This chapter examines the biological effects of ionizing radiation at the organ and tissue level. It discusses how radiation can cause cell death leading to visible changes in organs and tissues. The effects are initially seen as inflammation, edema and hemorrhage, which can progress to fibrosis, atrophy and obstruction with increased dose. Skin is an early responding tissue, with effects ranging from transient erythema to ulceration and necrosis depending on the radiation dose and area exposed.

1. Radiation Pathology
Chapter 6
(Part 1)
This chapter examines
ionizing radiation’s effects
at the biological level of
major organs and organ
systems

2. Cell death and the subsequent cell
loss from the organ/tissue is
the initial event that leads
to visible changes.

3. The visible effects of radiation (at the
level of organs and tissues) are not
unique to radiation. Other causes might
produce the same visible effects,
for example:
Thermal Burns
Chemical injuries
Allergic reactions
Disease processes

4. “Acute” vs. “Chronic” Effects
In this chapter, these terms are not
necessarily being used to describe when a
response occurs in terms of time units after
irradiation. They are being used to describe
different “phases” of response, with different
underlying causes of the response.
Additionally, either term may be describing
effects that can result from either “chronic” or
“acute” radiation exposure conditions.

5. In this sense, “acute” effects refer to the first
(or initial) phase of response [regardless of
whether it occurs after a brief or a long time after
irradiation]; and, the cause is depletion (loss)
of parenchymal cells from the organ/tissue.
•Example (from textbook);
•Esophagitis (acutely responding basal cell loss)
•Pneumonitis (late responding alveolar epithelial cells)
•Note: both are acute effects.

6. “Chronic” Effects [Also Sometimes
Called “Late” Effects] Occur As:
1. A secondary result of progressive
early changes (“Secondary Chronic
Effects”)
2. A result of loss of critical non-
parenchymal cells (“Primary Chronic
Effects”)

7. “Secondary” chronic effects are more
likely to appear sooner and progress
more quickly than “primary”
chronic effects.

8. Healing of Tissue and Organs
 Two basic mechanisms of healing
 Regeneration
 Repair

9. Regeneration: Replacement of
Damaged Cells by Same Type
of Cells.
 Reverses early radiation changes
 Restores organ or tissue to its pre-
irradiated state.

10. Repair: Replacement of
Depleted Original Cells
by Different Cell Types
 Follows catastrophic and irreversible
acute changes
 Does not restore organ to its pre-
irradiated condition.

11. Type of Healing Depends On:
 Magnitude of the radiation dose
 The specific organ or tissue
irradiated.

12. “Regeneration” Mostly Occurs:
1. After low to moderate doses
2. In tissues with whose cells normally
divide (or retain ability to divide)
[regeneration may even be possible
after high doses in such
organs/tissues]

13. “Repair” Mostly Occurs:
1. After high radiation doses
2. In late responding organs/tissues with
slowly dividing or non-dividing cells

14. Timing
 Acutely responding tissues show
response soonest
 Late responding tissues show response
later

15. Factors Influencing Response
 Total dose (normally, dose is relatively
low for diagnostic clinical modalities like
nuclear medicine or radiography)
 Dose rate
 Fractionation
 Volume irradiated

16. Volume Effects
 Partial irradiation may leave enough
undamaged organ to allow continued
sufficient function (and therefore
survival of the individual organism).

17. General Radiation-induced
Changes In Organs
 Acute changes:
 Inflammation
 Edema
 Hemorrhage
 Denuding of surfaces

18. General Radiation-induced
Changes (continued)
 Chronic Changes:
 Fibrosis
 Atrophy
 Ulceration
 Stricture
 Stenosis
 Obstruction

19. Specific Organ System
Response
 “System” means a collection or
grouping of anatomically or
functionally related organs or
tissues.

