Endocrinology- Regulation of Ca2+ and Phosphate

Question 1

Where is the majority of calcium in the body? And what compound is it stored as?

Answer 1

Skeleton and teeth

stored as hydroxyapatite crystals

Question 2

What 2 types of plasma calcium are there

Answer 2

Ionised (unbound) - Ca2+, BIOLOGICALLY ACTIVE compoment

Bound- plasma protiens OR anions such as bicarbonate

Question 3

Which 2 hormones increase serum levels of calcium and posphate?

how are they synthesized?

Answer 3

parathyroid hormone - secreted by para gland

Vit D- synthesized in skin or diet. actions via kidney and bone, gut

Question 4

Which hormones decrease Ca2+ and phosphate levels?

Answer 4

Calcitonin- not essneital, only reduces acutely

Question 5

Where is calcitonin synthesized?

Answer 5

By thyroid parafollicular cells, no negative effect if removed

(not essential for regulation)

Question 6

What are the 2 inactive molecules of Vit D and where are each one from?

Answer 6

Vitamin D3 (Cholecaliferol)- Skin when exposed sunlight

Vitamine D2 (Ergocalciferol) - from diet

Question 7

How does Skin make Cholecalciferol?

Answer 7

7-dehydrocholesterol (produced by skin cells) UV LIGHT

—->pre- vitamin D3

—–> Vit D3

(then goes off to produce activated Vit D3)

Question 8

What happens to the Vitamin D2 and D3 after take in (First step)?

Answer 8

1st hydroxylation- to liver

convert to 25(OH)cholecalicferol

by 25-hydroxylase enzyme

Question 9

What happens to the Vitamin D2 and D3 after take in (second step)?

Answer 9

2nd- hydroxylation

transported to kidney converted

by 1-alpha-hydroxylase

to 1,25 diol cholecalciferol WHICH IS ACTIVE VIT D

Question 10

Which molecule should be measured to determine Vitamin D levels?

Answer 10

25(OH)cholecalciferol as active Vitamin D is difficult to measure

Question 11

Does calcitriol -ve feedback itself? And how?

Answer 11

Yes,

regulates own synthesis by decrease transcripiton of

1-alpha hydroxylase enzyme of 2nd hydroxylation

Question 12

What effects does calcitriol have to increase phosphate levels and calcium?

Answer 12

Increases Ca2+ and phosphate reabsoportion from kidnet

increased Ca2+ and phosphate absorption from small intestine

Increased Ca2+ absoprtion into bones

Question 13

Where are parathyroid glands located?

Answer 13

4 small pieces on poterior of thryoid gland

Question 14

What types of cells in parathryoid glands secrete PTH?

Answer 14

Chief cells

Question 15

How is PTH secreted from the chief cells?

Answer 15

As a large precursor pre-pro-PTH

cleaved in cell to PTH

Question 16

How is PTH secretion from chief cells regulated?

Answer 16

have G coupled Ca2+ sensing receptor

detect circulating Ca2+ levels + secrete inversely to it

Question 17

Effects of PTH?

Answer 17

increases osteoclast activity, increasing bone and Ca2+ resaborption

increase calcium reabsorption and excretion of phosphate from kidney

increase Vit D synthesis so increase absorption of minerals from small intestine

Question 18

How does PTH regulate serum levels of Ca2+?

Answer 18

increases Ca2+ plasma concentration

by increasing Ca2+ mobilisation from bones and it’s reabsoprtion from kidney

absorption of Ca2+ from small intestine via increasing vitamin D

Question 19

How does PTH regulate serum levels of phosphate ?

Answer 19

It doesn’t

as phosphate levels increase by absorption in small intenstine

but increases excretion in kidney

so overall no increase

Question 20

What affect does PTH have on bones to regulate serum levels of calcium?

