EXPOSURE

EXPOSURE;The term exposure refers to the measurement of ionization in air produced by x-rays.

Standard unit-Roentgen (R)

SI unit -Coulombs per kilogram (C/kg)

One roentgen is equal to the amount of radiation that produces approximately two billion, or 2.08 × 10 9 , ion pairs in one cubic centimeter (cc) of air.

DOSE

DOSE;Dose can be defined as the amount of energy absorbed by a tissue.

Standard unit-Radiation absorbed dose (rad)

SI unit -Gray (Gy)

Rad: A special unit of absorbed dose that is equal to the

Deposition of 100 ergs of energy per gram of tissue (100erg/g).

DOSE EQUIVALENT

DOSE EQUIVALENT;Different types of radiation have different effects on tissues.The dose equivalent measurement is used to compare the biologic effects of different types of radiation.

Standard unit-Roentgen equivalent (in) man (rem)

SI unit -Sievert (Sv)

RADIOACTIVITY

• It is the process by which a nucleus of an unstable atom loses energy by emitting ionizing radiation.

Standard unit-Curie(Ci)

SI unit -Becquerel(Bq)

• One Curie is equal to 3.7x1010 (37 Billion Bq)disintegrations per second.

• One Becquerel is equal to one disintegration per second.

• DPS-The number of subatomic particles (e.g. alpha particles) or photons (gamma rays) released from the nucleus of a given atom over one second

CONTENTS

INTRODUCTION


RADIATION INJURY


Stochastic effects





Genetic effects

In-Utero Effects


RADIATION INJURY

• Radiation injury- tissue damage or changes caused by exposure to ionizing radiation-namely, gamma and x-rays such high-energy particles as neutrons, electrons, and positrons.

• In diagnostic radiography, not all x-rays pass through the patient and reach the dental x-ray film; some are absorbed by the patient’s tissues.

• Absorption

refers to the total transfer of energy from the x-ray photon to patient tissues.

Mechanisms of radiation injury

Two specific mechanisms of radiation injury are possible:

(1)ionization

(2)free radical formation

IONIZATION

• X-rays are a form of ionizing radiation; when x-rays strike patient tissues, ionization results.

• ionization is produced through the photoelectric effect or Compton scatter and results in the formation of a positive atom and a dislodged negative electron.

• The ejected high-speed electron is set into motion and interacts with other atoms within the absorbing tissues. The kinetic energy of such electrons results in further ionization, excitation, or breaking of molecular bonds, all of which cause chemical changes within the cell that result in biologic damage

FREE RADICALS FORMATION

• X-ray causes cell damage primarily through the formation of free radicals. Free radical formation occurs when an x-ray photon ionizes water, the primary component of living cells.

• Ionization of water results in the production of hydrogen and hydroxyl free radicals

• A free radical is an uncharged (neutral) atom or molecule that exists with a single, unpaired electron in its outermost shell.

Theories of Radiation Injury

• Two theories are used to describe how radiation damages biologic tissues:

• (1) Direct or Target Action Theory

• (2 Indirect Action or Poison Chemical Theory

Theories of Radiation Injury

Direct or Target Action Theory

• The direct theory of radiation injury suggests that cell damage results when ionizing radiation directly hits critical areas, or targets, within the cell.

• For example, if x-ray photons directly strike the DNA of a cell, critical damage occurs, causing injury to the irradiated organism.

• Direct injuries from exposure to ionizing radiation occur infrequently; most x-ray photons pass through the cell and cause little or no damage.

Indirect Action or Poison Chemical Theory

x-ray photons are absorbed by the water within a cell, free radicals are formed. These free radicals combine to form toxins.

(e.g., H 2 O 2 ), which cause cellular dysfunction and biologic damage.

The chances of free radical formation and indirect injury are great because cells contain 70% to 80% water.

Sequence of Radiation Injury

• Chemical reactions (e.g., ionization, free radical formation) that follow the absorption of radiation occur rapidly at the molecular level.

• However, varying amounts of time are required for these changes to alter cells and cellular functions.

• As a result, the observable effects of radiation are not visible immediately after exposure. Instead, following exposure, a latent period occurs.

• A latent period can be defined as the time that elapses between exposure to ionizing radiation and the appearance of observable clinical signs.

• After the latent period, a period of injury occurs. A variety of cellular injuries may result, including cell death, changes in cell function, breaking or clumping of chromosomes, formation of giant cells, cessation of mitotic activity, and abnormal mitotic activity.

• The last event in the sequence of radiation injury is the recovery period. Not all cellular radiation injuries are permanent. With each radiation exposure, cellular damage is followed by repair. Depending on a number of factors, cells can repair the damage caused by radiation.

• If effects of radiation exposure are additive, the unrepaired damage accumulates in the tissues. The cumulative effects of repeated radiation exposure can lead to health problems (e.g., cancer, cataract formation, birth defects).

