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EM Part 1 > Radiobio part 3 > Flashcards

Radiobio part 3 Flashcards

1
Q

Acute tissue damage

A
  • <90 days, early responding tissues
  • cell death after irradiation occurs mostly after cells attempt to divide
  • Therefore mainly effect ‘hierarchical tissues’ in high turnover compartments e.g GI tract, bone marrow, skin.
  • Have a rapidly proliferating stem cell compartment
  • high A/B

Processes:
- inflammatory paracrine mediators released
- Differentiated cells undergo depletion
- Vascular endothelium - increased permeability, - erythema, oedema
Mediated by cytokines - ILa & IL 6 that attract immune cells & TNF-a that promotes apoptosis
- Stem cell replenishment
- varies with life span of involved cells (eg. GI tract = days, bladder = months) - NOT dose dependent
- consequential late effect - if intensive fractionation schedules deplete stem cell population below levels needed for tissue restoration.

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2
Q

Late Tissue Damage

A
  • > 90 days, late responding tissues
  • Mainly affects flexible tissues (cells that rarely divide but can be induced to by damage)
  • Pathogenesis more complex - is progressive and irreversible
  • Doesn’t have a rapidly dividing stem cell compartment.
  • Clinical manifestation due to clinical depletion of functional cells
  • Late effects are progressive
  • Latent time & progression rate are dose dependent - decreased time to functional loss, increased endothelial cell damage, increased capillary loss, increased fibroblast differentiation.
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3
Q

Examples of early & late toxicity for:
Skin
CNS
Lung
GI
GU
Haem
H&N

A

SKIN
- E = vascular - erythema (vasodilation), oedema. Epidermal cells - desquamation.
- L = vascular - telangiectasis. Epidermal cells - atrophy & necrosis. Stromal cells - Fibrosis

CNS
E = nausea, vomiting, fatigue
L = necrosis

Lung. E= pneumoninit. L = fibrosis
GI. E = mucositis, diarrhoea. L = stricture, proctitis, telangiectasia.

GU. E = subfertility. L = infertile.

Haem. E = myelosuppression. L = aplasia

H&N. E = mucositis, oedema, erythema. L = xerostomia, loss of taste.

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4
Q

Normal Tissue Tolerance

A

= max dose in 2Gy fractions that a tissue can be given with an acceptable complication rate (usually 5%) for a given complication.

TD5/5 = max tolerance dose yielding risks of complication of 5% over 5 years.
TD50/5 = max tolerated dose yielding a complication rate of 50% over 5 years

TD = tolerance dose

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5
Q

EUD

A

= equivalent uniform dose
EUD assumes that any 2 dose distributions are equivalent if they cause the same biological effect.

  • considers dose heterogeneity.
  • reflects overall cell kill (hence TCP) produced by non-uniform dose distribution and is therefore potentially a better indicator of biological outcome than assessments based on the simple average of the physical dose.
  • It shows that even a small cold spot can play a disproportionate role in reducing overall treatment effectiveness.
  • BUT does not inherently allow for the possibility that clonogenic cells themselves may be non uniformly distributed.
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6
Q

TD5/5 Brain & endopoint

A

45 Gy

Infarction, necrosis.

  • most important injuries to brain post IR are late syndromes (months to years).
  • 1st year - changes nvolve white matter
  • beyond first 6 months - grey matter changes & vascular changes
  • Radionecrosis occurs 1-2 years post IR and accompanied by cognitive defects
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7
Q

TD5/5 Spinal cord

A

20cm = 45Gy
5-10cm - 50Gy

Simular to brain in terms of latency, tolerance dose and histology.
1. Early = l’hermittes sign - can be reversible. appearance does not predict future toxicity
2.Late = demyelination & necrosis of white matter (6-18 months later), vasculopathy = 1-4 years.

Tolerance depends on dose per fraction, need at least 6 hours between doses
SERIAL organ

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8
Q

TD5/5 Lens

A

10 GY
cataract
lacriam gland - dry eyes
optic nerve/chiasm - blindenss (50gy)

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9
Q

TD5/5 Lung

A

17.5 Gy
V20 = 30%

One of the msot sensitive of late responding organs.
Pneumonitis (2-6 months), fibrosis (months to years)
V sensitive to fractionation (a/b =3)

FSUs are arranged in parrallel. IR to lungs is only dose limiting if large volumes are irradiated and if remaining lung cannot provide adequate function.

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10
Q

Liver TD5/5

A

30Gy
V30 = 40%

3rd most sensitive late responding organ.
Acute & chronic hepatitis.
Parenchyma = parallel FSU, bile duct/hepatic artery can be thought of as serial.

