Bone Profile

Question 1

What role does calcium play?

Answer 1

Calcium ions combine with phosphate ions to form calcium phosphate which increases the rigidity and hardness of bones and enamel of teeth

Ca ions also involved in:
-signal transduction
-Blood clotting
-skeletal and cardiac muscle contraction
-nerve activity
-essential cofactors for many enzymes
-secretion
-milk production

Question 2

What factors influence the variable absorption of calcium from the small intestine?

Answer 2

-Conc in diet
-pH
-Presence of activated vitD
-Parathyroid hormone
-High protein diet
-Steatorrhoea
-Age

Question 3

Look at calcium homeostasis

Question 4

What acts as a natural antagonist of calcium?

Answer 4

Magnesium

Question 5

What is calcium regulated by and how?

Answer 5

1. Vitamin D - produced by adrenal gland and func to stimulate intestinal calcium and phosphate absorbance and increase renal reabsorption of calcium
2. Parathyroid Hormone (PTH) - produced by parathyroid gland and func to increase blood calcim - PTH increases intestinal absorption, increases osteoclast activity and increases renal absorption
3. Calcitonin (CT) - produced by thyroid gland and functions to lower blood calcium levels e.g CT inhibits osteoclast activity and decreases renal absorption of calcium

Question 6

How does PTH increase blood calcium?

Answer 6

1. Increasing intestinal absorption
2. Increasing osteoclast activity
3. Increasing renal absorption
   (acts on bone, kidney, intestine)

Question 7

When is PTH released/regulated?

Answer 7

-Released by parathyroid glands when extracellular calcium is decreased
-Regulated by serum calcium through a negative feedback mechanism

Question 8

LOOK at diagram on raising serum calcium

Question 9

What is PTH?

Answer 9

-MW is 9500
- single chain polypeptide composed of approx. 84 amino acids

Question 10

What is Calcitonin?

Answer 10

-32-amino acid peptide with one disulphide bond

Question 11

How does Calcitonin work?

Answer 11

1. CT inhibits osteoclast activity
2. decreases renal absorption of calcium
   (bone and kidneys are responsive to human calcitonin, may decrease intestinal absorption)

Question 12

Where is calcitonin secreted?

Answer 12

-By C cells of the thyroid in response to na increase in ionised calcium

Question 13

Look at lowering serum calcium diagram

Question 14

What does Vitamin D do and what are target tissues of vit D?

Answer 14

-Stimulates intestinal calcium and phosphate absorbance and increases renal reabsorption of calcium (also stimulates osteocytes)

-Target tissues are - intestine, bone, kidney

Question 15

What is activated vit D?

Answer 15

Activated vit D refers to 1,25-dihydroxycholecalciferol
-produced in adrenal glands
-fat soluble vitamin
-I-hydroxylase enzyme activity in kidney

Question 16

What forms is calcium present in the serum in?

Answer 16

1. Ionised or free (45-50%) - physiologically active
2. Complexed (5-10%) - w bicarbonate or citrate
3. Protein bound (40-50%) - physiologically inactive

(amount of calcium present in ECF is very small in comparison to stired in bone)

Question 17

What is total serum calcium usually and what is this bound to and what does this binding depend on?

Answer 17

-Non-diseased state total serum calcium is around 2.4mmol/L
-50% is protein bound - mostly to albumin
-Binding is pH dependent and is decreased in acidosis and increased in alkalosis

Question 18

What is the unbound calcium?

Answer 18

-Unbound calcium is the biologically active fraction of the total calcium in plasma and maintenance of its concentration within tight limits is required for nerve func, membrane permeability and glandular secretion
-Unbound calcium is recognised by the parathyroid hormone glands and the PTH acts to keep this conc constant

Question 19

What is adjusted calcium and why is it measured?

Answer 19

-Changes in serum albumin conc in ptients cause changes in total calcium conc
- To ensure patients with a low albumin arent mistakenly labelled as hypocalcaemic, use adjusted calcium - need to have done albumin test
-Also ensures patients w an apparently normal total calcium and a low albumin are not overlooked when they are hypercalcaemic

Question 20

What is the adjusted calcium formula?

Answer 20

total calcium + 0.02(47-albumin)

(still 5-10% is complexed)

Question 21

What are the causes of hypercalcaemia?

Answer 21

-Advanced multiple myeloma (MM)- increased osteoclast activity so release more calcium into blood
-Bone metastasis - imbalance between bone formation and absorption
-High levels of vitD
-Hyperparathyroidism - primary: gland produces excess PTH and secondary: hypoplasmia, vit D deficiency, increase production rate of cells

Question 22

Clinical features of Hypercalcaemia?

Answer 22

-Neurological and psychriatric features such as lethargy, confusion, irritability, depression
-gastrointestinal problems like anorexia (no desire to eat), abdominal pain
-renal features like thirst and polyuria
-cardiac arrhythmias

Question 23

Hypercalcaemia - diagnosis - hyperparathyroidism?

