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.

Hormonal upregulation of calcium

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.

Hormonal Down-Regulation of Calcium

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.

The influence of individual hormones on the level of calcium and phosphate in blood

	Vitamin D	Parathyroid hormone	calcitonin
Kidney	↑ reabsorption of Ca 2+ and phosphates	↑ resorption of Ca 2+ and excretion of phosphates, stimulates the production of calcitriol	↑ excretion of Ca 2+ , ↑ excretion of phosphates
Bone	bone mineralization high levels, on the other hand, decalcify	bone resorption (osteoclast activation), calcemia and phosphatemia rise	inhibition of osteoclasts, deposition of Ca 2+ in bones
Intestine	stimulates resorption of Ca 2+ and phosphates	stimulates the production of calcitriol → stimulates the resorption of Ca 2+ and phosphates	-

Cacium & Phosphate metabolism

Calcium Regulation

🔬 See Calcium-Phosphate Metabolism for more detailed Information

Disorders of calcium phosphate metabolism in children

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 ;
  1. phase: ↓ calcium → ↑ parathyroid hormone → normalization of calcium, phosphaturia, stimulation of calcitriol formation → ↑ osteoclast activity → ↑ alkaline phosphatase ;
  2. 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);
  3. 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.

Links

Related Articles

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