Calcium phosphate regulation

Question 1

What is the most abundant metal in the body?

Answer 1

Calcium

Question 2

What is the recommended adult intake of calcium per day?

Answer 2

1000mg/day

Question 3

Describe the calcium distribution in the body

Answer 3

99%- skeleton and teeth

1%- intracellular

0.1%- extracellular

Question 4

Further describe the extracellular calcium distribution in the body. Give values

Answer 4

Plasma- 2.5mmol/L

This is split up into ionised ca2+ and bound ca2+

Bound Ca2+ is either bound to plasma proteins(albumin) or anions(lactate/bicarbonate or phosphate)

Question 5

What calcium is very tightly regulated

Answer 5

Extracellular calcium

Question 6

What does the calcium in Skelton and teeth exist as?

Answer 6

Calcium hydroxyapatite

Question 7

Why is calcium important in the body

Answer 7

Muscle contraction

Bone strength

Question 8

Which extracellular calcium is biologically active

Answer 8

Unbounded free calcium ions

Question 9

What is the use of phosphate in the body

Answer 9

Essential in ATP

Act as 2nd messenger

Fundamental in DNA, RNA

Question 10

Describe the relationship between extracellular phosphate and extracellular calcium? What is the significance?

Answer 10

Extracellular phosphate is inversely proportional to extracellular calcium

Hence both regulated by same hormone

Question 11

What are the controls for increasing serum calcium and phosphate ? What hormones are involved; where are they made respectively

Answer 11

Parathyroid hormone - parathyroid gland

Vitamin D- skin or intakes via diet

Question 12

How does Vit D and PTH act to regulate calcium and phosphate- what organs?

Answer 12

Via actions on kidney, bone and gut

Question 13

What Hormone act to actively decrease calcium levels? What is its significance

Answer 13

Calcitonin- from thyroid gland Not critical/ significant in the body as calcium levels are stable after thyroidectomy

Question 14

What are the sources of Vitamin D?

Answer 14

Vitamin D2- Ergocalciferol- from diet

Vitamin D3- cholecalciferol- made in skin

Question 15

Describe the process of how vitamin D3 is synthesised from skin?

Answer 15

UVB light shine on skin

Converts 7-dehydrocholesterol to pre-vitamin D3

Then pre-vitamin D3 is converted to Vitamin D3

Question 16

How is vitamin D2 and D3 converted to the active vitamin calcitriol?

Answer 16

D3 and D2 are in blood stream; goes to liver

The enzyme- 25-hydroxylase converts D2 or D3 TO 25(OH) cholecalciferol- not active.

This is then transported to KIDNEY and converted to 1,25(OH)2 cholecalciferol aka CALCITRIOL. This is catalysed by 1 ALPHA-HYDROXYLASE

Question 17

How is vitamin D levels measured? What chemicals are measured?

Answer 17

The serum25-OH vitamin D is used as an indicator of vitamin D levels instead of calcitriol; very tricky to measure as it is light sensitive

Question 18

How does calcitriol regulate its own production?

Answer 18

Negative feedback; when too much it decreases transcription of 1 ALPHA hydroxylase

Question 19

Outline the effects of calcitriol in different regions of the body

Answer 19

GUT: increases Ca2+ and phosphate absorption KIDNEY: increases calcium and phosphate reabsorption Bone : increases osteoBLAST activity (bone mineralisation)

Question 20

What cells in parathyroid gland secrete PTH? What is the precursor of PTH

Answer 20

Chief cells

Precursor- pre-pro-PTH then cleaved after

Question 21

What type of receptor does calcium ion bind to on chief cells?

Answer 21

GPCR

Question 22

Describe the relationship between PTH secretion and serum calcium levels

Answer 22

Inversely proportional When calcium levels are high extracellular; calcium binds to GPCR; this inhibits secretion of PTH

Question 23

Describe the effects of PTH on bones

Answer 23

Increased osteoclasts activity; more bone resorption and increasing PLASMA calcium ions levels

Question 24

Describe the effects of PTH on kidney?

Answer 24

Increased calcium ions reabsorption and phosphate ions EXCRETION

Increased 1-alpha hydroxylase activity hence more calcitriol

Calcitriol has its own effects- list them

Question 25

Describe in detail how PTH increase osteoclasts activity?

Answer 25

PTH bind to PTH receptors on osteoBLASTS and causes it to make osteoCLAST activating factors to convert the osteoBLAST to osteoCLAST. Increased bone resorption

Question 26

How is PTH regulated? What are the ways

Answer 26

Too much plasma calcium ions levels will negatively feedback on chief cells on parathyroid gland Calcitriol inhibits PTH consumption

Question 27

What cels secrets calcitonin? what does calcitonin do?

Answer 27

Parafollicular cells of thyroid gland It reduces serum calcium Only used in medication when pt has very high calcium with bone pain- very rare. Not significant in body as removal of thyroid doesn’t affect calcium levels.

Question 28

What causes release of calcitonin?

Answer 28

Increased plasma calcium levels

Question 29

How does calcitonin reduce calcium plasma levels?

Answer 29

Reduce osteoCLAST activity Increased calcium ions excretion in kidney

Question 30

What growth factor regulates phosphate levels?

Answer 30

FGF23- fibroblast growth factor 23 in PCT kidney

Question 31

How is phosphate regulated? Describe exhaustively

Answer 31

PTH inhibits NA+/PO4 transporter in PCT; less phosphate reabsorbed FGF23 inhibits the transporter. FGF23 also inhibits calcitriol so less phosphate reabsorbed from the gut

Question 32

What are the two abnormal calcium amount in blood? Explain their general effects respectively

Answer 32

Hypercalcaemia- ca2+ blocks Na+ influx so LESS membrane excitability HYPOcalcaemia- MORE membrane excitability

Question 33

What are the signs and symptoms of hypocalcaemia?

Answer 33

Convulsions Arrhythmia Tetany- muscle contract but doesn’t relax Paraesthesia \***CATs go Numb**\* Osteo-malacia- bones easily break

Question 34

What are the main 2 signs of HYPOcalcaemia seen in clinics? Describe

Answer 34

CHVOSTEK’S sign- taps below cheek bones leads to twitching of facial muscles. TROUSSAES’s sign- BP cuffs inflated for several minutes and induces carpopedal spasm. Neuromuscular irritability due to hypocalcaemia

Question 35

What are the potential causes of hypocalcaemia

Answer 35

Low PTH Vitamin D deficiency

Question 36

Wha are the possible causes of hypoparathyroidism?

Answer 36

Surgically- neck surgery Autoimmune Magnesium deficiency Born with it

Question 37

What are the potential causes of vitamin D deficiency?

Answer 37

Inadequate sunlight exposure Malabsorption or insufficient intake Liver disease Renal disease Vitamin D receptor defects

Question 38

What are the signs and symptoms of hypercalcaemia?

Answer 38

Renal effects- kidney stones Abdominal moans- anorexia, nausea,constipation, heart burn Psychic CNS effects- fatigue, depression, impaired concentration, coma, altered mentation

Question 39

What are the potential causes of hypercalcaemia?

Answer 39

Primary hyperparathyroidism- parathyroid adenoma, no negative feedback Excess vitamin D Malignancy- Bone cancers metastatstes to make osteoclasts. Or cancer that make peptide that look exactly like PTH

Question 40

Describe the axis of the actions of calcitriol . Draw it on notability or paper

Answer 40

Question 41

Describe and draw the action of PTH on different parts of the body?

Answer 41

Question 42

Draw hoe PTH is regulated

Answer 42