Calcium metabolism 280721 Flashcards
What are the consequences of hypercalcaemia
Stones, bones, groans, moans, nephrogenic DI
What are the consequences of hypocalcaemia
CATS go numb
What is the n ormal range for calciu,
2.2-2.6mmol/l
How is the 1% calcium in serum divided
1) free ionised calcium - this is maintained at around 50%
2) 40% albumin bound
3) 10% citrate/phosphate bound
What is the corrected calcium calculation
serum calcium + 0.02 x(40-serum albumin)
what are the actions of PTH
activates 1 alpha hydroxylase which converts calcidiol to calcitriol
osteoclast activation -> calcium liberation
direct renal calcium resorption
direct renal phosphate excretion
What is Vitamin D3 called and where is it from
animal product + sunlight = cholecalciferol
D2
ergocalciferol, from plants
How does cholecalciferol become calcitriol
Vitamin D3 / Cholecalciferol -> liver-> 25-hydroxy vitamin D3 -> under PTH -> kidneys-> 1, 25 dihydroxy vitamin D3 / Calcitriol
summer hypercalcaemia
o Sarcoid = causes hypercalcemia (seasonal) – summer hypercalcemia
o In sunlight, calcium goes up (more vitamin D activation)
• Role of 1,25 (OH)2 Vitamin D / Calcitriol:
o Intestinal Ca2+ absorption and intestinal phosphate absorption
o Critical for bone formation (with osteoblasts)
o Other physiological effects
Vitamin D receptor controls many genes – cell proliferation, immune system
Vitamin D deficiency associated with cancer, autoimmune disease, metabolic syndrome
Osteomalacia clinical features
- Bone and muscle pain
- Increase fracture risk
- Bio-chem → low Ca2+ and phosphate and raised ALP
- Looser’s zones (pseudo fractures)
Rickets clinical features
- Bowed legs Costochondral swelling
* Widened epiphyses at the wrists Myopathy (weak muscles)
what are some of the causes of osteomalacia
o Bone is demineralised Caused by vitamin D deficiency
o Renal failure Anticonvulsants induce breakdown of Vitamin D (phenytoin)
o Lack of sunlight Chappatis – phytic acid (cause osteomalacia)
what happens to the bone mass and bone structure and calcium in osteoporosis
o Loss of bone mass, but residual bone normal in structure
o Osteoporosis has bone loss but with a normal calcium
o Reduction in bone density with normal mineralisation
Biochemistry NORMAL
How is osteoporosis diagnosed
using DEXA scan (Dual energy X-ray absorptiometry):
Hip (femoral neck) and lumbar spine
T score – SD from mean of young healthy population – determine fracture (#) risk
Z score – SD from mean of age-matched control – identify accelerated bone loss in younger people
Osteoporosis – T score
What are some of the treatments for osteoporosis
o Lifestyle
Weight bearing exercise
Stop smoking
Reduce ETOH
o Drugs
Vitamin D/Ca
Bisphosphonates (alendronate) – decrease bone resorption – osteonecrosis of jaw
Teriparatide – PTH derivative – anabolic
Strontium – anabolic + anti-resorptive
Oestrogens – HRT
SERMs (oestrogen-like drug) – raloxifene (like Tamoxifen)
Denosumab – biologic anti-RANK-L antibody
what are the symptoms of hypercalcaemia
• Symptoms o Polyuria or polydipsia o Bones o Stones o Abdo - constipation o Neuro – confusion, seizures, coma o Unlikely unless Ca >3mmol/L (2.2-2.6) o Overlap with symptoms of hyperPTH
what is the calcium, phosphate and PTH like in primary hyperparathyroidism
- Increased serum Ca
- Increased or inappropriately normal PTH
- Decreased serum phosphate
- Increased urine calcium due to hypercalcemia
Familial hypocalciuric hypercalcaemia
o calcium sensing receptor CaSR mutation
o Reduced sensitivity to calcium
o Higher set point for PTH release
o Mild hypercalcaemia
o Reduced urine Ca
What are the 3 types of hypercalcaemia in malignancy
- Humoral hypercalcaemia of malignancy – squamous cell lung cancer
a. PTHrP - Bone mets – breast ca
a. Local bone osteolysis - Haematological malignancy – myeloma
a. Cytokines
Other types of nonPTH driven hypercalcaemia
- Sarcoidosis – non renal 1α hydroxylation
- Thyrotoxicosis – thyroxine leads to bone resorption
- Hypoadrenalism – renal Ca transport
- Thiazide diuretics – renal Ca transport
- Excess vitamin D – sunbeds
Hypercalcaemia treatment
• FLUIDS (0.9% saline, 1L/hour and reassess)
- Treat underlying cause
- Cinacalcet acid – activates CaSR
Pagets disease signs and symptoms
• Signs & symptoms:
o Bone pain Warmth Cardiac failure
o Deformity Fracture Malignancy
o Compression (blindness, deafness)
o Pelvis, femur, skull and tibia
Investigations pagets and treatment
o Elevated alkaline phosphatase
Ca and PO4 are NORMAL as…
Osteoclasts and blasts are both active together
o Nuclear med scan / XR
• Treatment Bisphosphonates for pain
Hypocalcaemia signs and symptoms
• Signs and symptoms:
o Neuromuscular excitability Chvostek’s sign (face), Trousseau’s sign, hyperreflexia
o Convulsions
• When diagnosing…
o 1st repeat bloods and adjust for albumin (as the albumin can bind ionised calcium)
o 2nd what is the PTH?
what should you always do when checking blood calcium
repeat resuults and check albumin
examples of secondary hyperparathyroidism
vit D deficiency, chronic kidney disease PTH resistence (pseudohypoparathyroidism)
Pagets blood values
raised alk phos only
vitamin D deficiency blood values
low cal low phos, high PTH, high alk phos, low vit D
Renal failure blood values
very very low vit D, high PTH, low calcium, high phosphate, high PTH, high alk phos
