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Organ Radiation Pathology - University of Missouri - School of ...

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  • 1. Organ Radiation PathologyOrgan Radiation Pathology
  • 2. Types of ChangesTypes of Changes Acute tissue injuryAcute tissue injury Chronic tissue injuryChronic tissue injury Seen in both early and late respondingSeen in both early and late responding tissues.tissues. Degree of change evident is differentDegree of change evident is different
  • 3. Acute Tissue ChangesAcute Tissue Changes Acute changes are typically inflammatoryAcute changes are typically inflammatory ErythemaErythema EdemaEdema Dry > moist desquamationDry > moist desquamation HemmorhageHemmorhage NecrosisNecrosis Changes are the result of cells dying in theChanges are the result of cells dying in the tissues within the radiation field.tissues within the radiation field.
  • 4. Acute Tissue ChangesAcute Tissue Changes Cellular death attracts inflammatory cellsCellular death attracts inflammatory cells Radiation injury of these cells furtherRadiation 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 dose Other sources of trauma such as abrasionOther sources of trauma such as abrasion and infection will increase severityand infection will increase severity
  • 5. Acute Tissue ChangesAcute Tissue Changes Following the acute changes there are twoFollowing the acute changes there are two possible outcomes.possible outcomes. Regeneration - Replacement of the cells lostRegeneration - 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 inMay be complete or partial and is comonly seen in rapidly dividing cell lines and those arising fromrapidly dividing cell lines and those arising from blast cellsblast cells Generally is a low dose phenomenon but mayGenerally 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 theInfluenced by the response of other cells in the area (critical cells)area (critical cells)
  • 6. Acute Tissue ChangesAcute Tissue Changes Following acute tissue injury the tissueFollowing acute tissue injury the tissue may also undergo replacement.may also undergo replacement. Original cell population replaced by differentOriginal cell population replaced by different population – usually fribroblastspopulation – usually fribroblasts Results in permanent loss of the original cellResults 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 times Tends to occur more commonly at high dosesTends to occur more commonly at high doses
  • 7. Chronic Tissue ChangesChronic Tissue Changes Changes manifest after healing processChanges manifest after healing process May be minimal if regeneration is dominantMay be minimal if regeneration is dominant DepigmentationDepigmentation Hair loss and thinningHair loss and thinning AtrophyAtrophy Scar formantion and stricturesScar formantion and strictures Non-healing ulcers or necrosisNon-healing ulcers or necrosis
  • 8. Chronic Tissue ChangesChronic Tissue Changes Chronic changes may supersede apparentChronic changes may supersede apparent healing.healing. Occurs when a slowly dividing critical cell lineOccurs when a slowly dividing critical cell line dies off after early healing of rapidly dividingdies off after early healing of rapidly dividing cell lines.cell lines. Classic example is loss of vascular supply to aClassic example is loss of vascular supply to a tissue such as the intestine after mucosaltissue such as the intestine after mucosal regeneration has occurred.regeneration has occurred.
  • 9. Chronic Tissue ChangesChronic Tissue Changes Or, 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 tissue Classic example is a non-healing surgical incisionClassic example is a non-healing surgical incision made in a radiation field.made in a radiation field. Another example is bone necrosis is a radiationAnother example is bone necrosis is a radiation field months to years after soft tissues in thefield months to years after soft tissues in the radiation field have healed.radiation field have healed.
  • 10. Late vrs. Early Responding TissuesLate vrs. Early Responding Tissues Acute and chronic changes are both seenAcute 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) respondingOr late (slowly dividing cell lines) responding tissuestissues Generally speaking the changes are lessGenerally speaking the changes are less evident in late responding tissue unlessevident in late responding tissue unless necrosis occurs.necrosis occurs.
