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MEH Calcium metabolism Flashcards

1
Q

What are 7 roles of calcium in the body?

A 
Muscle contraction
Nerve conduction
2nd messenger
Coagulation
Activation of enzymes
Hormone secretion
Exocytosis
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2
Q

What form of calcium is tightly controlled in serum?

A

Free ionised calcium (Ca2+)

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3
Q

Why does it need to be tightly controlled?

A

Because too high or too low levels have an effect on cells - e.g. cell membrane/contraction/uncontrolled hormones production/uncontrolled nerve firing etc

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4
Q

How can hypocalaemia have an effect on coagulation?

A

As it is factor IV so is needed in the coagulation cascade

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5
Q

What three hormones regulate serum calcium?

A

Parathyroid
Dietary Vit D
Calcitonin

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6
Q

What is calcitriol?

A

Active vitamin D

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7
Q

How is serum calcium carried?

A

half free ionised
nearly half plasma proteins
small amount bound to citrate

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8
Q

Where is most of the calcium stored in the body? Is this a rigid or dynamic store?

A

Skeleton

Dynamic

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9
Q

Say Ca2+ effect on blood pressure colon cancer insomnia kidney function cholesterol?

A

Reduction in BP, colon cancer, cholesterol

Relieves insomnia and important for normal kidney function

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10
Q

How much Calcium do we contain? How much stored in bones?

A

1000g

99%

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11
Q

What is calcium stored in the bones as?

A

Hydroxyapatite crystals

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12
Q

How does skeleton buffer serum levels of Ca?

A

Releases calcium phosphate into interstitium and takes up calcium phosphate

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13
Q

How is Vit D –> calcitriol?

A

C-1 Hydroxylation stimulated by PTH

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14
Q

What are 3 actions of PTH

A

Stimulates bone resorption and release of Ca and phosphate into blood

Stimulates increased reabsorption of Ca at the kidney

Increases vit D –> calcitriol

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15
Q

What are the 3 effects of dietary vit D?

A

Increases intestinal absorption of calcium
Increases renal absorption of calcium
Increases bone resorption

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16
Q

What is the role of calcitonin? Where it is secreted from?

A

From thyroid gland C cells

Counter effects PTH but not that important in humans

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17
Q

Where are the parathyroid glands? How many?

A

On the thyroid glands anteriorly - x 4

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18
Q

What are chief cells vs oxyphil cells? Which are bigger?

A

Chief - products PTH

Oxyphil cells - bigger - not sure of function

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19
Q

Which is the rapid and which is the longer term control of Ca?

A

Rapid - PTH 4 min half life

Long - calcitriol - 6 hour half life

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20
Q

how is PTH synthesised/stored?

A 
Pre pro hormone
Cleaved
Secreted by chief cells 
Also degraded by chief cells (cleaves when serum Ca levels are high)
Not really stored
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21
Q

How is PTH synthesis regulated (3)?

A

Transcriptional and post transcriptional level

  • Low serum Ca2+ upregulates gene transcription (high serum does opposite opposite)
  • Low serum Ca prolongs survival of mRNA
  • High serum Ca stimulates cleavage by chief cells
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22
Q

Where is PTH that has been released into the circulation cleaved?

A

In the liver

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23
Q

How is parathyroid hormone secreted?

A

High Ca binds to GPR Gq
Inhibits release of PTH
and reduces transcription of PTH

Low Ca has opposite effect so increased transcription and increased release of PTH exocytosis

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24
Q

What are the three main target organs to PTH and its effect on them?

A

Bone - increased resorption to release Ca

Kidney - increased reabsorption to increase Ca

Gut - increased Vit D –> calcitriol and hence increases transcellular uptake from GI tract