CONTENTS

INTRODUCTION


RADIATION INJURY


Stochastic effects





Genetic effects

In-Utero Effects


Terminologies

• LINEAR ENERGY TRANSFER (LET)

• RELATIVE BIOLOGIC EFFECTIVENESS(RBE)

• LATENT PERIOD

• MAXIMUM PERMISSIBLE DOSE

• MAXIMUM ACCUMULATED DOSE

• TOTAL DOSE

• DOSE RATE

• MEDIAN LETHAL DOSE

LINEAR ENERGY TRANSFER (LET)

Amount of energy is transferd from ionizing radiation to soft tissue

36

RELATIVE BIOLOGIC EFFECTIVENESS(RBE)

Biologic response compared with two types of radiation

37

LATENT PERIOD

• THE TIME LAPSE BETWEEN EXPOSURE OF THE RADIATION AND THE APPEARENCE OF THE EFFECTS

38

maximum permissible dose

• Greatest dose of radiation which is not expected to cause detectable bodily injury to people at any time during their lifetime.

• The amount of ionizing radiation a person may be exposed to supposedly without being harmed

• The limits of ionizing radiation set for radiation workers and the general public by the International Commission on Radiological Protection. For radiology workers this limit for the whole body is 50 mSv.

Maximum Accumulated Dose

• Occupationally exposed workers must not exceed an accumulated lifetime radiation dose. This is referred to as the maximum accumulated dose (MAD). MAD is determined by a formula based on the worker’s age. To determine the MAD for an occupationally exposed person, the following formula is used:

• MAD=(N-18)x5 rems/ year

• MAD=(N-18)x0.05 Sv/ year

• where N refers to the person’s age in years. (Note that the number 18 refers to the minimum required age of a person who works with radiation.)

• Total dose: Quantity of radiation received, or the total amount of

radiation energy absorbed. More damage occurs when tissues absorb large quantities of radiation.

• Dose rate: The amount administered radiation per unit of time.(dose rate = dose/time).

More radiation damage takes place with high dose rates because a rapid delivery of radiation does not allow time for the cellular damage to be repaired.

• When organisms are exposed at lower dose rates, a greater opportunity exists for repair of damage, thereby resulting in less net damage.

median lethal dose

The amount of ionizing radiation that will kill 50 percent of a population in a specified time

Abbreviation: LD50

CONTENTS

INTRODUCTION


RADIATION INJURY


Stochastic effects





Genetic effects

In-Utero Effects


Stochastic effects

• Stochastic effects are those that may develop.Their development is random and depends on the laws of chance or probability. Examples of somatic stochastic effects include leukaemia and certain tumours.

• These damaging effects may be induced when the body is exposed to any dose of radiation.

• Experimentally it has not been possible to establish a safe dose — i.e. a dose below which stochastic effects do not develop. It is therefore assumed that there is no threshold dose, and that every exposure to ionizing radiation carries with the possibility of inducing a stochastic effect.

• However, the severity of the damage is not related to the size of the inducing dose. This is the underlying philosophy behind present radiation protection recommendations.

deterministic effects

• Nonstochastic effects (deterministic effects) are somatic effects that have a threshold and that increase in severity with increasing absorbed dose.

• Examples of nonstochastic effects include erythema, loss of hair, cataract formation, and decreased fertility.

• Compared with stochastic effects,deterministic effects require larger radiation doses to cause serious impairment of health.

Short-Term Effects

• Following the latent period, effects that are seen within minutes, days, or weeks are termed short-term effects. Short-term effects are associated with large amounts of radiation absorbed in a short time (e.g., exposure to a nuclear accident or the atomic bomb).

• Acute radiation syndrome (ARS) is a short-term effect and includes nausea,vomiting, diarrhea, hair loss, and hemorrhage.

• Short-term effects are not applicable to dentistry.

Long-term effects

• Effects that appear after years, decades, or generations are termed long-term effects.

• Long-term effects are associated with small amounts of radiation absorbed repeatedly over a long period. Repeated low levels of radiation exposure are linked to the induction of cancer, birth abnormalities, and genetic defects.

Somatic and Genetic Effects

• All the cells in the body can be classified as either somatic or genetic.

• Somatic cells are all the cells in the body except the reproductive cells.

• The reproductive cells (e.g., ova, sperm) are termed genetic cells.

• Depending on the type of cell injured by radiation, the biologic effects of radiation can be classified as somatic or genetic.

somatic effects

• Somatic effects are seen in the person who has been irradiated. Radiation injuries that produce changes in somatic cells produce poor health in the irradiated individual.

• Major somatic effects of radiation exposure include the induction of cancer, leukemia, and cataracts.

• These changes, however, are not transmitted to future generations

Genetic effects

• Genetic effects are not seen in the irradiated person but are passed on to future generations. Radiation injuries that produce changes in genetic cells do not affect the health of the exposed individual.

• Instead, the radiation-induced mutations affect the health of the offspring .

• Genetic damage cannot be repaired.

• Doubling dose: dose of radiation expected to double the number of genetic mutations in a generation.(or) Amount of radiation that doubles the incidence of stochastic effects.