20. Hemopoietic System
(Also Called “Hematopoietic” System)
 Pertaining to function of blood cells
 Consists of:
 Bone Marrow
 Circulating blood
 Lymph Nodes
 Spleen
 Thymus

21. Bone Marrow Consists Of:
 Parenchymal cells of marrow (stem
cells, material end cells in
circulating blood, and fat cells)
 Stromal connective tissue

22. Two Types of Marrow in
Adults
 “Red” contains stem cells for supplying
mature functional cells. Found in ribs,
ends of long bones, vertebra, sternum,
skull bones
 “Yellow” consists primarily of fat cells
and has few stem cells.

24. Primary Radiation Response
of Marrow Is a Decrease in
Stem Cells.
 Low Doses: Slight decrease with full
recovery in weeks.
 Moderate to high doses: more severe
depletion; longer recovery times;
permanent decrease in stem cell
numbers and increase in fat and
connective tissue (higher doses).

25. All marrow stem cells are radiosensitive but,
relatively speaking, sensitivity varies.
In order or sensitivity (highest to lowest):
1. Erythroblasts (RBC precursors)
2. Myelocytes (some WBC precursors)
3. Megakaryocytes (platelet precursors)

26. Circulating Blood
 Circulating blood cells themselves are
radioresistant (non-dividing, fully
differentiated cells).
 EXCEPTION: mature lymphocyte

28. Changes in numbers of circulating blood cells of
each type will be seen, due to the death of
precursor stem cells (and the sensitivity of the
mature lymphocyte).
 Observed changes dependent on:
 The relative radiosensitivity of the different
precursor stem cells (and of the mature
lymphocyte)
 The lifespan of each circulating blood cell
type (cell turnover)

29. Dose Effects
 Lymphocytes decrease at doses as low
as 10 rad (0.1 Gy).
 Neutrophils at doses of about 50 rad
(0.5 Gy).
 Platelets and RBCs at doses above 50
rad.

30. Timing – Circulating Blood
Cell Numbers Reach A
Minimum:
 Within a few days post-exposure for
lymphocytes
 Within about a week post-exposure for
granulocytes
 Within about 4 weeks post-exposure for
platelets
 Over about 90 to 120 days post-
exposure for RBCs

31. Examples: CBCs Following Whole Body Irradiation

34. Nuc.Med. Administrations Produce
an Observable Change in CBC
Counts?
 Examples:
 Tc-99m sulfur-colloid (8mci, IV injection,
adults)
 Tc-99m mertiatide (MAG3) (20mci, IV
injection, adults)
 Tc-99m sodium pertechnetate (30mci, IV
injection, adults)

38. Sulfur Colloid:
0.36 rad (marrow, normal liver)
[can be 0.63 rad in pt. with advanced liver disease]
0.15 rad total body
[Note: Total body dose approximates dose to
circulating blood cells]
Resulting Red Marrow and Total Body Doses

39. Resulting Red Marrow and
Total Body Dose (Adult)
 Mertiadide:
 0.050 rem/10 mci x 20mci = 0.1 rem
(marrow)
 0.065 rem/10 mci x 20mci = 0.130 rem
(total body)

40. Resulting Red Marrow and
Whole Body Doses (resting)
 Pertechnetate:
 0.57 rad/30 mCi (red marrow)
 0.42 rad/30 mCi (total body)

41. Question: Would changes in circulating blood
cell counts be observable for these diagnostic
studies?
Answer: NO!

42. What About Therapy Doses?
 Typical I-131 thyroid cancer dosage:
100 to 200 mCi (oral administration)

44. Red Marrow and Whole Body
Doses (Euthyroid Patients)
 I-131 Na-lodide, 25% uptake (worst
case)
 Red marrow:
 0.26 Rad/mCi x 100 mCi = 26 Rad
 0.26 Rad/mCi x 200 mCi = 52 Rad
 Total body:
 0.71 Rad/mCi x 100 mCi = 71 Rad
 0.71 Rad/mCi x 200 mCi = 141 Rad

45. Would Changes in CBC Counts Be
Observable for the Preceding I-131
Doses?
 Quite possibly, especially for circulating
mature lymphocytes; possibly for other
white blood cell types (at 200 mCi); but
not for platelets or RBCs.

