10

Question 1

why is calcium critical for normal physiology?

Answer 1

• intracellular Signaling
• hormone secretion
• blood clotting
• neural excitability
• muscle contraction
• building and maintaining bone

Question 2

3 locations of calcium

Answer 2

1. extracellular matrix
2. extracellular fluid
3. intracellular Ca2+

Question 3

total body Ca2+ =

Answer 3

intracellular + extracellular (ECF/plasma + bone)

Question 4

draw a flow chart of Ca2+ exchanges in the body

Question 5

how is calcium stored in bones?

Answer 5

• mainly in crystals (hydroxyapatite = Ca10(PO4)6(OH2))
• a small fraction is ionised and readily exchangeable with the plasma and ECF

Question 6

label a diagram of the bone

Question 7

what is constantly happening to bone?

Answer 7

it is constantly bing formed and resorbed

Question 8

3 cells responsible for the formation and maintenance of bone

Answer 8

1. osteoblasts
2. osteoclasts
3. osteocytes

Question 9

osteoblasts

Answer 9

bone forming cells

Question 10

osteoclasts

Answer 10

break down bone

Question 11

osteocytes

Answer 11

maintain bone. these are previously osteoblasts that are completely surrounded by bone matrix. therefore just maintain bone in its immediate vicinity

Question 12

what does making bone involve?

Answer 12

creating calcium phosphate complexes (calcium crystallisation)

Question 13

label the positioning of osteoblasts, osteocytes, and osteoclasts in the bone

Question 14

calcium turnover/year

Answer 14

100% in infants and 18% in adults

Question 15

define calcium turnover

Answer 15

the continuous process where calcium is exchanged between the body’s bones and the extracellular fluid, primarily the bloodstream, as part of the bone remodeling cycle

Question 16

describe how osteoclasts work

Answer 16

• multinucleated
• attach to the ruffled border of the bone matrix like a suction cup
• able to secrete HCl, which provides a low pH
• secrete proteases, which break down the bone
• acid and enzymes dissolve the bone matrix and the Ca2+ released becomes part of the ionised calcium pool, which can then enter the bloodstream

Question 17

how is HCl secreted by osteoclasts?

Answer 17

CO2 + H2O – (CA) -> H+ + HCO3-

CA = Carbonic Anhydrase

H+ + Cl- -> HCl

Question 18

what do bone dynamics (~100 days) consist of?

Answer 18

osteoclasts resorb, osteoblasts form, osteocytes (retired osteoblasts)

Question 19

why are bone dynamics important?

Answer 19

enable bones to grow, adapt to mechanical stress, maintain structural integrity, and heal damage over time.

Question 20

how do osteoblasts promote osteoclast formation?

Answer 20

via RANKL/RANK interaction
- RANK (osteoclast precursor) binds to RANKL (osteoblast), leading to differentiation and fusion of osteoblasts into osteoclasts

Question 21

RANK

Answer 21

receptor activator of nuclear factor kappa B

Question 22

RANKL

Answer 22

RANK ligand

Question 23

OPG

Answer 23

osteoprotegerin secreted by osteoblasts to block RANK/RANKL interaction

Question 24

Denosumab

Answer 24

monoclonal antibody that targets the interactions between RANK and RANKL, thus mimicking the effect of OPG and preventing bone loss

Question 25

what three hormones control plasma Ca2+ levels?

Answer 25

- parathyroid hormone (PTH) - calcitriol (aka 1,25-dihydroxycholecalciferol) - calcitonin

Question 26

three target sites for hormones that control plasma Ca2+ levels

Answer 26

- bones - kidneys - digestive tract

Question 27

Parathyroid hormone (PTH)

Answer 27

released from the parathyroid glands (chief cells), 4 of which are stuck to the thyroid function: increases plasma Ca2+ concentrations stimulus: low plasma Ca2+

Question 28

draw and explain a graph of [free Ca2+]blood (mM) vs [PTH]serum (% of maximum)

Question 29

how are the levels of extracellular Ca2+ monitored?

Answer 29

by Ca2+-sending receptor on the plasma membrane - as long as calcium is bound to this receptor, there will be: - inhibition of cell growth - inhibition of PTH secretion - reduction of PTH synthesis if calcium is not bound to the receptor, then the pathway for the synthesis of vitamin D3 will take place

Question 30

three ways in which PTH raises plasma Ca2+

Answer 30

1. PTH mobilises calcium from bone: - acts on osteoblasts by increasing cAMP to increase RANKL and decrease OPG expression - more osteoclasts are formed leading to bone resorption 2. PTH enhances renal reabsorption of Ca2+ (and kicks out phosphate) 3. PTH enhances the production of calcitriol

Question 31

formation of calcitriol

Answer 31

3 organs are crucial in the development of calcitriol: 1. skin 2. liver 3. kidney vitamin D --- (multiple enzymatic steps) -> calcitriol

Question 32

function of calcitriol

Answer 32

targets intestine, bone and kidney to increase serum calcium: - increases Ca2+ uptake from small intestine - causes renal Ca2+ absorption - causes mobilisation from the bone

Question 33

pathway for calcitriol formation

Answer 33

7-dehydrocholesterol in skin -> cholecalciferol (vitamin D3) in liver -> 25-hydroxycholecalciferol in kidney -> 1,25-dihydroxycholecalciferol (calcitriol)

Question 34

three other ways to call calcitriol

Answer 34

= 1,25-dihydroxycholecalciferol = 1,25(OH)VitD3 = Vitamin D3 hormone

Question 35

VDR

Answer 35

vitamin D nuclear receptor

Question 36

intracellular mechanism of calcitriol

Answer 36

Calcitriol diffuses into the cell → binds VDR → VDR heterodimerizes with RXR (retinoid X receptor) → complex binds VDREs in DNA → recruits co-regulators and mediator complexes that remodel chromatin → this facilitates assembly of basal transcription factors and RNA polymerase II at the core promoter → transcription of vitamin D–responsive genes (e.g., calcium channels/transporters) is activated.

Question 37

how is blood phosphate controlled by PTH and calcitriol?

Answer 37

PTH: - increases phosphate release from bone - decreases phosphate reabsorption in kidney Calcitriol: - increases phosphate absorption by intestine and reabsorption by kidney

Question 38

describe calcitonin

Answer 38

- peptide hormone secreted from C cells of the thyroid gland - release triggered by high plasma [Ca2+] - C cells (= parafollicular cells) also have Ca2+-sending receptors

Question 39

role of Calcitonin in humans

Answer 39

- protect the skeleton from Ca2+ loss during pregnancy and lactation - reduces activity of osteoclasts (inhibits bone resorption) - stimulates osteoblasts to deposit calcium - inhibits calcium reabsorption by kidneys

Question 40

hypercalcemia

Answer 40

too much calcium: - GROANS (constipation) - MOANS (psychic moans = fatigue, lethargy, depression) - BONES (bone pain) - STONES (kidney stones) - psychiatric OVERTONES (confusion and weakness)

Question 41

hypocalcemia

Answer 41

C = convulsions A = Arrhythmias T = tetany S = spasms, seizures, and stridor people can die from this