Calcium Flashcards
(90 cards)
1
Q
What are the difference forms of calcium found in the blood
A
45% = Protein bound (e.g. albumin)
45% = Free ionised Ca2+ - This is physiologically active!!!
10% = Complexed (e.g. phosphate, glucose)
2
Q
what is the total plasma calcium amount
what is the free ionised calcium amount
A
Total Plasma Calcium: 2.2 – 2.6 mmol/l
Free ionised Calcium: 1.15 – 1.3 mmol/l
3
Q
where is 99% of body calcium
A
99% of body calcium is in the bone
4
Q
how much bone calcium is exchangeable with extracellular fluid calcium
A
99% of bone calcium is in the crystal structure
1% of bone calcium is exchangeable with extracellular fluid calcium
5
Q
describe what happens to total amount so calcium in acidosis and alkalosis
A
Acidosis
- there is increased levels o free levels of ionised calcium (Ca2+) in the blood this is because calcium and hydrogen ions are completing for the same site in albumin and there are more hydrogen ions present in acidosis
alkalosis
- ionised calcium (Ca2+) is decreased there is more calcium bound to albumin as there is a decrease in the amount of hydrogen ions and more calcium present
6
Q
what is low calcium bad for
A
nervous tissue
7
Q
What are the 2 forms of vitamin D
A
2 important forms:
- Vitamin D2 (ergocalciferol) obtained from plants in diet
- Vitamin D3 (Cholecalciferol) produced by skin after UV light exposure and
obtained from fish, eggs, milk
8
Q
Vitamin D2 and vitamin D3 are both …
A
Both are prehormones that are converted to active form in body
9
Q
the amount of calcium inside the cell is…
A
greater than the amount of calcium outside the cell therefore it is an important intracellular signalling molecule
10
Q
what are the functions of Functions of Calcitriol (1,25 dihydroxy-vitamin
D3)
A
Increases dietary calcium absorption in intestine
- Upregulates synthesis of TRPV6, Calbindin & PMCA
Increases phosphate absorption from gut
Stimulates bone resorption and remodelling
Only actions of calcitriol increase total body calcium
11
Q
what does hypocalciemia cause in the heart
A
causes tachyarrhythmia if calcium falls
12
Q
why does calcium cause arrhythmia
A
Sodium ion channels are the right size for calcium ions to block them
- so if there is a large amount of calcium present they block the entry of sodium ion channels and prevent depolarisation of cardiomyocytes
- this slows down the heart rate
- if you have hypercalciemia this can cause bradycardia
- but if you have hypocalcemia then this can cause the reduction in the threshold for action potentials to fire as more sodium ions are entering thus this can cause tachyarrhytmia
13
Q
Name some effects of hypocalcemia
A
- tacyarrhythmia
- tetany
14
Q
how can calcium cause constipation
A
- if calcium rises outside the cell then this can cause blockage of sodium channels thus muscle in the gut fails to depolarise and this can lead to constipation as peristalsis slows down
15
Q
what forms does phosphate come in
A
- 85% of body phosphate is mineralised in bone
* Serum phosphate is almost all ionised
16
Q
what is phosphate important in
A
- it has roles in the formation of protein
- hypophosphatemia present with imapriemnt of organ function
17
Q
What and where are the parathyroid glands
A
Parathyroid glands are 4 small oval shaped glands posterior to thyroid
18
Q
what is parathyroid hormone produced by
A
PTH is produced by Chief cells in the parathyroid gland
19
Q
What is parathyroid hormone stimulated and inhibited by
A
Stimulated by:
- ↓serum calcium
- mild decreases in Mg
- phosphate
Inhibited by:
- ↑serum calcium
- calcitriol
- severe decreases in Mg
- Cinacalcet (calcimimetic)
20
Q
what regulates parathyroid hormone secretion
A
The calcium sensing receptor (CaSR)
21
Q
what does the calcium sensing receptor do
A
- regulate parathyroid hormone secretion
22
Q
where is the calcium sensing receptor
A
Parathyroid gland and renal tubules
23
Q
what are the effects of the calcium sensing receptor
A
Effects:
- increases intracellular Ca2+
- inhibits exocytosis of PTH
- degrades stored PTH
- inhibits PTH production
- activates PLC to block stimulation of cAMP
24
Q
what does a mutation in the calcium sensing receptor result in
A
Mutations: Familial hypocalciuric hypercalcaemia (FHH)
25
What does PTH do
* Kidney: decreases calcium excretion and increases phosphate excretion
* Bone: increases calcium and phosphate resorption
