Calciumoverload

Calciumoverload refers to a state in which intracellular calcium concentrations rise excessively, surpassing the cell’s buffering and regulatory capacity. Although calcium ions serve as vital signaling molecules, excessive levels trigger pathological processes leading to cell dysfunction and death.

Causes include systemic hypercalcemia from endocrine disorders (hyperparathyroidism), malignancy, or vitamin D intoxication; large influx of calcium across damaged or permeable cell membranes during ischemia, reperfusion, or toxin exposure; and release of calcium from intracellular stores such as the endoplasmic reticulum and mitochondria, amplified by excitotoxic stimuli in neurons and by uncontrolled muscular contraction.

Pathophysiology involves activation of calcium-dependent enzymes (peptidases, phospholipases, endonucleases), disruption of mitochondrial function with ATP depletion, generation of reactive oxygen species, and disruption of cytoskeletal and membrane integrity. The result is impaired energy production, loss of ion homeostasis, edema, and, depending on cell type, necrosis or apoptosis.

Clinical relevance includes conditions where systemic calcium is elevated (hypercalcemia) and tissue injury where local calcium influx contributes to damage, such as myocardial ischemia-reperfusion injury and various forms of neural injury during stroke, traumatic brain injury, or neurodegenerative processes. Intracellular calcium cannot be reliably inferred from serum calcium levels, so diagnosis typically relies on clinical context and, in research settings, intracellular calcium indicators in cells or tissues.

Management focuses on treating underlying causes of calcium overload, correcting electrolyte disturbances, and protecting tissues from calcium-mediated injury; in research and some clinical conditions, strategies aim to limit calcium entry, buffer intracellular calcium, or inhibit calcium-activated enzymes. The concept remains an important framework for understanding secondary injury in a variety of diseases.