Session 11: Calcium Metabolism Flashcards

1
Q

How much calcium does an adult human contain? Where can it be found?

A

Around 1000g of calcium. 99% of it is found in bone in the form of hydroxyapatite crystals. Around 1% is found in ECF (plasma calcium levels)

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2
Q

Serum calcium levels.

A

Around 2.2-2.6 mM or mmol/L

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3
Q

Free calcium ([Ca2+]) levels in blood.

A

Around 1.0-1.3 mM or mmol/L

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4
Q

How is calcium transported in the body?

A

~45% bound to protein (albumin) ~45% free calcium (Ca2+) ~10% complexed with low-molecular-weight organic ions like Pi and citrate.

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5
Q

Give roles of calcium.

A

Intracellular signalling pathways Nerve transmission Builds and maintains bone and teeth Regulate heart rhythm Eases insomnia Helps regulate passage of nutrients in and other of cell walls Assists in normal blood clotting Helps maintain proper nerve and muscle function Lowers BP Important to normal kidney function Needed for activity of some enzymes and some hormone receptor binding. Reduces blood cholesterol levels Reduces incidence of colon cancer.

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6
Q

Why is additional calcium given in major blood transfusions?

A

Because citrate is put into blood bags so the calcium doesn’t coagulate the blood. Citrate chelates calcium ions in the blood bags. So if you give a lot of blood all that blood will have the calcium bound to citrate and they will be prone to bleeding and other problems resulting in hypocalcaemia if you don’t give calcium at the same time.

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7
Q

Hormones important in regulation of calcium and phosphate.

A

Parathyroid hormone (PTH) Calcitriol aka active form of vitamin D. Calcitonin

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8
Q

Anatomy of parathyroid gland.

A

Small glands embedded in the thyroid gland. Usually 4, in rare cases can be 6. In very rare cases the mediastinum can be filled with parathyroid glands (Up to 100).

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9
Q

Label.

A
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10
Q

PTH synthesis briefly.

A

Pro-pre hormone activated by proteolytic cleavage.

Synthesised by chief cells in the parathyroid glands.

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11
Q

Regulation of synthesis of PTH.

A

Transcriptional and post transcriptional levels by serum calcium levels.

Low serum calcium up-regulates gene transcription

High serum calcium down-regulates gene transcription

Low serum calcium also prolongs survival of mRNA

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12
Q

How is PTH stored?

A

It is barely stored. It is just continuously synthesised.

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13
Q

What degrades PTH?

A

Chief cells both synthesise and degrade PTH.

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14
Q
A
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15
Q

Explain calcium homeostasis.

Which organs are involved etc.

A

Through diet we get areound 1000mg each day. 825 mg is excreted daily so there is a net gain of 175 mg.

Out of the 1000mg in the GI 500mg is absorbed and 325 is secreted. These numbers add up to the 825 excreted and 175 taken up in net. The amount absorbed is going to the ECF.

There is also turnover of calcium in the bone where around 280mg of ECF calcium is used to form bone daily and the same amount 280mg is broken down into ECF by resorption.

Lastly kidneys will filter a lot of calcium around 10000mg a day. 9825 mg is reabsorbed daily. Giving a net of 175 calcium excreted via urine each day.

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16
Q

Which organs does PTH target in calcium homeostasis?

A

Bone

Intestine (indirectly)

Kidneys

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17
Q

Explain how an increase in PTH levels affect bone.

A

Increase resorption of bone by stimulating osteolysis. This is by binding to osteoblasts which secrete cytokines to stimulate differentiation and increase activity of osteoclasts.

This breaks down bone to release calcium and phosphate (Pi) from the hydroxyapatite crystals into ECF.

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18
Q

Explain how an increase in PTH levels has an effect in kidneys.

A

Increases calcium reabsorption so less calcium is excreted in urine.

Additionally

Also promotes activation of vitamin D to the activated form calcitriol.

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19
Q

Explain how an increase in PTH levels has an effect on the GI tract.

A

It indirectly affects the intestines by promoting activation (increasing renal C-1 hydroxylase activity) of vitamin D to Calcitriol in the kidneys.

Calcitriol then increases transcellular uptake of calcium in the GI tract.

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20
Q

How is PTH transported in the blood?

A

Without any protein bound to it aka freely.

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21
Q

Half-life of PTH and its significance.

A

4 min half-life. This is important to give fine control of levels of calcium in the blood.

22
Q

What is corrected calcium levels?

Why is it important?

How is it calculated?

A

Corrected calcium levels are corrected for the amount of free calcium in the blood. The free amount is the active form of calcium.

The total level of calcium in blood account for calcium bound to albumin and other complexes like citrate or oxalate.

It is corrected depending on the levels of serum albumin.

23
Q

Source of vitamin D.

A

Major source is sunlight.

Also found in cheese, butter, and oter dairy products.

Also fish and fortified cereals.

24
Q

Explain what happens to PTH in an increased plasma calcium level.

A

PTH goes down.

Bone building exceeds breakdown because PTH is lower.

In Kidneys the levels of calcitriol and Ca2+ reabsorption goes down. More excretion of Ca2+ in urine.

