calcium homeostasis

Question 1

What points about Ca will be discussed?

Answer 1

Milk products contain calcium
Vit D helps absorb calcium
Needed for strong bones
Just for kids

Question 2

Is Ca important for strong bones?

Answer 2

1kg in body, 99% in bone
Blood and ECF has a total of 2.2mm and ~60% is ionised (Ca2+)
Intracellular 100nm basal cells

Question 3

Why is Ca needed for intracellular signalling?

Answer 3

100microM pulses
Cells excited by external stimuli and release Ca into cytosol

Stored in ER or mitochondria
Eg. Ca in SR released to cause actinomyosin reaction for contraction, it’s pumped back in for future use

Question 4

What is Trousseaus sign?

Answer 4

Reduce blood flow
Neuromuscular irritability
Hypocalcaemia causes Na+ influx
Tetanic contraction

Question 5

How much Ca is required?

Answer 5

<1yr 525mg
1-3yrs 350mg
4-6yrs 450mg
7-10yrs 550mg
800mg girls/1000mg boys for adolescents
700mg per day for adults
1250mg for breastfeeding 
1200mg past menopause 
1000mg coeliac disease
1000mg osteoporosis 
1000mg IBS
1200mg IBS + post menopause/men over 55yrs

USA- 1300mg adults

Question 6

What foods contain calcium?

Answer 6

Milk- 250mg
Tinned fish- 250mg
White bread (2 slices)- 100mg
Broccoli- 40mg

Question 7

How is Calcium uptaken?

Answer 7

In small intestine

2 routes-
Trancellular- low intake, active
Paracellular- high intake, passive

Question 8

What regulates homeostasis of Ca?

Answer 8

Parathyroid- parathyroid hormone released

Thyroid glands- calcitonin released to inhibit

Question 9

What is the parathyroid hormone?

Answer 9

Secreted by chief cells
84 AA peptide chain
Targets osteoclasts
Increases synthesis of dihydroxy form of Vit D in kidney- 1,25(OH)2D3
High Ca2+ levels in plasma inhibits release
Low Ca2+ released into circulation causing osteolytic osteolysis

Question 10

What is calcitonin?

Answer 10

Released by parafollicular cells
32 AA peptide
Released when Ca2+ high
Inhibits bone resorption
Role in pathology? Therapeutic target?

Question 11

What is Vit Ds role?

Answer 11

Aka calcitriol

Must be hydroxylated to become active
Allows small intestine absorption by up regulating carriers and changes junctions to make the mm more permeable to Ca

Fat soluble and can be stored from one month to another- could potentially retain for the year

Question 12

Where can Vit D come from?

Answer 12

Fortified cereal
OJ
Egg yolk
Mushrooms
Ricotta cheese
Fatty fish
Cod liver oil
Caviar

Difficult to obtain unless rich oily fish diet

Question 13

Is Vit D a vitamin?

Answer 13

Struggle to her much from diet
Can be synthesised in body

Pro-Vit D widespread in body (derivative of cholesterol) and can be converted in skin via sunlight into a semi active form- cholecalciferol which can be hydroxylated in kidney and liver into 1,25(OH)2D

People w higher melanin restricts amount of conversion

Receptor of Vit D is a transcription factor so it can downregulate and activate other genes

Perfect level of sunlight is just before skin goes red to synthesise Vit D

Question 14

What happens in Vit D deficiency?

Answer 14

Affects development of long bones
Osteocytes and osteoblasts around developing bone have receptors for Vit D
Role of Vit D in transporting Ca from plasma to bone
Most effect due to hypocalcaemia

Rickets in children

1:5 w deficiency have teeth defects (6-24months of age, enamel hypoplasia, enlarged pulp horns, delayed eruption, caries risk)

Question 15

How does Vit D affect bone turnover?

Answer 15

Activates osteoclasts to increase Ca levels
Works indirectly via osteoblasts on osteoclasts (osteoblasts release RANKL)
Depends on dose and if it’s being applied in vivo/in vitro

Question 16

What potential Vit D non skeletal roles are there?

Answer 16

Protective role in-
Cancer
Autoimmune disease
Hypertension and CVD
Diabetes
Muscle strength
Schizophrenia and depression

Question 17

What is osteomalacia?

Answer 17

Vit D deficiency in adults

Pathological amount of callus matrix
Pseudofractures
Bone pain
Muscle weakness
Perio disease

Question 18

What is osteoporosis?

Answer 18

Low bone density (thin trabeculae)
T-score- 0 is normal density
Derived from dual energy X-ray absorptiometry DEXA

Pathogenesis- reduced uptake of dietary Ca, imbalance of bone turnover, reduced density

Reduction in oestrogen
Oestrogen- inhibits osteoclasts and promotes Vit D in gut
Post menopause esp

Treatment - Ca and Vit D3 (Adcal-D3 of Alendronic acid) may cause reversal

Question 19

Why is weight training important?

Answer 19

Osteoblasts increase bone density via loading

Evidence- children yes, adults no but other benefits- improved muscle function and balance so less falls and less fractures