Hall 20 - Clinical Response of Normal Tissues Flashcards
What are key determinants of tissue/organ response to radiation?
- Inherent radiosensitivity of the individual cells
- Kinetics of the cells in the tissue (turnover/mutation rates, lifespan)
How are functional subunits of tissues defined?
Structurally defined = independent, only need one clonogen (nephrons, liver lobules)
Structurally undefined = clonogens can migrate between subunits (skin)
What affects serial organ tissue response?
High-dose regions and hot spots (Dmax)
Serial = integrity of each subunit is critical to organ function, little functional reserve (spinal cord)
What affects parallel organ tissue response?
Volume irradiated (or mean dose)
Parallel = sensitive to whole volume RT but large reserve capacity (kidney, lung)
What are the most radiosensitive parenchymal cells (per Casarett’s classification)?
Vegetative intermitotic cells
- Classic stem cells
- No differentiation
- Ex) hematopoietic stem cells, intestinal crypt cells, spermatogonia
- Vegetative intermitotic cells
- Differentiating intermitotic cells
- Reverting postmitotic cells
- Fixed postmitotic cells
What are the least radiosensitive parenchymal cells (per Casarett’s classification)?
Fixed postmitotic cells
- Do not divide
- Highly differentiated
- Ex) nerve, muscle
What cell type breaks the rules of Casarett tissue sensitivity?
Lymphocytes
Highly differentiated and usually do not divide but very radiosensitive
How does dose affect H-type populations?
Hierarchical model = cells compartmentalized into strict hierarchy from stem cells to maturing partially differentiated cells to functional fully differentiated non-dividing cells
Higher doses have a LONGER time to recovery
Ex) bone marrow, skin, gut epithelium
How dose dose affect F-type populations?
Flexible model = cells rarely divide under normal conditions but all damaged cells can be triggered to divide
Higher doses manifest sooner but have FASTER recovery (due to higher RT dose stimulating cells to divide)
Ex) liver, glandular organs
What is the mechanism of late tissue damage?
Acute inflammatory response followed by an aberrant chronic inflammatory/wound healing process
Vascular (endothelial) and parenchymal cell dysfunction and cell loss
Overproduction of particular cytokines and growth factors result in fibrosis/necrosis
What pro-inflammatory cytokines respond to tissue damage?
IL-1, IL-6, IL-8, TNF-alpha
*IL-10 is anti-inflammatory
What causes fibrosis after radiation?
TGF-beta
Promotes EMT, fibroblast recruitment, extracellular matrix
What blood elements decline first after bone marrow RT?
Lymphocytes < granulocytes < platelets < RBCs
What is the late effect of radiation on bone marrow?
Lipid infiltration (adipose) - not fibrosis
What are symptoms of radiation induced liver disease (RILD)?
Anicteric ascites, hepatomegaly, isolated alk phos elevation
What are symptoms of radiation induced liver veno-occlusive disease (VOD)?
Fibrosis of central and sublobular veins > congested sinusoids, atrophy of liver plates, hemosiderin in Kupffer cells (from phagocytosis of leaked RBCs)
Why does radiation induced heart disease happen?
Vascular endothelial damage
» inflammation > arteriosclerosis and microvascular dysfunction
What results from early radiation injury to nervous tissue?
White matter demyelination (glial injury)
May be reversible
What results from late radiation injury to nervous tissue?
Gray matter vascular damage
*Tolerance of spinal cord shows little dependence on overall treatment time but depends critically on dose per fraction (low alpha-beta ratio)
How much radiation is required to irreversibly inhibit growing cartilage?
20 Gy
(growth slowed at 10 Gy)
What total body dose inhibits the immune response against a new antigen?
3.4-4.5 Gy
- Macrophages most resistant (up to 100 Gy)
- Plasma cells very resistant (60-90 Gy) - B cell immunity often remains intact
- Granulocytes resistant up to 50 Gy
- NK cells up to 20 Gy
- T cells sensitive at 1-5 Gy but if primed can be more resistant to >10 Gy
- B cells are very sensitive <1 Gy
