Biochem: Calcium homeostasis and bone Flashcards

1
Q

Name as many physiological functions of calcium

A
Bone mineralisation
Tooth formation
Muscle contraction 
Enzyme co-factor 
First extracellular messenger 
Second intracellular messenher 
Secretion and exocytosis 
Stabilistion of membrane potentials 
Regulation of cellular division, proliferation and apoptosis
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2
Q

How much of the 1.2kg of Ca2+ is stored in the skeleton?

What is the mineral component?

A

99%
Hydroxyapatite

1% intracellular
0.1% extracellular

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3
Q

Where is the calcium intracellular

A

Sequested in intracellular organelles (endoplasmic reticulum, mitochondria, skeletal muscle sarcoplasmic reticulum)

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4
Q

What id the intracellular concentration of calcium

Serum concentration

A

100nmol/l

Serum: 2.5mmol/l

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5
Q

How does serum calcium circulate?

Effect of albumin levels
Effect of acidosis

A

45% free ionised form (free calcium)
55% bound (45% to albumin) - changes in albumin changes rain free to bound calcium, in acidosis H+ competes for albumin binding sites

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6
Q

How efficient is the absorption of Ca from the diet.

Where does it mostly occur?

A

Poor only 20-30% absorption
From the small intestine

Depends on Vit D availability

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7
Q

How does the Calcium balance change throughout a woman lifetime

A

Child positive
Adult neutral
Post menopausal negative

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8
Q

What are the 3 main hormones that control calcium levels

A

Parathyroid hormone (increases levels)
Vitamin D/Calcitriol (increase levels)
Calcitonin (decrease levels)

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9
Q

Where is parathyroid hormone produced. Which receptors does it act on?

A

Chief cells in parathyroid

G protein coupled receptor (PTHR1)

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10
Q

Where does PTH act? What changes does it illicit?

A

Bone: Activate osteoclasts resorb bone - release Ca and phos
Kindey: Increased phosphate excretion
Kindey: Decreases Calcium excretion
Kidney: Activated Vitamin D

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11
Q

What causes primary hyperparathyroidism?

What happens to levels of Ca/phos/vit d/PTH

A
Excess of PTH from parathyroid (often benign tumour)
High Ca
Low phos 
High Vit D
High PTH
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12
Q

What causes secondary hyperparathyroidism?

What happens to levels of Ca/phos/vit d/PTH

A

Defect in kidneys (CKD), unable to respond to PTH, renal reabsorption Ca not promoted and Vit D not reactivated.

Lead to bone demineralisation (osteomalacia)

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13
Q

What causes tertiary hyperparathyroidism?

A

Complication of secondary PTH continously excreted leading to parathyroid hyperplasia and appears similar to primary hyperparathyroidism.

Seen in end stage renal failure

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14
Q

Which hormone is released by malignant cells leading to hypercalcaemia

A

Parathyroid hormone related peptide (PTHrP) (no effect on active vitamin D)

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15
Q

How much vitamin D is from dietary intake vs synthesised in the skin?

A

10-20% diet

80-90% skin

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16
Q

What is the role of vitamin D

A

Normal bone remodelling

Increases levels of Ca2+ and phosphate by increasing intestinal absorption

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17
Q

What is considered the active metabolite

A

Calcitriol

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18
Q

Describe the synthesis of vitamin d in humans

A

7-dehydrocholesterol in kertinocytes is actived into vitamin D3 (cholecalciferol) mediated by ultraviolet light. It is then activated by i) hydroxylated in the liver ii) hydroxylated in the PCT of kidney to calcitriol.

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19
Q

Where can inactive metabolites of vitamin D be stored?

A

Body fat, released in winter

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20
Q

What are the physiological actions of vitamin D calcitriol

A

Bone: Increases bone formation and mineralisation
Bone: Increased bone remodelling
GI tract: Increased calcium absorption
Kidney: Increased calcium and phosphate reabsorption

also important immune system, inflammation and impair progression of cancer

21
Q

Causes of vit d deficiency

A
Poor nutritional (amount or absorption)
Failure to synthesis - kidney/liver insufficiency, lack of UV light
22
Q

How does vitamin D deficiency present in children

A

Rickets failure to minerlise endochondral bone

Deformity of limbs, soft skull ones, delayed clousre anterior fontanelle, harrison sulcus, thickening ankles/knees/wrists

Suffer bone pain, increased fracture, defects in tooth formation, muscle weakness

23
Q

How does vitamin D deficiency present in adults

A

Osteomalacia failure to mineralise newly formed osteoid

XRAY: bones thin, perhaps looser zones

24
Q

Where is calcitonin produced?