46. Note
Also:
 The doses indicated are delivered over
the total time it takes to eliminate I-131.
For euthyroid (normally functioning)
thyroid individuals, the effective half-life
(combined radiological and elimination
half-lives) is about 6.5 days.
 This means that………………….

47. About half of the dose is delivered over the
course of 6.5 days, 75% over 13 days, 87.5%
over 19.5 days; and it takes over 6 weeks to deliver
99% of the dose.
Result is reduced effectiveness in reducing
circulating blood counts.
Effective Half-Life (TEFF) = TR x TB
-------------
TR + TB
TR = Radiological Half-Life
T = Biological Elimination Half-Life

48. Also: Euthyroid Patients Should Not
Be Getting Therapy I-131 Doses!!!
 For actual therapies, marrow and total
body doses per millicurie will be lower
because biological elimination is faster
(Teff is about 3.5 days for hyperthyroid
patients; <20 hours [usually closer to 14
hours] for post-thyroidectomy patients).

49. Skin Response to Radiation

51. Skin Structure
 Outer layer (epidermis)
 Connective tissue layer (dermis)
 Subcutaneous layer (fat and connective
tissue)

53. Skin Layers

54. 54
Structure of SkinStructure of Skin
http://legacy.owensboro.kctcs.edu/gcaplan/Default.htm

55. Epidermis Subdivided Into
Layers Made Up Of:
 At the outermost surface (“stratum
corneum”), dead cells
 Mature, non-dividing cells (just under
the stratum corneum)
 Immature, dividing cells at the base of
the epidermis (the “basal” layer)

56. 56
Structure of SkinStructure of Skin
http://legacy.owensboro.kctcs.edu/gcaplan/Default.htm

58. 58
Mean + SD
50 + 22
42 + 12
60 + 19
(µm)
Structure of SkinStructure of Skin
Fingertips: 369 + 112
Fingers: 223 + 93
Ref: ICRP Pub. 59

59. 59
 Total skin area is about 2 m2
.
 Weight of skin is about 2.1 kg.
 Role of skin
 Physical barrier to protect the body from hazards in
the environment
 Cools the body
 Heat retention
 Sensory system for the external environment
 Epidermis – 25% of dermal tissue by dry weight
 Dermis – 75% of dermal tissue by dry weight
Structure of SkinStructure of Skin
Ref: ICRP Pub. 59

60. 60
 Stratum corneum
 15 to 20 layers of dead
cells
 Thicker on palms of
hands and soles of feet.
 Stratum granulosum
 4 to 5 layers of cells
 Become flattened and
lose nucleus
 Become the stratum
corneum
Structure of SkinStructure of Skin
www.biology-online.org

61. 61
 Stratum spinosum
 Variable number of cell
layers
 Stratum germinativum
 Single layer of cells
 Referred to as the basal
layer
 Stratum germinativum and
spinosum are the two
layers which determines
the response to radiation
induced injuries.
Structure of SkinStructure of Skin
www.biology-online.org

62. 62
 The dermis is composed of two layers:
the superficial papillary dermis and the
reticular dermis.
Structure of SkinStructure of Skin
www.biology-online.org

63. 63
 Papillary dermis
 consists of thin collagen
bundles interwoven with
elastic fibers
 Richly vascularized
 Provides thermoregulation
and maintains metabolic
requirements of the basal
layer.
www.biology-online.org
Structure of SkinStructure of Skin

64. 64
 Reticular dermis
 Primary structural
and mechanical
component of skin
 Densely fibrous
 Fewer blood cells
and vessels than
papillary dermis
Structure of SkinStructure of Skin
www.biology-online.org

65. 65
Structure of SkinStructure of Skin
www.biology-online.org

66. 66
Radiation Effects on Skin
 Transient Erythema
 Main Erythema
 Temporary and Permanent Epilation
 Dry desquamation
 Moist desquamation
 Ulceration
 Late Erythema
 Dermal Atrophy
 Telangiectasia
 Necrosis

