StatPearls [Internet].
Introduction
Calcium is a vital component that serves an vital position in skeletal mineralization. Greater than 99% of the calcium within the physique is saved in bone as hydroxyapatite. Calcium on this kind offers skeletal power in addition to a reservoir for calcium to be launched into the serum.
In serum, calcium exists in 3 types: protein-bound, ionized (free), and complexed (chelated). Protein-bound calcium, which accounts for 40% of the serum calcium, can’t be utilized by tissues. Albumin and globulin are the first calcium-binding proteins within the serum whereas calmodulin is the first calcium-binding protein within the cell. Chelated calcium, which accounts for 9% of the serum calcium, permits calcium to be absorbed by varied tissues or carried between components of the physique. Serum calcium is commonly chelated into the ionic complexes of calcium phosphate, calcium carbonate, and calcium oxalate. Lastly, free calcium, which makes up 51% of the serum calcium, is utilized by the physique to keep up physiologic features. If the serum calcium focus exceeds the 8.8 to 10.4 mg/dL, then the physique is taken into account in a state of calcium toxicity.[1][2]
Organ Programs Concerned
Calcium homeostasis is maintained by actions of hormones that regulate calcium transport within the intestine, kidneys, and bone. The three main hormones are parathyroid hormone (PTH) 1,25-dihydroxyvitamin D-3 (Vitamin D3), and calcitonin.
The parathyroid glands launch parathyroid hormone (PTH) in response to a lower in serum calcium. PTH acts on the kidneys to extend calcium reabsorption within the ascending loop of Henle, the distal convoluted tubule, and the accumulating duct. The kidney additionally responds to PTH by rising secretion of Vitamin D3, which in flip stimulates calcium absorption by means of the intestine. PTH acts on the bones to stimulate osteoclasts concerned in bone reabsorption and the discharge of free calcium. All of those processes contribute to the rise in serum calcium.
Calcitonin is launched by the thyroid parafollicular cells (C-cells) in response to a rise in serum calcium. Calcitonin acts on the bones to stimulate osteoblasts to deposit calcium in bones. Calcitonin additionally inhibits renal reabsorption of calcium, rising urinary calcium excretion. Lastly, calcitonin additionally inhibits calcium absorption within the intestines. These processes result in a lower in serum calcium.[3][4]
Operate – “calcium homeostasis physiology”
Ionized calcium performs an vital perform in muscle contraction. Skeletal muscle perform is ruled by an motion potential that releases calcium saved within the sarcoplasmic reticulum. This calcium then binds to tropomyosin and permits for the interplay of myosin and actin within the sarcomere, resulting in muscle contraction. In clean muscle, second messenger methods set off the discharge of calcium from the sarcoplasmic reticulum. Moreover, ligand-gated and voltage-gated calcium channels on the graceful muscle membrane permit for extracellular calcium to enter the cell. Calmodulin binds calcium ions and prompts myosin gentle chain kinase to phosphorylase the myosin head, which then binds actin and causes clean muscle contraction. Cardiac muscle is ruled each by motion potentials and extracellular calcium inflow. The motion potential triggers an inward circulation of calcium that potentiates extra calcium launch from the sarcoplasmic reticulum. The contraction of 1 cardiac muscle cell is communicated to adjoining cells by means of intercalated disks, thus permitting for the synchronized contraction of cardiac muscle. It’s by means of this mechanism that calcium is used to stabilize the cardiac cell membrane in opposition to depolarization in extreme hyperkalemia.
Ionized calcium additionally serves many microbiological features, together with activating protein kinases, enzyme phosphorylation, and mediating cell response to hormones akin to epinephrine, glucagon, vasopressin (ADH), secretin, and cholecystokinin.[5][6][7]
Scientific Significance
It is vital for the clinician to concentrate on the causes of hypercelcemia and hypocalcemia as a result of these ailments are doubtlessly harmful and both excessive could also be life-threatening.
Hypercalcemia
Gentle hypercalcemia (lower than 11.5 mg/dL) is normally asymptomatic. Elevations of calcium above 11.5 mg/dL can result in nonspecific signs together with nausea, vomiting, altered psychological standing, headache, confusion, belly or flank ache, constipation, despair, weak point, myalgias, arthralgias, polyuria, polydipsia, and nocturia. Extreme circumstances of hypercalcemia may cause coma. Bodily examination findings embrace hypertension, bradycardia, hyperreflexia, and tongue fasciculations.
