Calcium, Phosphate and Bone Flashcards
Homeostasis and Functions of Calcium
1000 mg/day intake (25 mmol/day)
- bone as the main depot in the body (35000 mmol - 99% body Ca; bone remodelling)
- calcium carbonate supplement (40% elemental Ca)
Functions:
- strength of skeleton
- coagulation cascade
- maintain cellular membrane potential
- cardiac contractility and rhythm
Calcium in circulation (1% body Ca)
*Ionised free Ca is the biologically active form (50% plasma Ca)
Ca bound to plasma albumin (40%)
Complexed with anions (10%)
Total plasma Ca RR: 2.1-2.55
Albumin-adjusted Ca
Total plasma Ca measured includes free ionised Ca and albumin-bound Ca
- cheaper to measure
- changes in albumin will affect Ca measurement
Adjusted Ca = measured [Ca] + [(40-albumin in g/L) x 0.025]
–> inaccurate for extremes (<25 g/L or>50g/L) – need ionised Ca measurement
Ionised Ca
- specialised collection bottle, freeze after collection
- useful in massive derangement of albumin/ neonates with high AFP (same binding as albumin - less blood required, faster measurement)
Manifestations of hyperCa and hypoCa
HyperCa
- Stones, Abdominal Groans, Painful bones and psychic moans
- nephrocalcinosis
- nausea, vomiting, ileus, peptic ulcer (increased gastrin), pancreatitis (deposition of Ca in duct, Ca +ve trypsinogen)
- brown tumour (rapid bone loss, replace by haemorrhage), osteitis fibrosa cystica
- lethargy, depression
- muscle weakness, bradycardia, polyuria, polydipsia
HypoCa
- enhanced neuromuscular excitability –> +ve chvostek’s sign, trousseau’s sign, tetany, seizures, cramps
- perioral numbness, paraesthesia
- arrhythmia
- irritability
- basal ganglia calcification, sub capsular infarcts (chronic Ca deposition)
Regulation of ionised Ca
- PTH
- increase Ca and decrease PO4
- **Bone: increase resorption (osteoblast–>osteoclast)
- Kidney: increase reabsorption of Ca (DT, TAL), decrease renal reabsorption of PO4 (PCT), increase 1-alpha hydroxylase (for calcitriol production)
- Intestines: increased 1-alpha hydroxylase leads to increase Ca and PO4 reabsorption - Vitamin D3/ Calcitriol/ 1,25 dihydroxycholecalciferol (slower response)
- increase Ca and PO4
- Bone: potentiate PTH action of resorption (but suppressed at high PTH and has neg feedback on PTH)
- Intestines: increase Ca and PO4 absorption - Calcitonin
- decrease Ca and PO4
- Bone: decrease osteoclast activity
HyperCa: causes
Common:
- Parathyroid disease
- hyperPTH: primary e.g. adenoma, hyperplasia or tertiary (autonomous PTH secretion due to chronic hypoCa and stimulation of parathyroid glands)
- MEN1 and MEN2a - Malignant disease (humoral hyperCa of malignancy)
- lytic lesions of bone e.g. breast CA metastasis
- malignant cells release other mediators e.g. osteoclast activating factors in myeloma
- PTHrP release e.g. SQCC of lung, HCC, head and neck CA, oesophagus
- ectopic production of calcitriol by lymphomas
Uncommon:
- endogenous calcitriol e.g. sarcoidosis, TB
- excessive absorption of Ca e.g. vitamin D overdose, milk-alkali syndrome
- thiazide diuretics
- familial hypocalciuric hyperCa (CaSR gene mutation; AD with full penetrance)
Primary HyperPTH vs Hypercalcemia of Malignancy: Ca levels, onset, renal stone formation, PTH levels, PO4 levels
Primary HyperPTH
- Ca <3.0 mmol/L
- chronic, insidious onset
- renal stones common (takes time to form)
- *plasma PTH high or inappropriately normal
- plasma PO4 usually low
Malignancy
- Ca >3.0 mmol/L (no physiological feedback mech)
- acute onset (months)
- renal stones rare
- *plasma PTH suppressed
(both have high Ca, low PO4 in HHM, high ALP)