68. 68
Skin Effects
 Target cells for:
 Cancer effects – 20 to 100 µm
 Deterministic effects – 300 to 500 µm

69. 69
Radiation Effects on Skin
 More than 50% of basal cells are at a depth of 200 µm,
distributed in the shaft of hair follicles.
 Total radiation dose of the basal layer and time between
repeat exposures will determine the severity of the damage.
 The size of the skin area exposed will determine the long-
term effects.
 As the dose increases, the number of viable basal and
clonogenic cells decreases.
 As the number of viable basal cells decreases beyond 50%,
the skin stem cells respond by rapidly producing more basal
cells.
Ref: ICRP Pub. 59

71. •Transit times for cells to go from basal (stem)
cell layer to the surface is 12 to 48 days
•Epidermis is “early responding”
•Dermis is “late responding”

75. Erythema Example:

76. 76
Radiation Effects on Skin
 Electrophysiology and ablation procedure
with a bi-plane fluoroscopy unit
Wagner LK, Radiation injury is a potentially serious complication to
fluoroscopically-guided complex interventions, Biomed Imaging Interv J 2007;
3(2):e22

78. 78
Radiation Effects on Skin
 Dry desquamation
 An atypical
thickening of the
stratus corneum
that may or may
not be observed.

81. Moist Desquamation = Blistering

82. 82
(a) Early erythema and developing moist desquamation in a diabetic woman
caused by a localization radiographic exposure.
Balter S et al. Radiology 2010;254:326-341
©2010 by Radiological Society of North America
Radiation Effects on Skin

83. 83
Radiation Effects on Skin
 Moist desquamation
 Sloughing of the epidermis and exposure
of the dermal layer clinically characterizes
moist desquamation.

87. 87
Radiation Effects on Skin
 Ulceration and
necrosis
 Basal layer and
clonogenic cells
sterilized
 Surrounding skin
not able to send
new cells
 Epidermis
sloughs off
Interact CardioVasc Thorac Surg 2011;12:290-292. doi:10.1510/icvts.2010.247395
© 2011 European Association of Cardio-Thoracic Surgery

88. Case Study 3
Jan04crcpd.org

89. Case Study 2
Image 4:
Jan04crcpd.org

94. Acute Changes After
Moderate to High Dose
Include:
 Inflammation (single dose threshold >
200 rad)
 Erythema (single dose threshold > 200
rad)
 Desquamation (single dose threshold >
800 rad)

95. The dose required to produce erythema is
called (logically), a “Skin Erythema Dose”
(SED)
“SED” was historically used as a “unit” to
quantify radiation exposure to individuals.

96. Chronic Changes:
(Following higher doses or repeated
lower doses over long periods of time)
 Atrophy (thinning) of epidermis
 Fibrosis
 Pigmentation changes
 Ulceration (high doses required)
 Necrosis (high doses required)

99. Effects on Skin: Accessory
Structures
 Hair follicles
 Temporary epilation at 300-600 rad
 Permanent epilation above 600 rad
 Sweat and sebaceous glands
 Atrophy and fibrosis (late responses,
chronic effects) following high doses

100. 100
Radiation Effects on Skin
 Epilation – hair loss
 Cells at the base of
the hair follicle are
affected.
 Detectable hair loss
after 6 weeks
occurs in about
50% of subjects at
5-10 Gy.
LA Times
Balter S et al. Radiology 2010;254:326-341
©2010 by Radiological Society of North America

101. 101
Effect
Time to
Onset
Dose
Threshold
(Gy)
Transient
Erythema
2-24 hrs 2
Main Erythema 10 d 6
Temporary
Epilation
3 wks 3
Permanent
Epilation
3 wks 7
Dry desquamation 4 wks 14
Moist
desquamation
4 wks 18
Ulceration >6wks 24
Late Erythema 8-10wks 15
Telangiectasia >1yr 10
Necrosis >1Yr >12
Radiation Effects on Skin (Wagner, 1994)

