L48 - Calcium Homeostasis

Question 1

What are some facts about calcium in the human body?

Answer 1

• most abundant
• ~1100g (27.5 mol) calcium
• 99% in skeleton, 1% blood and other tissue
• total plasma calcium ~2.5mmol/L

Question 2

What is the distribution of calcium in the blood?

Answer 2

• protein bound calcium
• cokmplexed calcium
• free ionised calcium

Question 3

What calcium is physiologically active?

Answer 3

Ionised calcium

Question 4

What are functions of calcium?

Answer 4

• nerve function
• muscle contraction
• blood clotting
• skeletal mineralisation
• cellular metabolism
• cell signaling

Question 5

A

Question 6

What regulates calcium homeostasis?

Answer 6

• calcitriol
• calcitonin
• parathryoid hormone

Question 7

What is parathyroid hormone (PTH) produced by?

Answer 7

• chief cells
• of parathyroid gland

Question 8

What is PTH?

Answer 8

• single chain polypeptide 84aa, MW 9500
• derived from larger precursor peptides (pre-proPTH and proPTH)

Question 9

What are the types of regulation of PTH secretion?

Answer 9

• minute to minute
• long term

Question 10

What is the minute to minute regulation of PTH secretion?

Answer 10

• CA2+ acting via GPC calcium sensing receptor (CaSR)
• dec in ionised (free) plasma Ca2+
• = inc in PTH secretion

Question 11

What is the long term regulation of PTH secretion?

Answer 11

Calcitriol acts directly on parathyroid gland to dec preproPTH and mRNA

Question 12

What does PTH secretion have an impact in?

Answer 12

• bone
• kidney
• intestine

Question 13

What does PTH do in bones?

Answer 13

Inc bone resorption

Question 14

What does PTH secretion do in the kidney?

Answer 14

• dec phosphate reabsorption (phosphaturia)
• inc Ca2+ reabsorption
• inc hydroxylation of 25 OH Vit D

Question 15

What does PTH secretion do in the intestine?

Answer 15

inc Ca2+ absorption (indirect 1,25- dihydroxycholecalciferol)

Question 16

What are the actions of PTH?

Answer 16

• inc action of osteoclasts by osteoblasts, inc release of Ca2+ into plasma
• inc reabsorption of Ca2+ into kidneys, red amount lost in urine
• inc activity of 1a-hydroxylase, dec 24-hydroxylase = inc intestinal abs of Ca2+ into blood
• lead to rise in plasma Ca2+

Question 17

What 2 forms does Vit D exist in?

Answer 17

• Vit D2 derived from diet
• Vit D3 formed by action of UV radiation from sunlight on cholesterol derivative in the skin

Question 18

What factors influence vit D synthesis in the skin?

Answer 18

• skin pigmentation
• geographic location
• sunscreen use
• season
• age

Question 19

What is the synthesis and regulation of calcitriol (active Vit D)? FINISH

Question 20

What is calcitriol?

Answer 20

• active metabolite of vit D3
• secosteroid
• only free fraction active
• t1/2 3-6hr

Question 21

What is vit D3 converted to?

Answer 21

Calcidiol in liver

Question 22

What are plasma levels of calcitriol determined by?

Answer 22

• rate of conversion of calcidiol to calcitriol (activation)
• rate of conversion of calcitriol to calcitroic acid (inactivation)

Question 23

What are the actions of calcitriol?

Answer 23

• inc intestinal absorption of Ca2+ = inc conc in blood
• inc action of osteoclasts = inc release of Ca2+ into plasma
• inc reabsorption of Ca2+ to kidneys = red amount lost in urine
• rise in plasma Ca2+

Question 24

What is calcitonin?

Answer 24

Single chain polypeptide 32 aa with MW 3500

Question 25

What is calcitonin secreted by?

Answer 25

- parafollicular C cells of thyroid gland - regulated by Ca2+

Question 26

What is the link in Ca2+ to calcitonin?

Answer 26

Increased Ca2+ = inc calcitonin secretion

Question 27

What are the actions of calcitonin?

Answer 27

- dec release Ca2+ from bone = osteoclast inhibit bone resorption - kidneys decrease tubular reabsorption Ca2+ - no effect on Ca2+ absorption in SI - fall in plasma Ca2+

Question 28

What are physiological roles of calcitonin?

Answer 28

- protect against postprandial hypercalcaemia - protect skeleton during pregnancy and lactation - act to prevent excessive bone destruction

Question 29

What is the endocrine regulation when Ca2+ levels fall?

Answer 29

- Parathyroid glands release PTH - stimulates Ca2+ release from bones - inc Ca2+ uptake in kidney - inc Ca2+ uptake in intestine

Question 30

What is the endocrine regulation when Ca2+ levels rise?

Answer 30

- thyroid gland release calcitonin - stimulates Ca2+ deposition in bones - red Ca2+ uptake in kidneys

Question 31

What does calcitonin, PTH and calcitriol target?

Answer 31

- osteoclast - osteocyte and osteoblast - osteoblasts

Question 32

What are the action of PTH and calcitriol on bone-resorbing cells? Mediated by?

Answer 32

- indirect - by cells of the osteoblast lineage (bone-forming)

Question 33

What is the effect of PTH on osteoblasts?

Answer 33

- PTH binds to osteoblast - osteoclast precursors attach to RANKL - form osteoclast

Question 34

What are disorders of calcium metabolism?

Answer 34

- hypercalcaemia - hypocalcaemia

Question 35

What is hypercalcaemia?

Answer 35

- XS PT hormone - // tumour of PT gland - affects bones, kidneys, GI tract, neurological symptoms

Question 36

What is hypocalcaemia?

Answer 36

- lack of PTH - lack of vit D effect - symptoms related to neuromuscular excitability - long term lack of vit D affects bone growth - // osteomalacia, rickets, osteoporosis

Question 37

What is the endocrine regulation of Ca2+ when blood conc decreased?

Answer 37

- PTH secretion - osteoclasts break down bone = Ca2+ released - PTH increases Ca2+ reabsorption from urine, stimulates active vit D - promotes Ca2+ absorption from SI

Question 38

What is the endocrine regulation of Ca2+ when blood conc increased?

Answer 38

- calcitonin secretion from thyroid gland - inhibits osteoclasts - enhanes osteoblast uptake of Ca2+ from blood into bone