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Disorders of Calcium Flashcards

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1
Q

1% of Ca2+ resides in the circulation. What are the 3 characteristics of Ca2+ when it is in the circulation?

A

1 - 50% is free (ionised) useable
2 -40% is bound (albumin and globulins)
3 - 10% is inorganic or organic

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2
Q

What are critical levels of Ca2+ in the circulation that will present as pathology? (high and low)

A
  • low = <6mg/dL

- high = >13mg/dL

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3
Q

What are the 2 main places Ca2+ is lost in the body, and aprox how much is lost to maintain normal Ca2+ homeostasis?

A

1 - GIT - 150mg

2 - Kidneys - 150mg

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4
Q

What are the 2 Ca2+ channels that we need to be aware?

A

1 - Transient receptor potential cation channel subfamily V (TRPV5 and 6)
2 - Epithelial Calcium Channel 2 (ECaC2)

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5
Q

Transient receptor potential cation channel subfamily V (TRPV5 and 6) are important 2 Ca2+ channels that are present in the kidneys. Where are these channels located and what is their function?

A
  • located on apical membrane (side facing the lumen)

- pumps Ca2+ from filtrate in lumen into tubules of the kidney

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6
Q

Transient receptor potential cation channel subfamily V (TRPV5 and 6) are important 2 Ca2+ channels that are present in the kidneys. They are located on apical membrane (side facing the lumen), where they pump Ca2+ from filtrate in lumen into tubules of the kidney. What then must happen to the Ca2+ for it to be re-absorbed?

A
  • Ca2+ binds with calbindin-D28K (regulated by vitamin D)

- then transported into plasma via a Ca2+ ATPase pump called basolateral membrane Ca 2-ATPase (PMCA1b)

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7
Q

What cation ion is Ca2+ re-absorption or excretion closely related with?

A
  • Na+
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8
Q

Parathyroid hormone is crucial for maintaining Ca2+ homeostasis. What is the precursor of vitamin D that is absorbed and then synthesised in the keritinocytes of the epidermal layer of the skin?

A
  • cholecalciferol (D3 is precursor of vitamin D)
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9
Q

Parathyroid hormone is crucial for maintaining Ca2+ homeostasis. Cholecalciferol (D3 is precursor of vitamin D) is the precursor of vitamin D that is absorbed and then synthesised in the keritinocytes of the epidermal layer of the skin. Once synthesised it then travels to another organ. What is this organ and what happens here?

A
  • travel to the liver

- enzyme 25- hydroxylase in liver converts cholecalciferol into 25- hydroxycholecalciferol or calcidiol

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10
Q

Parathyroid hormone is crucial for maintaining Ca2+ homeostasis. Cholecalciferol (D3 is precursor of vitamin D) is the precursor of vitamin D that is absorbed and then synthesised in the keritinocytes of the epidermal layer of the skin. Once synthesised it then travels to the liver, where enzyme 25- hydroxylase converts cholecalciferol into 25- hydroxycholecalciferol or calcidiol. What then happens to the 25- hydroxycholecalciferol or calcidiol?

A
  • travels to the proximal tubular cells of the kidney
  • enzyme 1-alpha-hydroxylase, which is also activated by PTH, turns 25- hydroxycholecalciferol into 1,25-dihydroxycholecalciferol, also known as calcitriol, or active vitamin D
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11
Q

1,25-dihydroxycholecalciferol (1,25 (OH) 2D3), also known as calcitriol, or active vitamin D becomes active vitamin D in the kidneys. What roles does it then have on Ca2+ re-absorptin?

A
  • 1-25 (OH) 2D3 up-regulates genes for transient receptor potential cation channel subfamily V (TRPV5 and 6)
  • up-regulation of TRPV5 and 6 means more membrane channels and more Ca2+ re-absorbed
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12
Q

What is the formula for calculating the non-bound Ca2+ (active) in the plasma?

A
  • total Ca2+ (mg/dL) + 0.8 x (40 - albumin)
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13
Q

When trying to calculate unbound (ionised) Ca2+ in plasma, why do we need to correct for albumin?

A
  • main protein that Ca2+ binds with

- elevated albumin = reduced ionised Ca2+ as more will be bound to albumin

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14
Q

What affect does pH have on unbound (ionised) Ca2+ levels in the plasma?

A
  • as pH decreases there is an increase in H+ which binds to proteins (albumin)
  • more H+ means less proteins for Ca2+ to bind with
  • increased pH = increased protein binding and decreased unbound (ionised) Ca2
  • decreased pH = decreased protein binding and increased unbound (ionised) Ca2

IMPORTANT IN ALKALOSIS AND ACIDOSIS

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15
Q

What are the 3 key organs/tissues, that if they are diseased can affect Ca2+ levels?

A

1 - bones
2 - kidneys
3 - GIT

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16
Q

What key gland is crucial for maintaining Ca2+ levels?