• Human data from Hiroshima/Nagasaki suggest somewhat average doubling dose is 1.6 Sv

Effects on the unborn child

• The developing fetus is particularly sensitive to the effects of radiation, especially during the period of organogenesis (2–9 weeks after conception).

• Exposures in the range of 2 to 3 Gy during the first few days after conception are thought to cause undetectable death of the embryo.

• The period of maximal sensitivity of the brain is 8 to 15 weeks after conception.

• The major problems are:1.Congenital abnormalities or death associated with large doses of radiation2.Mental retardation associated with low doses of radiation. As a result, the maximum permissible dose to the abdomen of a

woman who is pregnant is regulated by law.


1. Nature of tissue irradiated.

i. Radioresponsive.

ii. Radioresistant.

2. Area irradiated:

For the same dose, if a smaller area is irradiated, the effect of radiation is less.

3. Rate of dose:

Smaller the dose, distributed over a large period of time results in a smaller or lesser effect of the radiation.

4. Fractionization:

Division of the dose, with sufficient gaps, helps in tissue recovery resulting in lesser effect of the radiation.

5. Latent period:

This is the period between the time of irradiation and the appearance of the effect.

6. Age of the patient:

Younger the patient greater the chances of recovery.

CONT….

7. Recovery power of the tissue:

Undifferentiated cells have a greater power of recovery.

8. Type of cell:

The effect of radiation is seen in the same generation if a somatic cell is effected, and in case of the genetic cell the effect of radiation will be seen in the next generation.

9. Type of irradiation:

There are different types of irradiations—low energy, high energy or linear energy transfer.

10. Stage of development of the tissue:

The effect of irradiation depends on the stage of development of the tissue, e.g. primitive and undifferentiated and still undergoing mitosis when irradiated the

damage caused is greater.

CONT…

11. Tissue threshold: Greater the tissue threshold,lesser the damage seen. This depends on the amount of

radiation absorbed. Somatic changes do not occur until a minimum of tissue threshold is exceeded. Genetic changes occur with any given dose. 12. Species and individuals:

Different species respond differently. The median lethal dose varies in different species. Similarly in individuals of the same species the response may be variable. This variation of the Maximum Permissible Dose is approximately 50 percent. 13. Oxygenation:

Greater oxygenation of the tissue,chances of recovery are greater, e.g. hyperbaric oxygen is used to treat osteoradio necrosis.

• The presence of oxygen in a cell acts as a radiosensitizer, making the effects of the radiation more damaging. Tumor cells typically have a lower oxygen content than normal tissue.

• This medical condition is known as tumor hypoxia and therefore the oxygen effect acts to decrease the sensitivity of tumor tissue. Generally it is believed that neutron irradiation overcomes the effect of tumor hypoxia, although there are counterarguments.

http://en.wikipedia.org/wiki/Oxygen

http://en.wikipedia.org/wiki/Radiosensitizer

http://en.wikipedia.org/wiki/Tumor_hypoxia


1.DNA

2.CYTOPLASM

3.NUCLEUS

4.CHROMOSOMES

5.PROTEINS

6.CELL DIVISION

7.CELL DEATH


1.SKIN

2.BONE MARROW

3.THYROID

4.GONADAL

5.EYE



2.TASTE BUDS






2.HEMATOPOITIC SYNDROME3.



5.CENTRAL NERVOUS

Single strand break can repair

Double strand break is responsible for

.mutation

.cell death

.carcinogenisis

Point mutations: Effect of radiation on individual genes is referred to as point mutation.

CYTOPLASM

Increased permeability of plasma membrane to sodium and potassium ions.

Swelling and disorganization of mitochondria.

Focal cytoplasmic necrosis.

NUCLEUS

Nucleus is more radiosesitive than the cytoplasm

PROTEINS

Denaturation.

primary structure of the protein is usually not significantly altered

secondary and tertiary stuctures are effected by breakage of hydrogen or disulfide bonds

Inactivation of enzymes sometimes occures.

MITOCHONDRIA

• Mitochondria demonstrate –

• .Increased permeability

• .swelling

• .Disorganization of the internel cristae

CHROMOSOMS

• cell cycle:

Chromosome Aberrations

If radiation exposure occurs after DNA synthesis (I,e G2 or late s)only one arm of the effected chromosome is broken

If radiation occurs before DNA synthesis (G1 or early S) both arms are effected

The survivors of the atomic bombings of Hiroshima and Nagasaki have demonstrated chromosome aberrations in circulating lymphocytes more than two decades after the radiation exposure.

EXAMPLES OF MUTATIONS

EFFECTS ON CELL REPLICATION

Mild dose-mild mitotic delay

Moderate dose-longer mitotic delay

Severe dose-profound delay with incomplete recovery

CELL DEATH

Reproductive death in a cell population is loss of the capacity for mitotic division. The three mechanisms of reproductive death are

DNA damage,

Bystander effect

Apoptosis.

DNA DAMAGE

Single strand break can repair

Double strand break is responsible for

• .mutation

• .cell death

• .carcinogenisis

Bystander effect

It is the phenomenon in which unirradiated(normal) cells exhibit irradiated effects as a result of signals received from nearby irradiated cells.

