Chempath - Calcium

Question 1

Calcium normal range

Answer 1

2.2-2.6mmol/L

Question 2

% of body calcium in the serum

Answer 2

1%

Question 3

Parathyroid Hormone - actions

Answer 3

PTH increases in response to decrease in serum Ca2+

1) Increases tubular 1 a hydroxylation of VitD –> essentially increases via D activation
2) Mobilises calcium from bone
3) Increases renal calcium absorption and phosphate excretion

Question 4

Vit D/Calcitriol - actions

Answer 4

Increases calcium and phosphate absorption from the gut

Bone remodelling - stimulates bone formation and mineralisation by activating osteoclasts

Question 5

Sarcoidosis

Answer 5

Ectopic 1aOHase in lung tissue.

Get summer hypercalcaemia –> usually vit D def in winter but when sun comes out they get more resulting in hypercalcaemia

Question 6

Osteoporosis

Answer 6

Osteoporosis –> lose bone mass/density but the bone structure is normal, normal feature of aging

Normal blood bone profile. DEXA scan (of hip and lumbar spine) will show reduced bone density. T- score = no of SDs away from young healthy pop. Z-score = age-matched.

Osteroporosis = Z-score <2.5

Question 7

Vit D Deficiency (Osteomalacia/Rickets)

Answer 7

Defective bone mineralisation –> demineralised bone.

RFs: lack of sun exposure, dark skin, dietary, malabsorption. Anti-convulsants (induce vit D breakdown). Chappatis (physic acid –> vit D breakdown)

Causes secondary hyperparathyroidism picture (differentiate from renal osteodystrophy by vit D levels).

BONE PROFILE:
Decreased: vit D, Ca, P
Increased PTH, Alk phos

Question 8

Paget’s disease

Answer 8

Increased bone turnover.

Unknown cause (thought to be caused by a virus), v few new pts with paget’s, causes v active osteoblasts and clasts in 1/2/3 bones –> pain

Rx - Bisphosphonates

Bone profile normal except increased ALP.

Question 9

Primary Hyperparathyroidism

Answer 9

Increased PTH - commonest cause of hypercalcaemia. 80% caused by parathyroid adenoma. Other causes include hyperplasia and sarcoma. Assoc w/ MEN1. Women > men.

BONE PROFILE
Increased Ca
Decreased P
Increased/N PTH (NORMAL PTH IN CONTEXT OF HYPERCALCAEMIA IS ABNORMAL - SHOULD BE SUPPRESSED)
Increased/N ALP
Normal Vit D

Question 10

Secondary Hyperparathyroidism

Answer 10

Renal osteodystrophy: Renal failure –> can’t activate vit D –> can’t excrete phosphate & bones can’t form properly
Vit D deficiency.

BONE PROFILE
Reduced/normal Ca
Increased P
Increased PTH
Increased ALP
Normal vit D

Question 11

Tertiary Hyperparathyroidism

Answer 11

Autonomous PTH secretion post renal transplant.

BONE PROFILE
Increased Ca
Decreased P
Increased PTH
Increased/normal ALP
Normal vit D

Question 12

Hungry bone syndrome

Answer 12

Removal of PTH by thyroidectomy results in sudden increase in bone mineralisation and sequestration of Ca2+, resulting in dangerously low Ca2+ levels.

Question 13

Vit D Deficiency - Clinical Features

Answer 13

Osteomalacia:
Bone & muscle pain
Increased fracture risk
Biochem – low Ca2+ & P, raised ALP
Looser’s zones - pseudo fractures 

Rickets:
Bowed legs
Costochondral swelling
Widened epiphyses at the wrists
Myopathy

Question 14

Osteoporosis- RFs

Answer 14

(early) menopause, failure to achieve peak bone bass (e.g. childhood illness)

Lifestyle: sedentary, EtOH, smoking, low BMI/nutritional
Endocrine: hyperprolactinaemia, thyrotoxicosis, Cushings
Drugs: steroids
Others eg genetic, prolonged intercurrent illness

Question 15

Osteoporosis - Rx

Answer 15

Lifestyle:
Weight-bearing exercise
Stop smoking
Reduce EtOH

Drugs:
Vitamin D(+/-Ca)
Bisphosphonates (eg alendronate) –↓ bone resorption
Teriparatide (PTH derivative) – anabolic –> artificial PTH
Strontium – anabolic + anti-resorptive
(Oestrogens – HRT)
SERMs eg raloxifene –> agonist at bone receptor, antagonist at breast receptor

Question 16

Hypercalcaemia - Clinical Features

Answer 16

Stones (renal) - haematuria

Bones (pain) - Histo: brown tumours and multi-nucleate giant cells. Skeletal changes: lytic lesions, osteitis fibrosa et cystica, hand X-ray may show radial aspen cystic changes.

Groans (psych) - confusion, seizures, coma

Moans (abdo pain) - pancreatitis, peptic ulcer disease

Polyuria & polydipsia - nephrogenic DI

Muscle weakness

Sign: band keratopathy (corneal disease)

Question 17

Hypercalcaemia

Answer 17

FLUIDS - Correct dehydration - 0.9% normal saline
Bisphosphonates (if cause known to be cancer, otherwise avoid)
Correct cause

Question 18

Causes of Hypercamcaemia

Answer 18

PTH suppressed:
Malignancy is the main one. 
Sarcoidosis (non-renal 1α hydroxylation)
Thyrotoxicosis (thyroxine -> bone resorption)
Hypoadrenalism (renal Ca2+ transport)
Thiazide diuretics (renal Ca2+ transport)
Excess vitamin D (eg sunbeds…)
Milk alkali syndrome.

PTH raised/inappropriately normal: primary or secondary hyperparathyroidism

Question 19

Familial hypocalciuric (/benign) hypercalcaemia (FHH / FBH)

Answer 19

Calcium sensing receptor (CaSR) mutation
Higher “set point” for PTH release -> mild hypercalcaemia
Reduced urine Ca2+

Question 20

3 Types of Hypercalcaemia in Malignancy

Answer 20

Humoral hypercalcaemia of malignancy (eg small cell lung Ca) - PTHrP –> helps cancer cells to invade bone. Only present in foetus(to steal ca from mother) and malignancy.

Bone metastases (eg breast Ca) - Local bone osteolysis

Haematological malignancy (eg myeloma) - cytokines

Question 21

Hypocalcaemia - Clinical Features

Answer 21

Neuro-muscular excitability: CATs go numb

Convulsions
Arrythmias
Tetany
Numbness

+ Trousseau and Chvostek signs

Laryngeal spasm is a potentially fatal complication

Question 22

Hypocalcaemia - Causes

Answer 22

Non-PTH Driven (PTH increased–> secondary hyperPTH):
Vit D def
CKD (may progress to tertiary hyperPTH)
PTH resistance - pseudohyeperparathyroidism

PTH Driven (low PTH):
Surgical e.g. post thyroidectomy
Auto-immune hypoparathyroidism
Congenital absence of the parathyroids (e.g. DiGeorge syndrome)
Magnesium deficiency - linked to PTH regulation