ChemPath - Calcium handling and metabolism Flashcards
What are the forms of calcium in the body
bone - 99%
Blood/serum - 1%
Free/ionised (50%) - biologically active (important for nerves)
Protein-bound (40%) - bound to albumin
Complexe (10%) - citrate/phosphate
What us calcium needed for
Nerve function
Muscle function
Bone formation and maintenance
What is corrected calcium and how is it calculated
corrected calcium = serum Ca + 0.02(40-serum albumin)
When albumin conc. falls, the calcium is released and so the free calcium level remains the same despite an appearance of low calcium. If albumin is abnormal, this means that the Ca appears abnormal, but the corrected calcium would be NORMAL.
If corrected calcium is still abnormal - problem is not albumin
What is the role of PTH
84aa protein released from the thyroid
- Bone resorption for Ca release (osteoclast stimulation)
- Renal resorption of Ca + phosphate excretion
- Renal 1 a-hydroxylase activation (vit D synthesis)
- Intestinal Ca absorption
Describe the vitamin D’s role in calcium homeostasis
- 7-dehydrocholesterol in the skin is converted to cholecalciferol/vitamin D3 on exposure to UVB light
- Vitamin D from UVB (D3) or the diet (D2) is converted to 25-OH-D3 in the liver via 25 hydroxylase
- Renal 1 𝛼-hydroxylase is stimulated by PTH
- Renal 1 𝛼-hydroxylase converts 25-OH-D3 to calcitriol/1,25(OH)2D3
- Increased Ca reabsorption in the kidney and gut. Increased bone calcium maintenance
- -ve feedback on PTH
What is the difference between ergocalciferol and cholecalciferol
ergo = vit D2, chole = vit D3
Vit D2 - plant product (therefore vegan), Sourced from the diet
vit D3 - synthesised in the skin
Both are active, there is the difference of a double bond between them
What is the role of calcitriol (1,25 dihydroxy-vitamin D)
Active form of vit D
1. Intestinal Ca AND phosphate absorption
2. Renal Ca absorption
3. Bone Ca maintenance
Why might people with sarcoidosis get hypercalcaemia
1-alpha hydroxylase can be expressed unregulated in lung cells of sarcoid tissue → increases renal and intestinal abs. of Ca
Give examples of metabolic bone disease
Osteoporosis (bone normal but weak)
Osteomalacia (vit D deficiency)
Paget’s disease
Parathyroid bone disease
Renal osteodyrstophy
Describe vit D deficiency (what it causes), adults v children, % prevalence)
Defective bone mineralisation
Children - ricketts
Adults - osteomalacia
> 50% of adults have insufficient vit D, and 16% have severe deficiency in Winter and Spring
What are the risk factors for vit D deficiency
Lack of sunlight exposure
Dark skin
Dietary
Malabsorption
Pregnancy
breastfeeding from a mother with vit D deficiency
What are the causes of osteomalacia
Vitamin D deficiency
Renal failure
Anticonvulsants e.g. phenytoin (induces breakdown of active vit D)
Lack of sunlight
Phytic acid (found in Chappati flour)
What are the clinical features of osteomalacia and ricketts
Ricketts
* Bowed legs
* Costochondral swelling (lumps on the chest)
* Widened epiphyses at the wrists
* Myopathy (waddling gait)
Low calcium and phosphate
Osteomalacia
* Bone & muscle pain
* Increased fracture risk
* Looser’s zones (Pseudofractures that will not break until under pressure/trauma)
What are the biochemical features of osteomalacia and Ricketts
High PTH
Low calcium and phosphate
Raised ALP
Describe osteoporosis
Loss of bone mass, while the residual bone structure remains NORMAL
What are the causes of osteoporosis
Lifestyle: Immobility/sedentary, smoking, EtOH, low BMI
Lack of oestrogen (e.g. menopause, anorexia nervosa)
Hyperthyroidism / thyrotoxicosis
Cushing’s syndrome or steroid use
Hyperprolactinaemia (inhibits FSH/LH/Oe)
Failure to attain peak bone mass due to childhood illness or early menopause increases risk of EARLIER fracture
What are the clinical features of osteoporosis
Initial: fracture
- Neck of femur (NOF)
- vertebral
- Wrist (colle’s)
Otherwise asymptomatic
What are the diagnostic markers of osteoporosis
NORMAL biochemistry
Dual energy x-ray absorptiometry (DEXA) of femoral neck and lumbar spine
Bone mineral density >2.5 SDs below the average value for a young health adult (T-score <-2.5)
Osteopenia = -2.5 < T-score < -1