Chem Path

Question 1

Normal Calcium Range

Answer 1

2.2-2.6mmol/L

Free “ionised” - must remain fixed for muscle and nerve function.

Question 2

Calcium Stores

Answer 2

Bone: 99%
Serum : 1%
- Free/ionised = 50%
- Protein bound (albumin) = 40%
- Complexed (citrate/phosphate) = 10%
Use corrected calcium to compensate for changes in albumin.

Question 3

PTH MOA

Answer 3

Parathyroid glands detect hypocalcaemia and secrete PTH.

1) Bone - Ca2+ release
2) Gut - absorption
3) Kidney - resorption and renal 1 alpha hydroxylase activate -> activates Vit D

Question 4

Ca Metabolism Enzymes

Answer 4

25 hydroxylase (liver)
1 hydroxylase (kidney)

Question 5

Physiological Roles of Vit D

Answer 5

Activates absorption of calcium in the gut
Activates absorption of phosphate in the gut
Critical for bone formation

Question 6

Clinical Features of Osteomalacia

Answer 6

Bone and muscle pain
Increase # risk
Low Ca2+ and Phosphate
High ALP
Looser's zones (pseudo #)

Question 7

Clinical Features of Rickets

Answer 7

Bowed legs
Costochondral swelling
Widened epiphysis of wrist
Myopathy

Question 8

Causes of Osteomalacia (important)

Answer 8

BONE IS DEMINERALISED

• Vit D deficiency (secondry HPTH)
• Renal failure (renal oseodystrophy) = reduced 1aOHase (reduced activation Vit D)
• Anticonvulsants (e.g. phenytoin) - induce Vit D breakdown
• Lack of sunlight
• Chappatis (phytic acid) - chelates Vit D in gut and prevents absorption

Question 9

Features of Osteoporosis

Answer 9

LOSS OF BONE MASS (not demineralised)
Post-menopausal W - sex steroids maintain mass
Cushings - increased catabolism (bone loss)
Ca and Pi are NORMAL
# = NOF, vertebral, Colle’s

Question 10

Dx of Osteoporosis

Answer 10

DEXA scan

T score DEXA>-2.5 = osteopenia

Question 11

Causes of Osteoporosis

Answer 11

Failure to attain peak BM (e.g. childhood illness)
Early menopause
Rapid loss during adulthood:
- lifestyle (sedentary, EtOH, low BMI)
- endocrine (hyperprolactinaemia, thyrotoxicosis, Cushings)
- Drugs (steroids, e.g. pred)
- Other (genetic, prolonged illness)

Question 12

Tx of Osetoporosis

Answer 12

Lifestyle - weight bearing exercise, stop smoking, reduce EtOH
Vit D/Ca, Bisphosponates, teriparatide, strontium, HRT, SERMs

Question 13

Causes of hypercalcaemia

Answer 13

IS PTH SUPRESSED?
Yes = appropriate
Malignancy (Common)
Sarcoid, vit D excess, thyrotoxciosis, milk alkali syndrome (rare)

NO = inappropriate
PHPT (common)
Familial hypocalciuiric hypaercacaemia (Rare)

Question 14

Familial Hypocalciuric Hypercacaemia

Answer 14

CaSR mutation
Higher set point for PTH release
Mild hypercalcaemia
Reduced urine Ca2+

Question 15

Ca Sensing Receptor (CaSR)

Answer 15

Parathyroids (regulate PTH release)

Renal (influences Ca resorption - independent of PTH)

Question 16

Hypercalcaemia in Malignancy

Answer 16

1. Humoral hypercaclcaemia e.g. SCC secretes PTHrP
2. Bone mets e.g. breast - bone osteolysis (raised ALP)
3. Haematological malignancy e.g. myeloma (cytokines)

Question 17

Non-PTH Driven Hypercacaemia

Answer 17

Sarcoidosis (non renal 1a hydroxylation) (raised ALP)
Thyrotoxicosis (thyroxine -> bone resorption) (raised ALP)
Thiazide diuretics - stops you peeing out Ca2+
Excess Vit D - sunbeds

Question 18

Treatment Hypercalcaemia

Answer 18

Acute: Fluids +++
Ca>3
4L normal saline over 24hr
Elderly/ heart failure = 1L/4hrs - examine and repeat if not overloaded
Ca<3 = drink fluids/ discharge

Treat cause
If cause known malignancy - bisphosphonates for bone pain (hypercalcaemia is poor prognositc marker in malignancy)

Question 19

Presentation of Hypocalcaemia

Answer 19

Signs occur in severe or rapid onset

Severe = carpopedal spasm
Life threatening = laryngeal spasm and convulsions
Check Ca in patients presenting with fit

Question 20

Paget’s Disease

Answer 20

Focal bone remodelling disorder
Pain, warmth, deformity, fracture, SC compression, malignancy, cardiac failure
Pelvis, femur, tibia
ELEVATED ALP
NUclear med scan/X ray
Tx: Bisphosphonates for pain

Question 21

Osteitis Fibrosa

Answer 21

Loss of cortical bone and # risk in primary HPTH

Question 22

Renal Osteodystrophy

Answer 22

Due to secondary HPTH and retention of aluminium from dialysis