This leads to leads to less absorption of Ca2+ from GI as well

All of this leads to a decrease in plasma calcium levels.

25
Q

Explain what happens if there is a decrease in plasma calcium.

A

PTH secretion increases. Promotes activation of vitamin D and increases Ca2+ reabsorption. Also increases breakdown of bone exceeding that of bone building.

The increased activation of vitamin D leads to Ca2+ uptake in the GI tract.

All this leads to an increase plasma calcium levels.

26
Q

Symptoms and signs of chronic hypercalcaemia.

A

Renal calculi (kidney stones)

Kidney damage

Constipation

Dehydration

Tiredness

Depression

Remember

Bones

Stones

Moans

and

Groans (abdo pain)

27
Q

Common sites of bone metastases related to hypercalcaemia.

A

Vertebrae

Pelvis

Proximal parts of the femur

Ribs

Proximal parts of the humerus

Skull

28
Q

Common cancers that metastasise to bone and cause hypercalcaemia.

A

Breast cancer

Lung cancer

Renal cancer

Thyroid cancer

29
Q

Short term control of calcium levels.

A

PTH

30
Q

Long term control of calcium levels.

A

Calcitriol

31
Q

Explain primary hyperparathyroidism.

A

One of the four parathyroid glands develops an adenoma and secrete excessive PTH.

This causes an increase in serum calcium levels and decrease in serum phosphate.

32
Q

Signs and symptoms of hypocalcaemia.

A

CAT

Paraesthesia

Tetany (muscle spasms)

Paralysis/numbness

Convulsions

Death

33
Q

Why does hypocalcaemia lead to tetany?

A

Due to hyperexcitability of neuromuscular junction.

34
Q

Why does hypocalcaemia lead to hyperexcitability of NMJ?

A

The low serum calcium leads to an increase in Na+ entry into the neurones. This leads to depolarisation and increased likelihood of AP.

Usually calcium blocks the sodium channels inhibiting the sodium from opening and therefore inhibits depolarisation.

35
Q

Serum levels of calcium and phopshate in primary hyperparathyroidism.

A

Serum calcium rises

Serum phosphate falls

36
Q

Explain secondary hyperparathyroidism.

A

All 4 parathyroid glands become hyperplastic which can be seen in patients with vitamin D deficiency.

This leads to low calcitriol and reduced calcium absorption -> low serum calcium.

Results in a rise in PTH levels and increased phosphate levels.

37
Q

Label

A
38
Q

Causes of secondary hyperparathyroidism.

A

Chronic renal failure due to failure of the 25 hydroxylation of vitamin D.

Vitamin D deficiency because of diet or environment.

39
Q

Symptoms of primary hyperparathyroidism.

A

Stones, Moans, Groans and Bones.

Kidney stones and polyuria due to impaired sodium and water reabsorption.

Moans - tired, exhausted and depressed.

Groans - constipation, peptic ulcers, pancreatitis

Bones - bone and muscle aches

40
Q

Explain the neuronal activity in hypocalcaemia and hypercalcaemia.

A

Calcium raises the threshold for nerve membrane depolarisation. This makes the likelihood of an action potential to be generated decrease.

In hypercalcaemia the threshold is therefore raised and leads to suppression of neuronal activity. This makes the patient lethargic, confused and even comatosed.

In hypocalcaemia the threshold is lowered which leads to excitable nerves. This makes the patient feel tingling sensations, muscle tetany and even epilepsy.

41
Q

Signs, symptoms and complications of severe hypercalcaemia.

A

High levels of calcium can lead to dehydration which further exacerbates the hypercalcaemia signs.

This leads to:

Lethargy

Weakness

Confusion

Coma

Renal failure

42
Q

Mainstay treatment of severe hypercalcaemia.

A

Rehydration.

43
Q

Common cause of hypocalcaemia.

A

Total thyroidectomy with accidental removal of parathyroid glands.

Can also happen in total thyroidectomy where there has been any sorts of damage to the blood supply of the parathyroid glands leading to them becoming ischaemic.

44
Q

Where do you usually experience the sensory symptoms of hypocalcaemia?

(Paraesthesia)

A

Around mouth and hands.

45
Q

Where do you usually experience the motor symptoms of hypocalcaemia?

(Tetany)

A

Around mouth and hands.

46
Q

What is PTHrP?

A

Parathyroid hormone related peptide.

It is a peptide secreted by some cancer cells leading to humeral hypercalcaemia of malignancy.
It is commonly produced in patients with breast or prostate cancer (even though prostate cancer doesn’t lead to hypercalcaemia) and occasionally in patients with myeloma.

47
Q

Action of PTHrP

A

Shares many actions with PTH leading to increased calcium release from bone, reduced renal calcium excretion and reduced renal phosphate reabsorption.

48
Q

Give a good and invasive way to test whether the hypercalcaemia of a patient is related to PTH or PTHrP.

A

Check their calcitriol levels.

49
Q

Why would calcitriol not be raised in PTHrP?

A

PTHrP does not increase renal C-1 hydroxylase activity. This means that vitamin D is not converted into calictriol.

50
Q
A