  • 11. Other Factors in Radiation ResponseOther Factors in Radiation Response Volume of tissue irradiatedVolume of tissue irradiated Increased volume increases effectsIncreased volume increases effects Oxygenation at the cellular levelOxygenation at the cellular level Normal cells are typically 100% oxygenatedNormal cells are typically 100% oxygenated Tumor tissues may contain hypoxic areas.Tumor tissues may contain hypoxic areas. Presence of some chemicalsPresence of some chemicals Some chemotherapy agents increase effectsSome chemotherapy agents increase effects Some drugs such as Amophostine mitigateSome drugs such as Amophostine mitigate effectseffects
  • 12. Other Factors in Radiation ResponseOther Factors in Radiation Response Dose RateDose Rate Decreased dose rate decreases effectsDecreased dose rate decreases effects Cellular KeneticsCellular Kenetics Growth fraction - The percentage of cellsGrowth fraction - The percentage of cells actually moving through the cell cycle.actually moving through the cell cycle. Can blunt effects > repopulationCan blunt effects > repopulation Can increase effects > more cells irradiated inCan increase effects > more cells irradiated in MitosisMitosis
  • 13. Other Factors in Radiation ResponseOther Factors in Radiation Response Cellular KineticsCellular Kinetics Cell loss fraction – number of cells naturallyCell 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 effects Decreased loss Fx. – Blunts effects.Decreased loss Fx. – Blunts effects. Cell typeCell type Non-cycling population blunts effectsNon-cycling population blunts effects markedly.markedly. Critical cell line may supersede and cause effects.Critical cell line may supersede and cause effects.
  • 14. General Organ SystemGeneral Organ System ResponsesResponses Individual Organ/TissueIndividual Organ/Tissue “sensitivity to radiation injury”“sensitivity to radiation injury”
  • 15. HemopoieticHemopoietic (blood and lymph)(blood and lymph) Refers to the parenchymal cells of theRefers 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 themselves Critical cells are the marrow blast cellsCritical cells are the marrow blast cells and circulating small lymphocytes.and circulating small lymphocytes. Non-circulating lymphocytes and otherNon-circulating lymphocytes and other circulating white cells fairly radioresistantcirculating white cells fairly radioresistant
  • 16. HemopoieticHemopoietic (blood and lymph)(blood and lymph) Red Blood Cells are the most resistant cellRed 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 bodyIrradiation of a small region of the body generally has no effect on circulatinggenerally has no effect on circulating levelslevels An exception is lymphocyte counts followingAn exception is lymphocyte counts following therapy level doses to the chest.therapy level doses to the chest.
  • 17. HemopoieticHemopoietic (blood and lymph)(blood and lymph) Irradiation of a majority of the boneIrradiation of a majority of the bone marrow will cause marked decreases inmarrow will cause marked decreases in circulating cell levels post irradiation.circulating cell levels post irradiation. Platelets at 2-4 daysPlatelets at 2-4 days White cells at 5-10 daysWhite cells at 5-10 days Red cells at 3-4 weeksRed cells at 3-4 weeks Due to irradiation of stem cells of theseDue to irradiation of stem cells of these cell lines.cell lines.
  • 18. HemopoieticHemopoietic (blood and lymph)(blood and lymph) Effect is dose relatedEffect is dose related High dose = increase rate and severity of dropHigh dose = increase rate and severity of drop and longer recovery periodand longer recovery period Lower dose = decreased rate and severity ofLower dose = decreased rate and severity of drop and more rapid recovery.drop and more rapid recovery. At high doses recovery may only be partialAt high doses recovery may only be partial or not occur at all. Mor not occur at all. M
  • 19. HemopoieticHemopoietic (blood and lymph)(blood and lymph) High dose irradiation of the marrow toHigh dose irradiation of the marrow to sterilize it prior to bone marrow transplantsterilize it prior to bone marrow transplant is sometime done for cancer therapyis sometime done for cancer therapy Many metallic radioisotopes are boneMany metallic radioisotopes are bone marrow seekers and can result in marrowmarrow seekers and can result in marrow toxicity if ingestedtoxicity if ingested An example are the phophonates and calciumAn example are the phophonates and calcium containing chemicals.containing chemicals.
