Pathophysiology

Around 99% of calcium is contained in the bones, while the other 1% resides in the extracellular fluid. Of this extracellular calcium, approximately 40% is bound to albumin and the remainder is in the ionized, physiologically active form. Normal calcium levels are maintained by three primary factors: parathyroid hormone, 1,25-dihydroxyvitamin D, and calcitonin. Parathyroid hormone increases renal tubular calcium resorption and promotes bone resorption. The active form of vitamin D, 1,25-dihydroxyvitamin D, regulates absorption of calcium from the GI tract. Calciton-in serves as an inhibitory factor by suppressing osteoclast activity and stimulating calcium deposition into the bones.

The delicate balance maintained by these factors is altered in patients with cancer by two principal mechanisms: tumor production of humoral factors that alter calcium metabolism (humoral hypercalcemia) and by local osteolytic activity from bone meta-

stases. Humoral hypercalcemia causes around 80% of all hypercalcemia cases and is primarily mediated by systemic secretion of parathyroid hormone-related protein (PTHrP). This protein mimics the action of endogenous parathyroid hormone on bones. Local osteolytic activity causes 20% to 30% of hypercalcemia cases, although local osteolytic activity may also have a humoral component. Local production of various factors directly stimulates osteoclastic bone resorption which releases growth factors and cytokines (i.e., transforming growth factor-^) that are necessary for tumor growth. Thus, these metastatic tumors perpetuate their own growth through this mechanism. Calcium is also released by the osteolytic activity, resulting in hypercalcemia (Fig. 99-4). A third and less common mechanism is production of 1,25-dihydroxyvitamin D by tumor cells (usually lymphoma) which increases GI absorption of calcium and enhances osteoclastic bone resorption.

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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