calcium and phosphate metabolism

Question 1

what is calcium important for? (7)

Answer 1

1. bone growth and remodelling
2. secretion
3. muscle contraction
4. blood clotting
5. co - enzyme
6. stabilisation of membrane potentials
7. important secondary messenger - stimulus response coupling

Question 2

what is the distribution of calcium?

Answer 2

1. 99% in bones
2. extracellularly: 45% ionised and free and 45% bound to plasma proteins
3. very small amount intracellularly

Question 3

what are extracellular calcium levels controlled by? (2)

Answer 3

1. PTH

2. Vitamin D

Question 4

what are the functions of phosphate? (4)

Answer 4

1. constituent of DNA/RNA and phospholipid membranes
2. intracellular ion
3. activation of enzymes by phosphorylation

Question 5

what is the distribution of phosphate?

Answer 5

1. 90% in bones
2. small amount extracellular
3. 10% intracellularly.

Question 6

what is extracellular phosphate controlled by? (2)

Answer 6

1. PTH

2. FGF23

Question 7

what is PTH important for? (3)

Answer 7

1. delivering elements to bone with vitamin D
2. controlling flux of calcium in kidney
3. controlling flux of phosphate in kidney with FGF23

Question 8

Where is vitamin D’s major site of action?

Answer 8

in the gut for calcium and phosphate absorption.

Question 9

what builds bone?

Answer 9

osteoblasts

Question 10

what breaks or remodels bone?

Answer 10

osteoclasts

Question 11

what do osteoblasts turn into?

Answer 11

osteocytes (mononuclear)

Question 12

what are the two types of bone

Answer 12

1. cortical (outside)

2. trabecular (inside like bracing)

Question 13

what are osteoclasts actually

Answer 13

modified macrophages.

Question 14

where do osteoclasts come from?

Answer 14

hematopoietic stem cells

Question 15

where do osteoblasts come from?

Answer 15

mesenchymal derived cell

Question 16

what activates osteoclasts?

Answer 16

RANK ligand - through activation of nuclear kappa beta - stimulates differentiation into osteoclasts

Question 17

what signals the bone resorption and where are its receptors found?

Answer 17

1. PTH

2. osteoblasts

Question 18

what is the growth of the precursor promoted by?

Answer 18

GM - CSF promoted by T cells produced locally

Question 19

what does the PTH receptor on the osteoblast do?

Answer 19

allows co-ordinated resorption of bone.

Question 20

how do osteoblasts know where the line of stress is since bone grows on lines of stress?

Answer 20

because electricity is produced when you stress bone and tells osteoblasts when to switch on.

Question 21

what produces FGF23 and what is its action

Answer 21

produced by osteocytes.

acts on kidney to decrease synthesis of active vitamin D and to increase excretion of inorganic phosphate.

Question 22

what do osteoblasts produce that acts on pancreatic beta cells?

Answer 22

uncarboxylated osteocalcin.

Question 23

what does uncarboxylated osteocalcin do? (2)

Answer 23

1. increase insulin production and secretion.

2. acts on adipocytes to increase adiponectin on muscles to increase insulin sensitivity and glucose uptake

Question 24

what other hormones are involved in bone turnover and bone resorption? (4)

Answer 24

1. sex steroids - stimulate osteoblast precursors
2. growth hormones stimulatee bone via IGF - 1
3. thyroxine for boney growth
4. glucocorticoids inhibit osteoblast maturation

Question 25

what cells in the parathyroid gland produce PTH and what is the other type of cells that doesn't produce hormone?

Answer 25

1. chief cells | 2. oxyphil cells.

Question 26

what is the blood supply for parathyroid gland

Answer 26

inferior thyroid artery.

Question 27

what is the synthesis of PTH

Answer 27

preopro hormone (signalling sequence) prohormone hormone

Question 28

what is the process of using two antibodies to detect PTH, called?

Answer 28

immunometric assay

Question 29

what does an increase in plasma proteins and alkalosis mean?

Answer 29

a decrease in free ionised calcium

Question 30

what does an decrease in plasma proteins and acidosis mean?

Answer 30

an increase in ionised free calcium (H+ displaces calcium)

Question 31

what is free calcium sensed by

Answer 31

calcium receptors on PTH producing chief cells - ultra short feedback loop

Question 32

what happens in calcium receptors in PTH happen?

Answer 32

increase in PLC and decrease in cAMP - results in decrease PTH production.

Question 33

once ionised calcium goes outside normal range what happens?

Answer 33

PTH secretion immediately shuts off - calcium has to be tightly regulated.

Question 34

what does PTH do? (4) | produce it in response to low calcium in order to increase calcium

Answer 34

1. stimulates osteoblasts to produce M-CSF and RANK ligand which increase bone resorption 2. increases calcium reabsorption in DCT 3. increases phosphate excretion 4. increases 1-alpha hydroxyls in the PCT.

Question 35

what is calcium bound to and transported to the basolateral membrane by?

Answer 35

bound to calbindin

Question 36

how does PTH increase the amount of calcium channels on the luminal surface?

Answer 36

stimulates AC to increase cAMP and activates PKA which increases amount of calcium channels on the luminal surface.

Question 37

what does the foetus produce?

Answer 37

PTHrp

Question 38

what are the two major causes of hypercalcaemia?

Answer 38

1. primary hyperparathyroidism | 2. malignancy

Question 39

symptoms of hypercalcaemia?

Answer 39

1. shortening of QT interval - bradycardia 2. decreased concentration, confusion, fatigue, fitting 3. GI - hypo motility - constipation 4. excess gastrin - leading to peptic ulcer formation. 5. renal function - polyuria, polydipsia 6. muscular weakness and bone pain

Question 40

how is vitamin D produced

Answer 40

D3 - cholesterol to cholecalciferol | D2 - ergosterol to ergocalciferol

Question 41

what is the main regulating enzyme in the kidney for vitamin D

Answer 41

1-alpha hydroxylase - regulates calcitriol

Question 42

what is renal dysfunction tend to be associated with?

Answer 42

low levels of vitamin D

Question 43

what diseases can result in hypercalcemia?

Answer 43

sarcoidosis, tubercolosis, and other granulomatous

Question 44

what type of receptor are vitamin D receptors?

Answer 44

type 2 nuclear receptors

Question 45

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Answer 45

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