Calcium metabolism

Question 1

What is calcium fundamental for?

Answer 1

Muscle and nerve function

Question 2

Where must calcium be tightly regulated?

Answer 2

in the BLOOD PLASMA

It must be maintained regardless of any calcium /vit D deficiency, so bone may be sacrificed for this

Question 3

What portions of calcium is intracellular (bone) / extracellular (plasma)

Answer 3

Intracell = 99% 
Extracell = 1%

Question 4

Explain the three forms serum calcium is found in

Answer 4

Free - 50%
Protein bound - 40% (to albumin)
Complexed - 10% (citrate/phosphate)

Question 5

What occurs to total serum calcium in liver disease?

Answer 5

Liver disease means lower albumin
This means lower protein bound calcium
So the total serum calcium seems lower

Question 6

What must we do to correct for these low albumin levels?

Answer 6

CORRECTED CALCIUM

Question 7

How do you work out corrected calcium values?

Answer 7

Corrected calcium = serum calcium + 0.02 x (40- serum albumin)

Question 8

Explain the physiological response to low calcium

Answer 8

1. Fall in ionised calcium
2. Release of PTH from parathyroid gland
3. PTH causes:
   - increased bone calcium resorption
   - increased renal calcium resorption
   - increased 1,25OH vitamin D
   - Increased intestinal absorption of Calcium
4. This causes a rise in plasma calcium

Question 9

What organ secretes PTH?

Answer 9

Parathyroid gland

Question 10

Which three organs are involved in increasing plasma calcium?

Answer 10

KIDNEY (absorption + 1a hydroxylase production)
GI (absorption)
BONE (resporption)

Question 11

What is the role of PTH?

Answer 11

Liberate calcium from bone
Reabsorb calcium from kidneys and increase kidney secretion of 1alpha hydroxylase
Stimulate renal phosphate excretion in urine

Question 12

Which organ produces 1alpha hydroxylase?

Answer 12

KIDNEY

Question 13

What does the urine sample of someone with high PTH look like?

Answer 13

HIGH PO

LOW Ca

Question 14

What are the two forms of Vitamin D?

Answer 14

D2 ergocalciferol

D3 cholecalciferol

Question 15

Where is Vit D2 derived from?

Answer 15

From plants

Question 16

Where is Vit D3 derived from?

Answer 16

mammals

When UV light hits the skin and converts 7-dehydrocholesterol to cholecalciferol

Question 17

What organ produces 25 hydroxylase?

Answer 17

LIVER

Question 18

What triggers the liver to produce 25 hydroxylase?

Answer 18

NOTHING

The liver produces it itself, constantly

Question 19

What is the function of 25 hydroxylase?

Answer 19

Conver cholecalciferol to 25-hydroxycholecalciferol

Question 20

What is the rate limiting step in 1,25OH 2 D3 synthesis?

Answer 20

1alpha hydroxylase converting 25 OH D3 to 1,25OH2 D3

Question 21

What organ secretes 1 alpha hydroxylase

Answer 21

kidney

Question 22

What triggers 1alpha hydroxylase production in the kidney?

Answer 22

PTH release from the parathyroid gland

Question 23

What is Calcitriol?

Answer 23

The drug equivalent of 1,25 OH2 D3

Question 24

Who is Calcitriol prescribed to

Answer 24

To patients with renal dysfunction

So they cannot produce 1alpha hydroxylase

Question 25

What other tissue type can abnormally produce 1a hydroxylase?

Answer 25

Lung cells of sarcoid tissue

Question 26

When is it likely that lung cells of sarcoid tissues produce 1a hydroxylase?

Answer 26

Summer months | Because there is more sunlight > more vitamin D activation

Question 27

What are the functions of activated via D?

Answer 27

Increase intestinal Calcium absorption Increase intestinal phosphate absorption Critical for bone formation

Question 28

What enzyme will be high with high bone turnover?

Answer 28

Alkaline phosphatase

Question 29

What is the skeleton a reservoir for?

Answer 29

Calcium Phosphate Magnesium

Question 30

What is osteomalacia

Answer 30

Normal bone density, but abnormal bone structure | Caused by Vitamin D deficiency

Question 31

What is the mineralisation state of bone in osteomalacia?

Answer 31

DEMINERALISED

Question 32

What are risk factors for Vit D deficiency?

Answer 32

lack of sunlight dark skin Dietary Malabsorption

Question 33

What are clinical features of osteomalacia ia?

Answer 33

bone, muscle pain | increased fracture risk

Question 34

What are biochemical findings of osteomalacia ?

Answer 34

Low Ca Low PO High ALP

Question 35

What are radiological findings of osteomalacia?