* Intestine: increases absorption of calcium and phosphate; does this by a reaction with 1,25-hydroxyl vitamin D it causes you to absorb calcium from the gut
this is all in order to increase the amount of ECF calcium
26
what cells is the parathyroid gland made up of
oxyphilic cells - appear at the onset of puberty
| chief cells
27
what is a clinical use of oxyphilic cells
- when the parathyroid gland is overactive they take up technetium-sestamibi which is a stain
- after 15 minutes it will show the outline of the thyroid gland but after 2 hours of use it will show up the parathyroid adenoma uptake
28
how is parathyroid hormone synthesised
- PreproPTH then the rough ER converts it to ProPTH
- proPTH then the golgi converts it to PTH
- PTH then secreted into vesicles
29
what is parathyroid hormone secreted as
Secreted intact as PTH 1-84
30
what is parathyroid hormone metabolised by and what is its half life
extensively metabolised by the liver and kidney and has a circulation half life of only 2 minutes
31
what is the active portion of PTH
Active portion of PTH is at the N-terminal, although a number of inactive C-terminal fragments are also secreted as a result of storage in vesicles along with proteolytic enzymes such as cathepsin B
32
why type of receptor is the calcium sensing receptor
it is a G protein receptor
33
why does the bone decrease calcium excretion and increase phosphate exercise
- this is because you cannot release calcium from the bone without releasign phosphate as well
- but therefore even if phosphate is normal this will cause a high amount of phosphate to be produced
- calcium returns to normal
- therefore the kidney excretes the excess phosphate
34
what is the quickest way to release calcium
from the bone
35
how much is each part fo the kidney responsible for calcium reasborption
Proximal tubule
- Responsible for 65% of calcium reabsorption
loop of Henle
• 20% reabsorption
36
how does the proximal convoluted tubule reabsorb calcium
- paracellularly
- PTH independent
- driven by voltage gradient
37
how does the loop of Henle reabsorb calcium
• Para/transcellular
• Voltage dependent
- calcium sensing receptor is also on the loop of Henle
38
what is calcium reabsorboption in the loop of Henle inhibited by
- loop diuretics
39
How do loop diuretics inhibit calcium reabsorption in the loop of Henle
- loop diuretics inhibit the Na/K/2Cl channel
- this reduces the gradient of calcium reabsorption
- this means that serum calcium levels fall
- activation of the calcium sensing receptor by calcium itself will also inhibit the Na/k/2Cl channel
- therefore this leads to hypocalciaemia
40
how do thiazides effect the distal convoluted channel and therefore effect calcium reabsorption
- inhibits the sodium chloride channel int he distal coveted tubule
- if the sodium chloride channa inhibited then the amount of sodium inside the cell fall and this increases the gradient across the other cell memraben
- means more sodium goes from the blood into the distal convulted tubule and ore calcium goes into the blood as well
- this causes calcium levels to rise
- this causes hypercalemia
41
which diuretics cause hypocalemia and which cause hypercalemia
thiazide - hypercalemia
| loop diuretics - hypocalemia
42
what does PTH up regulate
* TRPV calcium channels
* Calcium ATPase
* Na/Ca exchanger
43
what does PTH do in the renal system
• Down-regulation of NaPi transporters
– Reduced phosphate reabsorption
• Vitamin D Activation
– Stimulation of 25(OH) D3 1,25(OH)2 D3
• Proximal tubule gluconeogenesis
• Inhibits sodium/water/bicarbonate reabsorption via effects on Na/H exchanger and Na/K ATPase
- PTH effects on increasing 1 alpha hydroxylase activity can be overridden by calcitriol or hypercalcemia
44
what is bone made out of
- Collagen plus hydroxyapatite
45
what does mineralisation of hydroxyapatite require
requires calcium, phosphate and alkaline phosphatase
46
where are osteoblasts and osteoclasts derived from
- Osteoblasts are derived from mesenchymal cells
| - Osteoclasts have a myeloid origin
47
what do osteoblasts do
Osteoblasts produce mineral AND signal to osteoclasts to resorb bone
48
what do osteoblasts do when mineralisation is complete
- When mineralisation is complete they differentiate into osteocyte, encased in mineralized bone *but* maintain connections with other osteoblasts in an extended syncytium.
