Biochem: Calcium homeostasis and bone Flashcards by Anna Hay

Name as many physiological functions of calcium

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

What is the mineral component?

99%
Hydroxyapatite

1% intracellular
0.1% extracellular

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Where is the calcium intracellular

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

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What id the intracellular concentration of calcium

Serum concentration

100nmol/l

Serum: 2.5mmol/l

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How does serum calcium circulate?

Effect of albumin levels
Effect of acidosis

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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How efficient is the absorption of Ca from the diet.

Where does it mostly occur?

Poor only 20-30% absorption
From the small intestine

Depends on Vit D availability

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How does the Calcium balance change throughout a woman lifetime

Child positive
Adult neutral
Post menopausal negative

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What are the 3 main hormones that control calcium levels

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

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

Chief cells in parathyroid

G protein coupled receptor (PTHR1)

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Where does PTH act? What changes does it illicit?

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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What causes primary hyperparathyroidism?

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

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

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What causes secondary hyperparathyroidism?

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

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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What causes tertiary hyperparathyroidism?

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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Which hormone is released by malignant cells leading to hypercalcaemia

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

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

10-20% diet

80-90% skin

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What is the role of vitamin D

Normal bone remodelling

Increases levels of Ca2+ and phosphate by increasing intestinal absorption

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What is considered the active metabolite

Calcitriol

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Describe the synthesis of vitamin d in humans

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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Where can inactive metabolites of vitamin D be stored?

Body fat, released in winter

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What are the physiological actions of vitamin D calcitriol

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

Causes of vit d deficiency

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

How does vitamin D deficiency present in children

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

How does vitamin D deficiency present in adults

Osteomalacia failure to mineralise newly formed osteoid

XRAY: bones thin, perhaps looser zones

Where is calcitonin produced?

What effects does it cause?

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

What effect does calcitonin cause

Acts on kidney and bone but decreases amount of Ca. Kidney: inhibits calcium & phosphate reabsorption Bone: Shrinks osteoclasts

What is dietary absorption of phosphate like?

Good 80% absorbed

How is phosphate excreted?

From the kidney - CKD suffer hyperphosphataemia.

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?

Baby is relative hyperpercalamic 1.4 to 1.0. In the 3rd trimester as this is when ossification occurs.

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

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

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

PTH normal/low Vit D Increased Calcitonin Increased Increased gut absorption

What is the function of bone

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

What the 2 main components of bone?

Osteoid - a protein matrix 25% secreted by osteoblasts. | Mineral component - hydroxyapatite 65% - requires high amounts of caclium and phosphate

What is osteoid made from

Type 1 collegen 90% | Non collagenous protein

What are the 2 types of bone tissue?

Trabecular - spondy appearance | Cortical strong heavy outer layer

What are the 3 types of bone cells

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

What is the importance of bone remodelling

Good quality bone and structural integrity

What id the effect of oestrogen on the bone cells

- Inhibits osteoclast function and osteoclastgensis - Promote osteoblast survival Hence why menopause is linked to osteoporosis

What hormone deficiency causes 20% osteoporosis in men

Testosterone deficiency

How can you asses bone remodeeling and bone mineral density

XRAY/DEXA | Biochemical markers of bone turnover

How many women are at risk of osteoporotic fractures >50

1 in 2 (1 in 5 in men)

What causes osteoporosis on a cellular level

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.

What advice can be offered to those with osteopenia

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

Who are DEXA scans offered to

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

WHO diagnosis of osteopenia/osteoporis

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

What 2 important factors determine risk of osteoporosis

Rate of bone loss (accelerated in menopause) | Peak bone mass obtained

How to manage osteoporosis

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

How much calcium a day does lactation require

280-400mg/day

Can pregnancy cause osteoporosis

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

Juvenile osteoporosis Causes effect on later life

Idiopathic Underlying condition (RA, endocrine disorder) Drugs (steroid) Lifestyle Lower peak bone mass, high risk of osteoporosis in later life