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25
What cell does PTH act on in bone?
Osteoclasts
26
What are 3 functions of skeleton?
Structural support Maintaining serum Ca concentration Haemopoiesis
27
What is the relevance of diseases that affect the bone in Ca serum levels?
Diseases that affect structural integrity of bone have effect on serum Ca level and vice versa
28
What is hydroxyapatite made up of?
Ca and phosphate
29
What is the relevance of hydroxyapatite in bone deposition?
Osteoblasts secrete ECM (collagen) | Mineralised by hydroxyapatite
30
How do osteoclasts dissolve hydroxyapatite crystals?
Produce acid micro-environment
31
How does PTH stimulate osteolysis? Talk through the process
1) PTH induces osteoblasts to secrete cytokines 2) Cytokines stimulate differentiation and activity in osteoclasts and protect them from apoptosis 3) PTH decreases osteoblasts activity exposing bony surface to osteoclasts 4) Increased osteoclast activity = increased bone resorption and release of Ca and phosphate into ECM
32
Why does phosphate have to be regulated at the kidney?
Because osteoclasts lead to release of Ca and Pi so need to regulate both Ca and Pi excretion Pi removal prevents kidney stone formation
33
How is Ca excretion regulated at the kidney?
Affects tubular cells within kidney - PTH increases Ca reabsorption in 1) Ascending limb of loop of henley 2) Distal convoluted tubule
34
How does PTH increase absorption of Ca in the gut?
It enhances Vit D --> active calcitriol which greatly enhances absorption of calcium in intestine via transcellular route
35
What is the inactive Vit D called? What do you need to do to get active calcitriol?
D3 or cholecalciferol | Two hydroxylation reactions
36
How is vit D3 transported?
Mostly by transcalciferin only a small amount in free form
37
What 2 major ways do we get vit D?
Sunlight | Diet
38
How is vit D stored in the liver and where is it activated?
Stored for 2 weeks as inactive form (25-hydroxyvitamin D) Activated in kidney proximal convoluted tubule
39
What is the half life of calcitriol?
6 hours so longer acting
40
What is the feedback mechanism for active calcitriol?
C-1 hydroxylation is under negative feedback to serum calcium levels - elevated Ca prevents C1 hydroxylation
41
How do we know calcitonin doesn't have that much of a role in humans? When might it?
Because thyroidectomy doesn't have a marked effect on Ca levels Maybe in pregnancy to protect maternal skeleton
42
How can calcitonin be used clinically?
TO lower serum Ca in cases of hypercalcaemia - is rapid acting
43
What are the symptoms of hypocalcaemia?
``` Hyperexcitibility of NMJ Tetany (muscle spasms) Pins and needles Paralysis Convulsions ```
44
What are the symptoms of chronic hypercalcaemia?
STONES - kidney damage and renal calculi - stones MOANS - tiredness/depression GROANS - abdominal pains/constipation/dehydration
45
Why is the fact Ca is a coagulant relevant in taking blood tests in medicine?
Need to add chelating agent to prevent blood samples from clotting EDTA
46
How about if giving transfusions?
Citrate chelates Ca in transfused blood so over about 5 units need to give IV Ca2+ otherwise prevents natural coagulation and could lead to bleeding
47
What is adjusted serum Ca level on a blood test?
Adjusted for albumin level
48
What is the one cancer that causes osteoblastic metastases? Do these increase serum Ca?
Prostate cancer No doesnt
49
What are four common osteolytic metastases?
Breast Lung Kidney Thyroid
50
What other primary may cause increased serum Ca?
Multiple myeloma
51
Where are more than 90% of bone mets found and why (6)
``` Vertebrae Pelvis Prox part of femur Ribs Prox part of humerus Skull ``` Due to microenvironment of marrow - particularly active and good blood supply
52
What are the primary and secondary causes of hyperparathyroidism?
Primary - one of 4 PT glands - develops adenoma and secretes PTH - causes serum Ca to rise and serum phosphate to fall Secondary - all 4 PT glands. Due to vit D déficience - can either be due to diet/environmental or chronic renal failure
53
Why does an adenoma secreting PTH lead to raised serum Ca and fall in phosphate serum?
As main action of PTH is at kidney - reabsorption of Ca and excretion of Phosphate
54
Why can renal failure lead to vit D deficiency?
As this is where the 25 hydroxylation of via D occurs
55
What is the main clinical feature of via D deficient hyperparathyroidism? What are two reasons for it?
BONE PAIN Osteomalacia - painful bones due to increased resorption in an attempt to increase serum Ca levels Renal osteodystrophy - bone abnormalities due to chronic renal failure
56
If your patient has a low serum phosphate what is the cause of the hyperparathyroidism?
Primary - due to adenoma secreting PTH | can also have no change in serum phosphate but only cause of low serum phosphate
57
Why would hyperparathyroidism (hypercalcaemia) lead to polyuria?
Due to impaired Na and water reabsorption
58
Can patients be asymptomatic with hyperparathyroidism?
Yes
59
Why do bone metastases lead to increased serum Ca without a change in PTH?
Because Ca is being released by osteoclastic action on bone
60
Which type of Cancer is the odd one out and causes osteoblastic action on bone mets?
Prostate
61
What why does primary hyperparathyroidism lead to increased Ca but decreased Pi and increased PTH?
Tumour secreting excess PTH so excess serum Ca levels Decreased Pi due to action of PTH at kidney that excretes Pi while reabsorbing Ca
62
Why does secondary hyperparathyroidism lead to reduced serum Ca but increased PTH with no change in Pi?
Because the cause of increased serum Ca is not due to PTH it is due to Vit D deficiency so reduced Ca absorption in the gut and therefore PTH is stimulated from parathyroids hence increased level.
63
How does hypercalcaemia lead to lethargy, confusion, coma, and hypocalcaemia lead to excitable nerves - tingling, tetany, epilepsy?
Because EC Ca raises the threshold for neuronal AP (more negative inside). So hypercalcaemia will lead to suppression of neuronal activity and hypo will lead to increased neuronal activity
64
If someone is in a coma - what might you need to consider as a reversible cause? Especially if malignant hypercalcaemia (it may not be a terminal event)
Hypercalcaemia - over 3mmol/l can cause coma
65
How can polyuria add to hypercalcaemia?
Further dehydrates and therefore adding to Ca conc
66
Someone post thyroidectomy has hypocalcaemia what might have happened? At what Ca level will symptoms be felt?
Accidentally removed/injured the parathyroid glands | Below 2.10mmol/l Ca
67
Why would neuronal symptoms of Ca be around the mouth and fingers in particular?
Because of the large representation of these areas sensually in the brain
68
What kind of tetany can you see with hypocalcaemia? Why flexed?
Carpopedal spasm As flexors are stronger than extensors in wrist and fingers
69
What is a major danger of hypocalcaemia? What is it called?
Chvostek's sign Tetany of laryngeal muscle tetany - needs treating quickly
70
How is osteomalacia different to osteoporosis? What can osteomalacia lead to in children?
Osteoporosis mineral:matrix normal Osteomalacia mineral:matrix reduced as less mineral being made/being broken down Can lead to ricketts in children soft bones prone to bending
71
What is the cause of osteomalacia?
Vit D deficiency
72
What are risk factors for osteoporosis?
``` Post menopausal women Low BMI Long term steroids Heavy drinking Smoking Inactivity ```
73
What kind of fractures are common in osteoporosis?
Hip Wrist Vertebral crush

ESA2 (37 decks)

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