Answer 20

Binds to osteoblasts to release oeseoclast activating factors like RANKL

stimulate OSTEOCLAST bone eating cells,

breakdown bone into calcium and phosphate, which then go to kidneys. (Ca2+ is reabsorbed phosphate excreted)

Question 21

What effect does calcitrol when low calcium serum levels on bones?

What effect does calictrol when normal calcium serum levels on bones?

Answer 21

increease calcium reabsoprtion from bone

clasts > blasts

increase bone formation

blasts > clasts

BOTH PTH and CALICITROL have similar effects on bone

Question 22

How is PTH (negatively) regulated?

Answer 22

2 ways

1).increase in plasma Ca2+

detected by parathyroid glands + secrete less PTH

2). Chief cells also have vitamin D receptors, too much Vit D less PTH

Question 23

Which types of cells produce calcitonin?

What is it’s effect?

Answer 23

Parafollicular cells of Thyroid cells

Reduce serum calcium levels

Question 24

How does calcitron decrease serum levels of Calcium?

Answer 24

Increase Ca2+ secretion by kidney

decrease osteoclast (bone consumtion cells) activity

Question 25

What molecule regulates phosphate? And where is it produced?

Answer 25

FGF-23 specific cells in Bones

Question 26

How does it reduce phosphate levels?

Answer 26

**2 ways** 1. Prevents re uptake of phosphate in kidney from urine( proximal tubule) blocks/prevents Na+/phosphate co-transporter 2. inhibits calcitriol, less phosphate absoprtion from gut

Question 27

How does PTH excrete phosphate in kidney?

Answer 27

**same way as FGF 23** Prevents re uptake of phosphate in kidney from urine( proximal tubule) blocks/prevents Na+/phosphate co-transporter

Question 28

Main affect of HYPOcalcaemia and HYPERcalcaemia

Answer 28

**HYPO- less** Ca2+ in blood serum, Ca more Na influx greater excitation of neurones membranes **HYPER- more** Ca2+ in blood serum, Ca blocks Na influx less excitation of neurones membranes

Question 29

What function does Ca2+ have on Na+ channels?

Answer 29

At resting state sodium channels are stablizied by Ca2+, prevents spontanous depolarisation **If low**

Question 30

Symptoms of hypocalcaemia?

Answer 30

sensitises, excitable tissues, cramps, tingling paresthesia (chilling, burning, numbness)- hands, mouth convulsions - fits arrhythmias - problem HR tetany- can't relax muscle

Question 31

What is Chvostek's sign?

Answer 31

Tap facial nerve below zygomatic arch, twitching of facial muscles, more sensitized common with hypocalcaemia

Question 32

What is trousseau's sign?

Answer 32

increase BP induced carpopedal spasm-muscles contract + can't stop , neuromusclar irritability

Question 33

Causes of hypocalcaemia?

Answer 33

hypoparathyroidism surgical- neck surgery, affect parathyroid gland autoimmune- attacks any organs magnesium. defincity- need to make PTH agensis- failure organ grow vitamin D deficincy- sun & diet

Question 34

Causes of vitamin D deficincy?

Answer 34

Question 35

Consequence of Vitamin D deficiency?

Answer 35

**has importance in mineralism of bone increase bone formation, increase osteoblast activity\> osteoclasts when Ca2+ levels are high** soft bones rickets- bendt bones osteomalacia- fractures, proximal mypoathy hips weakness

Question 36

Symptoms of hypercalcaemia?

Answer 36

stones- kidney lots of calcium excreted causes stones + neuphrocalcinosis adbominal moans- gut is long muscle, anoxia, dypsia- heart burn, conspitation, pancritis-inflmation pyshic groans- fatigue, depression, altered mentation atonal muscles

Question 37

Causes of hypercalcaemia?

Answer 37

**primary hyperparathyroidism- PTH** gland adeonma no negative feedback so increase PTH and Ca2= **cancer spread to bone, metastases.** local factors activate osteoclastsm increase calcium reabsoprtion from bone **excess vit D**