- Osteocytes have a role in sensation of bone deformation.
49
what inhibits osteoclasts from maturing
colony stimulating factor 1 to promote osteoclastogenesis and osteoclast function.
OPG: osteoprotegerin inhibits osteoclastogenesis.
50
what causes osteoclasts to mature
Osteoblast release RANKL: receptor activator for nuclear factor κB ligand and CSF-1: (colony stimulating factor 1 )
- this causes maturation of osteoclasts
51
what does PTH and calcitrol do in terms of osteoclasts
- PTH and calcitriol stimulate RANKL production
| - PTH and calcitriol downregulate OPG
52
what is the difference in bone reabsorption and formation in young adults and at menopause
* Young adults: bone resorption = formation happening at the same rate
* Menopause: increased remodelling; resorption > formation
53
what is the difference in deficiency of vitamin D and and increase in PTH
PHT - osteoporosis - porous brittle bone
vitamin D
- adults = osteomalacia - bones are soft and bendy
Children= rickets
54
describe what happens in menopause to the bone
* PTH increase RANKL; decreases OPG; increases IGF1 (leading to growth of the bone) and IL1
* Calcitriol increases RANKL in vitro; increases gut calcium absorption
* Glucocorticoid: reduce osteoblast numbers and mineral production; increase RANKL
on the other hand before menopause
• Estrogen: epiphyseal closure; reduce cytokine sensitivity and inhibits bone remodelling
55
what is the difference in giving PTH in bolus subcutaneous does and continuous infusion for bone
Bolus subcutaneous doses cause bone formation, and this is a treatment for osteoporosis
Continuous infusion causes bone resorption, and increased serum calcium. This is a treatment for hypoparathyroidism
56
what is rugger jersey spine
- Primary hyperparathyroidism
- Leads to osteoporosis and breakdown of bone
- Breakdown bone in spine and get stripes
- brown tumour - – this is an area where there was high levels of PTH which leads to degrardation of the bone and excess remodelling
57
what type of hormone is vitamin D
- This is a steroid hormone
| - It is produced from cholesterol
58
How does vitamin D form from the sun
7-dehydrocholesterol is cleaved under the influence of UV radiation to previtamin D, which isomerises to vitamin D over a period of 48 hours.
59
what does vitamin D binding to in circulation
- albumin
| - vitamin D binding protein - acts as a reservoir.
60
how is vitamin D converted to 25(OH)D
- unregulated process
| - under action of p450 enzymes
61
what is the half life of 25(OH)D
The half life of 25(OH)D is 2-3 weeks
62
How is 25(OH)D converted to 1,25(OH)D
- highly regulated
| - short half life of 6-8 hours
63
How do you increase someones gut absorption of calcium
- Give them a table of 1,25-hydroxy vitamin D or 1-hydroxy vitamin D with the expectation that it will be converted into vitamin D
64
How can TB and sarcoid granulomas lead to hypercalemia
- Activated macrophages found in TB and sarcoid granulomata
- These conditions can therefore lead to hypercalcemia
- There is a positive feedback loop of activated vitamin D production within activated macrophages, to up regulate their cytotoxic capacity. In these cells 1α hydroxylase is not regulated by PTH nor down regulated by VDR activation
65
what is the major role of calcitrol
- The major role of calcitriol is in increasing gut calcium and phosphate absorption.
66
what determines gut calcium absorption
- presence of bile salts
- free fatty acids
- fibre in the diet
- gastric acidcity
- calcitrol
67
what is used to reduce calcium uptake form the gut
Proton pump inhibitor use reduces calcium uptake.
68
how does calcium across the gut wall occur
- transcellular,
- paracellular
- vesicular routes
- all 3 are unregulated by vitamin D.
