Week 4- Regulation of Calcium & Phosphate

Question 1

What is the recommended adult intake of calcium?

Answer 1

1000mg per day

Question 2

What are the 3 key hormones in calcium regulation? Do they increase or decrease calcium?

Answer 2

Parathyroid hormone (increases calcium)
Vitamin D (increases calcium)
Calcitonin (decreases calcium)

Question 3

Where is parathyroid hormone secreted?

Answer 3

Parathyroid glands

Question 4

Where is vitamin D synthesised?

Answer 4

In the skin (or intaken via diet)

Question 5

Where is calcitonin secreted?

Answer 5

Thyroids parafollicular cells

Question 6

What are the 2 sources of vitamin D?

Answer 6

Ergocalciferol ie D2 (intaken via diet)

Cholecalciferol ie D3 (made in skin with sunshine)

Question 7

When measuring Vit D levels what do we measure?

Answer 7

25 (OH) cholecalciferol ie unactive form

Question 8

What 3 areas does calcitriol work on and what does it do?

Answer 8

Increases calcium absorbtion and phosphate reabsorbtion in the kidney

It works on the small intestine increasing phosphate and calcium absorbtion

Increases reabsorbtion of calcium in bones and stimulates osteoblasts (important for bone health)

Question 9

How many parathyroid glands are there and where are they located?

Answer 9

4- located at the back of the thyroid

Question 10

What is the precursor for parathyroid hormone?

Answer 10

Pre-pro-PTH

Question 11

What does PTH do?

Answer 11

Drives calcium to increase, when it does PTH switches off

Question 12

What happens when there is high extracellular calcium?

Answer 12

Binding of calcium to receptors on parathyroid gland cells inhibits PTH

Question 13

What happens when there is low extracellular calcium?

Answer 13

Less binding of calcium to receptors of parathyroid gland cells stimulates PTH secretion

Question 14

What 3 main areas does PTH effect and what does it do?

Answer 14

Kidney- increases calcium absorption and stimulates loss of phosphate. Stimulates action of 1 alpha hydroxylase allowing more active vit D (calcitriol) formation

Bone- stimulates calcium reabsorbtion

Gut- increases reabsorbtion of calcium and phosphate

Question 15

What do osteoblasts do?

Answer 15

Build bone

Question 16

What do osteoclasts do?

Answer 16

Consume bone

Question 17

How are osteoblasts converted to osteoclasts?

Answer 17

Binding of PTH to receptors causes osteoclast activating factors to be expressed turning the osteoblasts to clasts

Question 18

What are the 2 ways PTH regulated?

Answer 18

Increased serum calcium reduces PTH secretion

As PTH stimulates production of calcitriol, the calcitriol negatively feeds back onto parathyroid cells

Question 19

What does calcitonin do? What is special about it

Answer 19

It reduces serum calcium but it is possible to live without it

Question 20

What are the 2 mechanisms by which calcitonin works?

Answer 20

Increases calcium excretion from kidney

Lowers osteoclast activity on the bone

Question 21

What are the 2 mechanisms by which FGF23 inhibits phosphate reabsorbtion?

Answer 21

1- directly inhibits the cotransporter that reabsorbs phosphate that would otherwise be urinated

2- indirectly by inhibiting calcitrol production

Question 22

What happens to membrane excitability in hypercalcaemia?

Answer 22

Blocks Na influx so less excitability

Question 23

What happens to membrane excitability in hypocalcaemia?

Answer 23

Enables greater Na influx so more membrane excitability

Question 24

What are symptoms of hypocalcaemia? What mnemonic do we use to remember them?

Answer 24

Parasthesia (pins and needles) around lips, hands, mouths

Convulsions

Arrhythmia

Tetany (muscles contract then cant relax)

Cats go numb

Question 25

What is Chvostek’s sign and why is it used?

Answer 25

Tap the facial nerve (just below zygomatic arch) and facial muscle will twitch Indicates hypocalcaemia

Question 26

What is Trousseaus sign and why is it used?

Answer 26

Inflation of the BP cuff for several mins induces a carpopedal spasm Indicates hypocalcaemia

Question 27

What is it called when PTH levels are low?