This bystander effect has been demonstrated for both α particles and x rays and causes chromosome aberrations, cell killing, gene mutations, and carcinogenesis.

The abscopal effect is a phenomenon where the response to radiation is seen in an area distant to the irradiated area, that is, the responding cells are not juxtaposed(close) with the irradiated cells. T-cells and dendritic cells have been implicated to be part of the mechanism.

In suicide gene therapy, the "bystander effect" is the ability of the transfected cells to transfer death signals to neighboring tumor cells.

http://en.wikipedia.org/wiki/Abscopal_effect

http://en.wikipedia.org/wiki/Suicide_gene

APOPTOSIS

Leaves falling from tree

Also known as’ programmed cell death’

Apoptosis is particularly common in hemopoietic and lymphoid tissues.

Apoptosis vs Necrosis


1.DNA

2.CYTOPLASM

3.NUCLEUS

4.CHROMOSOMES

5.PROTEINS

6.CELL DIVISION

7.CELL DEATH


1.SKIN

2.BONE MARROW

3.THYROID

4.GONADAL

5.EYE



2.TASTE BUDS









5.CENTRAL NERVOUS


In dental radiography the critical organs receiving scattered radiation include:

SKIN

BONE MARROW

THYROID

GONADAL

EYE

1. Skin: The reaction of the skin to radiation may be categorized as:

i. Early or acute signs:

• Increased susceptibility to chapping.

• Intolerance to surgical scrub.

• Blunting and leveling of finger ridges.

• Brittleness and ridging of finger nails.

ii. Late or chronic signs:

• Loosening of hair and epilation.

• Dryness and atrophy of skin, due to destruction of the sweat glands.

• Progressive pigmentation, telangiectasis and keratosis.

• Indolent type of ulcerations.

• Possibility of malignant changes in tissue.

All these changes in the skin are due to radiation trauma to:

1-The blood vessels.

2- Connective tissue.

3- Epithelium.

• Early erythema may appear from a single dose of about 450 rads.

• With lower doses no erythema occurs.

BONE MARROW

• 13 mR for full mouth intraoral periapical radiographs.

• A maximum dose of 200 R is required for any damage to the marrow or blood forming organs.

• Hence, the risk of bone marrow damage from dental X-rays is small.

• The primary somatic risk from dental radiography is leukemia induction,especially in young individuals.

• This is because at birth all bones contain only red bone marrow. younger individuals are at a greater risk of developing leukemia.

THYROID

40 mR for full mouth intraoral periapical radiographs.

A dose of 10 R will produce thyroid cancer.

Gonadal – a single intraoral radiograph gives 100 to 900 mR to the face.

From this;

Male gonads receive 0.3 mR.

Female gonads receive 0.03 to 0.001 mR,

Eye – a series of full mouth intraoral periapical radiographs, will give only a few mR.

Cataract of the lens is produced after 500 R of exposure.


1.DNA

2.CYTOPLASM

3.NUCLEUS

4.CHROMOSOMES

5.PROTEINS

6.CELL DIVISION

7.CELL DEATH


1.SKIN

2.BONE MARROW

3.THYROID

4.GONADAL

5.EYE



2.TASTE BUDS









5.CENTRAL NERVOUS

RADIATION EFFECT ON ORAL TISSUES

• ORAL MUCOUS MEBRANE

• TASTE BUDS

• SALIVARY GLANDS

• RADIATION CARIES

• OSTEORADIO NECROSIS

94

ORAL MUCOUS MEMBRANE

• Pre-radiation Therapy Management Considerations

• A. A complete dental examination to identify preexisting problems.

• B. Prior to treatment, potentially complicating diseases should be corrected

• C. Patient adherence to hygiene protocols are critical

Mucositis

• Describes inflammation of oral mucosa resulting from chemotherapeutic agents or ionizing radiation,Typically manifests as erythema or ulcerations.

• May be exacerbated by local factors.

• Dysgeusia, or an alteration in taste perception

• Red,shiny, or awollen mouth and gums

• Blood in the mouth

• Sores in mouth,gums and tongue

• Difficulty swallowing or talking

• Soft, whitish patches in the mouth and tongue

• Increased mucous or thicker saliva

Pathophysiology

• The pathophysiology of mucositis can be divided into its 5 stages

1-initiation phase

2-message generation phase

3-signaling and amplification phase

4-ulceration phase

5-healing phase

Management of mucositis

• Good oral hygiene.

• Avoidance of spicy, acidic, hard, and hot foods and beverages.

• Use of mild-flavored toothpastes.

• Use of saline-peroxide mouthwashes 3 or 4 times per day.

• Bland rinses:

– 0.9% saline solution.

– Sodium bicarbonate solution.

• Topical anesthetics:– Lidocaine: viscous, ointments, Sprays.– Benzocaine: sprays, gels.– 0.5% or 1.0% dyclonine hydrochloride (HCl).– Diphenhydramine solution.

