08. Parathyroid and Calcium

• cancellous bone is found on the ends of bones, this has a huge surface area and is strong under compression
• calcification occurs with formation of hydroxyapatite crystals incorporates within collagen matrix to form bone
• bone is not a static tissue, is constantly built up and lost
• osteoclasts = bone resorption, releases calcium from bone
• osteoblasts = bone formation, producing collagen and promoting mineralisation of bone
• bone lining cells = involved in initiation of bone remodedlling
• osteocytes = mechanosensing, orchestrates microfracture repair

  • form spiderweb within bone
• calcium is essential for bone and mineral deposition, muscle contraction, blood clotting and nerve impulse transmission
• hypocalcaemia = muscle spasms, cramps, numbness and seizures
• vitamin D and PTH act on kidneys and intestines
• calcitonin acts on the bones
• parathyroid glands regulate calcium and phosphate levels - small glands within the thyroid gland

  • secrete PTH in response to low calcium and high phosphate
  • this increases calcium reabsorption in the distal tubule and intestines (via vitamin D activation)
  • stimulates osteoclasts
  • decreases phosphate reabsorption
• PTH is a peptide hormone binding to a GPCR

  • negative feedback mechanism due to serum calcaemia and vitamin D receptor
  • increases phosphate absorption slightly but increases phosphate excretion more
• vitamin D is a steroid hormone essential in calcium absorption in the intestines

  • vitamin D or calcium deficiency = osteomalacia, soft bones that are more bendy and prone to fractures
  • UV radiation from sunlight catalyzes the conversion of a cholesterol precursor in the skin to vitamin D3 (inactive)
  • D3 gets catalysed in the liver to a different compound which is activated in the kidney (catalysed by an enzyme upregulated by PTH)
• calcitonin is produced by c cells in the parafollicular gland, released in response to hypercalcaemia

  • inhibits bone resorption
• primary hyperparathyroidism:

  • tumour of parathyroid -> high PTH
  • lethargy, thirst, constipation, hypertension, depression
  • parathyroid gland gets removed and PTH and TH are replaced
• secondary hyperparathyroidism:

  • kidney failure -> can't reabsorb calcium and produce vitamin D
  • overactivation of parathyroid
• rickets = vitamin D/calcium deficiency in a growing skeleton, caused by diet/lack of sunlight

  • osteomalacia = adult version
• osteoporosis:

  • normal mineralisation but loss of bone volume
  • losing more bone than gaining
  • increased fracture risk
  • disease of ageing - prominent after menopause as osteoclasts are switched off by oestrogen
  • oestrogen replacement therapy