Chemical Pathology - Calcium Metabolism Flashcards
why does the blood calcium level need to be fixed
nerves and muscles rely on it for depolarisation
symptoms of hypercalcaemia
stones bones groans moans nephrogenic DI
symptoms of hypocalcaemia
epilepsy (aberrant firing of nerves/muscles)
CATS go numb (convulsions, arrhythmias, tetany and numbness)
normal Ca level
2.2-2.6mmol/l
3 forms Ca is found in the serum
- free and ionised (50%) –> can be measured on blood gas machine
- protein bound to albumin (40%)
- complexed with citrate/phosphate (10%)
why is it important to check the albumin level?
abnormal Ca affects free Ca (e.g. sepsis)
Corrected Ca compensated for albumin
corrected Ca shows if the problem is albumin and ionised Ca will be normal
when is PTH released
hypocalcaemia
what are the actions of PTH
- 1 alpha hydroxylase activation = calcidol to calcitriol = gut effects
- osteoclast activation = Ca liberation
- direct renal Ca resorption
- direct renal phosphate excretion
RESULT IN RISE IN PLASMA CA
what are the 2 steroid hormones involved in Ca homeostasis
PTH
Vit D
what are the 2 forms of Vit D and what are they activated by?
both are forms of alfacalcidol and are both activated by 1 alpha hydroxylase
D3 = CHOLECALCIFEROL (animal product synthesised in skin from sunlight)
D2 = ERGOCALCIFEROL (plant vitamin)
what happens next to cholecalciferol (Vit D3) and where does it happen?
Vit D3 from skin/food intake is hydroxylated at 25 position by 25 hydroxylase
IN LIVER
25 hydroxy vit D is inactive. Stored and measured form of Vit D
Where does the Vit D become activated? By which enzyme?
Activation of Vit D in kidney by 1 alpha hydroxylase
where can 1 alpha hydroxylase also be expressed?
in lungs of sarcoid tissue
sarcoid = hypercalcaemia especially in summer when sunlight and Ca go up (more Vit D activation)
summarise the activation pathway of Vit D
- Vit D3 (Cholecalciferol)
- 25 hydroxy Vit D3 (by 25 hydroxylase in liver)
- 1, 25 dihydroxy Vit D3 (Calcitriol) (by 1 alpha hydroxylase under action of PTH)
what is the role of Calcitriol?
- intestinal Ca and phosphate absorption
- bone formation (with osteoblasts)
what happens when you have a Vit D deficiency in children and adults?
Defective bone mineralisation
- childhood = rickets
- adults = osteomalacia
what are the risk factors for Vit D deficiency?
- lack of sunlight exposure
- dark skin
- dietary
- malabsorption
what are the clinical features of osteomalacia?
- bone and muscle pain
- inc fracture risk
- looser’s zones (pseudo fractures)
- bio chem: low Ca and P, raised ALP
what are the clinical features of rickets?
- bowed legs
- costochondral swelling
- widened epiphyses at the wrists
- myopathy
what are the causes of osteomalacia?
LACK OF CA
- renal failure
- lack of sunlight
- Vit D def
- anticonvulsants that induce breakdown of Vit D (phenytoin)
- Chappatis (phytic acid chelates Vit D, prevents absorption)
what is the most common cause of osteoporosis
lack of oestrogen
what happens in osteoporosis
- loss of bone mass
- residual bone is normal structure
- normal Ca
- normal mineralisation
- NORMAL biochemistry
what fractures does osteoporosis present with?
- NOF
- Vertebral
- Colle’s
how do you diagnose osteoporosis
DEXA scan T score (from young healthy population) Z score (age matched control)
T score for osteoporosis and osteopenia
Osteoporosis: T score < -2.5
Osteopenia: T score -1 and -2.5
what are the lifestyle treatments for osteoporosis
- weight bearing exercise
- stop smoking
- reduce alcohol
what are the drug treatments for osteoporosis
- Vit D/Ca
- bisphosphonates (dec bone resoprtion)
- teriparatide (PTH derivative)
- strontium (anti-resoptive)
- oestrogens (HRT)
- SERMS (oestrogen like drug e.g. Tamoxifen)
- Denosumab (biological anti-RANK-L antibody)
when a patient has hypercalcaemia what should you first think?
- is it a genuine result? (repeat)
2. what is the PTH
what is the commonest cause of hypercalcaemia?
primary hyperparathyroidism
what are the causes of primary hyperparathyroidism?
parathyroid adenoma (80%)
hyperplasia associated with MEN1, 2a
malignancy
biochemical results of primary hyperparathyroidism
- inc serum Ca
- inc PTH
- dec serum P
- inc urine Ca due to hypercalcaemia
- inc/normal Alk phos
what happens in Familial Hypocalciuric Hypercalcaemia (FHH)?
mutation in Calcium sensing receptor
reduced sensitivity to Ca
higher set point for PTH release
= mild hypercalcaemia and reduced urine Ca
what is the primary defect in secondary hyperparathyroidism?
renal failure
Vit D deficiency
biochemical results in secondary hyperparathyroidism
- low Ca
- high P
- high alk phos
- dec Vit D
what is the primary defect in tertiary hyperparathyroidism?
autonomous PTH secretion
biochemical results in tertiary hyperparathyroidism
- high Ca
- low P
- high PTH
- high Alk phos
- normal Vit D
what are the 3 types of hypercalcaemia in malignancy
- humoral hypercalcaemia of malignancy (PTHrP)
- bone mets (breast Ca)
- haematological malignancy (myeloma
what are some other causes of non-PTH driven hypercalcaemia
- sarcoidosis
- thyrotoxicosis (thyroxine = bone resorption)
- hypoadrenalism (renal Ca transport)
- thiazide diuretics (renal Ca transport)
- excess Vit D (sunbeds)
what is the tx of hypercalcaemia?
FLUIDS (0.9% saline, 1L/hour)
treat underlying cause
when should you give bisphosphonates?
if hypercalcaemia caused by malignancy
what are the signs of hypocalcaemia?
- NM excitability: Chvostek’s sign (face), Trousseau’s sign, hyperreflexia
- convulsions
what are the causes of hypocalcaemia when there is a high PTH
secondary hyperparathyroidism
- Vit D def
- CKD (lack of 1 alpha hydroxylase)
- PTH resistance
what are the causes of hypocalcaemia when there is a low PTH
- surgical (e.g. post-thyroidectomy)
- AI hypoparathyroidism
- congenital absence of parathyroids (e.g. DiGeorge)
- Mg def (PTH regulation)
What is Paget’s disease?
focal disorder of bone remodelling
what are the signs and symptoms of Paget’s?
- bone pain
- deformity
- warmth
- fracture
- cardiac failure
- malignancy
- compression (blindness, deafness)
which bones does Paget’s affect the most?
pelvis
femur
skull
tibia
biochemistry of Pagets
- high Alk phos
- Ca and P are normal
what is the tx of Pagets
bisphosphonates for pain
