T3 - L5 calcium metabolism Flashcards
1
Q
What type of ion is calcium?
A
Divalent cation (Ca2+)
2
Q
In which processes is calcium physiologically important?
A
- muscle contraction
- neuronal excitation
- enzyme activity (Na/K ATPase, hexokinase etc)
- blood clotting
3
Q
How is calcium structurally important?
A
Key component of hydroxyapatite Ca10(PO4)6(OH)2 - the predominant mineral in bone
4
Q
What type of ion is phosphate?
A
Monovalent anion (PO4-)
5
Q
Why is phosphate physiologically important?
A
- the P in ATP
- intracellular signalling
- cellular metabolic processes eg. glycolysis
6
Q
Why is phosphate structurally important?
A
- backbone of DNA
- component of hydroxyapatite
- membrane phospholipids
7
Q
Is phosphate predominantly intracellular or extracellular?
A
Predominantly intracellular
8
Q
When these electrolytes are out of balance, it can be attributed to what…
A
- increased or reduced intake
- increased or reduced excretion/loss
- increased or reduced storage
- tissue redistribution
9
Q
Calcium is normally tightly regulated at what levels?
A
2.20-2.60mmol/L
10
Q
The two key controlling factors for calcium are..
A
- PTH
- vitamin D and metabolites
11
Q
There are complex but well-characterised relations between calcium and what?
A
- GI uptake
- renal clearance
- bone
12
Q
how would you work out the total Ca2+t?
A
Total Ca = Ionised Ca + Bound Ca + Complexed Ca
13
Q
Which form of calcium is the physiologically active fraction?
A
Ionised calcium
- calcium sensing receptor
- cellular effects
- regulation of PTH
14
Q
Is bound calcium active?
A
Physiologically INACTIVE
15
Q
when calcium circulates bound to plasma proteins, what is the most common protein for it to be bound?
A
Albumin
16
Q
What are complexed calcium compounds?
A
Salts - calcium phosphate and calcium citrate
17
Q
Calcium values can be corrected for what? (adjusted calcium)
A
Corrected for changes in albumin
18
Q
What is adjusted calcium?
A
Total calcium + (40-Alb) x 0.025
19
Q
What is the reference range for adjusted calcium?
A
Same as normal
2.20-2.60mmol/L
20
Q
Describe the calcium distribution in the plasma
A
ionised calcium = 1.3mmol/L
bound calcium = 0.95mmol/L
complexed calcium = 0.05mmol/L
roughly
21
Q
Total calcium doesn’t necessarily reflect ionised calcium; why?
A
- total calcium affected by albumin
- pH influences ionised Ca
22
Q
Describe the ways that pH influences ionised/bound calcium
A
acidosis = reduced Ca-albumin
alkalosis = increases Ca-albumin
23
Q
Why does acidosis reduce Ca-albumin so reduce the amount of bound calcium?
A
Calcium and H+ ions compete for the albumin binding sites
- this means less bound calcium and more ionised calcium
24
Q
How does the distribution of calcium change in alkalosis?
A
Increased bound calcium and decreased ionised calcium
25
How does a reduction in binding protein change calcium distribution?
- decrease in bound calcium
- ionised calcium and complexed calcium stay the same
- overall decrease in total calcium
26
Calcium levels tend to increase as levels of which protein increase?
Albumin
27
What are the albumin levels reference range?
35-55g/L
28
Give examples of artifactual causes of hypocalcaemia
- EDTA contamination (chelates calcium ions)
| - venestasis will cause low adjusted calcium (total calcium is unaffected)
29
Which calcium disorder involves low serum ionised calcium and low plasma PTH?
Primary hypoparathyroidism
30
Which calcium disorder involves low-normal serum ionised calcium but high plasma PTH?
Secondary hyperparathyroidism (usually renal or nutritional)
31
Which calcium disorder involves high serum ionised calcium and but low plasma PTH?
PTH independent hypercalcaemia (eg. malignancy, vitamin D toxicity)
32
Which calcium disorder involves high serum ionised calcium and high plasma PTH?
Primary hyperparathyroidism
33
Calcium at what levels is a medical emergency requiring immediate treatment?
Over 3.5mmol/L or under 1.6mmol/L
34
how would a standard biochemistry test become contaminated with EDTA?
- Purple tube used for full blood count contain EDTA
| - if used first it can contaminate other samples.
35
what happens if your blood sample is contaminated by EDTA?
- chelate the calcium
| - cause of spuriously raised potassium (pseudohyperkalemia).
36
what colour tube is used for a full blood count?
purple
37
what 3 main forms does calcium circulate the body in?
- ionised "free" Ca2+ (50%) - biologically active
- bound to plasma proteins (41%) - predominantly albumin
- complexed to anions (9%) - e.g. phosphate, citrate, bicarbonate
38
which of the 3 forms of calcium that circulate the body is the biologically active form?
