ChemPath: Calcium and Clinical Chemistry Flashcards
Role of calcium
99% stored in skeleton
1% in blood extracellular fluid (for action potentials of intracellular signalling)
Normal level Ca
2.2-2.6 mmol/L
Serum Ca2+ (1%) in 3 forms
Free (“ionised”) ~50% - biologically active
Protein-bound ~40% - albumin
Complexed ~10% - citrate / phosphate
Serum Ca2+ + 0.02 * (40 – serum albumin in g/L)
Corrected Ca (to see if ionised Ca levels normal)
Function of circulating Ca
nerve and muscle function
chronic loss -> loss bone mass
Sx Hypercalcaemia
Bones - fracture Stones - renal Moans - constipation, pancreatiits Psychic overtones - confusion Coma ifCa >3 mmol/L
2 Questions to ask when assessming hypercalcaemia
Is this a genuine test? (repeat test)
what is the PTH?
high Ca, low PTH causes
- Cancer invading bone and releasing Ca (common)
- subtypes: Ca releasing PTHrP, bony mets (release Ca), haem malignnacy - Sarcoid (non renal 1a hydroxylase)
- Vit D excess
thyrotoxicosis (increases bone resorption) - milk alkali syndrome
- Hypoadrenalism (renal Ca transport)
- thiazide diuretics (stop Ca into urine)
high Ca, NORMAL PTH
low Pi, high urine Ca
Parathyroid adenoma (primary hyperparathyroidism) (commonest cause of high Ca) Familial hypocalciuric hypercalcaemia
Familial hypocalciuric hypercalcaemia caused by
abnormal Ca2+ sensing receptor (parathyroid + kidneys
high urine Ca and serum Ca
benign condition
no renal stones
Hypercalcaemia Tx
Fluids +++ (normal saline)
Bisophosphonates (if Cancer is cause, as stops it eating into bone)
Treat underlying cause
Signs of Hypocalcaemia
Trousseau's sign (BP cuff) Chvostek's sign Hyperreflexia Stridor (laryngeal spasm) Convulsions ECG prolonged Q-T interval Fundoscopy shows choked disk
Hypocalcaemia result, what 2 questions do you ask?
Is this a genuine result? (repeat)
What is the PTH?
low Ca, high PTH
Vit D deficiency (diet, lack sunlight, malabsorption)
CKD (no 1a hyproxylation)
PTH resistance (pseudohypoparathyroidism)
low Ca, low PTH
Surgical (e.g. ppost thyroidectomy
AI hypoparathyroidism
Di George syndrome
Mg deficiency (regulates PTH level)
Tx Hypocalcaemia
Calcium and Vit D
Calcium homeostasis
How does PTH get Ca?
Bone: increase Ca resorption
Kidney: increase Ca resorption
Gut: PTH activates renal 1aH enzyme -> more 1,25-OH D3 -> increase Ca absorption in gut
2 hormones of Ca regulation
PTH (84aa long) Vitamin D (steroid hormone)
Where do you get Vit D hormone?
- from cholesterol, synthesised to Vit D in skin
- D3 (cholecalciferol) from animals
- D2 (ergocalciferol) from plants
Steps of D3 activation
D3 synthesised in skin from diet 7-dehydrocholesterol
turns into 25-OH D3 in liver by 25-hydroxylase
turns into 1,25-OH D3 by 1aH from kidney (rate limiting step)
NB sarcoid tissue excretes ectopic 1aH -> high Ca
Roles 1,25-(OH)2 Vit D
increase Ca intestinal absorption
Pi absorption
bone formation by osteoblasts
Osteomalacia
Definition
Sx
Biochemistry
Defective bone mineralization i.e. lacks Ca. Called rickets in children. RF = lack sunlight, dark skin, dietary, malabsorption, anticonvulsants
Sx = bone and muscle pain, fracture risk, LOOSER’S ZONES (pseudofracture)
Biochem: low Ca high PTH low Pi, high ALP
Sx Rickets
Bowed legs (one side end plates grows faster) - stays like this forever
Costochondral swelling
Widened epiphyses at the wrists
Myopathy (weak)
Osteoporosis
Definition
Sx
Biochemistry
Reduction in bone density/loss bone mass but normal calcium/mineralisation
RF = Old age. Lifestyle: Due to bone disuse/ Immobility/sedentary. Diet - low Ca, EtOH, smoking. Endocrine: Lack of androgens (-> post-menopausal osteoporosis as no oestrogen, which needed by bones), hyperprolactinaemia, thyrotoxicosis (as cause increased catabolism), Cushing’s, Acromegaly (as tumour causes testosterone deficiency)
Drugs: steroids
Others e.g. genetic, prolonged intercurrent illness
Sx = fracture of NOF, wrist (Colle), vertebrae (lumbar)
Biochemistry NORMAL
Dx = DEXA (T score
Tx Osteoporosis
LIFESTYLE
• reduce causative factors
• Weight-bearing exercise (will maintain bone mass if exercise after 40 years)
• Stop smoking
• Reduce EtOH
DRUGS
1. Vitamin D/Ca mainstay
2. Bisphosphonates (e.g. alendronate) –↓ bone resorption (if other risk factors) and less fractures, but SE = nausea, gastric irritation
3. Teriparatide (PTH derivative)
4. SERMs (selective estrogen receptor modulators) e.g. raloxifene
Paget’s disease
Definition
Sx
Biochemistry/Ix
Tx
Focal disorder of bone remodelling
Sx = Focal pain, warmth, deformity, Fracture (pelvis, femur, skull, tibia)
SC compression
Malignancy
Cardiac failure
Nuclear med scan/ XR
Biochemistry: ELEVATED ALP
Tx = Bisphosphonate for pain
