Organ Radiation Pathology Organ Radiation Pathology

Organ Radiation Organ Radiation PathologyPathology

Types of ChangesTypes of Changes

Acute tissue injuryAcute tissue injuryChronic tissue injuryChronic tissue injurySeen in both early and late Seen in both early and late

responding tissues. responding tissues.

Degree of change evident is Degree of change evident is differentdifferent

Acute Tissue ChangesAcute Tissue Changes

Acute changes are typically Acute changes are typically inflammatoryinflammatoryErythemaErythemaEdemaEdemaDry > moist desquamationDry > moist desquamationHemmorhage Hemmorhage NecrosisNecrosis

Changes are the result of cells dying in Changes are the result of cells dying in the tissues within the radiation field. the tissues within the radiation field.


Cellular death attracts inflammatory cellsCellular death attracts inflammatory cellsRadiation injury of these cells further Radiation injury of these cells further

exacerbates the inflammation.exacerbates the inflammation.Severity proportional to the dose receivedSeverity proportional to the dose received Inversely proportional to time span of Inversely proportional to time span of

dosedoseOther sources of trauma such as abrasion Other sources of trauma such as abrasion

and infection will increase severityand infection will increase severity


Following the acute changes there Following the acute changes there are two possible outcomes. are two possible outcomes. Regeneration - Replacement of the cells Regeneration - Replacement of the cells

lost by cells of the same type.lost by cells of the same type.May be complete or partial and is comonly May be complete or partial and is comonly

seen in rapidly dividing cell lines and those seen in rapidly dividing cell lines and those arising from blast cellsarising from blast cells

Generally is a low dose phenomenon but Generally is a low dose phenomenon but may occur in some tissues at relatively high may occur in some tissues at relatively high doses. doses.

Influenced by the response of other cells in Influenced by the response of other cells in the area (critical cells)the area (critical cells)


Following acute tissue injury the tissue Following acute tissue injury the tissue may also undergo replacement. may also undergo replacement. Original cell population replaced by different Original cell population replaced by different

population – usually fribroblastspopulation – usually fribroblastsResults in permanent loss of the original cell Results in permanent loss of the original cell

population and its function. population and its function. Occurs in tissues with long cell cycle timesOccurs in tissues with long cell cycle timesTends to occur more commonly at high dosesTends to occur more commonly at high doses

Chronic Tissue ChangesChronic Tissue Changes

Changes manifest after healing Changes manifest after healing processprocessMay be minimal if regeneration is May be minimal if regeneration is

dominant dominant Depigmentation Depigmentation Hair loss and thinningHair loss and thinningAtrophyAtrophyScar formantion and stricturesScar formantion and stricturesNon-healing ulcers or necrosisNon-healing ulcers or necrosis


Chronic changes may supersede Chronic changes may supersede apparent healing. apparent healing. Occurs when a slowly dividing critical Occurs when a slowly dividing critical

cell line dies off after early healing of cell line dies off after early healing of rapidly dividing cell lines. rapidly dividing cell lines. Classic example is loss of vascular supply to Classic example is loss of vascular supply to

a tissue such as the intestine after mucosal a tissue such as the intestine after mucosal regeneration has occurred. regeneration has occurred.


Or, if a subsequent insult (infection, Or, if a subsequent insult (infection, trauma, etc) exceeds the repair trauma, etc) exceeds the repair tolerance of the tissuetolerance of the tissueClassic example is a non-healing surgical Classic example is a non-healing surgical

incision made in a radiation field.incision made in a radiation field.Another example is bone necrosis is a Another example is bone necrosis is a

radiation field months to years after soft radiation field months to years after soft tissues in the radiation field have healed. tissues in the radiation field have healed.

Late vrs. Early Responding Late vrs. Early Responding TissuesTissues

Acute and chronic changes are both Acute and chronic changes are both seen in either:seen in either:Early (rapidly dividing cell lines)Early (rapidly dividing cell lines)Or late (slowly dividing cell lines) Or late (slowly dividing cell lines)

responding tissuesresponding tissuesGenerally speaking the changes are less Generally speaking the changes are less

evident in late responding tissue unless evident in late responding tissue unless necrosis occurs.necrosis occurs.

