ChemPath: Calcium and Clinical Chemistry

Question 1

Role of calcium

Answer 1

99% stored in skeleton

1% in blood extracellular fluid (for action potentials of intracellular signalling)

Question 2

Normal level Ca

Answer 2

2.2-2.6 mmol/L

Question 3

Serum Ca2+ (1%) in 3 forms

Answer 3

Free (“ionised”) ~50% - biologically active
Protein-bound ~40% - albumin
Complexed ~10% - citrate / phosphate

Question 4

Serum Ca2+ + 0.02 * (40 – serum albumin in g/L)

Answer 4

Corrected Ca (to see if ionised Ca levels normal)

Question 5

Function of circulating Ca

Answer 5

nerve and muscle function

chronic loss -> loss bone mass

Question 6

Sx Hypercalcaemia

Answer 6

Bones - fracture
Stones - renal 
Moans - constipation, pancreatiits
Psychic overtones - confusion 
Coma ifCa >3 mmol/L

Question 7

2 Questions to ask when assessming hypercalcaemia

Answer 7

Is this a genuine test? (repeat test)

what is the PTH?

Question 8

high Ca, low PTH causes

Answer 8

1. Cancer invading bone and releasing Ca (common)
   - subtypes: Ca releasing PTHrP, bony mets (release Ca), haem malignnacy
2. Sarcoid (non renal 1a hydroxylase)
3. Vit D excess
   thyrotoxicosis (increases bone resorption)
4. milk alkali syndrome
5. Hypoadrenalism (renal Ca transport)
6. thiazide diuretics (stop Ca into urine)

Question 9

high Ca, NORMAL PTH

low Pi, high urine Ca

Answer 9

Parathyroid adenoma (primary hyperparathyroidism) (commonest cause of high Ca)
Familial hypocalciuric hypercalcaemia

Question 10

Familial hypocalciuric hypercalcaemia caused by

Answer 10

abnormal Ca2+ sensing receptor (parathyroid + kidneys
high urine Ca and serum Ca

benign condition
no renal stones

Question 11

Hypercalcaemia Tx

Answer 11

Fluids +++ (normal saline)
Bisophosphonates (if Cancer is cause, as stops it eating into bone)
Treat underlying cause

Question 12

Signs of Hypocalcaemia

Answer 12

Trousseau's sign (BP cuff)
Chvostek's sign
Hyperreflexia
Stridor (laryngeal spasm)
Convulsions
ECG prolonged Q-T interval
Fundoscopy shows choked disk

Question 13

Hypocalcaemia result, what 2 questions do you ask?

Answer 13

Is this a genuine result? (repeat)

What is the PTH?

Question 14

low Ca, high PTH

Answer 14

Vit D deficiency (diet, lack sunlight, malabsorption)

CKD (no 1a hyproxylation)

PTH resistance (pseudohypoparathyroidism)

Question 15

low Ca, low PTH

Answer 15

Surgical (e.g. ppost thyroidectomy

AI hypoparathyroidism

Di George syndrome

Mg deficiency (regulates PTH level)

Question 16

Tx Hypocalcaemia

Answer 16

Calcium and Vit D

Question 17

Calcium homeostasis

How does PTH get Ca?

Answer 17

Bone: increase Ca resorption

Kidney: increase Ca resorption

Gut: PTH activates renal 1aH enzyme -> more 1,25-OH D3 -> increase Ca absorption in gut

Question 18

2 hormones of Ca regulation

Answer 18

PTH (84aa long)
Vitamin D (steroid hormone)

Question 19

Where do you get Vit D hormone?

Answer 19

1. from cholesterol, synthesised to Vit D in skin
2. D3 (cholecalciferol) from animals
3. D2 (ergocalciferol) from plants

Question 20

Steps of D3 activation

Answer 20

D3 synthesised in skin from diet 7-dehydrocholesterol

turns into 25-OH D3 in liver by 25-hydroxylase

turns into 1,25-OH D3 by 1aH from kidney (rate limiting step)

NB sarcoid tissue excretes ectopic 1aH -> high Ca

Question 21

Roles 1,25-(OH)2 Vit D

Answer 21

increase Ca intestinal absorption
Pi absorption
bone formation by osteoblasts

Question 22

Osteomalacia

Definition

Sx

Biochemistry

Answer 22

Defective bone mineralization i.e. lacks Ca. Called rickets in children. RF = lack sunlight, dark skin, dietary, malabsorption, anticonvulsants

Sx = bone and muscle pain, fracture risk, LOOSER’S ZONES (pseudofracture)

Biochem: low Ca high PTH low Pi, high ALP

Question 23

Sx Rickets

Answer 23

Bowed legs (one side end plates grows faster) - stays like this forever
Costochondral swelling
Widened epiphyses at the wrists
Myopathy (weak)

Question 24

Osteoporosis

Definition

Sx

Biochemistry

Answer 24

Reduction in bone density/loss bone mass but normal calcium/mineralisation

RF = Old age. Lifestyle: Due to bone disuse/ Immobility/sedentary. Diet - low Ca, EtOH, smoking. Endocrine: Lack of androgens (-> post-menopausal osteoporosis as no oestrogen, which needed by bones), hyperprolactinaemia, thyrotoxicosis (as cause increased catabolism), Cushing’s, Acromegaly (as tumour causes testosterone deficiency)
Drugs: steroids
Others e.g. genetic, prolonged intercurrent illness

Sx = fracture of NOF, wrist (Colle), vertebrae (lumbar)

Biochemistry NORMAL

Dx = DEXA (T score

Question 25

Tx Osteoporosis

Answer 25

LIFESTYLE
• reduce causative factors
• Weight-bearing exercise (will maintain bone mass if exercise after 40 years)
• Stop smoking
• Reduce EtOH
DRUGS
1. Vitamin D/Ca mainstay
2. Bisphosphonates (e.g. alendronate) –↓ bone resorption (if other risk factors) and less fractures, but SE = nausea, gastric irritation
3. Teriparatide (PTH derivative)
4. SERMs (selective estrogen receptor modulators) e.g. raloxifene

Question 26

Paget’s disease
Definition

Sx

Biochemistry/Ix

Tx

Answer 26

Focal disorder of bone remodelling

Sx = Focal pain, warmth, deformity, Fracture (pelvis, femur, skull, tibia)
SC compression
Malignancy
Cardiac failure

Nuclear med scan/ XR
Biochemistry: ELEVATED ALP

Tx = Bisphosphonate for pain