4.6: Regulation of calcium and phosphate

Question 1

What is the most abundant metal in the body

Answer 1

Calcium

Question 2

Where does 99% of calcium reside in the body, what is it stored as

Answer 2

In the skeleton and teeth
Calcium hydroxyapatite crystals

Question 3

What is Extracellular calcium

Answer 3

Calcium that is present in the bloodstream - measured during a blood test

Question 4

Why is Extracellular calcium tightly regulated

Answer 4

Lives in circulation, often bound to albumin

Question 5

Unbound ionised calcium is a

Answer 5

Biologically active component

Question 6

Hormones involved in calcium control (increase)

Answer 6

Parathyroid hormone (PTH)
Vitamin D

Question 7

What is parathyroid hormone secreted by

Answer 7

Parathyroid glands

Question 8

How is vitamin D synthesised

Answer 8

In skin or intake via diet

Question 9

How do Vit D and PTH regulate Ca and PO4 homeostasis

Answer 9

Via actions on kidney, bone and gut

Question 10

What is calcitonin

Answer 10

Hormone that can reduce calcium acutely, but no negative effect if parafollicular cells are removed

Question 11

Two types of Vitamin D

Answer 11

Ergocalciferol
Cholecalciferol

Question 12

What is ergocalciferol derived from

Answer 12

UV irradiation of plants - consumed in vegetables

Question 13

What is cholecalciferol derived from

Answer 13

UV irradiation of skin and certain foods (oily fish, egg yolk)

Question 14

Vitamin D metabolism

Answer 14

1) UVB from the sun causes 7-dehydrocholesterol to convert to Pre-vitamin D3 in the skin
2) this is then converted to Vit D3 which enters the circulation
3) Vit D2 is present in the diet and absorbed from the gut
4) D3 and D2 pass into the liver (25-hydroxylase) and are hydroxylated at position 25 producing 25(OH)cholecalciferol
5) this is then hydroxylated again in the kidneys to form active vitamin D : using enzyme 1 alpha-hydroxylase

Question 15

Active form of vitamin D is called

Answer 15

Calcitriol

Question 16

2 Characteristics of serum 25-OH cholecalciferol

Answer 16

Biologically inactive
Good indicator of body vitamin status

Question 17

How is Vitamin D synthesis regulated

Answer 17

1,25(OH)2cholcalciferol regulates own synthesis by decreasing transcription of 1 alpha-hydroxylase

Question 18

Major role of calcitriol

Answer 18

Increase Ca2+ and PO4 ^3- reabsorption from the gut

Question 19

Role of calcitriol in kidney

Answer 19

Increases Ca2+ and PO4 ^3- reabsorption, less lost in urine more in bloodstream

Question 20

Role of 1,25(OH)2D3 in bone

Answer 20

Increased Ca2+ reabsorption from bone

Question 21

What cells secrete PTH

Answer 21

Chief cells in parathyroid glands

Question 22

What is PTH secreted as

Answer 22

Large precursor and cleaved to PTH

Question 23

feedback (regulation) of PTH

Answer 23

G-protein coupled calcium sensing receptor on chief cells detect change in circulating calcium concentration

Question 24

What is PTH secretion inversely proportional to

Answer 24

Serum calcium

Question 25

High levels of ECF (Ca2+)

Answer 25

Ca2+ binds to receptors on parathyroid cells PTH secretion inhibited

Question 26

At low levels of ECF (Ca2+)

Answer 26

Less Ca2+ binding to receptors on parathyroid cells PTH secreted

Question 27

When serum calcium increases, what happens to parathyroid hormone (PTH)

Answer 27

PTH decreases

Question 28

Function of osteoblast

Answer 28

Build bone

Question 29

Function of osteoclast

Answer 29

Consume bone

Question 30

PTH in bone

Answer 30

PTH binds to receptors Osteoblast build bone If osteoclast activating factors are present Osteoblast turns into osteoclasts Causing bone reabsorption

Question 31

Calcitriol action in bone depend on

Answer 31

Serum calcium

Question 32

During low serum calcium calcitriol has a ___ effect

Answer 32

Calcitriol works with PTH to increase calcium reabsorption from bone Osteoclast > osteoblasts