Other Factors in Radiation Other Factors in Radiation ResponseResponse

Volume of tissue irradiatedVolume of tissue irradiatedIncreased volume increases effectsIncreased volume increases effects

Oxygenation at the cellular levelOxygenation at the cellular levelNormal cells are typically 100% oxygenatedNormal cells are typically 100% oxygenatedTumor tissues may contain hypoxic areas. Tumor tissues may contain hypoxic areas.

Presence of some chemicalsPresence of some chemicalsSome chemotherapy agents increase Some chemotherapy agents increase

effectseffectsSome drugs such as Amophostine mitigate Some drugs such as Amophostine mitigate

effectseffects


Dose RateDose RateDecreased dose rate decreases effectsDecreased dose rate decreases effects

Cellular KeneticsCellular KeneticsGrowth fraction - The percentage of cells Growth fraction - The percentage of cells

actually moving through the cell cycle. actually moving through the cell cycle. Can blunt effects > repopulation Can blunt effects > repopulation Can increase effects > more cells irradiated in Can increase effects > more cells irradiated in

MitosisMitosis


Cellular KineticsCellular KineticsCell loss fraction – number of cells naturally Cell loss fraction – number of cells naturally

being lost from the cell population.being lost from the cell population.Increased loss Fx. - Accelerates effectsIncreased loss Fx. - Accelerates effectsDecreased loss Fx. – Blunts effects. Decreased loss Fx. – Blunts effects.

Cell typeCell typeNon-cycling population blunts effects Non-cycling population blunts effects

markedly.markedly.Critical cell line may supersede and cause Critical cell line may supersede and cause

effects.effects.

General Organ System General Organ System ResponsesResponses

Individual Organ/Tissue Individual Organ/Tissue “sensitivity to radiation “sensitivity to radiation

injury”injury”

HemopoieticHemopoietic (blood and lymph) (blood and lymph)

Refers to the parenchymal cells of the Refers to the parenchymal cells of the bone marrow and the circulating blood.bone marrow and the circulating blood.

Does not refer to the vessels themselvesDoes not refer to the vessels themselvesCritical cells are the marrow blast cells Critical cells are the marrow blast cells

and circulating small lymphocytes. and circulating small lymphocytes. Non-circulating lymphocytes and other Non-circulating lymphocytes and other

circulating white cells fairly radioresistantcirculating white cells fairly radioresistant


Red Blood Cells are the most Red Blood Cells are the most resistant cell in the mammalian body resistant cell in the mammalian body to radiation injury. to radiation injury.

Irradiation of a small region of the Irradiation of a small region of the body generally has no effect on body generally has no effect on circulating levelscirculating levelsAn exception is lymphocyte counts An exception is lymphocyte counts

following therapy level doses to the following therapy level doses to the chest. chest.


Irradiation of a majority of the bone Irradiation of a majority of the bone marrow will cause marked decreases marrow will cause marked decreases in circulating cell levels post in circulating cell levels post irradiation.irradiation.Platelets at 2-4 daysPlatelets at 2-4 daysWhite cells at 5-10 daysWhite cells at 5-10 daysRed cells at 3-4 weeksRed cells at 3-4 weeks

Due to irradiation of stem cells of Due to irradiation of stem cells of these cell lines. these cell lines.


Effect is dose relatedEffect is dose relatedHigh dose = increase rate and severity High dose = increase rate and severity

of drop and longer recovery periodof drop and longer recovery periodLower dose = decreased rate and Lower dose = decreased rate and

severity of drop and more rapid severity of drop and more rapid recovery. recovery.

At high doses recovery may only be At high doses recovery may only be partial or not occur at all. Mpartial or not occur at all. M


High dose irradiation of the marrow High dose irradiation of the marrow to sterilize it prior to bone marrow to sterilize it prior to bone marrow transplant is sometime done for transplant is sometime done for cancer therapycancer therapy

Many metallic radioisotopes are bone Many metallic radioisotopes are bone marrow seekers and can result in marrow seekers and can result in marrow toxicity if ingestedmarrow toxicity if ingestedAn example are the phophonates and An example are the phophonates and

calcium containing chemicals. calcium containing chemicals.


