1: Calcium Metabolism Flashcards
4 functions of calcium in the body
muscle contraction
action potential
coagulation cascade
pancreatic enzyme release and activation

calcium normal range
2.2 - 2.6 mmol/L
3 forms of serum calcium
normal albumin range
free (ionised) = 50%
- biologically active
protein-bound = 40%
- to albumin
- albumin normal range = 35 - 50 g/L
complexed = 10%
- citrate/phopshate
effect of abnormal albumin levels on serum calcium -> corrected calcium formula
corrected calcium = serum calcium + (0.02 x (40 - serum albumin in g/L))
in low albumin states, the bound calcium is low but free calcium will be normal
blood gas machines can measure ionised/free calcium

calcium homeostasis pathway
hypocalcaemia detected by parathyroid gland
gland releases PTH
PTH:
- increased 1,25 OH Vit D -> increased intestinal Ca absorption: RATE LIMITING STEP
- increased renal Ca resorption
- increased bone Ca resorption
rise in plasma Ca

2 key hormones in in calcium homeostasis
PTH: 84 aa protein, only from parathyroid gland
- liberates Ca from bone
- Stimulates 1a-hydroxylase activity -> production of calcitriol (1,25-dihydroxycholcalciferol)
- stimulates renal phosphate excretion in urine PHOSPHATE TRASHING HORMONE
Vit D: steroid hormone, derived from cholesterol
- in 2 forms (both active, straight to liver if taken by mouth)
- D2 (ergocalciferol) = from plants (extra double bond)
- D3 (cholecalciferol) = produced when 7-dehydrocholesterol -> cholecalciferol. This reaction takes place when UV light hits skin. Vit D synthesised in skin.
Vitamin D synthesis

UV light on skin = 7-dehydrocholesterol -> cholecalciferol (vit D3)
25-hydroxylase in liver = cholecalciferol (vit D3) -> 25-hydroxycholecalciferol (inactive, stored THIS IS WHAT IS MEASURED)
1a hydroxylase (activated by PTH) in kidneys = 25-hydroxycholecalciferol -> 1,25-dihydroxycholecalciferol (calcitriol)

Relationship with sarcoidosis
1a-hydroxylase can be expressed in lung cells of sarcoid tissue, hence why some patients with sarcoidosis present with features of hypercalcaemia. However, this is seasonal (patients tend to develop hypercalcaemia in summer months due to increased sun exposure (-> more vitamin D activation).
3 roles of activated 1,25(OH)2 Vitamin D
other effects
what is vit D deficiency associated with
Increased intestinal Ca2+ absorption
Increased intestinal phosphate absorption
Critical for bone formation
Other effects:
- vit D receptor controls many genes (e.g. cell proliferation, immune system)
- associations between vit D deficiency and cancer, autoimmune disease, metabolic disease etc.
Vit D deficiency associated with poverty and poor diet. Cancer and metabolic disease prevalent amongst pooror popualtions (perhaps associative rather than causative)
Role vit D in bone
ALP
activates osteoclasts
- liberate Ca from bone -> holes in bone
osteoblasts activated to patch up these holes
- ALP by-product of osteoblast activity and riseds when bone resportion is stimulated by vitamin D or PTH = states amount of BONE TURNOVER
ALP is raised (bone causes) = 3
post-fracture
abnormal PTH secretion
Children when growing
Bone is a reservoir of (3)
calcium
phosphate
magnesium (important in PTH synthesis as deficiency in magnesium -> hypocalcaemia)
Role of the skeleton
Structural framework
Strong, yet relatively light weight
Mobile
Protects vital organs
Capable of orderly growth and remodelling
Metabolic role in calcium homeostasis
Main reservoir of calcium, phosphate and magnesium
NB: bold is endocrine view non-bold is orthopaedic view
overview of metabolic bone diseases (5)

Vitmain D deficiency = which conditions, pathophysiology
impaired absorption of BOTH calcium and phosphate across intestinal wall
defective bone mineralisation
osteomalacia (adults), rickets (children)
Risk factors for vitamin D deficiency (4)
Lack of sunlight
Dark skin (less sunlight can reach cells that produce vitamin D)
Dietary changes
Gut malabsorption (e.g. coeliac disease)
Clinical features of vitmain D deficiency: osteomalacia vs rickets

Osteomalacia: most common cause
SECONDARY HYPERPARATHYROIDISM -> vit D deficiency
low calcium, high PTH, high ALP = as a result of vit D deficiency
leads to osteoclast activtion to liberate calcium form the bone
whilst this normalises plasma calcium levels, it leads to weak and demineralised bone
Other causes of osteomalacia aka vit D deficiency (4)
mx for one of them
Renal failure
- lack of 1a-hydroxylase -> unable to activate vit D
- Mx: calcitriol analogues (e.g. alphacalcidiol)
- this drug is pre-activated and does not require kidney action
Anticonvulsants (carbamazepine): induce vit D breakdown
- newer drugs do not
- children started on these drugs are at an increased risk of developing rickets
Lack of sunlight
Chappatis (phytic acid)
- phytic acid chelates vit D in the gut and reduces absorption
osteoporosis definition
what is it accelerated by
normal wear and tear old age condition, occur more often as people live longer
reduction in bone density, normal mineralisation and normal biochemistry
bone mass gradually decreases after the age of around 20 years
accelerated by:
- low testosterone
- oestrogen
- Cushing’s syndrome
- Hyperthyroidism
osteoporosis presentation
cause of pathological fracture
- neck of femur (NOF)
- vertebral
- wrist (Colle’s)
- hip
ASYMPTOMATIC BEFORE FRACTURE (fractive is first symptom)
- by this point it is too late
Causes of osteoporosis
Age-related decline in bone mass (failure to attain peak bone mass -> fracture earlier on)
Normally from disuse of bones
Endocrine:
- Hyperthyroidisim + Cushing’s syndrome = increased catabolism
- Acromegaly = testosterone deficiency -> osteoporosis
- Early menopause
More rapid bone loss during adulthood, due to:
- sedentary lifestyle
- alcohol, smoking
- low BMI
- hyperprolactinaemia
- thyrotoxicosis
- Cushing’s syndrome
- steroids (young and male)
- prolonged recurrent illness
- CKD

osteoporosis diagnosis
vs osteopenia
DEXA scan
- often hip or lumbar spine
- T-score: number of standard deviations from the mean of a young healthy population (useful to determine fracture risk)
- Z-score: number of standard deviations from the age-matched control (useful to identify accelerated bone loss in younger patients)
Osteoporosis = T-score < -2.5 (more than 2.5 standard deviations below the mean)
Osteopenia = T-score between -1 and -2.5
Lifestyle tx of osteoporosis
weight-bearing exercise
stop smoking
reduce alcohol consumption













