Parenchymal cells perform the functional role of an organ. Casarett classified parenchymal cells into four categories:
- Type I Cells are cells actively dividing that do not differentiate. They are the most sensitive to radiation, and are often the cause of radiation induced early effects. They include the stem cells of most rapid turnover tissues:
- Basal cells of the skin epithelium
- Intestinal crypt cells
- Bone marrow stem cells
- Type II Cells are dividing cells that are in the process of differentiating. They include the offspring of Type I cells that do not continue as stem cells. These cells may divide several times, creating numerous offspring that eventually become terminally differentiated cells. Examples include:
- Skin cells of the stratum spinosum
- Type III Cells are cells that are functional but have the capacity to re-enter the cell cycle if necessary. They typically have a long life span and show late effects following radiation exposure. Examples include:
- Liver cells
- Type IV Cells are postmitotic and are usually unable to re-enter the cell cycle. These cells are typically very radioresistant as they do not ever enter mitosis. Examples include:
- Cardiac muscle
- Lymphocytes are a special case. Unlike other type IV cells, they are extremely radiosensitive and often die apoptotic death following radiation exposure.
Connective Tissue Cells
The endothelium is the specialised layer of squamous cells that line the inner aspect of arterial, venous and lymphatic vessels. They have a relatively long lifespan and divide rarely. When exposed to radiation, they may be involved in early releases of cytokines that attract immune cells to the region. After 3 - 6 months, there may be death of endothelial cells as they try to divide. This leads to abnormal proliferation of the surviving endothelial cells and several of the hallmarks of late effects:
- Abnormal proliferation may cause obstruction and destruction of vessels.
- Denudation of vessel walls may lead to haemorrhage, thrombosis or obliteration of vessels
- Surviving capillaries tend to become larger and dilated, leading to telangiectasia
- Loss of vessels leads to hypoxia of the supplied tissue
Fibrocytes are found in most tissue outside of the CNS. They are involved in constructing the extracellular matrix. When exposed to radiotherapy, some fibrocytes may terminally differentiate into fibroblasts and produce large quantities of collagen. This can cause increased firmness and less elasticity of the involved tissue, typically referred to as radiation fibrosis. Fibrocytes may also be stimulated to transform in response to hypoxia (often caused by concurrent damage to endothelial cells) and inflammation (which may occur as a result of ongoing cell death due to radiotherapy and hypoxia), causing a positive feedback loop and further fibrosis and damage to the affected organ.