Ionised “free” Ca2+ (50%)
39
how much is Total body phosphorous? and how is this distributed between bone, intracellular and extracellular?
Total body phosphorous (23 mol, ~700g)
- bone 85%
- intracellular 14%
- extracellular 1%
40
what two main forms does phosphorus circulate in the blood?
- Organic form (covalently bound) ~70%
e. g. phospholipids
- Inorganic form as phosphate ~30%
Predominantly HPO42- & H2PO4-
41
what is the adult reference range for phosphate?
0.8 - 1.5mmol/L
42
PTH is secreted by the parathyroid glands, stimulated in response to what?
- low calcium
- high phosphate
- high magnesium in low calcium environments
43
how does magnesium effect the secretion of PTH?
- Mg acts on Ca Receptor
- intimates negative feed back loop (in place of calcium)
- high Mg = decreased secretion of PTH
- However high Mg is only able to reduce PTH when parathyroid glands were exposed to low Ca concentrations.
- With normal to high Ca concentrations, only an extremely high Mg concentration of 5.0 mM was able to decrease PTH secretion
44
what direct action does PTH have on bone?
drive resorption of Ca and PO4
45
what direct action does PTH have on the kidneys?
- increase reabsorption of Ca from the filtrate
| - increase excretion of PO4
46
what indirect action does PTH have on the kidneys?
increase conversion of vitamin D to its active
form (1,25(OH)2 vitamin D)
NB: this increases Ca and PO4 absorption from the gut
47
what is the active form of Vitamin D?
(1,25(OH)2 vitamin D)
calcitriol (also known as 1,25-dihydroxycholecalciferol)
48
high calcium has what affect on PTH release?
decrease the release of PTH
High calcium results in negative feedback on PTH release (via calcium sensing receptors of
the parathyroid gland)
49
where can we get Vitamin D from?
- Diet (especially oily fish)
- Synthesis in the skin from a cholesterol precursor by the action of UV-B from the
sunlight
50
where does Vitamin D have to go to become "Activated"?
- The liver to undergo the first hydroxylation
- The kidneys to undergo the second hydroxylation step by 1α-hydroxylase
NB: This last step produces the active form of Vitamin D (1,25(OH)2 vitamin D)
51
which enzyme in the liver hydroxylates vitamin D to its active form?
1α-hydroxylase
52
how does PTH increase the activation of Vitamin D?
PTH acts on the kidneys to increase the activity of 1α-hydroxylase enzyme to increase the activation of Vitamin D
53
why is the precursor of Vitamin D measured in the lab instead of the active form of Vitamin D?
As it is present at a greater concentration in the blood and more stable
54
what does the active form of vitamin D act on?
Acts on the intestine to increase the absorption of Calcium and Phosphate
NB: Has some other effects including beneficial effects for the immune system and
anti-cancer effects]
55
For bone health, is 25-OH Vitamin D < 75 nmol/L sufficient?
NO
25-OH Vitamin D < 75 nmol/L is deficient or depleted
56
For bone health, is 25-OH Vitamin D >75 nmol/L sufficient?
YES
25-OH Vitamin D >75 nmol/L is sufficient
57
For bone health, is 25-OH Vitamin D > 500 nmol/L sufficient?
NO
25-OH Vitamin D > 500 nmol/L suggests toxicity
58
For bone health, is 25-OH Vitamin D 54 nmol/L sufficient?
NO
25-OH Vitamin D < 75 nmol/L is deficient or depleted
59
For bone health, is 25-OH Vitamin D 95 nmol/L sufficient?
YES
25-OH Vitamin D >75 nmol/L is sufficient
60
For bone health, is 25-OH Vitamin D 632 nmol/L sufficient?
NO
25-OH Vitamin D > 500 nmol/L suggests toxicity
61
what percentage of under 18s in the UK have insufficient vitamin D (<50 nmol/L)?
29%
62
Due to children having insufficient vitamin D in the UK, there has been a resurgence of what disease?
rickets
63
what factors affect your vitamin D level?
- season
- latitude/climate
- clothing
- use of sunscreen
- time spent indoors/outdoors
- skin tone
- age
- diet
- body fat and BMI
64
how does the season affect vitamin D levels
more sun in summer
65
how does your clothing affect vitamin D levels?
More susceptible to Vitamin D deficiency when
| choosing to cover up
66
how does your skin tone affect vitamin D levels?
Darker skin tones contain more melanin will require more exposure to sunlight to
synthesise the same amount of Vitamin D as someone with lighter skin
67
what is FG23?
Fibroblast growth factor 23
68
FG23 is secreted by osteocytes in response to what?
increase in the active form of vitamin D (calcitriol)
69
what does FG23 do?
