TBL6 Calcium Flashcards

1
Q

Calcium is found in 3 forms in blood serum.

A
  1. Ionised calcium (free and bioactive)
  2. Bound to albumin
  3. Calcium complexed to serum constituents
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2
Q

Most calcium is found in bone as ________, thus it serves as a major reservoir.

A

hydroxyapatite crystals

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3
Q

Any changes in concentration of ________ affects the concentration of ionised calcium in the blood.

A

albumin

- changes in albumin causes changes in the amount of calcium bound to albumin, hence total calcium concentration.

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4
Q

Binding of calcium to albumin is pH-dependent. (Acidosis/alkalosis) increases calcium binding to protein.

A

Alkalosis increases calcium binding to protein

=> decreased ionised calcium proportion => increased neuromuscular excitability

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5
Q

(increased/decreased) ionised calcium concentration increases neuromuscular excitability.

A

Decreased ionised calcium concentration

  • Calcium ions inhibits sodium transport. Thus, lower calcium levels will increase neuromuscular excitability, caused by increased sodium transport leading to depolarisation.
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6
Q

Clinical conditions that cause changes in total but not ionised calcium

A
  1. Hypo/hyperalbuminemia

2. Multiple myeloma - causes elevated calcium levels due to increased renal calcium reabsorption

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7
Q

Clinical conditions that causes changes to ionised calcium but not total calcium

A
  1. Acid-base disorders
  2. PTH disorders
    - promotes bone resorption that increases blood serum ionised calcium levels
  3. Hyperhosphataemia
    - Phosphate complexes serum calcium, leading to lower levels of normal ionised calcium
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8
Q

Vitamin D3 (calcitriol) is acquired from 2 main sources.

A
  1. Diet

2. Skin (via UV radiation)

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9
Q

Vitamin D3 (Calcitriol) synthesis occurs in ________ where ________ is photoconverted to previtamin D3, which is then converted to Vitamin D3.

A
  • occurs in skin keratinocytes

- 7-dehydrocholesterol (precursor) –> pre-vitamin D3 –> vitamin D3 (Calcitriol)

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10
Q

2-step reaction to convert inactive Vitamin D3 to active metabolite ____________.

  1. Hydroxylation reaction in the _____ to produce 25-hydroxyvitamin D
  2. Hydroxylation reaction in the _______ to produce the active metabolite.
A

active metabolite 1,25-dihydroxyvitaamin D/cholecalciferol

  1. Hydroxylation reaction in the liver
    (Vitamin D3 –> 25-hydroxyvitamin D)
  2. Hydroxylation reaction in the kidneys
    (25-hydroxyvitamin D –> 1,25-dihydroxyvitamin D)
    by enzyme 1a hydroxylase
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11
Q

In calcitriol synthesis, negative feedback occurs as 1,25-dihydroxyvitamin D inhibits _________ enzyme to reduce the production.

A

1,25-dihydroxyvitamin D inhibits 1a-hydroxylase enzyme (in the kidneys)

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12
Q

Calcitriol is a principal regulator of calcium. It mainly acts on _______ and bones.

A

Calcitriol
- mainly acts on intestines to increase intestinal calcium absorption
- acts on bones to increase bone resorption
=> increases total serum calcium levels

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13
Q

PTH is synthesised and secreted by the _______

A

chief cells of the parathyroid glands

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14
Q

The dominant regulator of PTH is _______.

A

plasma calcium

- High calcium levels inhibit PTH secretion.

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15
Q

How does calcium concentration affect PTH secretion?

A
  • via membrane-bound calcium-sensing receptors (CASR) present on chief cells
  • calcium binds, activating PLC and inhibiting adenylyl cyclase
  • increases intracellular calcium concentration
    => prevents exocytosis of PTH-containing granules
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16
Q

The overall action of PTH is to (increase/decrease) plasma calcium levels and (increase/decrease) phosphate levels.

A

PTH:

  • increase plasma calcium levels
  • decrease plasma phosphate levels
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17
Q

Action of PTH:

  1. on bone
  2. on kidneys
  3. on intestines (indirectly)
A
  1. [bone] increases bone resorption by osteoclasts
  2. [kidneys] increases renal calcium reabsorption in the distal tubules and stimulate phosphate excretion
  3. [intestines] stimulate 1,25-dihydroxyvitamin D3 synthesis by stimulating 1a hydroxylase
    => intestinal effects of calcitriol
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18
Q

If excess 1,25-dihydroxyvitamin D3 is produced, _________ catalyses the 24-hydroxylation of calcitriol, inactivating it.

A

CYP24 (cytochrome P450 enzyme)

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19
Q

Calcitonin is synthesised and secreted by __________.

A

parafollicular cells of thyroid gland

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20
Q

Calcitonin is stimulated mainly by

A

increased plasma calcium levels

- the overall action of calcitonin is to decrease plasma calcium levels.

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21
Q

Main effects of calcitonin on:

1. bone

A
  • inhibits osteoclast motility and inactivates them

=> inhibits bone resorption

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22
Q

Calcitonin is a useful histological marker for ________.

