IPLab:Lab 12:Radiation Fibrosis
This 60-year-old white female had developed retraction of her left nipple six years earlier, at which time breast carcinoma was found. A radical mastectomyA radical mastectomy involves removal of the breast, underlying pectoralis muscles, and axillary lymph nodes. was performed. Examination of the surgical specimens showed metastases in regional lymph nodes and local irradiation was thus administered. Two years later, carcinoma of the right breast was found. Following a modified mastectomy, more irradiation was given. A year later the patient developed recurrences for which chemotherapy (cytoxan and adriamycin) was given. After a two year period without problems, the patient developed decreased exercise tolerance, dyspnea on exertion, shortness of breathShortness of breath is a common clinical manifestation of heart failure., paroxysmal nocturnal dyspnea, and orthopnea increasing in severity over 10 days. Chest examination revealed decreased breath sounds with dullness over the left base. Chest x-ray showed a globose cardiac silhouette and left pleural effusion. A pericardiectomyA pericardiectomy is a surgical procedure in which the pericardial sac is opened, a piece is removed, and the sac is left open. was done because of suspected cardiac tamponadeCardiac tamponade is compression of the heart by an acute accumulation of fluid within the pericardium.; however, the patient died soon after the operation.
There was metastatic carcinoma in the pericardium, chest wall, diaphragm, both lungs, and mediastinal lymph nodes. Severe nonobstructive cardiomyopathy, probably secondary to adriamycin, was found. Areas of pleural thickening with adhesions and interstitial fibrosis were found involving the anterior aspect of both lungs.
The lungs are extremely vascular; thus, the radiation changes seen in the vasculature can have a profound effect on the lungs. During the immediate post-irradiation period, endothelial cell swelling and vacuolization can be seen in the alveolar capillaries. The increased vascular permeability may lead to marked pulmonary congestionPulmonary congestion is the engorgement of pulmonary vessels with blood. The increased pressure caused by this engorgement leads to transudation of fluid through the capillary walls and into the alveolar and interstitial spaces. and edema and the other changes similar to those encountered in adult respiratory distress syndromeRespiratory distress syndrome (or hyaline membrane disease) is a common complication of prematurity, though it can also be seen in term births. The syndrome results from the functional immaturity of the neonatal lung. The syndrome usually presents within one hour of birth and is initially exhibited clinically by rapid respirations, grunting, and substernal retractions..
Long-term pulmonary consequences of radiation injury include fibrosis of the alveolar walls as well as the vascular changes seen in the previous case (vessel narrowing). The respiratory dysfunction due to the combined alveolar wall fibrosis and thickening as well as the poor perfusion due to the vascular lesions can severely inhibit pulmonary function. This radiation pneumonitis creates a profound alveolocapillary block.
- What are the vascular changes seen in radiation injury and what are the consequences of these changes?
Vascular changes, which are dose/rate dependent, are prominent in all irradiated tissues.
Endothelial cells are not specifically radiosensitive but with high exposure vascular changes can occur. There is endothelial swelling and vacuolation or even death of the endothelial cells which can then lead to secondary thrombosis or hemorrhage.
At later time points, intimal hyperplasia and fibrosis occurs which results in thickening of the vessel wall and narrowing of the vessel lumen. These vascular changes can lead to poor blood flow to the tissues.
Radiation can lead to alterations in the mitotic process resulting in cells that have abnormal mitotic figures. These changes can lead to death of the cell.
Subtle genetic injuries, such as DNA strand breaks, are responsible for translocations and deletions. These changes lead to the mutagenic, teratogenic, and carcinogenic potentials of ionizing radiation that become evident many years after the radiation exposure. During this long time interval, sequential mitotic divisions are occurring that will ultimately lead to these untoward consequences. This phenomenon is known as radiation "latency."
- eMedicine Medical Library: Interstitial (Nonidiopathic) Pulmonary Fibrosis
- Merck Manual: Radiation Exposure and Contamination
- White P. Evaluation of pulmonary infiltrates in critically ill patients with cancer and marrow transplant. Crit Care Clin 2001 Jul;17(3):647-70.