Calcium and bones Flashcards
What is the minimum dietary requirement for calcium?
12.5mmol/24 hours - higher in growth, pregnancy and lactation
What is the role of an osteoclast?
- mediate bone resorption - activity triggers osteoblast differentiation
What is the role of an osteoblast?
- form new bone - control osteocytes - evolve into osteocytes
What does an osteocyte do?
- sense bone strain or micro fractures - control amount of osteoclast resorption
What is bone tissue made up of?
- osteoid - collagenous organic matrix - hydroxyapetite - osteocytes, osteoclasts, osteoblasts - haversian canals contain vessels, sympathetic and sensory nerves
What hormones control bone growth?
- testosterone and GH stimulate periosteal bone - oestrogen maintains trabecular bone
In what forms does Ca exist in the blood?
- bound to protein (albumin mainly + globulins) - complexed with citrate and phosphate - free ions - physiologically active form
How does alkalosis effect Ca?
hydrogen ions dissociate from albumin so Ca binding to albumin increases - fall in free ionised Ca - hypocalcaemia e.g. hyperventilation
How does acidosis effect Ca?
hydrogen ions bind to albumin, decreasing binding of Ca - increase in free ionised Ca - hypercalcaemia
What hormones regulate ECF calcium concentrations?
PTH and calcitriol (1,25-dihydroxycholecalciferol)
What is the role of PTH?
- mobilises Ca from bone by increasing osteoclastic reabsorption
- increases Ca reabsorption at the renal tubules and decreases phosphate reabsorption at the kidney
- increases hydroxylation of vit D to calcitriol, which increases reabsorption of Ca from the gut
- decreases bicarb reabsorption
effect: increased plasma Ca, decreased plasma PO4, acidosis
How is vitamin D metabolised?
- a photosensitive reaction in the skin results in synthesis of cholecalciferol
- Cholecalciferol is hydroxylated in the liver to form 25-(OH)D
(25-hydroxylation) - this is NOT subject to feedback control
- PTH stimulated 1 alpha-hydroxylation in the kidney to form calcitriol - 1,25(OH)2D
What is the role of calcitriol?
- Stimulates caclium and phosphate reabsorption in the gut, increasing Ca and PO4 levels
- Promotes bone mineralisation
INCREASED VIT D -> INCREASED Ca and PO4
List the causes of hypercalcaemia (9)
- Primary hyperparathyroidism
- Malignancy
- these account for 90% of cases - Vit D excess syndromes
- granulomatous disease: Sarcoid, lymphoma, TB
- macrophages hydroxylate 25-hydroxycholecalciferol in granumolas (I thought that was interesting and cool) - Immobilisation with high turnover states
- bed rest, Paget’s disease adolescents - Secondary hyperparathyroidism
- PTHrP tumours (acts like PTH but not detected on assay)
- Meds
- Familial Hypocalciuric hypercalcaemia
- Endocrine disorders
- Hyperthyroidism
- acute adrenal failure (Addison’s) - Sampling error
- Assay error, dehydration, tourniquet on
What is the prevalence of primary hyperparathyroidism?
1/1000
increases with age
What biochemical pattern is seen in primary hyperparathyroidism?
raised Ca
raised or inappropriately normal PTH
low or low/normal PO4 (unless renal failure also present)
ALP raised in the late stages only
What are some other causes of hyperparathyroidism?
- Parathyroid adenoma - most common
- 10% familial
- MEN type 1: 100% pentrance by age 45-50
- MEN type 2
- Familial isolated hyperparathyroidism
- Familial hypocalciuric hypercalcaemia - Dfifuse hyperplasia of the gland
rarely due to parathyroid Ca
How do you diagnose a parathyroid adenoma?
Sestamibi scan +/- US
What is the treatment for primary hyperparathyroidism?
If Ca < 3
- high fluid intake (avoid renal stones)
- monitor for osteoporosis and development of renal impairment
Surgery indicated if:
- Ca > 3
- marked hypercalciuria
- complications - nephrolithiasis, osteroporosis, renal imp
- age < 50
What is the pathophysiology behing Familial hypocalciuric hypocalcaemia?
- mutation in the CaSR gene which encodes a calcium sensing receptor in the parathyroid and kidneys
- there is a perceived hyponatraemia with resultant raised PTH
- the raised PTH results in hypercalcaemia and hypophosphataemia (sometimes)
- autosomal dominant
How do you diagnose Familial hypocalciuric hypocalcaemia?
- FH of mild hypercalcaemia
- urine calcium:creatinine ratio of <0.01
- urine calcium level of <200mg/24hours (do a 24h urine)
What malignancies release PTHrP?
NSCLC, breast, renal, bladder, ovary, head/neck
- PTHrP has similar activity as PTH but is not detected on the PTH assay
Name some drugs that can cause hypercalcaemia?
Vit D excess
Thiazides - mild increase
Lithium - serum Ca normalises on stopping
Antacids - usually chronic high doses w assoc renal impairment “milk alkali syndrome”
Vit A