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