Answer 23

-Hyperparathyroidism is often due to a single parathyroid adenoma which secretes PTH independently of feedback control by plasma calcium

Question 24

Treatment of Hypercalcaemia

Answer 24

-Treatment is urgent if adjusted calcium is greater than 3.5mmol/L - priority is to reduce to a safe level
-Intravenous saline is administered first to restore GFR and promote a diuresis
-Aminohydroxyproplidene diphosphonate (ADP) has become treatment choice in patients w hypercalcaemia of malignancy - acts by inhibiting bone resorption

Question 25

What is urgent adjusted calcium level?

Answer 25

3.5 mmol/L

Question 26

Hypocalcaemia causes?

Answer 26

-Renal disease -Vit D deficiency -Hypoparathyroidism -Calcipenic risks -Osteomalaciav- softening of bones - severe vitD deficiency

Question 27

What are the clinical features of hypocalcaemia?

Answer 27

Neurologic features such as tingling, tetany and mental changes, cardiovascular signs cataracts

Question 28

Treatment of Hypocalcaemia?

Answer 28

-The management calls for the treatment of the cause of hypocalcaemia oral calcium supplements are commonly described in mild disorders -1, 25-dihydroxycholecalciferol (1,25DHCC) - calcitrol (a hormonally-active, synthetic vit D analogue) can be administered

Question 29

LOOK at differential diagnosis of hyper and hypo calcaemia

Question 30

How is calcium ion conc measured - what assay is used?

Answer 30

-Colorimetric assay which can be read spectrophotometrically at 540nm - 8-hydroxyquinoline ca2+ + ortho-cresolphthalein > Ca-ortho-cresolphthalein complex (violet) -pH 10.6 (alkaline)

Question 31

Calcium reference ranges?

Answer 31

2.1-2.6 mmol/L -hypocalcaemia < 2.1mmol/L -hypercalcaemia >2.6mmol/L

Question 32

Magnesium (Mg2+)

Answer 32

-Second most common intracellular cation -its abundance facilitates its multiple funcs in common, essential intracellular porcesses -an average dietary intake is around 15mmol per day - children and lactating mothers have higher requirements

Question 33

Sources of Magnesium?

Answer 33

-Plant foods like legumes, dark green leafy vegetables, nuts, seeds, whole grains, fortified cereals fish, poultry and beef

Question 34

Functions of Mg2+?

Answer 34

-Cofactor in multiple enzymatic rxns -Regulation of ion channels -Regulation of: muscular contraction, blood pressure, insulin metabolism, cardiac excitability, vasomotor tone, nerve transmission, neuromuscular conduction

Question 35

What can hypomagnesemia cause?

Answer 35

-May cause hypocalcaemia through activation of calcium-sensing receptors in the parathyroid glands thus suppressing PTH secretion -Hypermagnesemia is uncommon but occasionally seen in renal failure as there is no magnesium regulatory system other than urinary excretion

Question 36

Where is hypomagnesaemia common?

Answer 36

-In hospitalised patients or in cases of hypercalcaemia (hyperparathyroidism) -Symptoms of hypomagnesaemia are v similar to those of hypocalcaemia; impaired neuromuscular func such as tetany, hyperirritability, tremor, convulsions nd muscle weakness

Question 37

Laboratory diagnosis of Magnesium levels?

Answer 37

-Spectrophotometric with metallochromic indicators, calmagite and methylthymol blue, formazan dye, magon and phosphoazo III

Question 38

Treatment of Magnesium decrease?

Answer 38

-Repeated demonstration of magnesium conc of <0.7mmol/L in a serum sample is evident of marked intracellular depletion - benefit from magnesium therapy -Provision of magnesium supplements in oral diets is complicated as may cause diarrhoea -Aadministration of magnesium salts contraindicated when there is evidence of renal impairment

Question 39

What is phosphorous/phosphate?

Answer 39

-important intracellular and extracellular anion -much of phosphate inside cells is covalently attached to lipids and proteins -phosphorylation and dephosphorylation of enzymes are important mechanisms in the regulation of metabolic activity -most of bodys phosphate is in bone -phosphate changes accompany calcoium deposition or resorption of bone

Question 40

How is control of ECF phosphate concentration achieved?

Answer 40

By the kidney - where tubular reabsorption is reduced by PTH - decrease phosphate reabsorption

Question 41

What might hyperphosphataemia cause?

Answer 41

Persistent hyperphosphataemia may result in deposition of calcium phosphate in soft tissues

Question 42

Causes of hyperphosphataemia?

Answer 42

1. Renal failure - failure to excrete phosphorous 2. Hypoparathyroidism 3. Haemolysis 4. Pseudohypoparathyroidism - rare induced genetuc diorder - resistant to PTH

Question 43

Causes of hypophosphataemia?

Answer 43

Severe hypophosphataemia is rare and causes muscle weakness - lead to respiratory impairment - modest hypophosphataemia is more common 1. Hyperparathyroidism - primary can chnage from low to normal phosphate levels 2. Congenital defects of tubular phosphate reabsorption 3. Ingestion of non-absorbable antacids 4. Severe dietary deficiency