Physiology and Causes of Imbalance
Calcium absorption takes place in the duodenum and small intestine. This process requires bile and fatty acids, as well as a specific carrier protein in the epithelium. In the blood, the element circulates in free (ionized) and bound forms. Shifts in its concentration lead to severe systemic disorders.
Hypocalcemia occurs in endocrine disorders (hypoparathyroidism, Conn syndrome), renal failure, increased calcium demand (pregnancy, lactation), or alkalosis (gastric from vomiting or respiratory from hyperventilation). Clinically, it manifests as tetanic seizures, bronchospasm, and laryngospasm.
Hypercalcemia is most commonly associated with parathyroid hormone (PTH) excess. Several types of hyperparathyroidism are distinguished:
- Primary: Due to an adenoma or hyperplasia of the parathyroid glands (manifests as osteitis fibrosa cystica / Recklinghausen disease of bone).
- Secondary: A compensatory response to prolonged hypocalcemia (in rickets, malabsorption, chronic renal failure).
- Tertiary: A consequence of long-term hemodialysis.
Hypercalcemia is also caused by paraneoplastic syndromes (when cancer cells, such as in squamous cell lung carcinoma, secrete PTH-related protein [PTHrP]), bone destruction from metastases, thyrotoxicosis, corticosteroid excess, vitamin $D_3$ hypervitaminosis, and prolonged immobilization. Calcium excess causes dyspepsia, and a sharp spike leads to a hypercalcemic crisis with severe psychiatric disorders up to coma.
Dystrophic Calcification
In this type of calcinosis, blood calcium levels remain normal. Salts are deposited locally—exclusively in areas of necrosis or sclerosis. Typical examples include calcified lesions (petrificates) in foci of caseous necrosis in tuberculosis, calcification of atherosclerotic plaques, and heart valve involvement during aging or rheumatic diseases.
Pathogenesis includes two phases:
- Initiation (nucleation). Can occur intracellularly (in mitochondria of dead cells) or extracellularly. Extracellular initiation occurs in membrane-bound vesicles where calcium binds to acidic phospholipids, and microcrystals form under the action of phosphatases.
- Propagation (growth). Calcium phosphate microcrystals (in the form of hydroxyapatite) increase in size. This process is accelerated by collagen and regulated by non-collagenous matrix proteins: osteopontin, osteonectin, and osteocalcin.
Metastatic Calcification
Develops against the background of marked hypercalcemia. Unlike the dystrophic variant, salts precipitate in entirely normal tissues. Causes include hyperparathyroidism, vitamin D intoxication, sarcoidosis, Addison disease, leukemias, and multiple myeloma.
Calcium deposits are most commonly localized in the interstitium of the gastric mucosa, kidneys, lungs, myocardium, and arteries. The organ selection is not random: during their physiological function, these tissues lose acid. Local alkalinization of the environment predisposes to the precipitation of calcium salts. Typically, these deposits do not cause organ dysfunction, except for massive renal involvement (nephrocalcinosis), which leads to renal failure.
Special Forms: Cutaneous Calcinosis and Calciphylaxis
- Cutaneous calcinosis presents as focal dystrophic calcification characteristic of systemic connective tissue diseases (scleroderma, systemic lupus erythematosus). Nodules form under the skin of the hands and feet. Over time, they become inflamed, ulcerate, and form fistulas discharging a paste-like mass.
- Calciphylaxis (calcific uremic arteriolopathy) is a rare, life-threatening condition occurring predominantly in chronic renal failure. Notably, blood calcium and phosphate levels are not the deciding factors here. Calcification of the media of small and medium-sized arteries occurs with the development of proliferative endovasculitis and thrombosis. This leads to acute ischemia and painful skin necroses. The prognosis is often unfavorable due to the risk of gangrene and sepsis.