• Mucosal coating agents:– Amphojel.– Kaopectate.– Hydroxypropyl methylcellulose film-forming agents (e.g., Zilactin).– Gelclair-Bioadherent (approved by the U.S. Food and Drug

Administration [FDA] • Analgesics:

– Benzydamine HCl topical rinse – Opioid drugs: oral, intravenous (e.g., bolus, continuous infusion,

patient-controlled analgesia [PCA]), patches, transmucosal.



• TASTE BUDS

• SALIVARY GLANDS



102

TASTE BUDS

• These are sensitive to radiation and patient realizes a loss of taste in the second or third week of radiation therapy.

• Radiation directed to the mouth will affect taste buds located on the tongue. Foods may taste differently to you or you may have a temporary aversion to some foods. It may take 2 or 3 months or more before your taste sensations return.

• The tongue's lining and taste buds are susceptible to radiation. A decrease in saliva also causes changes in taste.

• It is common to have an increased sensitivity to sour and bitter taste,or to have a “metallic” taste in your mouth

• Changes in taste may cause you to lose your appetite.

MANAGEMENT

• At this time, there is no treatment for taste changes.

• Research has shown that taking zinc sulfate during treatment may be helpful in expediting the return of taste after head and neck irradiation.

• Try these tips to help reduce the impact of taste changes on your ability to get good nutrition and avoid weight loss.

• Do not eat 1-2 hours before chemotherapy and up to 3 hours after therapy. It is common to develop a taste aversion to foods eaten during this time, so it is particularly important to avoid your favorite foods.

• Rinse mouth with water before eating.

• Eat small, frequent meals and healthy snacks.

• Eat meals when hungry rather than at set mealtimes.

• Have others prepare the meal.

• Substitute poultry, fish, eggs and cheese for red meat.

• Eat meat with a marinade or sauce; try something sweet.

• Use plastic utensils if food tastes like metal.

• Use mints, lemon drops or chewing gum to mask the bitter or metallic taste.

• Chilled or frozen food may be more acceptable than warm or hot food.

• Try tart foods, such as citrus fruits or lemonade, unless you have mouth sores.

• Avoid bad odors, as these may affect your appetite.



• TASTE BUDS

• SALIVARY GLANDS



108

SALIVARY GLANDS

• Parotid gland is more radio sensitive than the other glands

• Increase the growth of st.mutans,lactobacillous,candida

• Decrease the ph leads to decalcification of enamel

• Difficult to swallow(DISPHAGIA)

• Decrease salivary secretion(XEROSTOMIA)

• The parenchymal component of the gland is sensitive to radiation. The gland demonstrates progressive fibrosis adiposis, loss of fine vasculature and simultaneous parenchymal degeneration.

• There is marked decrease in the salivary flow.

• The composition of saliva is affected.

• There is increased concentration of sodium,chloride, calcium, magnesium ions and proteins.

• The saliva loses its lubricating properties.

• The mouth becomes dry and tender due to xerostomia.

• The pH of saliva is decreased which may initiate decalcification of enamel.

• A compensatory hypertrophy of the salivary gland may take place and the xerostomia may subside after six to twelve months after therapy.

• In recent years, doctors have found that newer forms of radiation therapy may work better than the standard treatment.

• Accelerated hyperfractionated radiation therapy: In this approach, radiation is given twice a day over a shorter total length of time.

• Three-dimensional conformal radiation therapy (3D-CRT): 3D-CRT uses the results of imaging tests such as MRI and special computers to precisely map the location of the tumor.

• Several radiation beams are then shaped and aimed at the tumor from different directions. Each beam alone is fairly weak, which makes it less likely to damage normal tissues, but the beams converge at the tumor to give a higher dose of radiation there.

• Intensity modulated radiation therapy (IMRT): IMRT is an advanced form of 3D therapy. It uses a computer-driven machine that actually moves around the patient as it delivers radiation.

• In addition to shaping the beams and aiming them at the tumor from several angles, the intensity (strength) of the beams can be adjusted to limit the dose reaching the most sensitive nearby normal tissues.

• Many major hospitals and cancer centers now use IMRT as the standard way to deliver external beam radiation.

• Fast neutron beam radiation: Instead of using x-rays, neutron radiation therapy uses a beam of high-energy neutrons. Neutrons are neutral particles in atoms. Some studies have suggested that this type of radiation may be more effective, but it may also lead to more side effects. Neutron therapy machines are available in only a handful of cancer centers in the United States at this time.

• A neutron radiotherapy facility would probably cost $20 to $25 million dollars today.

• Neutron therapy is especially good at controlling salivary gland cancer at the tumor site and in the same region. Neutron therapy also works best on tumors below 4 centimeters in diameter, controlling about 80 percent of tumors this size. But it is used with success on many larger tumors as well.



• TASTE BUDS

• SALIVARY GLANDS

• TEETH(RADIATION CARIES)


115

Teeth

• Evidence in changes of crystalline structure of enamel, dentin, or cementum following RT is unclear.