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11
Q

Heart TD5/5

A

V40 = 50%
40GY

Acute pericarditis - most common, seldom occurs in 1st year. Varies in severity.
Cardiomyopathy (at 10 years)
Increased risk of IHD

a/b is low (1) so fractionation results in a substantial sparing effect

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12
Q

Oesophagus TD5/5

A

55Gy

oesophagitis 10-12 days - resolves soon after treatment.
Late effects related to muscle layer - perforation/stricture

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13
Q

Stomach TD5/5

A

50Gy

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14
Q

Small bowel TD5/5

A

40Gy
obstruction/perforation

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15
Q

Colon TD 5/5

A

45 Gy
obstruction/perforation

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16
Q

Rectum TD5/5

A

60Gy
Proctitis/fistula

17
Q

Bladder TD5/5

A

75GY
cystitis at 20-30GY
Late effect = fibrosis
Shrinkage & ulceration at 50Gy
Urethral stricture at 60Gy

18
Q

Urethra TD5/5

A

70 Gy

19
Q

Kidney TD5/5

A

23 Gy
2nd mot sensitive late responding organ
V20 = 20%

In contrast to most tissues, increasing treatment time does not allow higher doses to be tolerated.
Parrallel FSUs.

Nephropathy with arterial hypertension & anaemia.
Part of one or even both kidneys can receive a much higher dose.

20
Q

Femoral head TD 5/5

A

52 Gy
avascular necrosis

21
Q

Testes TD 5/5

A

Sterilisation 1 Gy
(spermatocytes - temporary sterilisation at LD, permanent at HD)

Hormone failure 30Gy
(Leydig cells can tolerate much higher doses - secrete testosterone)

therefore see sterilisation with minimal effect on libido

22
Q

Ovary Td5/5

A

2Gy - sterilisation
(different to testis fixed number from birth - EXTREMELY RADIOSENSITIVE & IMMEDIATE)

20GY - menopause. (hormonal secretion is assocaited with follicular maturation, sterilisation by radiation leads to loss of libido & menopause).

23
Q

Marrow td5/5

A

2.5 Gy
Aplasia, pancytopenia

24
Q

Skin TD5/5

A

2gy - temporary erythema (1 day) - vasodilation

7gy - permanent epilation (3 days)

14 Gy - desquamation (4 weeks) - depletion of basal cell layer

  • telangiectaisa (> year - late developing vascular injury)
  • ulceration/necrosis
  • Epidermis (outer layer) - site of early radiation reactions
  • Dermis (deeper layer) - actively dividing stem cells which then takes 14 days to migrate to epidermis & desquamate. Site of late reactions.
25
Q

Parotid TD 5/5

A

Radiation damage primarily occurs to serous acinar cells.
Occurs early and cells die by apoptosis. Mucous cells are more radioresistant.

Demonstrates little response to change in does/fraction.

Quantec 1 gland dose <20GY.

26
Q

Deterministic Effects

A

increases in severity with increasing dose
only above a threshold dose because effects arise in a population of cells e.g. lens/cataract

27
Q

Stochastic effects

A

probability of occurrence increased with higher dose BUT severity is not dose related.

No threshold dose as these effects arise in single cells eg. cancer induction/genetic effects.

28
Q

Total Body Irradiation

A

Unplanned whole body exposure to radiation - acute radiation syndrome leading to death.

LD 50/60 = the dose that leads to death within 60 days of 50% of the population

= 3.5Gy without medical care, 7Gy with medical care

Time course and severity of clinical features are a function of overall body volume irradiated, inhomogeneity of dose exposure, absorbed dose, dose rate & particle type.

29
Q

TBI

A

Doses of 1Gy or more = prodromal reaction - fatigue, anorexia, vomiting.

Doses of 2.5 GY or more = HPO syndrome - death within 30 days

Doses of 10 Gy or more = GI syndrome. N&V, bloody diarrhoea (depopulation of epithelial lining due to sterilisation of crypt cells).

Very high doses= cerebovascular syndrome - death within 24-48 hours

30
Q

Haematopoietic Syndrome

A

BM stem cells are very radiosensitive with little sparing from reduced dose rate or fractionating the dose. Transit time for each component varies hence the differences in time to drop.
- Macrophages very radioresistant.
- Granulocytes (neuts, basophilis, eosinophils) = temporary increased (mobilisation from reserve pool) to rapid fall by day 7
- Lymphocytes (b then t) 0 drop around day 10
- Platelets at 20 days
Hb drops last

1ory cause of death from infection & haemorrhage

31
Q

4 phases to radiation sickness

A
  1. Prodromal
    - initial phase appears within 1-3 days, N&V, headache, fever, skin erythema. Duration of phase is inversely proportional to dose. V high doses there is no latent phase.Onset of vomiting is also related to absorbed dose and can be seen within a few minutes after a high exposure.
  2. Latent Phase - characterised by improvement in symptoms and apparent cure. Pts look & feel well but lab tests become abnormal with granulopenia/lymphopenia
    Also dose dependent and may last hours to weeks.
  3. Manifest illness phase
    - specific signs & symptoms of each syndrome appear depending on the dose.
    - HPO develops at 1-8Gy (can see changes in blood counts at <1Gy)
    - GI syndrome 5-20Gy - small bowel paneth cells are most sensitive
    - CVS syndrome at >20 Gy
  4. Final phase - recovery or death depending on the adsorbed dose, dose rate & heterogeneity of exposure.

EM Part 1 (7 decks)

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