Disorders of Calcium And Phosphate Metabolism

Disorders of calcium phosphate metabolism are accompanied by abnormal levels of calcium and/or phosphorus and include disorders in the absorption, transport, storage and utilization of these minerals.

Calcium phosphate metabolism
99% of calcium is stored in mineralized bone mass and 1% is part of the body's internal environment in the form of calcium ions. Calcemia is mainly regulated by vitamin D and parathyroid hormone, and to a lesser extent by calcitonin.

The exogenous source of vitamin D is mainly fish, and the endogenous source is 7-dehydrocholesterol, which is transformed in the skin by the effect of UV radiation into cholecalciferol (vitamin D 3 ) → in the liver to calcidiol (25(OH)D 3 ) → in the kidneys to calcitriol (1 ,25(OH) 2 D 3 ), the most effective metabolite.

Parathyroid hormone (PTH) is a peptide hormone produced by the parathyroid glands. Synthesis and secretion is controlled by a simple feedback loop – during hypocalcemia, the release of PTH into the blood increases.

Calcitonin (thyrocalcitonin) is a peptide hormone produced by the parafollicular (C-cells) of the thyroid gland; the concentration of calcitonin increases with hypercalcemia, so it has a hypocalcemic effect. See Calcium-Phosphate Metabolism for more details

Hypocalcemia

 * serum calcium < 2.0 mmol/l.


 * Clinical manifestations:


 * acute : apnea in newborns, tetany, convulsions (resemble epilepsy), muscle spasms, laryngospasm, dysarthria from spasm of the masseters, carpopedal spasms, prolonged QT interval on ECG
 * latent tetany: Chvostk's sign (a tap on the face in front of the jaw joint at the site of the nervus facialis leads to a twitch in the face), Trousseau's sign (an inflated tonometer cuff on the arm causes the obstetric hand sign within a few minutes)
 * chronic : hair and nail growth disorders, possibly deposition of calcium in soft tissues → cataract, basal ganglia calcification, nephrocalcinosis, subcutaneous calcification in places of hematomas and minor trauma.


 * Differential diagnosis


 * reduced secretion or reduced effects of PTH : hypoparathyroidism ( DiGeorge syndrome, activating mutation of the calcium sensing receptor, autoimmune destruction – autoimmune polyglandular syndrome type I , iatrogenic damage during thyroid surgery), pseudohypoparathyroidism (target organ resistance to PTH), hypomagnesemia ;
 * vitamin D deficiency or dysfunction : vitamin D deficiency rickets, vitamin D-dependent rickets type I and II;
 * hyperphosphatemia : chronic renal insufficiency, cytostatic treatment, excessive supply of phosphates;
 * malabsorption syndrome.

Hypercalcemia

 * serum calcium > 2.6 mmol/l.


 * Clinical manifestations


 * reduced motility of the gastrointestinal tract, constipation, loss of appetite, nausea, vomiting,
 * neurological symptoms: muscle weakness, somnolence, confusion, hallucinations, coma,
 * cardiovascular symptoms: hypertension, tachycardia, ECG changes.


 * Differential diagnosis


 * hyperparathyroidism : adenoma of the parathyroid gland (the most common cause of hypercalcemia), inactivating mutation of the calcium sensing receptor;
 * increased resorption of calcium by the intestine and/or kidneys : phosphate deficiency (premature children), treatment with thiazide diuretics, vitamin D, A intoxication, sarcoidosis ;
 * increased resorption of calcium from bone : thyrotoxicosis, immobilization, malignancies, bone metastases, paraneoplastic secretion of PTH or PTH-related protein.

