Metastatic Calcification

In contrast to dystrophic calcification, which occurs in injured tissues, metastatic calcification occurs in normal tis­sues as the result of increased serum calcium levels (hyper-calcemia). Almost any condition that increases the serum calcium level can lead to calcification in inappropriate sites, such as the lung, renal tubules, and blood vessels. The major causes of hypercalcemia are hyperparathyroidism, either primary or secondary to phosphate retention in renal fail­ure; increased mobilization of calcium from bone, as in Paget disease, cancer with metastatic bone lesions, or im­mobilization; and vitamin D intoxication.

In summary, cells adapt to changes in their environment and in their work demands by changing their size, number, and characteristics. These adaptive changes are consistent with the needs of the cell and occur in response to an appropriate stim­ulus. The changes are usually reversed after the stimulus has been withdrawn.

When confronted with a decrease in work demands or ad­verse environmental conditions, cells atrophy or reduce their

5-4 Calcific aortic stenosis. Large deposits of calcium salts are evident in the cusps and free margins of the thickened aortic valve as viewed from above. (From Rubin E., Farber J.L. [1999]. Pathology [3rd ed., p. 28]. Philadelphia: Lippincott-Raven)

size and revert to a lower and more efficient level of function­ing. Hypertrophy results from an increase in work demands and is characterized by an increase in tissue size brought about by an increase in cell size and functional components in the cell. An increase in the number of cells in an organ or tis­sue that is still capable of mitotic division is called hyperplasia. Metaplasia occurs in response to chronic irritation and repre­sents the substitution of cells of a type that are better able to survive under circumstances in which a more fragile cell type might succumb. Dysplasia is characterized by deranged cell growth of a specific tissue that results in cells that vary in size, shape, and appearance. It is a precursor of cancer.

Under some circumstances, cells may accumulate abnormal amounts of various substances. If the accumulation reflects a correctable systemic disorder, such as the hyperbilirubinemia that causes jaundice, the accumulation is reversible. If the dis­order cannot be corrected, as often occurs in many inborn er­rors of metabolism, the cells become overloaded, causing cell injury and death.

Pathologic calcification involves the abnormal tissue de­position of calcium salts. Dystrophic calcification occurs in dead or dying tissue. Although the presence of dystrophic cal­cification may only indicate the presence of previous cell in­jury, it is also a frequent cause of organ dysfunction (e.g., when it affects the heart valves). Metastatic calcification occurs in normal tissues as the result of elevated serum calcium levels. Almost any condition that increases the serum calcium level can lead to calcification in inappropriate sites such as the lung, renal tubules, and blood vessels.