regulation of calcium and phosphate

Question 1

What is the most abundent metal in the body?

Answer 1

Calcium

Question 2

What is the recommended adult intake of calcium?

Answer 2

1000mg/day

Question 3

Where is the majority of calcium in the body

Answer 3

99% in the skeleton as calcium hydroxyapatite crystals 1% intracellular 0.1% extracellular outside the cells in the plasma-tightly regulated

Question 4

how much calcium in per litre of plasma?

Answer 4

2.5mmol/L

Question 5

What are the 2 types of plasma calcium?

Answer 5

Ionised (free in the plasma)-45%, more active Bound calcium

Question 6

Why is calcium important?

Answer 6

-muscle contraction -bone strength -intracellular 2nd messenger -intracellular coenzyme -hormone/neurotransmitter stimulus secretion coupling -blood coagulation (factor IV)

Question 7

What is the importance of phosphate?

Answer 7

-component of high energy compounds e.g. ATP -2nd messengers -Fundamental molecules e.g.DNA, RNA, Phospholipids

Question 8

what relationship do calcium and phosphate have?

Answer 8

inversely proportional to eachother

Question 9

What are the 3 key hormones in calcium regulation?

Answer 9

Increase calcium levels: -PARATHYROID HORMONE -comes from parathyroid hormone in the neck -VITAMIN D-comes from diet or sun (these are main hormones regulating calcium and phosphate via actions of the kidney, bone and gut) Decrease calcium levels: CALCITONIN-secreted by thyroid parafollicular cells

Question 10

How important is the role of calcitonin in calcium regualtion?

Answer 10

unknown because if the thyroid parafollicular cells (that produce this hormone) are removed there is no negative effect

Question 11

What are the two forms of vitamin D and where do they come from

Answer 11

-Vitamin D2(ergocalciferol)-from the diet -Vutamin D3 (cholecalciferol)-made from sun

Question 12

How is vitamin D metabolised?

Answer 12

1-UVB light from the sun shines on the skin 2-7-dehydrocholesterol is converted to previtamin D3 which is then converted into VIitamin D3 3-Vitamin D2 from our diet and D3 from the sun is transported to the liver 4-In the liver they get hydroxylated at the 25 position by 25 hydroxylase to produce 25 hydroxycholecalciferol which is the unactive from 5 -this is transported to the kidney and is hydroxylated by 1-alpha hydroxylase to produce 1,25-dihydroxycholecalciferol which is ACTIVE vitamin D

Question 13

What is the simple name for active vitamin D

Answer 13

calcitriol

Question 14

How do we measure how much vitamin D is in the body?

Answer 14

By measuring how much inactive vitamin D we have as it is a good indicator and measuring active vitamin D is difficult

Question 15

What happens once you make calcitriol?

Answer 15

Theactive vitamin D negatively feedbacks onto 1 -alpha hydroxylase to switch it off

Question 16

What does vitamin D do?

Answer 16

1-works on the kidney to increase calcium and phosphate reabsorption 2-works on the gut to stimulate the absorption of calcium and phoshate reabsorption from the gut 3-Increases OSTEOBALST activity(key bone cells for making new bone)

Question 17

Where is the parathyroid hormone from?

Answer 17

-secreted from the CHIEF CELLS in the PARATHYROID GLANDS (4 on the back of the thyroid glands) -It is secreted as a large precursor(pe-pro-PTH) and then cleaved to form PTH

Question 18

What is the relationship between PTH and serum calcium? What detects calcium levels in parathyroid gland?

Answer 18

-inversely proportional to eachother:calcium low=PTH secreted=calcium increase=less PTH secreted now -G-PROTEIN coupled calcium receptors on chief cells detect the change in circulating calcium concentration

Question 19

What happens when calcium is high extracellularly?

Answer 19

high EC calcium=calcium ions bind to receptors on the parathyroid cells= PTH secretion inhibited low EC Calcium=less calcium binds to receptor=more PTH secreted as this will increase calcium again

Question 20

How does PTH increase calcium?

Answer 20

-Increase ca2+ reabsorption from the kidney -stimulates the loss of phosphate -stimulates the action of 1-alpha hydroxylase(this forms active vitamin D which indirectly increase calcium as vitamin d increases calcium and phosphate absorption from the gut) -stimulates calcium reabsorption from the bone increasing osteoclast activity in the bone

Question 21

What do osteoclasts and osteoblasts do?