69
What are the other effects of vitamin D
* Parathyroid: modest reduction in PTH transcription
* Bone: reduces expression of type 1 collagen; increases levels of osteocalcin & RANKL; facilitates osteoclast differentiation
* Increases phosphate absorption from the gut AND increases levels of FGF23 to remove it via renal excretion
* Widespread effects in reducing cellular proliferation and favouring differentiation
* Increases amino acid uptake: deficiency in vitamin D myopathy
70
what does glucortcoid do to vitamin D
Glucocorticoid reduces the expression of the vitamin D receptor – contributing to the myopathy and low bone mineral density seen in Cushing’s syndrome
71
what is another word for 1,25 OH-2 vitD3
calctirol
72
What can only increase total body calcium
Only vitD3 can increase total body calcium
73
What can cause a vitamin D deficiency
Poor diet, malabsorption, lack of sunlight
74
What are the characteristics of rickets
Growth retardation
Knock-kneed
Bow-legged
75
What is FGF23
Synthesized by osteoblasts/cytes in response to a high phosphate level
76
what does FGF-23 do
Actions:
🡻phosphate
- Increases renal phosphate secretion
🡻calcium
- Inhibits 1aplha hydroxylase activity (less 1,25OH2vitD3)
77
what are the mutations in FGF23
Activating mutation in FGF23: AD hypophosphataemic
rickets
Tumour induced osteomalacia: paraneoplastic FGF23
Familial tumoral calcinosis: low levels FGF23
78
What is calcitonin produced by and a marker of
Produced in Thyroid C-cells
| Marker for Medullary thyroid cancer
79
what is the form of PTH in fatal life
PTHrP
80
What causes hypoparathyroidism
| - what does it result in
- Low PTH
- Uncommon
- Iatrogenic
Results in:
- Hypocalcaemia
- Convulsions
- Arrhythmia
- Tetany
- Death
81
what is hyperparathyroidism
- Too much PTH
82
what are the types of hyperparathyroidism
- primary
- secondary
- tertiary
83
describe the types of hyperparathyroidism
Primary- problem=gland, no hypocalcaemia:
- Parathyroid adenoma/carcinoma
- Parathyroid hyperplasia
- causes too much PTH to be produced this leads to hypercalemia
Secondary- problem=low calcium, compensation for hypocalcaemia:
- vitD deficiency
- Chronic renal failure (CRF)
Tertiary- autonomous PTH (PTH produced without being stimulated)
- due to chronic secondary
- CRF (disruption of -ve feedback mechanism)
- leads to hypercalemia
84
What does hyperparathyroidism cause
Results in Hypercalcaemia
This causes
‘Bones, stones, groans and psychic moans’
- Bones- osteoporosis
- Stones- renal calculi
- Groans- abdominal pain, constipation, polyuria
and polydipsia
- Psychic moans- depression, confusion
85
How do you diagnose hyperparathyroidism
a) Serum calcium and PTH
b) 24 hr urine calcium - this would show high PTH
c) Urine calcium creatinine excretion index
d) Renal ultrasound - looks for nephrocalcinosis indicates surgical treatment
e) DXA scan - looks for oestoeporsis
86
How do you locate an adenoma
a) Neck Ultra sound (USS)
b) MIBI scan
c) CT scan
d) Parathyroid Venous Sampling – putting a canaula in through the wrist and taking PTH levels in all the venins in the neck to work out where the adenoma is
87
what are the signs and symptoms of hypocalemia
- Convulsions
- Confusion
- Tetany
- Tachyarrhythmia
88
what can cause hypocalemia
```
• Hypoparathyroidism
– Iatrogenic
– Autoimmune
– Genetic
• Vitamin D deficiency
• Chronic kidney disease
• PTH resistance
```
89
How do you treat hypoparathyrodism
- Acutely – calcium replacement
- Chronically – PTH but this is difficult as it is a peptide hormone so gets digested need to administer subcutaneously via injections – best can do is give them 1 hydroxy vitamin d3 orally which increases calcium from the gut
90
why do you get kidney stones in both hyperparathyroidism and hypoparathyrpdism
hyperparathyroidism – increase serum calcium increase urinary calcium -get kidney stones
Hypoparathyroidsum – don’t have PTH cant absorb calcium well and they have high levels of urinary calcium which leads to kidney stones