Radiation doses to the entire marrow Radiation doses to the entire marrow of greater than 8 gray are quite likely of greater than 8 gray are quite likely to result in marrow death and patient to result in marrow death and patient death unless a successful marrow death unless a successful marrow transplant can be performed.transplant can be performed.

Doses of the this magnitude are very Doses of the this magnitude are very unlikely to occur in clinical medicineunlikely to occur in clinical medicineException is pre transplant marrow Exception is pre transplant marrow

sterilizationsterilization

Skin and Oral MucosaSkin and Oral Mucosa

The surface of the skin is covered by The surface of the skin is covered by cells that are essentially FPM cellscells that are essentially FPM cells

The deep basement layers of the skin The deep basement layers of the skin are composed of Stem cells which are composed of Stem cells which give rise to the superficial cell layers. give rise to the superficial cell layers. Basal cells of the skinBasal cells of the skinSource of skin sensitivity to radiationSource of skin sensitivity to radiationSkin recovery dependent on this cellsSkin recovery dependent on this cells


Little or no reaction below 6-8 grayLittle or no reaction below 6-8 grayErythema w/ early and late effects at Erythema w/ early and late effects at

10 gray and above. 10 gray and above. Early effectsEarly effects

ErythemaErythemaDry desquamationDry desquamationMoist desquamationMoist desquamationNecrosisNecrosis


Late effects occur and increase with Late effects occur and increase with dosedose

Recovers well from fairly high doses Recovers well from fairly high doses but late effects seen:but late effects seen:Thinning of skinThinning of skinPigmentation or depigmentationPigmentation or depigmentationLoss or thinning of hair. Loss or thinning of hair. Loss or thinning of subcuntaneous fatLoss or thinning of subcuntaneous fatCancer induction years later.Cancer induction years later.


Sources of radiation injurySources of radiation injurySolar UVSolar UV

Probably major threat for most peopleProbably major threat for most peopleDiagnostic x-rayDiagnostic x-ray

Fluoroscopy – Especially cardiacFluoroscopy – Especially cardiacCT – High speed spiral in juvenilesCT – High speed spiral in juveniles

Radiation therapyRadiation therapyModern techniques keep dose low – below 5 Modern techniques keep dose low – below 5

graygrayException is when skin is primary target.Exception is when skin is primary target.

Digestive SystemDigestive System

Extends from mouth through rectumExtends from mouth through rectumSensitivity of individual parts rests Sensitivity of individual parts rests

with the number and reproductive with the number and reproductive activity of the stem cells in the basal activity of the stem cells in the basal mucosal layermucosal layerMouth and esophagus relatively resistantMouth and esophagus relatively resistantStomach more sensitive and has more Stomach more sensitive and has more

secretory cellssecretory cellsSmall bowel very sensitive > highly activeSmall bowel very sensitive > highly activeColon and Rectum similar to esophagusColon and Rectum similar to esophagus

Digestive System Digestive System

Early effects are mucosal depopulationEarly effects are mucosal depopulationClinical soreness and possible ulcerationClinical soreness and possible ulcerationWith very high doses bleeding and With very high doses bleeding and

necrosisnecrosisLoss of secretory cells Loss of secretory cells

Stomach and Intestine – decreased mucus Stomach and Intestine – decreased mucus Decreased digestive enzyme productionDecreased digestive enzyme productionDecreased hormone productionDecreased hormone production

Clinical infections Clinical infections


Late effectsLate effectsRepopulation – functional recovery ~ Repopulation – functional recovery ~

partial?partial?Epithelial metaplasia – loss of functionEpithelial metaplasia – loss of functionScarring – severe loss of functionScarring – severe loss of function

Chronic clinical signsChronic clinical signsStricture - obstruction of GI tractStricture - obstruction of GI tract

Surgical mediation required. Surgical mediation required.


Severity of response is dose and Severity of response is dose and volume dependent;volume dependent;High dose and low volumeHigh dose and low volumeLower dose and larger volumeLower dose and larger volume

Diagnostic x-ray and nuclear medicine Diagnostic x-ray and nuclear medicine procedures not generally a threat. procedures not generally a threat.