A
  • parathyroid gland

- located on back of thyroid gland

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17
Q

How can vitamin D affect Ca2+ levels?

A
  • increased re-absorption in kidneys and GIT
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18
Q

What are the 3 key hormones in the body that regulate Ca2+ levels?

A

1 - parathyroid hormone (PTH)
2 - 1,25- dihydroxyvitamin D [1,25(OH)2D the active form of vitamin D in the body
3 - fibroblast growth factors 23 (FGF 23)

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19
Q

Parathyroid hormone (PTH) is synthesised and secreted by the parathyroid glands. PTH is a polypeptide of how many amino acids in its intact form?

A
  • 84 amino acids
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20
Q

Parathyroid hormone (PTH) is synthesised and secreted by the parathyroid glands. How is the level of ionised (unbound) Ca2+ detected by the parathyroid gland?

A
  • contains Ca2+-sensing receptors (CaSR)

- CaSR are GPCRs (Gaq)

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21
Q

Parathyroid hormone (PTH) is synthesised and secreted by the parathyroid glands. The level of ionised (unbound) Ca2+ are detected by the parathyroid gland through Ca2+-sensing receptors (CSR) located on chief cell, which are GPCRs (Gaq). What would happen to the secretion of PTH in high and low extracellular Ca2+ levels?

A
  • high = reduced PTH secretin

- low = increased PTH secretion

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22
Q

What is the half life of parathyroid hormone?

A
  • aprox 4 minutes
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23
Q

Which cation, when in low levels is able to inhibit the release of parathyroid hormone, mimicking hypoparathyroidism?

A
  • Mg2+
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24
Q

When Mg2+ levels are low, this is able to inhibit the release of parathyroid hormone (PTH), mimicking hypoparathyroidism. What can acute low levels of Mg2+ therefore do to ionised (unbound) Ca2+ levels?

