Chem Path Flashcards
Normal Calcium Range
2.2-2.6mmol/L
Free “ionised” - must remain fixed for muscle and nerve function.
Calcium Stores
Bone: 99% Serum : 1% - Free/ionised = 50% - Protein bound (albumin) = 40% - Complexed (citrate/phosphate) = 10% Use corrected calcium to compensate for changes in albumin.
PTH MOA
Parathyroid glands detect hypocalcaemia and secrete PTH.
1) Bone - Ca2+ release
2) Gut - absorption
3) Kidney - resorption and renal 1 alpha hydroxylase activate -> activates Vit D
Ca Metabolism Enzymes
25 hydroxylase (liver) 1 hydroxylase (kidney)
Physiological Roles of Vit D
Activates absorption of calcium in the gut
Activates absorption of phosphate in the gut
Critical for bone formation
Clinical Features of Osteomalacia
Bone and muscle pain Increase # risk Low Ca2+ and Phosphate High ALP Looser's zones (pseudo #)
Clinical Features of Rickets
Bowed legs
Costochondral swelling
Widened epiphysis of wrist
Myopathy
Causes of Osteomalacia (important)
BONE IS DEMINERALISED
- Vit D deficiency (secondry HPTH)
- Renal failure (renal oseodystrophy) = reduced 1aOHase (reduced activation Vit D)
- Anticonvulsants (e.g. phenytoin) - induce Vit D breakdown
- Lack of sunlight
- Chappatis (phytic acid) - chelates Vit D in gut and prevents absorption
Features of Osteoporosis
LOSS OF BONE MASS (not demineralised)
Post-menopausal W - sex steroids maintain mass
Cushings - increased catabolism (bone loss)
Ca and Pi are NORMAL
# = NOF, vertebral, Colle’s
Dx of Osteoporosis
DEXA scan
T score DEXA>-2.5 = osteopenia
Causes of Osteoporosis
Failure to attain peak BM (e.g. childhood illness)
Early menopause
Rapid loss during adulthood:
- lifestyle (sedentary, EtOH, low BMI)
- endocrine (hyperprolactinaemia, thyrotoxicosis, Cushings)
- Drugs (steroids, e.g. pred)
- Other (genetic, prolonged illness)
Tx of Osetoporosis
Lifestyle - weight bearing exercise, stop smoking, reduce EtOH
Vit D/Ca, Bisphosponates, teriparatide, strontium, HRT, SERMs
Causes of hypercalcaemia
IS PTH SUPRESSED?
Yes = appropriate
Malignancy (Common)
Sarcoid, vit D excess, thyrotoxciosis, milk alkali syndrome (rare)
NO = inappropriate
PHPT (common)
Familial hypocalciuiric hypaercacaemia (Rare)
Familial Hypocalciuric Hypercacaemia
CaSR mutation
Higher set point for PTH release
Mild hypercalcaemia
Reduced urine Ca2+
Ca Sensing Receptor (CaSR)
Parathyroids (regulate PTH release)
Renal (influences Ca resorption - independent of PTH)
Hypercalcaemia in Malignancy
- Humoral hypercaclcaemia e.g. SCC secretes PTHrP
- Bone mets e.g. breast - bone osteolysis (raised ALP)
- Haematological malignancy e.g. myeloma (cytokines)
Non-PTH Driven Hypercacaemia
Sarcoidosis (non renal 1a hydroxylation) (raised ALP)
Thyrotoxicosis (thyroxine -> bone resorption) (raised ALP)
Thiazide diuretics - stops you peeing out Ca2+
Excess Vit D - sunbeds
Treatment Hypercalcaemia
Acute: Fluids +++ Ca>3 4L normal saline over 24hr Elderly/ heart failure = 1L/4hrs - examine and repeat if not overloaded Ca<3 = drink fluids/ discharge
Treat cause
If cause known malignancy - bisphosphonates for bone pain (hypercalcaemia is poor prognositc marker in malignancy)
Presentation of Hypocalcaemia
Signs occur in severe or rapid onset
Severe = carpopedal spasm
Life threatening = laryngeal spasm and convulsions
Check Ca in patients presenting with fit
Paget’s Disease
Focal bone remodelling disorder Pain, warmth, deformity, fracture, SC compression, malignancy, cardiac failure Pelvis, femur, tibia ELEVATED ALP NUclear med scan/X ray Tx: Bisphosphonates for pain
Osteitis Fibrosa
Loss of cortical bone and # risk in primary HPTH
Renal Osteodystrophy
Due to secondary HPTH and retention of aluminium from dialysis