  • 20. HemopoieticHemopoietic (blood and lymph)(blood and lymph) Radiation doses to the entire marrow ofRadiation doses to the entire marrow of greater than 8 gray are quite likely togreater than 8 gray are quite likely to result in marrow death and patient deathresult in marrow death and patient death unless a successful marrow transplant canunless a successful marrow transplant can be performed.be performed. Doses of the this magnitude are veryDoses of the this magnitude are very unlikely to occur in clinical medicineunlikely to occur in clinical medicine Exception is pre transplant marrowException is pre transplant marrow sterilizationsterilization
  • 21. Skin and Oral MucosaSkin and Oral Mucosa The surface of the skin is covered by cellsThe surface of the skin is covered by cells that are essentially FPM cellsthat are essentially FPM cells The deep basement layers of the skin areThe deep basement layers of the skin are composed of Stem cells which give rise tocomposed of Stem cells which give rise to the superficial cell layers.the superficial cell layers. Basal cells of the skinBasal cells of the skin Source of skin sensitivity to radiationSource of skin sensitivity to radiation Skin recovery dependent on this cellsSkin recovery dependent on this cells
  • 22. Skin and Oral MucosaSkin and Oral Mucosa Little or no reaction below 6-8 grayLittle or no reaction below 6-8 gray Erythema w/ early and late effects at 10Erythema w/ early and late effects at 10 gray and above.gray and above. Early effectsEarly effects ErythemaErythema Dry desquamationDry desquamation Moist desquamationMoist desquamation NecrosisNecrosis
  • 23. Skin and Oral MucosaSkin and Oral Mucosa Late effects occur and increase with doseLate effects occur and increase with dose Recovers well from fairly high doses butRecovers well from fairly high doses but late effects seen:late effects seen: Thinning of skinThinning of skin Pigmentation or depigmentationPigmentation or depigmentation Loss or thinning of hair.Loss or thinning of hair. Loss or thinning of subcuntaneous fatLoss or thinning of subcuntaneous fat Cancer induction years later.Cancer induction years later.
  • 24. Skin and Oral MucosaSkin and Oral Mucosa Sources of radiation injurySources of radiation injury Solar UVSolar UV Probably major threat for most peopleProbably major threat for most people Diagnostic x-rayDiagnostic x-ray Fluoroscopy – Especially cardiacFluoroscopy – Especially cardiac CT – High speed spiral in juvenilesCT – High speed spiral in juveniles Radiation therapyRadiation therapy Modern techniques keep dose low – below 5 grayModern techniques keep dose low – below 5 gray Exception is when skin is primary target.Exception is when skin is primary target.
  • 25. Digestive SystemDigestive System Extends from mouth through rectumExtends from mouth through rectum Sensitivity of individual parts rests with theSensitivity of individual parts rests with the number and reproductive activity of thenumber and reproductive activity of the stem cells in the basal mucosal layerstem cells in the basal mucosal layer Mouth and esophagus relatively resistantMouth and esophagus relatively resistant Stomach more sensitive and has moreStomach more sensitive and has more secretory cellssecretory cells Small bowel very sesitive > highly activeSmall bowel very sesitive > highly active Colon and Rectum similar to esophagusColon and Rectum similar to esophagus
  • 26. Digestive SystemDigestive System Early effects are mucosal depopulationEarly effects are mucosal depopulation Clinical soreness and possible ulcerationClinical soreness and possible ulceration With very high doses bleeding and necrosisWith very high doses bleeding and necrosis Loss of secretory cellsLoss of secretory cells Stomach and Intestine – decreased mucusStomach and Intestine – decreased mucus Decreased digestive enzyme productionDecreased digestive enzyme production Decreased hormone productionDecreased hormone production Clinical infectionsClinical infections
  • 27. Digestive SystemDigestive System Late effectsLate effects Repopulation – functional recovery ~ partial?Repopulation – functional recovery ~ partial? Epithelial metaplasia – loss of functionEpithelial metaplasia – loss of function Scarring – severe loss of functionScarring – severe loss of function Chronic clinical signsChronic clinical signs Stricture - obstruction of GI tractStricture - obstruction of GI tract Surgical mediation required.Surgical mediation required.
  • 28. Digestive SystemDigestive System Severity of response is dose and volumeSeverity of response is dose and volume dependent;dependent; High dose and low volumeHigh dose and low volume Lower dose and larger volumeLower dose and larger volume Diagnostic x-ray and nuclear medicineDiagnostic x-ray and nuclear medicine procedures not generally a threat.procedures not generally a threat. Radiation therapy can result in severeRadiation therapy can result in severe changes.changes.
