day 2 - calcium and bone

Question 1

 There are constant exchanges of calcium between pools at the level of:

Answer 1

Kidney - glomerular filtration v. tubular reabsorption (key regulatory site) GI Tract - absorption v. secretion
Bone - formation v. resorption
i.e. these are the points of homeostatic control

Question 2

 Calcium homeostasis threatened by:

Answer 2

Disorders of gut, kidney & skeleton
Parathyroid disorders
Abnormal vitamin D metabolism (intake, synthesis, metabolism)

Question 3

 The routine laboratory measurement is of total plasma calcium
 Plasma calcium comprises

Answer 3

Plasma calcium comprises albumin bound (40%), complexed (10%) and free ionised
(50%) fractions
 Only IONISED calcium is physiologically active and homeostatically regulated

Question 4

Laboratories usually issue total calcium results. These should be corrected to mean
normal serum albumin to avoid misinterpretation. There are various nomograms to do this but an easily remembered one is:

Answer 4

Corrected calcium = calcium + 0.02 (40-albumin)

e.g. total calcium 2.0, albumin 30, corrected calcium 2.2mmol/L

Question 5

 The ionised serum calcium has key roles in:

Answer 5

• structure of bone and teeth
• neuromuscular activity
• coagulation (enzyme co-factor)

Question 6

 PTH is released from parathyroid glands in response to:

Answer 6

• A fall in plasma ionised Ca (most important, detected by calcium receptor)
• A rise in plasma phosphate (chronic effect only)

Question 7

Target organs of PTH are:

Answer 7

Kidney: Increases Ca reabsorption Decreases PO4 reabsorption

Increases 1 alpha-hydroxylation of Vit D (i.e. activation) Bone: Increases osteoclastic resorption of bone

Question 8

vitamin d source

Answer 8

Sources are dermal synthesis (action of UV light on 7-dehydrocholesterol>cholecalciferol) and diet
 Initial hepatic hydroxylation forms inactive 25-OH cholecalciferol
 Regulated renal hydroxylation forms active 1,25 dihydroxycholecalciferol (calcitriol)
 Calcitriol formation (1alpha-hydroxylase activity) stimulated by:
- low ionised calcium (via PTH)
- low phosphate

Question 9

Calcitriol has actions on:

Answer 9

Gut - increased absorption of Ca and PO4 Kidney - increased Ca and PO4 reabsorption Bone - (resorption/mineralisation, remodelling)

Question 10

Calcitonin action

Answer 10

 Has hypocalcaemic actions and is stimulated by increased serum ionised calcium
 Physiological importance in man unclear

Question 11

the typical symptoms of hypercalcemia.

Answer 11

A helpful mnemonic, “painful bones, renal stones, abdominal groans, and psychic moans,” can be used to recall the typical symptoms of hypercalcemia. Painful bones are the result of abnormal bone remodeling due to overproduction of PTH. Nephrolithiasis occurs secondary to hyperparathyroid disease–induced hypercalcemia and resultant hypercalciuria. Abdominal groans refers to hypercalcemia-induced ileus. Psychic moans or depression may occur in the presence of persistently elevated serum calcium levels.

however,  Often asymptomatic and detected by chance

Question 12

Causes of Hypercalcaemia

Answer 12

 Common
- Primary hyperparathyroidism (prevalence 1/1000)

• Malignant disease (including myeloma):
• Bony metastases
• Neoplastic synthesis of PTH-related peptide
• Neoplastic synthesis of other hypercalcaemic agents

 Others

• Sarcoidosis (increased calcitriol synthesis)
• Vitamin D intoxication
• Tertiary hyperparathyroidism (e.g. chronic renal failure —–> post Tx) - Immobilisation (Paget’s, adolescents)
• Thyrotoxicosis, if severe
• Thiazide diuretics
• Familial hypocalciuric hypercalcaemia (rare)

Simple Guide in Hypercalcaemia
 Hypercalcaemia + suppressed PTH = non-parathyroid cause
 Hypercalcaemia + raised (or detectable) PTH = PTH-mediated cause

Question 13

Some Clinical Features of Hypocalacaemia

Answer 13

 Numbness, parasthesiae, muscle cramps, convulsions
 Positive Chovstek’s and Trousseau’s signs
 Prolonged QT on ECG
 Myopathy & bone pain (vitamin D deficiency)

Question 14

Causes of Hypocalcaemia (but beware hypoalbuminaemia)

Answer 14

 Vitamin D deficiency
 Disordered vitamin D metabolism (e.g. renal failure)
 Hypoparathyroidism (congenital; autoimmune; post thyroid surgery; infiltration)
 Pseudohypoparathyroidism (PTH resistance)
 Magnesium depletion (impaired PTH synthesis/release)
 Acute pancreatitis
 Neonatal
 Massive blood transfusion (citrated blood)
 Artefactual (blood sample collected into EDTA or citrate!)

Simple Guide in Hypocalcaemia
 Hypocalcaemia + low/undetectable PTH = hypoparathyroidism
 Hypocalcaemia + elevated PTH = non-parathyroid cause (except pseudo hypo-
parathyroid)

Question 15

what is Osteomalacia

Answer 15

(Known as Rickets in Children)
Characterised by defective mineralisation of bone (calcium deficiency) and increased osteoid.
Causes of Osteomalacia
 Dietary calcium and/or Vitamin D deficiency
 Inadequate exposure to sunlight
Malabsorption
Disordered Vitamin D metabolism
- Renal disease (decreased 1-hydroxylation)
- Vitamin D-dependent rickets (1alpha-hydroxylase deficiency) - Anticonvulsant therapy (induces metabolism)
Phosphate deficiency (renal tubular leak)

Question 16

Laboratory Findings in Osteomalacia

Answer 16

 Low serum calcium and phosphate
 High alkaline phosphatase (osteoblastic response; N.B. interpreted with age-related
reference range)
 ? Low circulating 25-OH cholecalciferol (useful marker of dietary deficiency)
 Elevated serum PTH (—–> 2o hyperparathyroidism)

Question 17

what is Osteoporosis

Answer 17

Characterised by reduction in bone mass via loss of matrix; excessive bone loss; normal mineral:matrix ratio.

Question 18

Causes of Osteoporosis

Answer 18

 Old age - post menopausal
 Endocrine
- Premature ovarian failure (early menopause) - Cushing's
- Thyrotoxicosis
 Drugs: steroids, heparin