- Suppresses 1α hydroxylation of vitamin D by the kidneys (negative feedback)
- Increases renal phosphate excretion
70
what affect does FG23 have on the active form of vitamin D?
less active vitamin D secreted
- Suppresses 1α hydroxylation of vitamin D by the kidneys (negative feedback)
71
Calcitonin is secreted by the C-cells of the thyroid gland in response to what?
increased calcium
| concentration
72
what does calcitonin do?
Opposes the effect of PTH by acting on osteoclasts to inhibit bone resorption
NB: Function is usually insignificant in the regulation of normal calcium homeostasis
73
list some signs and symptoms of hypocalcaemia.
- tetany
- Paraesthesia (pins and needles)
- cramps
- convulsions
- psychosis
74
what is hypocalcaemia?
low level of calcium in the blood
75
list some causes of hypocalcaemia.
- vitamin D deficiency
- Inadequate dietary calcium intake
- Hypoproteinaemia
- Hypoparathyroidism
- Pseudo-hypoparathyroidism
- High phosphate
- High citrate
- EDTA contamination
76
what is the most common cause of hypocalcaemia?
vitamin D deficiency
77
what is Hypoproteinaemia?
abnormally low level of protein in the blood
78
how can you distinguish between a vitamin D deficiency and hypoparathyroidism?
- Patient with high PTH has vitamin D deficiency
| - Patient with almost undetectable PTH has hypoparathyroidism
79
list some signs and symptoms of hypercalcaemia.
- renal stones
- bone pain/osteoporosis
- lethargy, fatigue, depression
- Abdominal pain, constipation, nausea, vomiting
- dehydration
80
how does hypercalcaemia cause dehydration?
via renal resistance to ADH
81
list some causes of hypercalcaemia?
- hyperparathyroidism
- malignancy
- medications
- vitamin D excess
- hyperthyroidism
- bone disease/immobilisation
82
how can hyperparathyroidism cause hypercalcaemia?
[Too much PTH causing too much resorption of Ca from bones and urine]
83
which medications can cause hypercalcaemia?
Thiazides [diuretics], lithium
84
how can hyperthyroidism cause hypercalcaemia?
[Thyroid hormones act on the bones to drive ongoing resorption]
85
how can you differentiate between hyperparathyroidism and bone metastases?
- Patient with appropriately suppressed PTH as expected with high
Ca has bony metastases
- Patient with inappropriately high PTH and high calcium has
hyperparathyroidism
86
what are the first line biochemical investigations for hypo- hypercalcaemia?
- consider adjusted calcium equation
- bone profile
- vitamin D
- Magnesium
- Simultaneous measurement of Ca & PTH
87
what are symptoms of phosphate deficiency?
- Haemolysis, thrombocytopenia and poor granulocyte function
- Severe muscle weakness, respiratory muscle failure [most severe result] and
rhabdomyolysis
- Convulsions, coma, death
- Chronic phosphate deficiency will cause rickets (children) / osteomalacia (adults)
88
what is refeeding syndrome?
When feeding a patient after a prolonged period of malnutrition or
starvation, the arrival of calories prompts the secretion of insulin,
stimulating glycolysis & other processes e.g. protein synthesis & lipogenesis
this can lead to a phosphate deficiency
89
what is Hyperphosphataemia?
elevated level of phosphate in the blood
90
what type of ion is Mg?
Divalent cation, Mg2+
91
what is the physiological importance of Mg?
● Cofactor for ATP – our fuel!
● Neuromuscular excitability
● Enzymatic function
● Regulates ion channels
92
what is the structural importance of Mg?
Comprises 0.5 – 1% of bone matrix
93
how much is the total body magnesium? and how is this distributed between, bone, intracellular and extracellular?
Total body magnesium (~1.1 mol)
● Bone (54%)
● Intracellular (45%)
● Extracellular (1%)
94
what are the 3 forms of Mg that circulate the body?
similar to calcium -
- ionised "free" Mg 60\5
- bound to plasma proteins (25%) predominantly albumin
- complexed to anions (15%) e.g. phosphate, citrate, bicarbonate
95
what is the reference range for magnesium?
0.7 - 1.0mmol/L
96
where does homeostasis of Mg occur?
predominantly in the kidneys
97
a decrease in Mg stimulates the release of PTH, so why does severe hypomagnasaemia result in hypercalcaemia?
PTH release is stimulated by a decrease in magnesium and inhibited by an increase in
magnesium (but calcium is a much more potent stimulus)
● HOWEVER, PTH release is magnesium-dependent, so severe hypomagnasaemia will
inhibit PTH release and cause hypocalcaemia.
98
Hypermagnesaemia is rare since kidneys have a large capacity to excrete excess, therefore it is usually iatrogenic. What does this mean?
caused by medical examination or treatment.