• Pulp shows decrease in vascular elements, with accompanying fibrosis and atrophy.

• Pulpal response to infection, trauma, and various dental procedures appears compromised.

Level as low as 2500 cGy can have marked effect on tooth development.

Exposure

• before calcification completion - tooth bud may be damaged .

• At later stage of development - may arrest growth.

• Children receiving radiation therapy to the jaws may show defects in the permanent dentition such as retarded root development, dwarfed teeth, or failure to form one or more teeth

• If exposure precedes calcification, irradiation may destroy the tooth bud. Irradiation after calcification has begun may inhibit cellular differentiation,causing malformations and arresting general growth.

• Eruptive mechanism of teeth is relatively radiation resistant• Adult teeth are resistant to the direct effects of radiation

exposure.• Radiation has no direct effect on the crystalline structure of

enamel, dentin, or cementum, and radiation does not increase their solubility.

RADIATION CARIES

• Radiation caries is a rampant form of dental decay that may occur in individuals who receive a course of radiotherapy that includes exposure of the salivary glands.

• Patients receiving radiation therapy to oral structures have increases in Streptococcus mutans,Lactobacillus, and Candida .

• Caries results from changes in the salivary glands and saliva, including reduced flow, decreased pH, reduced buffering capacity, increased viscosity, and altered flora.

TYPES

• Clinically, three types of radiation caries exist.

1-The most common is widespread superficial lesions attacking buccal, occlusal, incisal, and palatal surfaces.

2-Another type involves primarily the cementum and dentin in the cervical region. These lesions may progress around the teeth circumferentially and result in loss of the crown.

3-A final type appears as a dark pigmentation of the entire crown. The incisal edges may be markedly worn.

Combinations of all these lesions develop in some patients

• Radiation has a rapid effect on the salivary glands.

• In the first two weeks, with a cumulative RT dose of 20 Gy, around 80% of salivary function is lost.

• Above 58 Gy there was a complete loss of salivary gland function.

Reduce the incidence of RC

PREVENTION AND MANAGEMENT

• Although radiation caries is a multifactorial condition, its main risk factor in HNC patients is radiation treatment-induced reduction of salivary flow.

• Exclusion of the major and minor salivary glands from the irradiation field.

• Intensity-modulated radiotherapy (IMRT) and Three-

dimensional conformal radiation therapy (3D-CRT): techniques will be of great benefit to patients.

• There are also artificial salivas (saliva substitutes) capable of increasing tissue lubrication, hydration, salivary clearance, and pH neutralization.

• Pilocarpine(pilomax)-5mg,3 times a day for 12 weeks.

• Cevimeline(Evoxac)-30mg,3 times a day for 12 weeks.

Qualitative improvement

• 1% neutral sodium fluoride gel applied daily in custom trays could significantly reduce caries in irradiated patients.

• combination of fluoride and chlorhexidine used daily has been shown to offer better results for patients with a high risk of developing radiation caries.

• Composite and glass-ionomer fillings.



• TASTE BUDS

• SALIVARY GLANDS



126

OSTEORADIO NECROSIS

DEFINITION;

An exposure of irradiated bone which fails to heal with out intervention (Marx 1983)

It is a chronic nonhealing wound caused by hypoxia, hypocellularity, and hypovascularity (3H)of irradiated tissue. Marx and Johnson (1987)

Clinical definition by Van Merkesteyn (1995)

Bone and soft tissue necrosis of 6 months duration excluding radiation induced periodontal breakdown

INCIDENCE

• Mandible is affected more commonly; because most oral tumors are peri mandibular. More extensive blood supply in maxilla

• Incidence 8.2%

• 3 fold higher in Men

• Body of mandible

• Extraction -50%

• Presurgical earlier ORN

• Combined radio and chemo

Etiology

Radiation in excess of 50Gy- kills bone cells – osteoblasts & fibroblasts leading to hypocellularity

Vessels -tunica intima endarteritis, periarteritishyalinization and fibrosis

Progressive obliterative arteritis.—hypovascularityPeriosteal vessels and inferior alveolar artery involved

Hypoxia

Precipitating factors

• Triad RADIATION

TRAUMA INFECTION

Pathophysiology

Osteoradionecrosis - cumulative tissue damage

induced by radiation rather than trauma or bacterial

invasion of bone.

Complex metabolic and tissue homeostatic

deficiency seen in hypocellular, hypovascular, and

hypoxic tissue.

Effects of radiation on bone

• Depletion of osteoblasts - Increased osteoclasticresorption of bone

Reduced bone rebuilding potential

+

• Progressive endarteritis - reduction of blood flow through the Haversian and Volkmann’s canals

=

OSTEOPOROSIS

OSTEONECROSIS

• SPONTANEOUS ORN (39%) – degradative function exceeds new bone production.

• TRAUMA INDUCED ORN (61%) – reparative capacity of bone is insufficient to overcome an insult.

