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Hypercalcaemia, also spelled hypercalcemia, is a high calcium (Ca2+) level in the blood serum. The normal range is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L) with levels greater than 2.6 mmol/L defined as hypercalcemia. Those with a mild increase that has developed slowly typically have no symptoms. In those with greater levels or rapid onset, symptoms may include abdominal pain, bone pain, confusion, depression, weakness, kidney stones, or an abnormal heart rhythm including cardiac arrest.
Most cases are due to primary hyperparathyroidism or cancer. Other causes include sarcoidosis, tuberculosis, Paget disease, multiple endocrine neoplasia (MEN), vitamin D toxicity, familial hypocalciuric hypercalcaemia, and certain medications such as lithium and hydrochlorothiazide. Diagnosis should generally include either a corrected calcium or ionized calcium level and be confirmed after a week. Specific changes, such as a shortened QT interval, may be seen on an electrocardiogram (ECG).
The neuromuscular symptoms of hypercalcemia are caused by a negative bathmotropic effect due to the increased interaction of calcium with sodium channels. Since calcium blocks sodium channels and inhibits depolarization of nerve and muscle fibers, increased calcium raises the threshold for depolarization. This results in diminished deep tendon reflexes (hyporeflexia), and skeletal muscle weakness. There is a general mnemonic for remembering the effects of hypercalcaemia: "Stones, Bones, Groans, Thrones and Psychiatric Overtones"
Stones (kidney or biliary)
Bones (bone pain)
Groans (abdominal pain, nausea and vomiting)
Thrones (polyuria) resulting in dehydration due to nephrogenic diabetes insipidus from nephrocalcinosis
Psychiatric overtones (Depression 30–40%, anxiety, cognitive dysfunction, insomnia, coma)
Other symptoms include cardiac arrhythmias (especially in those taking digoxin), fatigue, nausea, vomiting (emesis), anorexia, abdominal pain, constipation, & paralytic ileus. If renal impairment occurs as a result, manifestations can include polyuria, nocturia, and polydipsia. Psychiatric manifestation can include emotional instability, confusion, delirium, psychosis, & stupor. Limbus sign seen in eye due to hypercalcemia.
Hypercalcemia can result in an increase in heart rate and a positive inotropic effect (increase in contractility).
Symptoms are more common at high calcium blood values (12.0 mg/dL or 3 mmol/l). Severe hypercalcaemia (above 15–16 mg/dL or 3.75–4 mmol/l) is considered a medical emergency: at these levels, coma and cardiac arrest can result. The high levels of calcium ions decrease the neuron membrane permeability to sodium ions, thus decreasing excitability, which leads to hypotonicity of smooth and striated muscle. This explains the fatigue, muscle weakness, low tone and sluggish reflexes in muscle groups. The sluggish nerves also explain drowsiness, confusion, hallucinations, stupor and / or coma. In the gut this causes constipation. Hypocalcaemia causes the opposite by the same mechanism.
hydration, increasing salt intake, and forced diuresis.
hydration is needed because many patients are dehydrated due to vomiting or kidney defects in concentrating urine.
increased salt intake also can increase body fluid volume as well as increasing urine sodium excretion, which further increases urinary potassium excretion.
after rehydration, a loop diuretic such as furosemide can be given to permit continued large volume intravenous salt and water replacement while minimizing the risk of blood volume overload and pulmonary oedema. In addition, loop diuretics tend to depress calcium reabsorption by the kidney thereby helping to lower blood calcium levels
can usually decrease serum calcium by 1–3 mg/dL within 24 hours
caution must be taken to prevent potassium or magnesium depletion
bisphosphonates are pyrophosphate analogues with high affinity for bone, especially areas of high bone-turnover.
they are taken up by osteoclasts and inhibit osteoclastic bone resorption
current available drugs include (in order of potency): (1st gen) etidronate, (2nd gen) tiludronate, IV pamidronate, alendronate (3rd gen) zoledronate and risedronate