organ radiation pathology

Organ Radiation PathologyOrgan Radiation Pathology

Types of ChangesTypes of Changes

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

tissues. tissues. Degree of change evident is differentDegree of change evident is different

Acute Tissue ChangesAcute Tissue Changes

Acute changes are typically inflammatoryAcute changes are typically inflammatoryErythemaErythemaEdemaEdemaDry > moist desquamationDry > moist desquamationHemmorhage Hemmorhage NecrosisNecrosis

Changes are the result of cells dying in the Changes are the result of cells dying in the tissues within the radiation field. 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 doseInversely proportional to time span of doseOther sources of trauma such as abrasion Other sources of trauma such as abrasion

and infection will increase severityand infection will increase severity

Acute Tissue ChangesAcute Tissue ChangesFollowing the acute changes there are two Following the acute changes there are two

possible outcomes. possible outcomes. Regeneration - Replacement of the cells lost Regeneration - Replacement of the cells lost

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

rapidly dividing cell lines and those arising from rapidly dividing cell lines and those arising from blast cellsblast cells

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

Influenced by the response of other cells in the Influenced by the response of other cells in the area (critical cells)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 processChanges manifest after healing processMay be minimal if regeneration is dominant May be minimal if regeneration is 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 Tissue ChangesChronic Tissue Changes

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

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

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

Chronic Tissue ChangesChronic Tissue ChangesOr, if a subsequent insult (infection, trauma, Or, if a subsequent insult (infection, trauma,

etc) exceeds the repair tolerance of the tissueetc) exceeds the repair tolerance of the tissueClassic example is a non-healing surgical incision Classic example is a non-healing surgical incision

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

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

Late vrs. Early Responding TissuesLate vrs. Early Responding Tissues

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

tissuestissuesGenerally 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 ResponseOther Factors in Radiation Response

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 effectsSome chemotherapy agents increase effectsSome 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 effects.Critical cell line may supersede and cause effects.

General Organ System General Organ System ResponsesResponses

Individual Organ/Tissue Individual Organ/Tissue “sensitivity to radiation injury”“sensitivity to radiation 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 resistant cell Red Blood Cells are the most resistant cell in the mammalian body to radiation injury. in the mammalian body to radiation injury.

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

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


Irradiation of a majority of the bone Irradiation of a majority of the bone marrow will cause marked decreases in marrow will cause marked decreases in circulating cell levels post irradiation.circulating cell levels post 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 these Due to irradiation of stem cells of these cell lines. cell lines.


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

and longer recovery periodand longer recovery periodLower dose = decreased rate and severity of Lower dose = decreased rate and severity of

drop and more rapid recovery. drop and more rapid recovery.

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


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

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

containing chemicals. containing chemicals.


Radiation doses to the entire marrow of Radiation doses to the entire marrow of greater than 8 gray are quite likely to greater than 8 gray are quite likely to result in marrow death and patient death result in marrow death and patient death unless a successful marrow transplant can unless a successful marrow transplant can be performed.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 cells The surface of the skin is covered by cells that are essentially FPM cellsthat are essentially FPM cells

The deep basement layers of the skin are The deep basement layers of the skin are composed of Stem cells which give rise to composed of Stem cells which give rise to the superficial cell layers. 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 10 Erythema w/ early and late effects at 10

gray and above. gray and above. Early effectsEarly effects

ErythemaErythemaDry desquamationDry desquamationMoist desquamationMoist desquamationNecrosisNecrosis


Late effects occur and increase with doseLate effects occur and increase with doseRecovers well from fairly high doses but Recovers well from fairly high doses but

late effects seen: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 grayModern techniques keep dose low – below 5 grayException is when skin is primary target.Exception is when skin is primary target.

Digestive SystemDigestive SystemExtends from mouth through rectumExtends from mouth through rectumSensitivity of individual parts rests with the Sensitivity of individual parts rests with the

number and reproductive activity of the number and reproductive activity of the stem cells in the basal mucosal layerstem cells in the basal mucosal 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 sesitive > highly activeSmall bowel very sesitive > 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 necrosisWith very high doses bleeding and necrosisLoss 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

Digestive SystemDigestive System

Late effectsLate effectsRepopulation – functional recovery ~ partial?Repopulation – functional recovery ~ 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.

Digestive SystemDigestive System

Severity of response is dose and volume Severity of response is dose and volume dependent;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 SystemDiagnostic 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 causes Radiation therapy including testis causes sterility and possibly loss of function. sterility and possibly loss of function. Functional sperm present 1-2 weeks after 1Functional sperm present 1-2 weeks after 1 stst

dosedose

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 SystemOocytes do not divide like spermatagoniaOocytes do not divide like spermatagonia

Themselves 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

EyesEyesEyes 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 is Occupational dose from diagnostic x-ray is a threat for cataract formation.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 SystemVesselsVessels

Endothelium 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 degreeEndothelium can repopulate to limited degree

Exuberant replacement may occlude vesselsExuberant replacement may occlude vesselsEndothelium can be default critical cell lineEndothelium can be default critical cell line

Other cells in vessel wall are FPM and Other cells in vessel wall are FPM and RPM hence resistant RPM hence resistant

HeartHeartConsidered resistantConsidered resistant

Late effects maybe seen years later.Late effects maybe seen years later.Acute or Fibrosing pericarditis most commonAcute or Fibrosing pericarditis most commonAt 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 osteocytesGrowing 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 Multi-Diagnostic exposure in children from Multi-slice spiral CT can be enough to at least slice spiral CT can be enough to at least cause some growth arrest.cause some growth arrest.

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

Liver and KidneysLiver and KidneysLarge organs which are fairly radiation Large organs which are fairly radiation

sensitive sensitive RPM cells with limited repopulation at lower RPM cells with limited repopulation at lower

doses.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 lethalWhole organ doses of 30 gray are lethalGreater tolerance if partially irradiatedGreater tolerance if partially irradiated

Liver and KidneysLiver and Kidneys

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

The kidneys in particular may be at risk for The kidneys in particular may be at risk for damage from some Nuclear Medicine damage from some Nuclear Medicine studies.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 the 10 gray single dose or 30 gray fractionated to the

whole lung cause progressive fibrosiswhole 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 effectDose to less than ½ lung has minimal clinical effect

Central Nervous SystemCentral Nervous System CNS is considered quite radioresistant in adults.CNS is considered quite radioresistant in adults.

Development continues to 12 years of age therefore Development continues to 12 years of age therefore whole brain dose can reduce developmentwhole brain dose can reduce development

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

organ radiation pathology

Documents

chronic tissue changesor

result of cells

percentage of cells

dividing cell linesor

original cell population

late responding tissues

early healing

radiation field months