Chempath - Calcium Flashcards
Calcium normal range
2.2-2.6mmol/L
% of body calcium in the serum
1%
Parathyroid Hormone - actions
PTH increases in response to decrease in serum Ca2+
1) Increases tubular 1 a hydroxylation of VitD –> essentially increases via D activation
2) Mobilises calcium from bone
3) Increases renal calcium absorption and phosphate excretion
Vit D/Calcitriol - actions
Increases calcium and phosphate absorption from the gut
Bone remodelling - stimulates bone formation and mineralisation by activating osteoclasts
Sarcoidosis
Ectopic 1aOHase in lung tissue.
Get summer hypercalcaemia –> usually vit D def in winter but when sun comes out they get more resulting in hypercalcaemia
Osteoporosis
Osteoporosis –> lose bone mass/density but the bone structure is normal, normal feature of aging
Normal blood bone profile. DEXA scan (of hip and lumbar spine) will show reduced bone density. T- score = no of SDs away from young healthy pop. Z-score = age-matched.
Osteroporosis = Z-score <2.5
Vit D Deficiency (Osteomalacia/Rickets)
Defective bone mineralisation –> demineralised bone.
RFs: lack of sun exposure, dark skin, dietary, malabsorption. Anti-convulsants (induce vit D breakdown). Chappatis (physic acid –> vit D breakdown)
Causes secondary hyperparathyroidism picture (differentiate from renal osteodystrophy by vit D levels).
BONE PROFILE:
Decreased: vit D, Ca, P
Increased PTH, Alk phos
Paget’s disease
Increased bone turnover.
Unknown cause (thought to be caused by a virus), v few new pts with paget’s, causes v active osteoblasts and clasts in 1/2/3 bones –> pain
Rx - Bisphosphonates
Bone profile normal except increased ALP.
Primary Hyperparathyroidism
Increased PTH - commonest cause of hypercalcaemia. 80% caused by parathyroid adenoma. Other causes include hyperplasia and sarcoma. Assoc w/ MEN1. Women > men.
BONE PROFILE Increased Ca Decreased P Increased/N PTH (NORMAL PTH IN CONTEXT OF HYPERCALCAEMIA IS ABNORMAL - SHOULD BE SUPPRESSED) Increased/N ALP Normal Vit D
Secondary Hyperparathyroidism
Renal osteodystrophy: Renal failure –> can’t activate vit D –> can’t excrete phosphate & bones can’t form properly
Vit D deficiency.
BONE PROFILE Reduced/normal Ca Increased P Increased PTH Increased ALP Normal vit D
Tertiary Hyperparathyroidism
Autonomous PTH secretion post renal transplant.
BONE PROFILE Increased Ca Decreased P Increased PTH Increased/normal ALP Normal vit D
Hungry bone syndrome
Removal of PTH by thyroidectomy results in sudden increase in bone mineralisation and sequestration of Ca2+, resulting in dangerously low Ca2+ levels.
Vit D Deficiency - Clinical Features
Osteomalacia: Bone & muscle pain Increased fracture risk Biochem – low Ca2+ & P, raised ALP Looser’s zones - pseudo fractures
Rickets: Bowed legs Costochondral swelling Widened epiphyses at the wrists Myopathy
Osteoporosis- RFs
(early) menopause, failure to achieve peak bone bass (e.g. childhood illness)
Lifestyle: sedentary, EtOH, smoking, low BMI/nutritional
Endocrine: hyperprolactinaemia, thyrotoxicosis, Cushings
Drugs: steroids
Others eg genetic, prolonged intercurrent illness
Osteoporosis - Rx
Lifestyle:
Weight-bearing exercise
Stop smoking
Reduce EtOH
Drugs:
Vitamin D(+/-Ca)
Bisphosphonates (eg alendronate) –↓ bone resorption
Teriparatide (PTH derivative) – anabolic –> artificial PTH
Strontium – anabolic + anti-resorptive
(Oestrogens – HRT)
SERMs eg raloxifene –> agonist at bone receptor, antagonist at breast receptor
Hypercalcaemia - Clinical Features
Stones (renal) - haematuria
Bones (pain) - Histo: brown tumours and multi-nucleate giant cells. Skeletal changes: lytic lesions, osteitis fibrosa et cystica, hand X-ray may show radial aspen cystic changes.
Groans (psych) - confusion, seizures, coma
Moans (abdo pain) - pancreatitis, peptic ulcer disease
Polyuria & polydipsia - nephrogenic DI
Muscle weakness
Sign: band keratopathy (corneal disease)
Hypercalcaemia
FLUIDS - Correct dehydration - 0.9% normal saline
Bisphosphonates (if cause known to be cancer, otherwise avoid)
Correct cause
Causes of Hypercamcaemia
PTH suppressed: Malignancy is the main one. Sarcoidosis (non-renal 1α hydroxylation) Thyrotoxicosis (thyroxine -> bone resorption) Hypoadrenalism (renal Ca2+ transport) Thiazide diuretics (renal Ca2+ transport) Excess vitamin D (eg sunbeds…) Milk alkali syndrome.
PTH raised/inappropriately normal: primary or secondary hyperparathyroidism
Familial hypocalciuric (/benign) hypercalcaemia (FHH / FBH)
Calcium sensing receptor (CaSR) mutation
Higher “set point” for PTH release -> mild hypercalcaemia
Reduced urine Ca2+
3 Types of Hypercalcaemia in Malignancy
Humoral hypercalcaemia of malignancy (eg small cell lung Ca) - PTHrP –> helps cancer cells to invade bone. Only present in foetus(to steal ca from mother) and malignancy.
Bone metastases (eg breast Ca) - Local bone osteolysis
Haematological malignancy (eg myeloma) - cytokines
Hypocalcaemia - Clinical Features
Neuro-muscular excitability: CATs go numb
Convulsions
Arrythmias
Tetany
Numbness
+ Trousseau and Chvostek signs
Laryngeal spasm is a potentially fatal complication
Hypocalcaemia - Causes
Non-PTH Driven (PTH increased–> secondary hyperPTH):
Vit D def
CKD (may progress to tertiary hyperPTH)
PTH resistance - pseudohyeperparathyroidism
PTH Driven (low PTH):
Surgical e.g. post thyroidectomy
Auto-immune hypoparathyroidism
Congenital absence of the parathyroids (e.g. DiGeorge syndrome)
Magnesium deficiency - linked to PTH regulation