Approach to HyperCa
- Confirm hyperCa (albumin-adjustment)
- PTH assessment
- -> high/ inappropriately normal = hyperPTH (normal/ high 24 hr urine Ca; primary or tertiary depending on RFT) or familial hypocalciuric hyperCa (low 24 hr urine Ca)
- -> suppressed = malignancy, TB, others
DDx patterns for hyperCa
Low PO4
- primary hyperPTH
- PTHrP releasing malignancy
High PO4
- malignancy (primary or secondary deposits)
- post-dialysis in renal failure, tertiary hyperPTH
- TB (overproduction of Vit D)
- Vit D overdose
DDx of hypoCa
Exclude artefact from contamination of tubes with EDTA or oxalate
High PO4
- hypoparathyroidism e.g. thyroidectomy, congenital absence of glands
- secondary hyperparathyroidism i.e. renal failure –> PO4 retention in CKD and failure of vitamin D activation causes hypoCa which stimulates PTH release (can lead to renal osteodystrophy)
- pseudohypoparathyroidism (tissue resistance to PTH; PTH very high)
- hypoMg – required for PTH secretion and action
Low PO4
- vitamin D deficiency e.g. little sun exposure, malnutrition, fat malabsorption –> *high ALP and low 25-OH-Vitamin D (storage form)
- acute pancreatitis –> Ca and PO4 sequestration in abdomen leading to saponification
Beware! Vitamin D deficiency will never cause high Ca!
Primary hyperPTH can cause low Vitamin D (suppressed at high PTH) but will have high Ca –> not vit D deficiency!!
Mg and causes of deficiency
Cofactor required for PTH secretion and action (and also affects K excretion)
Reduced intake
- alcoholism, malnutrition, total parenteral nutrition
Abnormal loss
- renal: renal disease e.g. RTA, Barter/Gitelman, chronic pyelonephritis
- extra-renal: primary or secondary hyperaldosteronism/ diuresis; primary or tertiary hyperPTH
=> insensitive to vitamin D or Ca supplement
Metabolic Bone Diseases
Most with normal Ca and PO4 except rickets and osteomalacia
definition, aetiology, bone turnover markers
Osteoporosis
Common disorder affecting 1/4 older women
- LOW BONE MASS and susceptibility to vertebral, forearm and hip fractures
- structure and composition of bone is normal
- -2.5 SD from peak bone mass (osteopenia if -1.5 SD)
Ca, PO4, ALP, PTH all normal
Osteomalacia and Rickets
Vitamin D deficiency or disturbed metabolism of vitamin D
- SOFT BONES (DEFECTIVE MINERALISATION, abrnomal composition)
- rickets in children
- osteomalacia in adults
Diffuse bone pain, tenderness, muscle weakness
XR: decreased density and *thinning of bone cortex
Deformed bones in advanced disease e.g. concavity of vertebral bodies, bowed legs
Fissures/ Cracks (looser’s zones)
Low Ca, PO4, 25-OH-Vit D
High ALP, PTH
Osteopetrosis
Marble bone disease (very rare inherited)
- bones harden and become denser
Ca, PO4, PTH normal
High ALP
Paget’s disease of bone
Dysregulated bone remodelling leading to deformity and abnormal architecture
Dx:
- characteristic XR appearance
- high ALP with normal Ca and PO4 in elderly
Osteitis Fibrosa Cystica
Long term effect of untreated hyperPTH
- prone to pathological fractures
Same lab picture as hyperPTH (High Ca, low PO4, High ALP and PTH)
Renal osteodystrophy
Osteomalacia + secondary hyperPTH
- poor RFT
High/Low Ca
High PO4, ALP and PTH
Treatment of acute hyperCa
Dx and treat underlying cause
Correct dehydration (ensure sufficient renal filtration and Ca excretion)
Bisphosphonates (inhibit osteoclast activities and improve osteoblast survival)
Further Mx: chemo in malignancy, steroids in sarcoidosis, calcitonin also inhibit osteoclasts
Biologics:
- denosumab (Ab against human RANKL) – treat osteoporosis and acute severe hyperCa