• Bone injury can occur through direct trauma -

1. tooth extraction [84%],

2. related cancer surgery or biopsy [12%],

3. denture irritation [1%]) or

4. by exposure of the oral cavity to the environment

secondary to overlying soft tissue necrosis.

Types of osteoradionecrosis

• By Marx(1983)

Type I – Develops shortly after radiation, Due to synergistic effects of surgical trauma and radiation injury.

Type II – Develops years after radiation and follows a traumaRarely occurs before 2 year after treatment &

commonly occurs after 6 years. Due to progressive endarteritis and vascular effusion.

Type III

Occurs spontaneously without a preceding a traumatic event.

Usually occurs between 6 months and 3 years after radiation.

Due to immediate cellular damage and death due to radiation

treatment.

CLASSIFICATION OF

OSTEORADIONECROSIS

• Stage I – Resolved healed osteonecrosis

(A) – No pathologic fracture

(B) – Pathologic fracture

• Stage II – Chronic persistent and non-progressive osteonecrosis



• Stage III – Active progressive osteonecrosis



• Grade I, ORN confined to alveolar bone;

• Grade II, ORN limited to the alveolar bone and/or mandible above the level of inferior alveolar canal;

• Grade III, ORN involving the mandible below the level of inferior alveolar canal and ORN with a skin fistula and/or pathologic fracture.

• Radiation factors

• Tumor factors

• Dental factors

• Others

CLINICAL FEATURES

• Within two years • Asymptomatic dehiscence of mucosa• Glabrous skin • As necrosis progresses site more erythematous and severe, deep

burning pain• Evidence of exposed bone• Tissue surrounding may be ulcerated from infection or recurrent

tumor. • Trismus• Fetid breath • Elevated temperature • Exposed bone with a grey to yellow color• Intraoral and extra oral fistula• Pathological fracture

Signs and symptoms

• Pain

• Swelling

• Trismus

• Halitosis

• Food impaction in the area of the lesion

• Exposed bone

• Pathologic fracture

• Oro-cutaneous fistula

Radiographic changes

• Little-evident

• sequestra or involucra occur late

• radiolucent modeling -nonsclerotic

Histologically

• look like MICROANATOMIC DESERT

• Reduced vascularity, fibrosis

Management ofosteoradionecrosis

• Aim - To control infection

• Antibiotics

• Penicllin plus metronidazole or clindamycin

• Supportive therapy with fluids

• Pulsating irrigation device can be used. High pressure should not be used debris might be forced deeply into tissues

• Exposed bone can be mechanically debrided and smoothed with round burs and covered with a pack saturated with zinc peroxide and neomycin

• local irrigation (saline solution, or chlorhexidine), systemic antibiotics in acute infectious episodes, avoidance or irritants and oral hygiene instruction.

• Simple management refers to the gentle removal of sequestra in sequestrating lesions

• Had 48% success rates

Treatment of osteonecrotic wounds

• Rule out neoplastic disease

• Stabilize the patient medically especially nutritional status

• Preoperative hyperbaric oxygen

• Debridement of necrotic mass

• Postoperative hyperbaric oxygen

• Soft tissue vascular flap support

• Bony reconstruction

Ultra sound therapy

• Is non invasive and reportedly promotes neovascularity and neocellularity of ischemic tissues

HYPERBARIC OXYGEN THREAPY

What is HBO

• 100% oxygen in an enclosed chamber at higher-than-atmospheric pressure where oxygen dissolves in arterial plasma in increased amounts---up to 10 to 15 fold increase.

• Typical course consists of 30 or more treatments done daily for six weeks.

Some Basics

• HBOT has been used in chronic wounds for about 40 years.

• 100% oxygen is delivered to a chamber under high pressure (2 to 2.4 ATA) for 90 minutes

• Typical HBOT treatment course consists of 30 or more treatments daily.

• Administering oxygen to hypoxic tissue shown to activate fibroblast proliferation, down-regulate inflammatory responses, cytokines, up-regulate growth factors – all proxies for wound healing.

Hyperbaric Chamber Designs

Clinical Hyperbaric Oxygen Therapy

Clinical

Hyperbaric

Oxygen

Therapy

Emergency Indications•Acute Traumatic Ischemia

Crush Injuries and

Compartment Syndrome

•Carbon Monoxide Poisoning

•Gas Gangrene

•Surgical Infections

•Failed Flaps and Grafts

•Diving Injuries

Scheduled Indications•Non-Healing Diabetic and problem

Wounds

•Radiation soft tissue necrosis, cystitis,

and proctitis.