What effects does it cause?

A

Produced parafollicular cells in the thyroid gland in response to high calcium

25
Q

What effect does calcitonin cause

A

Acts on kidney and bone but decreases amount of Ca.

Kidney: inhibits calcium & phosphate reabsorption
Bone: Shrinks osteoclasts

26
Q

What is dietary absorption of phosphate like?

A

Good 80% absorbed

27
Q

How is phosphate excreted?

A

From the kidney - CKD suffer hyperphosphataemia.

28
Q

How does the levels of calcium concentration compare between mother and inutero fetus?

At what stage of the pregnancy does most accumulation of calcium occur?

A

Baby is relative hyperpercalamic 1.4 to 1.0.

In the 3rd trimester as this is when ossification occurs.

29
Q

When can the fetus produce PTH. What are the concentrations like at birth.

A

12 weeks. But serum conc remains low until 2-3days postpartum, high calcitonin

30
Q

What happens to the mothers levels of PTH, Vit D and calctionin

A

PTH normal/low
Vit D Increased
Calcitonin Increased

Increased gut absorption

31
Q

What is the function of bone

A
Structure 
protection
production of blood cells 
Attachment muscles, tendons and ligaments
Storage (buffer) of mineral (ca po Mg)
32
Q

What the 2 main components of bone?

A

Osteoid - a protein matrix 25% secreted by osteoblasts.

Mineral component - hydroxyapatite 65% - requires high amounts of caclium and phosphate

33
Q

What is osteoid made from

A

Type 1 collegen 90%

Non collagenous protein

34
Q

What are the 2 types of bone tissue?

A

Trabecular - spondy appearance

Cortical strong heavy outer layer

35
Q

What are the 3 types of bone cells

A

Osteoclasts - reabsorb bone
Osteoblasts - bone production
Osteocyte - terminally differentiated osteoblasts trapped in bone - maintain contact withsurface by fluid filled canalicil.

36
Q

What is the importance of bone remodelling

A

Good quality bone and structural integrity

37
Q

What id the effect of oestrogen on the bone cells

A
  • Inhibits osteoclast function and osteoclastgensis
  • Promote osteoblast survival

Hence why menopause is linked to osteoporosis

38
Q

What hormone deficiency causes 20% osteoporosis in men

A

Testosterone deficiency

39
Q

How can you asses bone remodeeling and bone mineral density

A

XRAY/DEXA

Biochemical markers of bone turnover

40
Q

How many women are at risk of osteoporotic fractures >50

A

1 in 2 (1 in 5 in men)

41
Q

What causes osteoporosis on a cellular level

A

Osteoclast reabsorption exceeds osteoblast bone formation. In bone remodelling the resorption pits are not fully rested by the osteoblasts and micro fracture are not repaired effectively.

42
Q

What advice can be offered to those with osteopenia

A

Increase Ca intake
Light weight bating exercise
Vt D
Stop smoking reduced ETOH

43
Q

Who are DEXA scans offered to

A
Long term steroids 
Premature menupasuse 
Prolonged secondary amenorrhoea
Hx fragility fracture 
radiological osteopenia 
vertebral defmorty 
Fix early severe osteoporosis
44
Q

WHO diagnosis of osteopenia/osteoporis

A

Normal above -0.1
Osteopenia -1 to -2.5
Osteoporosis below -2.5

45
Q

What 2 important factors determine risk of osteoporosis

A

Rate of bone loss (accelerated in menopause)

Peak bone mass obtained

46
Q

How to manage osteoporosis

A

Maintain current BMD
Lifestyle/diet
Drug Tx (bisphosphonates, selective oestrogen receptor modulator, PTH and denosumab)
Early detected with DXA
prevent fractures
Minimise falls, good footwear/glasses/walking aids/muscle strength & balance

47
Q

How much calcium a day does lactation require

A

280-400mg/day

48
Q

Can pregnancy cause osteoporosis

A

Yes - pregnancy related osteoporosis, BF related osteoporosis

41% 3rd trimester
56% postpartum

presents same pain/loss of height/ vertebral fractures

difficult to assess as imaging contains radiation

Resolved 6 months after birth/weaning

49
Q

Juvenile osteoporosis
Causes
effect on later life

A

Idiopathic
Underlying condition (RA, endocrine disorder)
Drugs (steroid)
Lifestyle

Lower peak bone mass, high risk of osteoporosis in later life