Calcium and Phosphate Metabolism

Made up of calcium hydroxyapatite

Calcium is transported in the blood bound to proteins (mainly albumin), as free ionised calcium, or complexed with small molecules.

Bone mineralisation; Coagulation; Nerve function; Neurotransmitter release; Muscle contraction; Hormone secretion

ATP production; Bone mineralisation; Phosphorylation; Cell membranes

Intracellular

Increasing calcium absorption in the gut; Increasing calcium reabsorption in the kidneys; Releasing calcium from bone via osteoclast activity

Bound to proteins such as albumin and other globulins; Ionised calcium - free calcium in the blood; Complexed calcium - calcium joined to other small molecules such as phosphate

Decrease in H+ makes albumin more negatively charged so it binds more calcium; This decreases the amount of free calcium; Leads to reduced ionised calcium (which can cause symptoms of hypocalcaemia)

Acidosis increases H+ so there is more competition for albumin binding sites; Less albumin binds to calcium so there is more free ionised calcium; Leads to increased ionised calcium

Calcium that is free in the blood and not bound to a protein or any other molecules

Activates calcium-sensing receptors, reducing PTH secretion

Constipation; Pancreatitis; Renal dysfunction - renal failure, polyuria, polydipsia, kidney stones

FHH; Granulomatous diseases such as sarcoidosis; Malignancy - PTHrP; Thiazide diuretics; Primary hyperparathyroidism

Hypocalcaemia

Phase 0 - rapid depolarisation due to sodium influx; Phase 1 - initial repolarisation due to potassium efflux; Phase 2 - plateau due to calcium influx balanced by potassium efflux; Phase 3 - repolarisation due to potassium efflux; Phase 4 - resting membrane potential

PTH; Vitamin D - calcitriol; FGF23; Calcitonin

Phase 2

Bone

Parathyroid gland

Inferior - third pharyngeal pouch; Superior - fourth pharyngeal pouch

Parathyroid cells with an unclear function; They can absorb sestamibi and are used in parathyroid imaging

Chief cells secrete parathyroid hormone

PTH secretion decreases

Calcium-sensing receptor

Stimulates PTH secretion; Phosphate binds to calcium, reducing the amount of free calcium in the blood

Impairs PTH synthesis and secretion because magnesium is needed for normal PTH regulation

Reduces PTH secretion; Increases breakdown of stored PTH; Suppresses transcription of the PTH gene

G protein-coupled receptor

An inherited condition usually caused by an inactivating mutation of the calcium-sensing receptor, leading to reduced urinary calcium excretion and mild hypercalcaemia

Vitamin D - Calcitriol

Increases calcium reabsorption but decreases phosphate reabsorption

Stimulates osteoclast activity indirectly via RANKL activation

Increases calcium absorption in the intestine; Increases phosphate absorption in the intestine

Proximal convoluted tubule

Proximal convoluted tubule and distal convoluted tubule

Increases blood calcium levels because it increases calcium reabsorption by inhibiting the sodium-chloride cotransporter in the distal convoluted tubule

Increases RANKL production

PTH

Ergocalciferol

Cholecalciferol

1-alpha-hydroxylase; Found in the kidneys

In the nucleus of the cell

Calcitriol increases FGF23 production, which inhibits 1-alpha-hydroxylase and reduces further calcitriol production. Vitamin D production is mainly regulated by negative feedback.

Suppresses PTH secretion; Reduces expression of type I collagen; Increases phosphate absorption; Increases levels of RANKL

Rickets; Osteomalacia

Defective mineralisation of bone in adults

Calcitonin; FGF23; PTHrP

Osteocytes and osteoblasts

Lowers blood phosphate levels by decreasing phosphate reabsorption in the kidneys and decreasing 1-alpha-hydroxylase activity; Decreases calcium and phosphate absorption in the gut; Prevents excess mineralisation

Increased phosphate levels; Calcitriol

Decreases blood calcium levels by inhibiting osteoclast activity

Parafollicular cells

Excessive secretion of PTH by the parathyroid glands, usually due to a parathyroid adenoma, causing hypercalcaemia

Muscle cramps and tetany; Paraesthesia; Seizures; Prolonged QT interval and cardiac arrhythmias; Laryngospasm

Hypoparathyroidism; Vitamin D deficiency; Chronic kidney disease; Hypomagnesaemia; Acute pancreatitis; Massive blood transfusion

Oral supplements; IV calcium gluconate for severe or symptomatic hypocalcaemia

Muscle weakness; Respiratory failure; Cardiac dysfunction; Osteomalacia

Refeeding syndrome; Hyperparathyroidism; FGF23 excess; Fanconi syndrome

Often asymptomatic; Hypocalcaemia; Muscle cramps and tetany; Soft tissue and vascular calcification

Chronic kidney disease; Renal failure; Hypoparathyroidism; Vitamin D excess; Rhabdomyolysis