102. 102
 Mettler, 2008 – Skin erythema or reddening occurs
if a single dose of 6 to 8 Gray is given and is not
identified till 1 to 2 days after irradiation.
 Balter, 2010 – For most patients, clinically important
skin and hair reactions occur only when the skin
dose is higher than 5 Gy.
 ICRP Pub. 59 – Early erythematous reaction well
documented in man is seen within a few hours after
irradiation of large fields with acute doses of > 2
Gray.
Radiation Effects on Skin

103. Cutaneous Radiation Injury (CRI)
 Visit the following website
 http://www.bt.cdc.gov/radiation/criphysicianfactsheet.asp
 http://www.fda.gov/Radiation-EmittingProducts/RadiationEmittin

104. Course of Cutaneous Radiation
Injury (CRI)
 Visible effects and their severity depend
on magnitude of dose and depth of
radiation penetration (plus size of
irradiated area)
 Visible effects generally do not appear
for hours or days post exposure
 CRI progresses in stages
 CRI can be graded by severity

105. Stages of CRI
 Prodromal
 Latent
 Manifest illness
 Third wave erythema
 Recovery
 Late effects

106. Prodromal Stage
 Early, transient erythema (“first wave”)
possible
 Sensations of heat and itching possible
 Appearance within/duration typically 1-2
days

107. 107
Radiation Effects on Skin
 Early transient erythema
 May be seen within a few hours after
irradiation of large fields (15x20 cm) and
subsides after 24 – 48 hours.
 Response is early phase of inflammation
from increased permeability in the
capillaries.
 The repair of sub-lethal damage to DNA
is completed within 24 hours.
Ref: ICRP Pub. 59

108. Latent Stage
 No apparent injury or symptoms
 Lasts generally <1 to 2 days

109. Manifest Injury Stage
 Main erythema (“second wave”)
 Sense of heat
 Edema possible
 Pigmentation changes
 Appears and lasts days to weeks post
exposure

110. Pigmentation Changes
Manifest Injury Phase, approximately 12 weeks post-exposure, ~8 -10 Gy)

111. Third Wave Erythema
 Doses above ~ 1500 rad
 Late erythema
 Injury to vasculature
 Edema
 Increased pain
 Ulcers, necrosis, atrophy possible
 Appearance ~ 10-16 weeks post-exposure

112. Recovery
 Healing (if possible) occurs
 Days to months post-exposure

113. Late Effects
 Doses above ~ 1000 rad
 Skin atrophy
 Ulcer recurrence
 Telangiectasia (dilation of capillaries or
terminal arteries)
 Skin cancer risk increases

114. Note - As Dose Goes Up:
 Time to symptom appearance shortens.
 Lengths of prodromal and latent periods
shorten.
 Length of manifest injury period
increases.
 Healing takes longer and becomes
more difficult.
 Severity of injuries increases.

122. 6 to 8 weeks
post
fluoroscopy
procedure

123. 16 to 21 weeks
post fluoroscopy
procedure

124. 18 to 21 months
post fluoroscopy
procedure

125. Close-up at 18-21
months

126. Injured area
post skin graft

127. Case Study 2
Image 2:
Jan04crcpd.org

128. Case Study 2
Image 3:
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129. Case Study 2
Image 4:
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130. Case Study 2
Image 5:
Jan04crcpd.org

131. Case Study 4
Jan04crcpd.org

132. Case Study 5
1 2
Jan04crcpd.org

133. Case Study 5
3 4
Jan04crcpd.org

134. Nuclear Medicine Occupational Risks
 The preceding described injuries are deterministic
effects (i.e., have a threshold).
 Normal occupational dose levels are below
deterministic effect thresholds.
 Only a non-deterministic theoretical cancer risk
increase is possible.
 Extended skin contamination by sufficient activity of
higher energy charged particle emitters like I-131
(initial beta skin dose rate on the order of 6.5 rad per
microcurie per cm2
skin deposition) could conceivably
result in deterministic effects.

135. End Chapter 6, Part 1