Week 12

• Calcium is an essential element that serves an important role in skeletal mineralization and is one of the most carefully controlled variables in the body.
• Small changes in the extracellular fluid calcium have major effects on neuromuscular functions.
• More than 99% of the calcium in the body is stored in bone as hydroxyapatite.
• In circulation, Ca ++ is approximately 40% protein-bound (albumin or globulin) and approximately 9% chelated (phosphate, carbonate, oxalate).
• Within the cells, calcium is controlled by storage in different cellular compartments (ER, mitochondria, lysosomes) and binding to proteins.
• Hypercalcaemia can be caused by primary hyperparathyroidism, hypercalcaemia of malignancy, and familiar hypocalciuric hypercalcaemia.
• Hypocalcaemia can be caused by PTH problems, vitamin D problems, and hungry bone syndrome.
• Calcium is necessary for bone remodeling and plays a role in PTH, vitamin D, and FGF23 regulation.
• Once PTH is normalised, bones will reabsorb the missing Ca, causing hypocalcaemia.
• Hungry bone syndrome is a common complication of parathyroid surgery seen in 13 – 30% of cases.
• These missense mutations decrease FGF23's susceptibility to proteolytic cleavage, inhibit FGF23 degradation, and elevate FGF23 circulating levels, leading to hypophosphatemia.
• Hypercalcaemia can be caused by primary hyperparathyroidism, hypercalcaemia of malignancy, and familial hypocalciuric hypercalcaemia.
• Hypocalcaemia can be caused by PTH problems, vitamin D problems, and hungry bone syndrome.
• Prolonged hypocalcaemia following parathyroidectomy can occur due to bones exposed to prolonged high PTH, leading to prolonged osteoclasts activation.
• Bone remodelling and turnover repair micro-damage, maintain mineral homeostasis, and ensure mechanical competence by modifying the micro-architecture.
• Bone remodelling follows a sequence of events: activation, recruitment of osteoclasts to begin resorption, degradation and removal of bone, and reversal, and formation of new bone by osteoblasts.
• Osteoprotegerin (OPG) is produced by osteoblasts.
• In women in menopause, there is an acceleration of bone resorption due to the loss of oestrogen.
• The main functions of PTH are calcium homeostasis, vitamin D activation, phosphate homeostasis, and more.
• During adolescence, bone formation is greater than bone resorption, leading to an increase in skeletal mass.
• Chief cells produce and secrete parathyroid hormone (PTH).
• There are two parathyroid cell types: Chief Cells and Oxyphil cells.
• In young adults, there is a perfect balance between resorption and bone formation, resulting in a constant skeletal mass.
• RANKL is the primary mediator of osteoclast differentiation and activation.
• RANK and RANKL are produced by the osteoblasts.
• The parathyroid glands are four endocrine glands located on the back of the thyroid gland.
• Osteoclasts resorb mineralized bone matrix in a manner that mobilises skeletal calcium.
• Osteoblasts then refill the resorption spaces with a collagenous matrix that incorporates extracellular calcium as it mineralizes and gains biomechanical stiffness.
• Hypocalcaemia can be caused by renal disease, where if there is renal failure, calcidiol is not converted to calcitriol, therefore, no reabsorption of calcium via the intestine, and there is retention of phosphate which causes calcium-phosphate salt precipitation.
• FGF23 was discovered in 2000 due to an inherited pathology called Autosomal Dominant Hypophosphatemic Rickets (ADHR), which is a rare hypophosphatemia disorder with incomplete penetrance.
• Vitamin D deficiency can lead to chronic hypocalcaemia and hyperparathyroidism.
• In ADHR there are missense mutations in FGF23 gene.
• The aetiology of Vitamin D deficiency includes Low exposure to ultraviolet light, Diet with poor vitamin D intake, Low maternal vitamin D concentrations, Some anti-epileptic drugs, Patient with small bowel disease, where absorption is reduced.
• Several preparations of vitamin D are available, including Vitamin D3 (cholecalciferol) and Vitamin D food fortification (e.g. milk).
• Calcium, bones, and hormones involve Calcium, Bone remodelling, PTH, Vitamin D, FGF23, Hypercalcaemia, Primary hyperparathyroidism, Hypercalcaemia of malignancy, Familiar hypocalciuric hypercalcaemia, Hypocalcaemia, PTH problems, Vitamin D problems, Hungry bone syndrome.
• Vitamin D deficiency causes Hypocalcaemia, Osteomalacia or Rickets in children, Osteoporosis in adults.
• Primary Hyperparathyroidism is the most common cause of hypercalcaemia and is usually benign adenoma in one of the parathyroid glands.
• Hypocalcaemia can be caused by PTH problems, vitamin D problems, and hungry bone syndrome.
• Hypercalcaemia can be caused by primary hyperparathyroidism, hypercalcaemia of malignancy, and familial hypocalciuric hypercalcaemia.
• Hyperparathyroidism can cause psychiatric symptoms such as depression and hallucination.