Answer 35

Looser zones

Question 36

What are clinical features of rickets?

Answer 36

Bowed legs | Myopathy

Question 37

What are radiological findings of rickets?

Answer 37

Costochondral swelling widened epithets at risk Loozer zone on X ray

Question 38

What drugs can trigger osteomalacia?

Answer 38

Anticonvulsants | because anticonvulsants promote vitamin D breakdown

Question 39

What type of food can trigger osteomalacia?

Answer 39

Phytic acid e.g. chapatis | Phytic acid chelates vitamin D in the gut and reduces absorption

Question 40

What is osteoporosis'

Answer 40

Normal bone mineralisation and structure, but loss of bone density

Question 41

What symptoms does osteoporosis present with

Answer 41

NONE | other than pathological fractures

Question 42

What are risk factors / precipitants for osteoporosis?

Answer 42

Old age (bone disuse) Hyperthyroidism, Cushings Acromegaly Early menopause (loss of protective effect of oestrogen)

Question 43

What fracture is typical in postmenopausal women?

Answer 43

Colles fracture (of wrist)

Question 44

What is the biochemistry of someone with osteoporosis?

Answer 44

normal Ca, Po

Question 45

How do you diagnose osteoporosis?

Answer 45

DEXA scan

Question 46

What is a T score

Answer 46

Number of st dev from mean of young healthy population (20yo)

Question 47

What is a Z score

Answer 47

Number of st dev from mean of age matched control population (20yo)

Question 48

Define osteoporosis:

Answer 48

T score below -2.5

Question 49

Define osteopoenia

Answer 49

T score between -1 and -2.5

Question 50

What are lifestyle treatments for osteoporosis?

Answer 50

Weight bearing exerciser Stop smoking Reduce alcohol consumtion

Question 51

What are drug treatments for osteoporosis?

Answer 51

``` vitamin D/ calcium Biphosphonates Teriparatide Strontium HRT SERMS e,.g. raloxifere ```

Question 52

How do biphosphonates work?

Answer 52

Osteoblasts incorporate calcium BIPHOSPHONATE into bone Osteoclasts can't break this down Very strong bone is produced However long term, this bone is brittle

Question 53

What are symptoms of Hypercalcemia?

Answer 53

Poluyuria/polydipsia Constipation Neuro - seizures, confusion, coma

Question 54

Above what Ca level do hypercalcaemia symptoms occur?

Answer 54

>3

Question 55

What are causes of hypercalcaemia?

Answer 55

Suppressed PTH: - malignancy - sarcoidosis - vit D overdose - thyrotoxicosis Non suppressed PTH - Primary hyperparathyroidism - Familial hypercalciuric hypercalcaemia

Question 56

What causes - Primary hyperparathyroidism

Answer 56

Parathyroid adenoma Parathyroid hyperplasia Parathyroid carcinoma

Question 57

What is the biochemistry in - Primary hyperparathyroidism

Answer 57

high Ca Low PO Raised PTH (inappropriate)

Question 58

What are clinical features of - Primary hyperparathyroidism

Answer 58

BONES STONES MOANS GROANS BONES: loss of calcium in bone > fracture STONES: calcium phosphate stones as phosphate is "thrashed" MOANS: abdominal pain due to constipation, pancreatitis GOANS: psychiatric features e.g. confusion

Question 59

What receptor does the parathyroid gland use to detect calcium?

Answer 59

Calcium Sensing Receptor (CaSR)

Question 60

Explain familial benign hypercalcaemia

Answer 60

Mutation in CaSR | There is a slightly increased set point for PTH release, leading to mild hypercalcaemia

Question 61

What are the three types of hypercalcaemia of malignancy

Answer 61

Humoral Hypercalcemia of malignancy (PTHrP) Bone metastases (e.g. breast cancer) Haematological malignancy

Question 62

How do you treat hypercalcaemia?

Answer 62

Acutely - FLUIDS If cancer - BIPHOSPHONATES Treat underlying cause

Question 63

What are symptoms of hypocalcaemia?

Answer 63

``` Due to heightened neuromuscular excitability - Carpo pedal spasm Trusseau Chvostek Convulsions Hyperreflexia ```

Question 64

What are causes of hypocalcaemia?

Answer 64

Due to low PTH: - surgical - AI thyroiditis - DiGeorge Non-PTH driven - Vit D deficiency - CKD - Pseudohypoparathyroidism (PTH resistance)

Question 65

How do you treat hypocalcaemia?

Answer 65

Calcium + vit D

Question 66

what is renal osteodystrophty

Answer 66

Renal failure > no 1alpha hydroxylase > no Ca absorption. > altered bone formation