A
  • reduces Ca2+ as no PTH to stimulate increased Ca2+ release from bones and re-absorption from the kidneys and GIT
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25
When Mg2+ levels are low, this is able to inhibit the release of parathyroid hormone (PTH), mimicking hypoparathyroidism. What can chronic low levels of Mg2+ do to phosphate levels?
- raise phosphate levels
26
What is the difference between the structure of parathyroid hormone (PTH) and PTH-related peptide (PTHrP)?
- PTH is 84 amino acid peptide | - PTHrP is 35 amino acid peptide
27
Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) are related but have different structures - PTH is 84 amino acid peptide - PTHrP is 35 amino acid peptide But what is the difference in their function?
- PTH = metabolise active vitamin D and increase Ca2+ re-absorption from GIT, kidney and bones - PTHrP = activate increased Ca2+ re-absorption from bone
28
Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) are related but have different structures - PTH is 84 amino acid peptide - PTHrP is 35 amino acid peptide Are clinical laboratories able to detect both PTH and PTHrP levels in blood?
- no | - just PTH
29
Parathyroid hormone (PTH) and PTH-related peptide (PTHrP) are related but have different structures - PTH is 84 amino acid peptide - PTHrP is 35 amino acid peptide What is the known source of secretion of PTHrP, which can then go on cause hypercalcaemia?
- tumours
30
What is calcitriol?
- active form of vitamin D | - also known as 1,25-dihydroxycholecalciferol
31
Is ergocalciferol also known as vitamin D2, a synthetic form of vitamin D fortified to foods as biologically active as the active form of vitamin D3?
- yes - metabolised in the liver to via enzyme 25- hydroxylase into into 25- hydroxycholecalciferol or calcidiol - 25- hydroxycholecalciferol or calcidiol is then metabolised in the kidney to 1,25-dihydroxycholecalciferol, also known as calcitriol, or active vitamin D
32
Ergocalciferol also known as vitamin D2 and active form of vitamin 1,25-dihydroxycholecalciferol, also known as calcitriol or D3 need to be measured separately in the clinical lab. Why is this?
- identify where the deficiency is, skin or diet
33
What are 4 main thing that can affect vitamin D levels through the skin?
1 - melanin pigmentation of skin 2 - age 3 - season 4 - geographic location
34
What effect can prolonged use of suncream have on vitamin D levels?
- low levels of vitamin D
35
Which enzyme in the liver is responsible for converting the precursor of vitamin, cholecalciferol into 25- hydroxycholecalciferol, also known as calcidiol?
- cytochrome P450 hydroxylase
36
Cytochrome P450 hydroxylase is the enzyme in the liver responsible for converting the precursor of vitamin, cholecalciferol into 25-hydroxycholecalciferol, also known as calcidiol. What is the importance of this?
- 25-hydroxycholecalciferol, also known as calcidiol is the major circulating vitamin D metabolite - normal levels range fro 30-50ng/mL USED TO ASSESS VITAMIN D STATUS
37
Is calcidiol (following metabolism in the liver, but prior to metabolism in the kidney) and calcitriol (active form of vitamin D) more active?
- calcitrol by 1:10 or even 1:100
38
Hypercalcaemia is elevated levels of Ca2+. This can occur if calcitrol (1,25 (OH)2D)), the active form of vitamin D if levels are consistently above what level?
- 375-500nmol/L
39
What type of receptor are vitamin D receptors?
- nuclear receptors | - able to bind and change the function of the DNA
40
What is calcitonin?
- 32 amino acid hormone secreted by para-follicular C cells of the thyroid gland - opposes parathyroid hormone, so inhibits Ca2+ release
41
How does the thyroid hormone detect levels of Ca2+ in plasma?
- calcium-sensing receptor (CSR)
42
The thyroid hormone detect levels of Ca2+ in plasma via Ca2+-sensing receptors (CSR) and releases calcitonin. What happens to the secretion of calcitonin when extracellular levels of Ca2+ are high or low?
- elevated Ca2+ = increased secretion of calcitonin | - decreased Ca2+ = decreased secretion of calcitonin
43
Which hormone secreted by the stomach is able to inhibit the secretion of calcitonin by the thyroid gland?
- gastrin
44
What effect does calcitonin have on the bone?
- calcitonin binds to GPCR (Gas) on osteoclasts - osteoclasts are then inhibited from re-absorbing bone - reduces Ca2+ release into plasma
45
What effect does calcitonin have on the kidneys?
- binds with GPCR on principle cells in distal convoluted tubules - GPCR inhibits the Na+/Ca2+ channels and reduces Ca2+ re-absorption - increase Ca2+ and phosphate excretion in the urine
46
Although not conclusive, what effect does calcitonin have on the GIT?
- buffer the absorption of Ca2+
47
In women who have oestrogen-deficient states, they are likely to have osteoperosis and increased plasma Ca2+, why is this?
- calcitonin levels are decreased - calcitonin does not bind with osteocytes - osteocytes continually degrade bone and release Ca2+ into the blood - bones become brittle and at increased risk of fracture
48
Clinically, calcitonin is a useful marker of pathogenesis, for what?
- medullary carcinoma of the thyroid gland | - medullary is the inside part of the thyroid
49
Fibroblast growth factor-23 (FGF-23) is a hormone that is primarily secreted by bones. What are the 2 key functions of FGF-23?
- regulate phosphate levels | - regulate vitamin D levels
50
Fibroblast growth factor-23 (FGF-23) is a hormone that is primarily secreted by bones, and is involved in the regulation of phosphate and vitamin D levels. How does FGF-23 influence phosphate levels?
- FGF23 acts on the kidneys, decreasing sodium-phosphate co-transporters in the proximal tubule - phosphate re-absorption is therefore reduced
51
Fibroblast growth factor-23 (FGF-23) is a hormone that is primarily secreted by bones, and is involved in the regulation of phosphate and vitamin D levels. FGF-23 acts on the kidneys, decreasing sodium-phosphate co-transporters in the proximal tubule and therefore reduces phosphate re-absorption. What 2 other molecules is FGF-23 able to influence?
- Ca2+ re-absorption | - reduces the conversion of 25-hydroxyvitamin D3 into the active form of vitamin D 1,25 (OH)
52
What is hypophosphatemia and what hormone is strongly associated with this?
- low levels of the phosphate | - fibroblast growth factor-23
53
Although Ca2+ is an essential cation, what can high levels of Ca2+ do to a cell?
- cause apoptosis - this is what happens during programmed cell death - lots of energy used by the cell to keep Ca2+ out of the cell
54
Does hypercalcemia always present with severe symptoms?
- no - patients can be atypical, generally younger patients - older patients are more susceptible
55
What are the main symptoms associated with hypercalcaemia?
- impaired renal function - GIT problems - cardiovascular - neuromuscular - central nervous systems (CNS)
56
What is primary hyperparathyroidism?
- condition in which one or more of the parathyroid glands makes too much parathyroid hormone
57
If a patient presents with hypercalcaemia, what would be the first thing to address?
- fluid levels to address any potential dehydration and volume loss
58
If a patient presents with hypercalcaemia, would you address the diet?
- consider reducing Ca2+ in the diet
59
Why is mobilisation important in patients who are hypocalcaemic?
- if immobilised Ca2+ will be released into the blood as bones are not stressed - mobilisation maintains bone mineral density
60
What are the most common symptoms of hypocalcaemia?
- CNS impairment - neuromuscular impairment (muscle cramping) - impaired ocular function (cataract formation) - cardiovascular function (arrhythmias) - ectodermal systems (calcification)
61
Albumins contain a + and a - hydroxyl (OH group). This means they can bind negative and positive ions (cations = + and anions = - charge) such as H+ and Ca2+ amongst others. What happens to free ionised and bound Ca2+ when a patient has acidosis?
- albumin binds with increased H+ in plasma - albumin becomes + charged and repels Ca2+ - Ca2+ bound to albumin is released - causes an increase in ionised (free) Ca2+ in plasma - BUT total Ca2+ is the same

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