Rickets

 * bone mineralization disorder due to lack of vitamin D or calcium or disorders of their metabolism:
 * vitamin D deficiency rickets (children) / osteomalacia (adults)
 * it arises when there is a lack of vitamin D and/or calcium;
 * risk groups: fully breastfed dark-skinned children whose parents do not provide vitamin D, dark skin, strict vegetarian (vegan) diet, malabsorption syndromes with impaired fat absorption, cystic fibrosis, other pancreatic exocrine disorders, bile secretion disorders, untreated celiac disease ;
 * phase: ↓ calcium → ↑ parathyroid hormone → normalization of calcium, phosphaturia, stimulation of calcitriol formation → ↑ osteoclast activity → ↑ alkaline phosphatase ;
 * phase: bone resorption (parathyroid hormone+calcitriol) → classic clinical symptoms of rickets and typical X-ray picture of the skeleton (craniotabes, delayed closure of the large fontanelle, caput quadratum, rachitic rosary, Harrison's furrow, pectus carinatum, genua valga, genua vara, delayed eruption of milk dentition, enamel defects, tooth decay);
 * phase: depletion of calcitriol reserves, without which PTH cannot break down bone → ↓ calcium despite pronounced hyperparathyroidism → clinical symptoms of hypocalcemia (spasmophilia, tetany, laryngospasm, convulsions) and vitamin D deficiency (frequent and more serious ongoing respiratory infections);
 * laboratory findings: Ca 2+ at the lower limit, then decreased, phosphate increased → normal → decreased, ALP high, parathyroid hormone increased, 25-OH-vitamin D decreased;
 * treatment: vitamin D (cholecaciferol im eventual. po), calcium; with manifest tetany 10% calcium gluconicum iv
 * vitamin D-dependent rickets type I – AR hereditary defect of renal 25-OH-D α-hydroxylase → blocked calcitriol synthesis → clinical manifestations of rickets in the 2nd trimester → lifelong calcitriol substitution;
 * vitamin D-dependent rickets type II – AR hereditary receptor defect that causes resistance of target organs (gut and skeleton) to calcitriol → lifelong substitution of very high doses of calcitriol, difficult to treat;
 * familial hypophosphatemic vitamin D-resistant rickets – X-linked disorder of reabsorption of phosphates in the proximal tubules of the kidneys → high losses of phosphates in the urine (“phosphate diabetes”) → manifestations after the start of walking: deformation of the lower limbs, growth retardation → substitution of phosphates and calcitriol.

See Rickets Page for more information

Osteoporosis

 * systemic metabolic disease of the skeleton, characterized by a disorder of the mechanical resistance of the bone, increasing the risk of fractures;
 * diagnostic criteria in children: clinically significant history of fractures and abnormal densitometry (two-photon X-ray absorptiometry, peripheral quantitative computed tomography);
 * primary osteoporosis (rare in children): osteogenesis imperfecta, idiopathic juvenile osteoporosis, etc.;
 * secondary osteoporosis in oncological diseases ( leukemia treated with chemotherapy), systemic diseases with high-dose corticosteroid treatment ( JIA ), endogenous overproduction of cortisol ( Cushing's syndrome, Cushing's disease ) and neuromuscular diseases ( spina bifida , muscular dystrophy), anorexia nervosa , untreated celiac disease or immobilization;
 * therapy: bisphosphonates;
 * prevention: adequate physical activity and nutrition, vitamin D and calcium.

See the Osteoporosis page for more detailed information

Familial disorders of calcium phosphate metabolism

 * Familial hypocalciuric hypercalcemia (FHH) – mutation in the calcium receptor,
 * neonatal hyperparathyroidism,
 * hypercalciuric hypocalcemia,
 * hereditary hypophosphatemic rickets.

Related Articles

 * Osteoporosis • Osteogenesis imperfecta
 * Rickets
 * Indicators of Bone Remodeling
 * Metabolic bone disease s

Reference

 * 1) LEBL, J, J JANDA and P POHUNEK, et al. Clinical Pediatrics. 1st edition. Galén, 2012. 698 pp. pp. 189-196.  ISBN 978-80-7262-772-1.
 * 2) ↑Jump up to:a b SILBERNAGL, Stefan and Agamemnon DESPOPOULOS. Atlas of Human Physiology: 6th Edition, Completely Revised and Expanded. 3rd edition. Prague: Grada, 2004. pp. 290-293.  ISBN 80-247-0630-X.
 * 3) ↑ ŽOFKOVÁ, I.  Familial hypercalcemia and hypophosphatemia and their importance in the differential diagnosis of calcium-phosphate metabolism disorders  [online]. ©2010. [feeling. 2011-04-17]. < https://www.prolekare.cz/casopysi/vnitrni-lekarstvi >.

Category: Pathologic Physiology