Question 33

During normal serum calcium levels, calcitriol has a ___ effect

Answer 33

Calcitriol promotes bone formation Osteoblast > osteoclasts

Question 34

2 processes of Negative feedback in PTH regulation

Answer 34

PTH increase and 1,25 (OH)2D3 synthesis Increased plasma Ca2+ and parathyroid cell’s increased PTH

Question 35

Calcitonin is secreted from

Answer 35

Parafollicular cells of thyroid gland

Question 36

Function of calcitonin

Answer 36

Reduces serum calcium

Question 37

Calcitonin actions and regulation

Answer 37

Increased plasma Ca2+ detected by parafollicular cells of thyroid Secretes calcitonin Decreases osteoclast activity in bone Increases Ca2+ excretion in kidneys Both decrease claims Ca2+ limited effect

Question 38

What is serum phosphate regulated by

Answer 38

FGF23

Question 39

What is FGF23 secreted by

Answer 39

Bone cells

Question 40

Function of FGF23 and two ways in which this occurs

Answer 40

Promotes phosphate loss: Blocks sodium phosphate cotransporter in kidneys Switches off calcitriol More phosphate into urine

Question 41

Hypercalcaemia is

Answer 41

High serum calcium

Question 42

Hypocalcaemia is

Answer 42

Low serum calcium

Question 43

Characteristics of the membrane during Hypercalcaemia

Answer 43

High Extracellular calcium, blocks Na+ influx so less membrane excitability

Question 44

Characteristics of the membrane during hypocalcaemia

Answer 44

Low Extracellular calcium, so greater Na+ influx enables, so more membrane excitability

Question 45

Signs and symptoms of hypocalcaemia (4)

Answer 45

Paraesthesia Convolutions Arrhythmias Tetany (CATs go numb)

Question 46

Process of Chvosteks sign test

Answer 46

Tap facial nerve below zygomatic arch Positive response = twitching of facial muscles = neuromuscular irritability due to hypocalcaemia

Question 47

How to test for hypocalcaemia (2)

Answer 47

Chvosteks sign Trousseaus sign

Question 48

Process of trousseaus sign test

Answer 48

Inflation of BP cuff for several minutes Induces carpopedal spasm Neuromuscular irritability due to hypocalcaemia

Question 49

2 Causes of hypocalcaemia

Answer 49

Low PTH levels = hypoparathyroidism Vitamin D efficiency

Question 50

4 causes of hypoparathyroidism

Answer 50

Surgical - neck surgery Auto immune Magnesium deficiency Congenital (agenesis, rare)

Question 51

5 Causes of vitamin D deficiency

Answer 51

Malabsorption or dietary insufficiency Inadequate sun exposure Liver disease Renal disease Vit D receptor defects (rare)

Question 52

Consequences of vitamin D deficiency in children

Answer 52

Rickets (bowling of bones)

Question 53

Consequences of vitamin D deficiency in adults

Answer 53

Osteomalacia (Fractures, proximal myopathy)

Question 54

Vitamin D deficiency effect on bones

Answer 54

Lack of bone mineralisation, leading to soft bones

Question 55

Signs of Hypercalcaemia

Answer 55

Reduced neuronal excitability- atonal muscles

Question 56

3 symptoms of Hypercalcaemia

Answer 56

Stones - renal effects : Nephrocalcinosis, kidney stones, renal colic Adbominal moans - GI defects: anorexia, nausea, dyspepsia, constipation, pancreatitis Psychic groans - CNS effects : fatigue, depression, impaired concentration, altered mentation, coma

Question 57

3 causes of Hypercalcaemia

Answer 57

Primary hyperparathyroidism Malignancy Vitamin D excess (rare)

Question 58

3 causes of primary hyperparathyroidism

Answer 58

Too much PTH Parathyroid gland adenoma No negative feedback- high PTH, but high calcium

Question 59

Cause of malignancy

Answer 59

Bony metastases produce local factors to active osteoclasts, increasing calcium reabsorption from bone