Answer 21

Osteoblasts (B=BULID Bone) Osteoclasts(C=consume bone)

Question 22

What is PTH action on bone?

Answer 22

PTH binds to PTH receptor on osteoblasts causing the activation of osteoclast activating factors which turn osteoblasts into osteoclasts This results in calcium being released from the bone as bone is consumed

Question 23

describe PTH regulation?

Answer 23

calcium falls in blood stream=more PTH released=stimulates serum calcium increase=less PTH produced AND active vitamin D (produced as a result of PTH increase previously) binds to chief cells on the parathyroid gland causing PTH to decrease =stabilise calcium levels

Question 24

What is calcitionin?

Answer 24

-secreted from the parafolllicular cells of the thyroid gland -reduces serum calcium -has effects on calcium but doesnt seem to be critcial as there are no negative effects if someone doesnt produce it

Question 25

What are the actions of calcium?

Answer 25

-increasing calcium excretion for the kidney so more is lost in the urine -reduces osteoclast activity so less calcium released from the bone

Question 26

How is serum phosphate regulated?

Answer 26

1-sodium and phosphate can be reabsorbed by sodium phosphate transporter 2-PTH inhibits phosphate reabsorption so you pee out more phosphate as PTH inhibits the sodium phosphate transporter on the epithelia of the proximal tubule(kidney) 3-FGF23 works by inhibiting phosphate reabsorption by inhibiting sodium phosphate transporter(like PTH) and inhibits calcitriol production (therefore less phosphate reabsorption for the gut)

Question 27

What are the names for high and low serum calcium?

Answer 27

Hypercalcaemia Hypocacaemia

Question 28

What happens if there is hypercalcaemia?

Answer 28

high extracellular calcium=ca2+ blocks the sodium channels =less sodium enters nerve cells=less membrane excitability

Question 29

What happens if the is hypocalcaemia?

Answer 29

low extracellular calcium =less sodium channels blocked=more membrane excitability

Question 30

What are the symptoms of Hypoclacaemia?

Answer 30

excitable tissues=muscle cramps, tetany and tingling -Paraesthesia(hands, mouth, feet, lips)-numb -convulsions, seizures -arrythemias -tetany(muscles contract but cant relax again) remember these symptoms with the mnemonic (CATs go numb )

Question 31

What are the 2 signs that indicate low calcium?

Answer 31

Chvosteks sign- when you tap the facial nerve just below the zygomatic arch and twitching occurs (due to excitable cell membranes) Trousseau’s sign- inflation of blood pressure cuff for several minutes induces CARPOPEDAL SPASMS -where muscles contract but cant relax again

Question 32

When do we check for low calcium?

Answer 32

usually after thyroid surgery as we worry that the parathyroid glands may have been damaged

Question 33

What are the causes of hypocalcaemia?

Answer 33

Low PTH levels (hypoparathyroidism): -due to neck surgery -autoimmune -magnesium deficiency(needed for PTH to work) -born without parathyroid glands(rare) Vitamin D defficiency: -Malabsorbtion or dietary insufficiency -inadequate sun exposure -liver disease-prevents you from doing the first hydroxlation step to make active vitamin D -Renal disease- cant do the 2nd hydroxylase reaction needed to make active vitamin D -Vitamin D receptor defects(rare)

Question 34

What is the consequence of vitamin D defficiency?

Answer 34

Lack of mineralisation of the bones =soft bones =bendy(bowed) bones in children In adults-OSTEOMALACIA- (fractures and muscle weakness)

Question 35

What are the symptoms of hypercalcaemia?

Answer 35

Stones-renal effects(kidney stones) abdominal moans-GI effects (anorexia, nausea, dyspepsia, constipation, pancreatitus) Physic groans-CNS effects(fatigue, depression, impaired concentration, altered mentation, coma

Question 36

What are the causes of hypercalcaemia?

Answer 36

Primary hyperparathyroidism: -Too much PTH (due to parathyroid gland adenoma (tumour) which means there is no negative feedback so PTH levels keep increasing-increased calcium) -Malignancy -cancer spreads to bone(metastasis) which causes local factors to activate osteoclasts-release calcium from the bone -certaincancers secrete PTH related peptide that acts at the PTH receptor =stimulates calcium increase -Vitamin D excess(rare)