The analysis of hypercalcemia is split into PTH-mediated and non-PTH-mediated causes. PTH-mediated hypercalcemia is because of elevated intestinal calcium absorption in response to elevated PTH ranges. Non-PTH-mediated hypercalcemia may be on account of malignancy, granulomatous issues, pharmacologic brokers, endocrinopathies, and genetic causes.
Hypocalcemia
Acute hypocalcemia (lower than 8.5 mg/dL) can result in syncope, congestive coronary heart failure, numbness and tingling, muscle spasms and tetany, bronchospasm and wheezing, laryngospasm and dysphagia, irritability, despair, fatigue, and seizures. Power hypocalcemia can result in coarse hair, brittle nails, psoriasis, dry pores and skin, pruritus, poor dentition, and cataracts. The most typical bodily examination findings embrace neural hyperexcitability, psychological disturbances, and cardiac arrhythmias. The Chvostek and Trousseau indicators are indicative of hypocalcemic states.
Sepsis and septic shock may cause hypocalcemia on account of an unknown mechanism; sufferers with coexisting sepsis and hypocalcemia have greater mortality charges. A radical treatment historical past ought to be obtained to rule out hypocalcemia brought on by drugs akin to cinacalcet, cisplatin, bisphosphonates, anticonvulsants, and denosumab.[8]
Analysis
The analysis of hypocalcemia is first achieved by measuring serum albumin, which distinguishes true hypocalcemia from factitious hypocalcemia on account of hypoalbuminemia. If albumin is regular, PTH ranges ought to be checked to find out if the hypocalcemia is because of a dysfunction of PTH akin to hypoparathyroidism resulting in fast hypocalcemia referred to as a hungry bone syndrome. If PTH ranges are regular, then magnesium, vitamin D, and phosphate ranges may be checked to find out if calcium ranges are being affected by different electrolyte abnormalities. It’s at all times a good suggestion to test kidney and liver perform to find out an end-organ explanation for hypocalcemia. Equally, an electrocardiogram ought to be ordered to evaluate for the impact of hypocalcemia on the center. Radiography is commonly indicated to find out the etiology of power hypocalcemia on account of issues akin to rickets or osteomalacia.
Laboratory checks to find out the causes of hypercalcemia begin with an albumin stage and ionized calcium to verify the hypercalcemia. As soon as confirmed, PTH ranges ought to be checked to rule out hyperparathyroidism. Renal perform and thyroid stimulating hormone (TSH) can hone in on nephrogenic and endocrine origins of hypercalcemia. At all times contemplate electrolyte abnormalities in magnesium, vitamin D, and phosphate. An electrocardiogram could show a shortened QT interval, T wave flattening or inversion, J waves, or prolongation of the PR and QRS intervals.
The most typical explanation for quickly progressive hypercalcemia is a malignancy, and sufferers ought to be evaluated radiographically for lots within the lung, breast, and kidney and have laboratory research to judge for blood cancers akin to a number of myeloma, lymphoma, and leukemia.
Remedy
The therapy of hypercalcemia or hypocalcemia focuses on correcting the underlying dysfunction, which is normally inflicting a disturbance in calcium homeostasis. In excessive circumstances, calcium supplementation or calciuresis can right for extreme derangements in calcium ranges. For milder circumstances, supportive measures that improve the perform of the parathyroid glands, thyroid glands, kidneys, intestine, and bone will permit the physique to compensate for the surplus or lack of calcium and make the most of inner hormonal regulatory methods to carry the calcium ranges again into homeostasis.
Dietary Use
A balanced weight loss plan consists of 1000 mg of calcium every day. The gut absorbs 200 to 400 mg of this with the remainder excreted within the stool. Any extra calcium absorbed is secreted in urine. Calcium supplementation is frequent in aged people, the place it’s prescribed with Vitamin D dietary supplements to enhance bone mass that’s misplaced with rising age.
Pharmacologic Use
The calcium salts of calcium chloride and calcium gluconate are administered in cases of extreme hyperkalemia to stabilize the membrane potential and forestall extended cardiac muscle depolarization.[9][10]
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