  • 29. Male Reproductive SystemMale Reproductive System Adult sperm are FPM cells – resistantAdult sperm are FPM cells – resistant But, chromosomal damage may be passed onBut, 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 sterility 5-6 gray to testis causes permanent steritity5-6 gray to testis causes permanent steritity Other secretory and hormonal cells moreOther secretory and hormonal cells more resistant because RPM and FPM cellsresistant because RPM and FPM cells Hormonal activity may be retained w/ sterilityHormonal activity may be retained w/ sterility
  • 30. Male Reproductive SystemMale Reproductive System Diagnostic x-ray and nuclear medicineDiagnostic x-ray and nuclear medicine studies not a threat to functionstudies not a threat to function Mutation threshold may be lowerMutation threshold may be lower Radiation therapy near testis probablyRadiation therapy near testis probably cause temporary sterilitycause temporary sterility Radiation therapy including testis causesRadiation 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 1stst dosedose
  • 31. Female Reproductive SystemFemale Reproductive System Radiation therapy is major sterility threatRadiation therapy is major sterility threat 6.25 Gray to both ovaries – expect sterility6.25 Gray to both ovaries – expect sterility Oocytes do not divide – thus no repopulationOocytes do not divide – thus no repopulation Radiation therapy is hormonal functionRadiation therapy is hormonal function threat.threat. Hormonal function decreased/lost above 25Hormonal function decreased/lost above 25 graygray May require hormonal supplementationMay require hormonal supplementation
  • 32. Female Reproductive SystemFemale Reproductive System Oocytes do not divide like spermatagoniaOocytes do not divide like spermatagonia Themselves relatively resistantThemselves relatively resistant Chromosomal damage carried on and mayChromosomal damage carried on and may become evident after fertilization.become evident after fertilization. Ovarian sensitivity more tied to follicularOvarian sensitivity more tied to follicular cells which support oocytes duringcells which support oocytes during During follicle development there is greatDuring 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
  • 33. EyesEyes Eyes are a major dose limiting structureEyes are a major dose limiting structure The lens is vary sensitive to radiationThe lens is vary sensitive to radiation Cataract formation is major effectCataract formation is major effect Seen with doses as low as 2 graySeen with doses as low as 2 gray Very likely at 4 grayVery likely at 4 gray Occupational dose from diagnostic x-ray isOccupational 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
  • 34. Cardiovascular SystemCardiovascular System VesselsVessels Endothelium is target cell typeEndothelium is target cell type Endothelial injury causes thrombosis andEndothelial 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 vessels Endothelium can be default critical cell lineEndothelium can be default critical cell line Other cells in vessel wall are FPM andOther cells in vessel wall are FPM and RPM hence resistantRPM hence resistant
  • 35. HeartHeart Considered resistantConsidered resistant Late effects maybe seen years later.Late effects maybe seen years later. Acute or Fibrosing pericarditis most commonAcute or Fibrosing pericarditis most common At higher doses myocardial fibrosis seenAt higher doses myocardial fibrosis seen Late effects seen are slowly progressiveLate effects seen are slowly progressive Revealed or exacerbated by chemotherapyRevealed or exacerbated by chemotherapy Diagnostic radiation not usually a threatDiagnostic radiation not usually a threat Radiation therapy dose/volume relatedRadiation therapy dose/volume related threatthreat
  • 36. Bone and CartilageBone and Cartilage Mature bone is composed of FPM cellsMature bone is composed of FPM cells from hierarchical cell lines ~ resistantfrom hierarchical cell lines ~ resistant At 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 areGrowing 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
  • 37. 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 leastslice spiral CT can be enough to at least cause some growth arrest.cause some growth arrest. Radiation Therapy exposure will causeRadiation Therapy exposure will cause permanent growth arrest in open growthpermanent growth arrest in open growth plate of a young personplate of a young person Osteonecrosis and fracture possible in adult.Osteonecrosis and fracture possible in adult.
  • 38. Liver and KidneysLiver and Kidneys Large organs which are fairly radiationLarge organs which are fairly radiation sensitivesensitive RPM cells with limited repopulation at lowerRPM 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 parallelFunctional 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 lethal Greater tolerance if partially irradiatedGreater tolerance if partially irradiated
  • 39. Liver and KidneysLiver and Kidneys Major radiation threat is from radiationMajor radiation threat is from radiation therapy fields which include these organstherapy fields which include these organs The kidneys in particular may be at risk forThe kidneys in particular may be at risk for damage from some Nuclear Medicinedamage from some Nuclear Medicine studies.studies. Kidneys and bladder are major excretionKidneys and bladder are major excretion route for many isotopesroute for many isotopes Liver is excretion route for a few isotopes.Liver is excretion route for a few isotopes.
  • 40. 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 the10 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
  • 41. 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 thereforeDevelopment 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 criticalGlial 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 toLarge volumes irradiated above 40 Gray lead to decreased function.decreased function.

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