•Osteoradionecrosis

•Osteomyelitis

Primary Mechanisms

• Hyper---oxygenation

• Vasoconstriction—reduce inflammation

• Microbiological effects

• Activate fibroblast and collagen synthesis

Secondary Mechanisms

• Angiogenesis

• Osteogenesis

• WBC Oxidative Killing

• Cell wall permeation

Side Effects of HBO

• Claustrophobia/ Confinement anxiety

• Barotrauma

• Reversible myopia

Contraindications

Absolute: • Untreated pneumothorax• Cis-Platin; Doxorubicin; Disulfiram• Emphysema w/air trapping

Relative:• Emphysema with CO2 retension• Pulmonary lesion in CXR• Uncontrolled high fever• Claustrophobia• Seizure disorder• Malignant disease


1.DNA

2.CYTOPLASM

3.NUCLEUS

4.CHROMOSOMES

5.PROTEINS

6.CELL DIVISION

7.CELL DEATH


1.SKIN

2.BONE MARROW

3.THYROID

4.GONADAL

5.EYE



2.TASTE BUDS






2.HEMATOPOITIC SYNDROME



5.CENTRAL NERVOUS SYNDROME

EFFECTS IN WHOLE BODY

158

.ACUTE RADIATION SYNDROME

.HEMATOPOITIC SYNDROME

.GASTROINTESTINAL SYNDROME

.CARDIOVASCULAR SYNDROME

.CENTRAL NERVOUS SYSTEM SYNDROME

ACUTE RADIATION SYNDROME

Acute Radiation Syndrome (ARS) is an acute illness caused by irradiation of the entire body (or most of the body) by a high dose of penetrating radiation in a very short period of

time (usually a matter of minutes)

stages of ARS

• Prodromal stage (N-V-D stage): The classic symptoms for this stage are nausea, vomiting, as well as anorexia and possibly diarrhea (depending on dose), which occur from minutes to days following exposure. The symptoms may last (episodically) for minutes up to several days.

• Latent stage: In this stage, the patient looks and feels generally healthy for a few hours or even up to a few weeks.

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

• Recovery or death: Most patients who do not recover will die within several months of exposure. The recovery process lasts from several weeks up to two years

Bone marrow (hemopoietic) syndrome:

• (2 to7 Gy) Here severe damage may be caused to the circulatory system.

• The bone marrow being radiosensitive, results in fall in the number of granulocytes, platelets and erythrocytes.

• Clinically this is manifested as lymphopenia, granulocytopenia and hemorrhage due to thrombocytopenia and anemia due to depletion of the erythrocytes.

Gastrointestinal syndrome

• (7 to 15 Gy): This causes extensive damage to the gastrointestinal tract, leading to anorexia, nausea, vomiting,severe diarrhea and malaise.

Cardiovascular and central nervous systemsyndrome

• (more than 50 Gy): This produces death within one or two days. Individuals show incordination,disorientation and convulsions suggestive of extensive damage to the nervous system.

REFERENCES

1.White and pharoh-Oral Radiology-Principles and Interpretation 6th

2.Karjodkar Textbook of dental and maxillofacial radiology.

3.Eric Whaites.Essentials of Dental Radiography and Radiology.4th edition.

4.Iannucci-Dental Radiography - Principles and Techniques, 4E.

OSTEORADIO NECROSISOsteoradionecrosis of jaws-Marciani RD, Ownby H E .J Oral

Maxillofac Surg 44; 218223; 1986 Conservative management of osteoradionecrosis

J K Wong, R E Wood, Mc Lean Triple O 1997; 84:16-21 Hyper baric oxygen in therapeutic management of

osteoradionecrosis of facial bones-S. Vudiniabola, P J Williamson, A N Goss Int J Oral Maxillofac Surg 2000; 29:435-438

SALIVARY GLANDS Sensitivity of Salivary Glands to Radiation from Animal Models

to Therapies-J Dent Res. Oct 2009; 88(10): 894–903 http://www.cancer.org/cancer/salivaryglandcancer/detailedgui

de/salivary-gland-cancer-treating-radiation-therapy

MUCOSITIS

Effect of radiotherapy on oral mucosa assessed by quantitative exfoliative cytology.J Clin Pathol. Sep 1989; 42(9): 940–943.

Mucositis as a biological process: a new hypothesis for the development of chemotherapy-induced stomatotoxicity. Oral Oncol 34 (1): 39-43, 1998. [PUBMED]

RADIATION CARIES:

A Review of the Biological and Clinical Aspects of Radiation Caries-The Journal of Contemporary Dental Practice, Volume 10, No. 4, July 1, 2009

• REFERENCES

• [1] Epstein JB, Phillips N, Parry J, Epstein MS, et al. Quality of life, taste, olfactory and oral function following high-dose chemotherapy and allogeneic hematopoietic cell transplantation. Bone Marrow Transplant. 2002 Dec;30(11):785-92.

• [2] Plata-Salaman CR. Cytokines and anorexia: a brief overview. Semin Oncol. 1998 Feb;25(1 Suppl 1):64-72.

• [3] Ripamonti C, Zecca E, Brunelli C, et al.: A randomized, controlled clinical trial to evaluate the effects of zinc sulfate on cancer patients with taste alterations caused by head and neck irradiation. Cancer 82 (10): 1938-45, 1998.

• [4] Overview of nutrition in cancer care: Nutrition suggestions for symptoms relief. http://www.cancer.gov/cancerinfo/pdq/supportivecare/nutrition/patient/#Section_42 accessed 1/14/04.

http://news.cancerconnect.com/taste-changes/#_ednref1




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