Radiation therapy can result in severe Radiation therapy can result in severe changes.changes.

Male Reproductive SystemMale Reproductive System

Adult sperm are FPM cells – resistantAdult sperm are FPM cells – resistantBut, chromosomal damage may be passed on But, chromosomal damage may be passed on

to a fetus. Mutations can result.to a fetus. Mutations can result.Germinal cells very sensitive thoughGerminal cells very sensitive though

2.5 gray to testis causes temporary sterility2.5 gray to testis causes temporary sterility5-6 gray to testis causes permanent steritity5-6 gray to testis causes permanent steritity

Other secretory and hormonal cells more Other secretory and hormonal cells more resistant because RPM and FPM cellsresistant because RPM and FPM cellsHormonal activity may be retained w/ sterilityHormonal activity may be retained w/ sterility

Male Reproductive SystemMale Reproductive System

Diagnostic x-ray and nuclear medicine Diagnostic x-ray and nuclear medicine studies not a threat to function studies not a threat to function Mutation threshold may be lowerMutation threshold may be lower

Radiation therapy near testis probably Radiation therapy near testis probably cause temporary sterilitycause temporary sterility

Radiation therapy including testis Radiation therapy including testis causes sterility and possibly loss of causes sterility and possibly loss of function. function. Functional sperm present 1-2 weeks after Functional sperm present 1-2 weeks after

11stst dose dose

Female Reproductive SystemFemale Reproductive System

Radiation therapy is major sterility threatRadiation therapy is major sterility threat6.25 Gray to both ovaries – expect sterility6.25 Gray to both ovaries – expect sterilityOocytes do not divide – thus no repopulationOocytes do not divide – thus no repopulation

Radiation therapy is hormonal function Radiation therapy is hormonal function threat.threat.Hormonal function decreased/lost above 25 Hormonal function decreased/lost above 25

graygrayMay require hormonal supplementationMay require hormonal supplementation

Female Reproductive SystemFemale Reproductive System

Oocytes do not divide like Oocytes do not divide like spermatagoniaspermatagoniaThemselves relatively resistant Themselves relatively resistant Chromosomal damage carried on and may Chromosomal damage carried on and may

become evident after fertilization. become evident after fertilization. Ovarian sensitivity more tied to follicular Ovarian sensitivity more tied to follicular

cells which support oocytes duringcells which support oocytes duringDuring follicle development there is great During follicle development there is great

cellular growth activity in these cells.cellular growth activity in these cells.Inactive follicular cells are less sensitiveInactive follicular cells are less sensitive

EyesEyes

Eyes are a major dose limiting structureEyes are a major dose limiting structureThe lens is vary sensitive to radiationThe lens is vary sensitive to radiation

Cataract formation is major effectCataract formation is major effectSeen with doses as low as 2 graySeen with doses as low as 2 grayVery likely at 4 grayVery likely at 4 gray

Occupational dose from diagnostic x-ray Occupational dose from diagnostic x-ray is a threat for cataract formation.is a threat for cataract formation.Wear eye shields, esp. during fluoroscopyWear eye shields, esp. during fluoroscopy

Major side effect of RT to head and neckMajor side effect of RT to head and neck

Cardiovascular SystemCardiovascular System

VesselsVesselsEndothelium is target cell typeEndothelium is target cell typeEndothelial injury causes thrombosis and Endothelial injury causes thrombosis and

possibly hemorrhage.possibly hemorrhage.Endothelium can repopulate to limited Endothelium can repopulate to limited

degreedegreeExuberant replacement may occlude vesselsExuberant replacement may occlude vessels

Endothelium can be default critical cell lineEndothelium can be default critical cell lineOther cells in vessel wall are FPM and Other cells in vessel wall are FPM and

RPM hence resistant RPM hence resistant

HeartHeart

Considered resistantConsidered resistantLate effects maybe seen years later.Late effects maybe seen years later.Acute or Fibrosing pericarditis most Acute or Fibrosing pericarditis most

commoncommonAt higher doses myocardial fibrosis seenAt higher doses myocardial fibrosis seen

