calcium roles and regulation

• Calcium


  Roles & regulation (PTH, calcitonin & Vit D)

  
• Calcium


  • Excitability of nerves
  • Control of Ca2+ channels (both voltage and ligand gated)
  • Cardiac, skeletal and smooth muscle contractility (excitation-contraction coupling and cross bridge cycling)
  • Neurotransmitter release & hormone secretion (stimulus-secretion coupling)
  • Blood clotting
  • Maintenance of cellular integrity
  • Bone and teeth structure and strength

  
• How free plasma [Ca2+] is controlled


  1. Exchange between fixed and free pools (transfer from bone to plasma)

  2. Absorption/excretion (involving intestines and kidneys)
• Parathyroid hormone (PTH)


  Primary hormone responsible for maintenance of Ca2+ homeostasis
• Parathyroid glands


  • 4 rice grain-sized glands located on the posterior surface of the thyroid
• Calcium sensing receptors


  In the parathyroid gland are exquisitely sensitive to free [Ca2+]

  
• Plasma [Ca2+] decreases


  PTH increases
• PTH actions


  1. Stimulates osteoclasts indirectly by binding to osteoblasts - increases RANKL expression, decreases OPG - increases osteoclast maturation

  2. Enhances transfer of Ca2+ from bone fluid into circulation
• Calcitonin


  Produced by the C cells of the thyroid, protective against hypercalcemia

  
• Calcitonin


  • Decreases the movement of Ca2+ from the labile pool and inhibits osteoclast activity in bones (decreasing bone resorption/dissolution)
  • Decreases reabsorption of both Ca2+ and PO43+ from the kidney tubules - thereby decreases plasma [Ca2+] and [PO43-]

  
• Vitamin D


  Synthesized from cholesterol derivative when exposed to sunlight, must be activated to calcitriol by liver and kidneys before it can exert its effect on intestines

  
• Vitamin D mechanism of action


  Active vitamin D, binds to the VDR, which forms a heterodimer with the retinoid-X receptor. This then binds to hormone response elements on DNA resulting in expression of specific gene products.
• Vitamin D


  • Increases Ca2+ uptake and translocation across intestinal epithelia
• Regulation of plasma [Ca2+]


  • Parathyroid
  • Thyroid
  • Vitamin D

  
• A/Prof Elizabeth Beckett: '[e-mail]'
• Radiographs


  • Showing alveolar bone loss in patient with osteoporosis

  
• Hyperparathyroidism


  Overproduction of PTH leads to hypercalcemia and hypophosphatemia
• Hyperparathyroidism

  • Predominant cause (80%) is adenoma of the parathyroid
  • Bone disease (osteitis fibrosa cystica) – high bone turnover due to increased osteoclast number; bone pain. Osteoporosis
  • Kidney Disease – kidney stones, and loss of normal kidney function
  • CNS dysfunction – stupor/coma, fatigue, depression, difficulty in concentrating, personality changes
• Hyperparathyroidism: '"stones, bones, abdominal groans and psychic moans"'
• Hypoparathyroidism


  Resulting hypocalcemia can cause: Neuromuscular effects – Increased neuromuscular excitability and tetany (severe muscle contractions of the hands and face); Cardiac effects – prolongation of the QT interval, and impaired excitation-contraction coupling; Ophthalmologic effects – cataracts; Dermatologic effects – dry flaky skin and brittle nails
• Hypoparathyroidism


  1. Surgical – removal/destruction of parathyroid glands; failure to secrete PTH

  2. Idiopathic – autoimmune diseases (mostly in girls aged 5-10 yrs). PTH or Vitamin D deficiency or insensitivity

  3. Familial – rare; failure to produce PTH
• Hypoparathyroidism: '"CATS go numb" - Convulsions, Arrhythmias, Tetany and numbness/paresthesias in hands, feet, around mouth and lips'
• Pseudo-hypoparathyroidism


  A heritable disorder characterised by normal PTH levels but insensitivity of the target tissues to PTH. This causes hypocalcaemia.
• Pseudo-hypoparathyroidism


  • Characterised by short stature, round face, short neck and short digits – also termed Albright Hereditary Osteodystrophy
• Figures 4 & 5

  • From: GOMES MF et al, 2002. Oral manifestations of Albright hereditary Osteodystrophy: a case report. Rev. Hosp. Clín. Fac. Med. S. Paulo 57(4):161-166

  
• Vitamin D deficiency


  Generally arises from a combination of three causes: 1. Inadequate sunlight, 2. Inadequate nutrition, 3. Malabsorption of Vitamin D
• Vitamin D deficiency

  • Hereditary forms: Type I - failure to synthesis 1,25(OH)2D, Type II - lack of Vitamin D receptor
• Vitamin D deficiency


  In infancy/childhood chronic hypocalcaemia can lead to rickets - bowing of the legs, protuberant abdomen, poor growth, listless, apathetic and weak. In adults chronic hypocalcaemia can lead to osteomalacia – symptoms include aches and pain particularly in lumbar region, chronic fatigue.
• Calcium deficiency and teeth


  Progressive osteopenia/porosis of jawbone – teeth loosen, gaps develop → periodontal disease, dental caries
• Calcium deficiency and teeth


  • Teeth appear to have a biological priority over bone when calcium is limited. With rickets: Defects in the structure of teeth; holes in the enamel; pitted appearance & yellow discoloration; Delayed formation of teeth; Decreased jaw muscle tone (loss of muscle strength); Muscle cramps or involuntary movement of jaw muscles can result in teeth grinding (bruxism)