Calcium Homeostasis

Question 1

The main roles of Calcium are?

Answer 1

Muscle contractions, neurotransmitter release, calcification of bones and teeth, cell adhesion, blood clotting and excitation (contraction coupling)

Question 2

How is Calcium in the body regulated?

Answer 2

Via principle organ systems (gut, bones and kidneys) and via hormones (PTH, Vit D3 and Calcitonin)

Question 3

PTH, Vitamin D3 and Calcitonin regulate what in the body?

Answer 3

Calcium levels

Question 4

What is a hormone?

Answer 4

An agent that is released at one site, diffuses systemically and acts at another site.

Question 5

What is the Vitamin D3 precursor (it’s in your skin!)?

Answer 5

7-dehydrocholesterol

Question 6

What catalyses the activation of Vitamin D3?

Answer 6

UV light

Question 7

What is detected in the blood to find the levels of Vitamin D3?

Answer 7

25-hydroxy D3

Question 8

Calcitriol is another term for what?

Answer 8

1,25-dihydroxyvitamin D3 - the active form of Vitamin D3

Question 9

What are our main sources of Vitamin D3?

Answer 9

Diet, self generated & supplements

Question 10

Self generated Vitamin D3 isn’t toxic, but supplements are in high doses, why is this?

Answer 10

Supplements aren’t the activated form and therefore aren’t excreted like the self generated form via the urine and faeces.

Question 11

Which hormone takes longer to act; a nuclear hormone or a peptide hormone?

Answer 11

Nuclear hormones take longer!

Question 12

How does vitamin D3 help regulate Calcium levels?

Answer 12

Stimulates the gut to take up serum calcium and directly stimulates the terminal differentiation of osteoclasts and activates osteoblasts in bones to increase serum calcium uptake.

Question 13

What does PTH stand for?

Answer 13

Parathyriod hormone

Question 14

What is the role of PTH in maintaining calcium levels?

Answer 14

PTH stimulates bone resorption of serum calcium, renal tubular reabsorption of Ca2+ and stimulates renal 1α-hydroxylation of 25(OH)vitamin D3  indirectly  intestinal absorption of Ca2+ and therefore serum Ca2+

Question 15

I’m a 32 amino acid peptide and I’m synthesised by the parafollicular cells of the thyriod gland (C-cells). What am I?

Answer 15

Calcitonin

Question 16

What is the role of Calcitonin in Calcium homeostasis?

Answer 16

Calcitonin has no role in normal day to day Calcium homeostasis.

Question 17

What is the term for high calcium levels?

Answer 17

Hypercalcaemia

Question 18

What are the main symptoms of hypercalcaemia?

Answer 18

Altered mental state, lethargy, depression. Decreased gut motility, diuresis and impaired renal concentrating ability. Fractures, shortened QT interval and exacerbation of hypertension.

Question 19

Hypercalcaemia is a risk factor for which common kidney pathology?

Answer 19

Kidney Stones.

Question 20

How is PTH controlled?

Answer 20

Negative feedback loop - when Ca levels rise, PTH self inhibits its own transcription.

Question 21

What regulates the thyriod gland’s production of Calcitonin?

Answer 21

Serum Ca levels

Question 22

In stress situations the role of calcitonin is thought to be what?

Answer 22

Decreasing bone resorption when plasma Ca is high

Question 23

Stimulation of PTH, increase in bone resorption of CA and increased 1,25(OH)2 D3 production suggests what?

Answer 23

Falling Blood Calcium

Question 24

What happens when blood calcium increases?

Answer 24

Down regulation of PTH, decreased bone resorption, increase in urinary Ca loss and a decrease in 1,25(OH)2 D3 production.

Question 25

The following are indications of what? • Stones (renal or biliary) • Bones (bone pain) • Groans (abdominal pain, nausea and vomiting) • Thrones (polyuria) • Psychiatric overtones (Depression 30–40%, anxiety, cognitive dysfunction, insomnia, coma)

Answer 25

Hypercalcaemia

Question 26

What hormonal changes can cause hypercalcaemia?

Answer 26

Hormonal changes such as: primary hyperthyriodism, hypervitaminosis D or paraneoplastic changes.

Question 27

What are the non-hormonal changes that cause hypercalcaemia?

Answer 27

Renal failure, milk alkali syndrome, thiazides/litium/other drugs or Cestrum diurnum ( a plant).

Question 28

What is milk alkali syndrome?

Answer 28

Milk-alkali syndrome is characterized by high blood calcium caused by taking in too much calcium and absorbable alkali; common sources of calcium and alkali are dietary supplements taken to prevent osteoporosis and antacids. If untreated, milk-alkali syndrome may lead to kidney failure or death.

Question 29

What is the term for low blood calcium levels?

Answer 29

Hypocalcaemia

Question 30

At what blood calcium level does hypocalcaemia cause symptoms?

Answer 30

As with hypercalcaemia - no fixed level of blood calcium at which signs and/or symptoms develop, it varies from patient to patient, and may be influenced by comorbid conditions.

Question 31

What is the primary mechanism that causes symptoms of hypocalcaemia?

Answer 31

De-repression of activty - ie activation threshold is lowered and hyperactivity ensues.

Question 32

What are the main symptoms of hypocalcaemia?

Answer 32

``` • Perioral tingling and parasthesia, 'pins and needles‘ - earliest symptom. • Tetany. • Facial spasms. • Hyperactive tendon reflexes. • Laryngospasm. • Cardiac arrhythmias. ```

Question 33

What is tetany?

Answer 33

A condition marked by intermittent muscular spasms, caused by malfunction of the parathyroid glands and a consequent deficiency of calcium.

Question 34

What are the causes hypocalcaemia?

Answer 34

``` Hypoparathyroidism – Postsurgical (most common) – Autoimmune – Pseudohypoparathyroidism (PTH resistance) – Idiopathic ``` • Hypovitaminosis D – Dietary deficiency – Rickets, osteomalacia • Organ dysfunction – GI malabsorption, renal loss • Endocrine response to non-hypoparathyroid hypocalcaemia – Secondary hyperparathyroidism

Question 35

Name two common conditions caused by disorder of calcium metabolism.

Answer 35

Rickets and osteomalasia.

Question 36

Rickets primarily affects which age group?

Answer 36

Children

Question 37

What is rickets caused by?

Answer 37

A deficiency of Vitamin D in children – their bones has abnormal amounts of unmineralised osteoid.

Question 38

What are the signs and symptoms of rickets?

Answer 38

Bowing of long bones in the legs. Lack of bone rigidity which means bones are soft & easily fractured.

Question 39

What causes osteomalacia?

Answer 39

Deficiency of Vitamin D in adults: | •Increased unmineralised osteoid content results in a decline in bone strength.

Question 40

What are the signs and symptoms of osteomalacia?

Answer 40

• Long bone growth has completed in adults – bowing of weight-bearing bones does not occur, instead fractures develop.