Late effects seen are slowly progressiveLate effects seen are slowly progressiveRevealed or exacerbated by chemotherapyRevealed or exacerbated by chemotherapy

Diagnostic radiation not usually a threatDiagnostic radiation not usually a threatRadiation therapy dose/volume related Radiation therapy dose/volume related

threatthreat

Bone and CartilageBone and Cartilage

Mature bone is composed of FPM cells Mature bone is composed of FPM cells from hierarchical cell lines ~ resistantfrom hierarchical cell lines ~ resistantAt high RT doses osteonecrosis and fx. SeenAt high RT doses osteonecrosis and fx. Seen

D/t loss of mature osteocytesD/t loss of mature osteocytes

Growing cartilage cells at growth plate are Growing cartilage cells at growth plate are a target at risk. Especially at < 2 yrs old. a target at risk. Especially at < 2 yrs old. Causes stunted growth and possibly deformityCauses stunted growth and possibly deformity

High dose to joint can cause “dry” jointHigh dose to joint can cause “dry” joint

Bone and CartilageBone and Cartilage

Diagnostic exposure in children from Diagnostic exposure in children from Multi-slice spiral CT can be enough to Multi-slice spiral CT can be enough to at least cause some growth arrest.at least cause some growth arrest.

Radiation Therapy exposure will Radiation Therapy exposure will cause permanent growth arrest in cause permanent growth arrest in open growth plate of a young person open growth plate of a young person Osteonecrosis and fracture possible in Osteonecrosis and fracture possible in

adult.adult.

Liver and KidneysLiver and Kidneys

Large organs which are fairly radiation Large organs which are fairly radiation sensitive sensitive RPM cells with limited repopulation at RPM cells with limited repopulation at

lower doses.lower doses.Vascular injury may play an important role. Vascular injury may play an important role. Functional subunits arranged in parallel Functional subunits arranged in parallel In kidneys fractionation has minimal effectIn kidneys fractionation has minimal effect

Whole organ doses of 30 gray are Whole organ doses of 30 gray are lethallethal

Greater tolerance if partially irradiatedGreater tolerance if partially irradiated

Liver and KidneysLiver and Kidneys

Major radiation threat is from Major radiation threat is from radiation therapy fields which include radiation therapy fields which include these organsthese organs

The kidneys in particular may be at The kidneys in particular may be at risk for damage from some Nuclear risk for damage from some Nuclear Medicine studies.Medicine studies.Kidneys and bladder are major excretion Kidneys and bladder are major excretion

route for many isotopes route for many isotopes Liver is excretion route for a few isotopes.Liver is excretion route for a few isotopes.

LungsLungs

One of the most radiosensitive organsOne of the most radiosensitive organs RPM populations of epithelium & endotheliumRPM populations of epithelium & endothelium 10 gray single dose or 30 gray fractionated to 10 gray single dose or 30 gray fractionated to

the whole lung cause progressive fibrosisthe whole lung cause progressive fibrosis Type II pneumocyte is critical cell > edemaType II pneumocyte is critical cell > edema

Edema is acute toxicity (radiation pneumonitis)Edema is acute toxicity (radiation pneumonitis) Fibrosis is the late effect.Fibrosis is the late effect.

The lung has large functional reserve >The lung has large functional reserve > Dose to less than ½ lung has minimal clinical Dose to less than ½ lung has minimal clinical

effecteffect

Central Nervous SystemCentral Nervous System

CNS is considered quite radioresistant in CNS is considered quite radioresistant in adults.adults. Development continues to 12 years of age Development continues to 12 years of age

therefore whole brain dose can reduce therefore whole brain dose can reduce developmentdevelopment

Glial cells and vascular endothelium are the Glial cells and vascular endothelium are the critical cells of interest. critical cells of interest.

RT usually avoided in childern. RT usually avoided in childern. Increasing volume or dose ^ the effectsIncreasing volume or dose ^ the effects

Large volumes irradiated above 40 Gray lead to Large volumes irradiated above 40 Gray lead to decreased function. decreased function.

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Organ Radiation Pathology Organ Radiation Pathology