Answer 27

Hypoparathyroidism

Question 28

What are the 2 main causes of hypocalcaemia and how do they arise?

Answer 28

Low PTH levels (due to neck surgery, autoimmunity, magnesium deficiency, congenital) Vit D deficiency

Question 29

What are the 5 causes of Vit D deficiency?

Answer 29

``` Dietary insufficiency Inadequate sun exposure Liver disease Renal disease Vit D receptor defects (rare) ```

Question 30

What is vit D deficiency called in children and in adults? What are the symptoms in each

Answer 30

Children- rickets (soft bones that bow) | Adults- osteomalacia (fractures, proximal myopathy)

Question 31

What is the phrase we use to describe the symptoms of hypercalcaemia? Describe the symptoms

Answer 31

Stones, abdominal moans and psychic groans Reduced neuronal excitability Stones- renal effects ie kidney stones, renal colic Abdominal moans- GI effects ie nausea, dyspepsia, constipation Psychic groans- CNS effects ie coma, fatigue, depression

Question 32

What are the causes of hypercalcaemia?

Answer 32

Primary hyperparathyroidism (too much PTH) Malignancy (bone metastases activate osteoclasts and some cancers secrete peptides that act at PTH receptors) Vit D excess (rare)

Question 33

How is calcium distributed in the body?

Answer 33

99% in the skeleton and teeth Very small amount of extracellular calcium that is tightly regulated

Question 34

Why is calcium important in the body?

Answer 34

Muscle contraction Bone strength Intracellular 2nd messenger and coenzyme Blood coagulation

Question 35

Why are phosphates required in the body?

Answer 35

They are essential components of high energy compounds eg ATP, 2nd messengers and fundamental molecules eg RNA/DNA

Question 36

What is the link between extracellular calcium and phosphate?

Answer 36

Their levels are inversely proportional to each other and they are regulated by the same hormones

Question 37

What 2 forms does serum calcium exist as?

Answer 37

Unbound (ie free/ionised) and bound

Question 38

What is the normal serum calcium level for unbound calcium and how much of total serum calcium is found unbound?

Answer 38

Normal level: 1.25mM | % of total serum calcium: 50%

Question 39

What is the normal serum calcium level for bound calcium and how much of total serum calcium is found bound?

Answer 39

Normal level: 1.13 mM | % of total serum calcium: 45%

Question 40

What is the other name by which vitamin D2 is known?

Answer 40

Ergocalciferol

Question 41

What is the other name by which vitamin D3 is known?

Answer 41

Cholecalciferol

Question 42

How do we gain vitamin D2?

Answer 42

Via diet

Question 43

How do we gain vitamin D3?

Answer 43

Make it from sunshine in the skin

Question 44

Describe the general process by which vitamin D is metabolised

Answer 44

Skin cells absorb UVB light from the sun This triggers conversion of 7 dehydrocholesterol to pre vitamin D3 which is converted to vit D3 Vit D3 alongside vit D2 from diet is transported to the liver and hydroxylated at position 25 to form 25 hydroxylase which is not active The enzyme 1 alpha hydroxylase carries out the 2nd hydroxylation step forming calcitriol, the active form of vitamin D

Question 45

What type of sunlight does the skin absorb?

Answer 45

UVB

Question 46

What 2 molecules are synthesised before vit D3 is made in the skin?

Answer 46

7 dehydrocholesterol and pre vitamin D3

Question 47

Where is the first hydroxylation step of vit D metabolisation carried out?

Answer 47

Liver

Question 48

Where is the second hydroxylation step of vit D metabolisation carried out?

Answer 48

Kidney

Question 49

What is the name of the enzyme that carries out the second hydroxylation step during vitamin D metabolisation?

Answer 49

1 alpha hydroxylase

Question 50

What is the active form of vitamin D known as?

Answer 50

Calcitriol

Question 51

What type of receptor detects changes in calcium and where is it found?

Answer 51

G protein coupled receptors in parathyroid glands

Question 52

What is the relationship between PTH secretion and serum calcium?

Answer 52

PTH secretion is inversely proportional to serum calcium levels

Question 53

Where is calcitonin secreted from?

Answer 53

Parafollicular cells of the thyroid gland