A

medullary thyroid carcinomas

23
Q

_______ mainly functions to regulate phosphate concentration in plasma.

A

Fibroblast Growth Factor 23 (FGF23)

- secreted by osteocytes

24
Q

Main effects of FGF23

A
  1. Inhibits PTH secretion
  2. Inhibits calcitriol synthesis
  3. Suppresses phosphate reabsorption
25
Q

PTH stimulates osteoBlast to secrete _______, increasing osteoClastic activity and increased bone resorption.

A

RANKL

26
Q

Negative feedback by calcitriol:

A
  • inhibits PTH gene expression by upregulating the calcium sensor
  • represses CYP1a and stimulates CYP24
27
Q

______________ (clinical condition) involves mutations of the calcium-sensing receptor in chief cells, leading to inappropriate release of PTH secretion and elevated serum calcium.

A

Familial benign hypocalciuric hypercalcemia (FBHH)

28
Q

PTH binds to transmembrane receptors which activate ________ and _________.

A

PTH: activates both adenylyl cyclase (leading to increased cAMP) and PLC (increased IP3)

29
Q

Osteoblasts are involved in bone (synthesis/breakdown).

Osteoclasts are involved in bone (synthesis/breakdown).

A

Osteoblasts - bone synthesis

Osteoclasts - bone breakdown

30
Q

In bones, PTH receptors are found only on _________.

=> how to activate osteoclasts..?

A

osteoblasts
(involved in bone matrix synthesis)
- inhibited in their main activity, but stimulated to produce osteoclast activating factors which stimulate osteoclasts to increase bone resorption.

31
Q

Stimuli of PTH production

A
  1. Decreased plasma calcium levels

2. Catecholamines

32
Q

PTH production is negatively feedbacked by

A
  1. Calcium

2. Calcitriol (via raised Ca2+)

33
Q

Calcitriol effect on bones

A

(opposite of PTH)

- increases bone osteoblast activity to increase bone matrix synthesis, leading to the storage of Ca2+

34
Q

Calcitriol effect on small intestines

A
  1. increases calcium reabsorption

2. increases phosphate reabsorption

35
Q

Calcitonin and PTH are ________ hormones.

A

polypeptide

36
Q

Calcitonin mainly acts on the bone to __________.

It also has effects on the kidney.

A

Calcitonin:
- inhibits osteoclastic breakdown of bone matrix
=> reduces bone resorption and release of calcium and phosphate into the blood

  1. Effects on kidneys
    => natriuretic hormone as it increases excretion of Na+, Ca2+ and phosphate.
37
Q

Administration of _______ helps to stimulate calcitonin production from parafollicular cells to test their function.

A

gastrin

38
Q

Stimuli for calcitonin release:

A
  1. gastrin

2. increased plasma calcium concentration

39
Q

3 other hormones affecting calcium metabolism

A
  1. thyroid iodothyronines
  2. adrenal glucocorticoidds (cortisol)
  3. sex steroids
40
Q

Hypocalcaemia may present with ______.

A

tetany
- low calcium levels that causes neuromuscular excitability
=> intermittent muscular spasms

41
Q

3 endocrine causes of hypocalcemia

A
  1. hypoparathyroidism
  2. pseudohypoparathyroidism
  3. vitamin D deficiency
42
Q

Hypomagnesaemia (low magnesium levels) can cause (hypo/hyper)parathyroidism.

A

Hypomagnesaemia causes hypoparathyroidism.

Low Mg –> more calcium released from SR –> high Ca2+ levels –> inhibits PTH release –> hypoparathyroidism

43
Q

__________ occurs due to target organ resistance to PTH. (not actually low PTH levels)
This is mainly believed to be due to _________.

A

Pseudohypoparathyroidism
- due to defective Gs protein
=> no response to PTH binding can occur

44
Q

Vitamin D deficiency presents as _____ in children and ______ in adults.

A

rickets in children; osteomalacia in adults (softening of the bones due to decreased mineralisation of bone matrix)

45
Q

Treatment of acute hypocalcemia

A

IV calcium gluconate to replenish calcium

46
Q

Treatment of chronic hypocalcemia

A
  • oral supplements
  • IV calcium salts
  • in combination with vit D preparations, bisphosphonates, oestrogens, calcitonin
47
Q

3 endocrine causes of hypercalcemia

A
  1. Primary hyperparathyroidism
  2. Tertiary hyperparathyroidism
  3. Vitamin D toxicosis
48
Q

Primary hyperparathyroidism

A
  • increased PTH levels resulting in increased Ca2+ levels

- loss of negative feedback

49
Q

Causes of primary hyperparathyroidism

A
  • Parathyroid adenoma

- Chief cell hyperplasia

50
Q

Secondary hyperparathyroidism

A
  • (physiological) increased PTH levels in response to hypocalcemia
51
Q

Causes of secondary hyperparathyroidism (hypocalcemia)

A
  • renal failure (cannot reabsorb calcium)

- vitamin D deficiency

52
Q

Tertiary hyperparathyroidism

A
  • long-standing secondary hyperparathyroidism leading to autonomous production of PTH and thus increased Ca2+
  • loss of negative feedback with persistent stimulation
53
Q

Causes of tertiary hyperparathyroidism

A
  • Autonomous parathyroid hyperplasia

- chronic renal failure