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Sem 2 - MEH > Calcium Regulation and its Role in Clinical Practice > Flashcards

Calcium Regulation and its Role in Clinical Practice Flashcards

1
Q

What is calcium and what is it for?

A
  • Adult human contains about 1000g of calcium
  • 99% is sequestered in bone in the form of hydroxyapetite crystals
  • Skeleton provides:
    • Structural support
    • Major reserve of calcium
    • Helps to buffer serum levels
    • Releasing calciumphosphate into interstitium
    • Up taking calcium phsphate
  • 300-600mg of calcium is exchanged between bone and ECF each day
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2
Q

What should the level of plasma Ca be in different places?

A
  • Serum (ECF) calcium: 2.2-2.6 mM
  • ECF Ca2+ conc in a very small fraction of total-body calcium (less than 1%)
  • Distributed among three interconvertible fractions
  • Biologically active free ionised Ca2+ conc. closely regulated to 1.0-1.3 mM
  • Most of the calcium in the body is stored in skeleton.
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3
Q

Why is calcium important?

A
  • Builds and maintains teeth and bones
  • Regulates heart rhythm
  • Eases insomnia
  • Helps regulate the passage of nutrients in and out of cell walls
  • Assists in normal blood clotting
  • Helps to maintain proper nerve and muscle function
  • Lowers blood pressure
  • Important to normal kidney function
  • Needed for activity of some enzymes and some hormone receptor binding
  • Reduces blood cholestrol levels
  • Reduces the incidence of colon cancer
  • Important in intracellular signalling pathways
  • Appropriate levels of calcium required for nerve transmission at neuromuscular junctions
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4
Q

What happens if you get hypocalcaemia

A
  • Hyper-excitability of neuro-musclular junctions
    • Pins and needles
    • Tetany (muscle spasms)
    • Paralysis
    • Convulsions
    • Death!
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5
Q

What happens if you get chronic hypercalcaemia?

A

“stones, moans and groans”

  • Renal calculi
  • Kidney damage
  • Constipation
  • Dehydration
  • Tiredness
  • Depression
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6
Q

Where are the parathyroid glands?

A

One at the top and one at the bottom of each lobe of the thyroid. They are attatched to the back of the thyroid gland.

Usually get four on back of thyroid gland BUT can have more and can be anywhere.

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7
Q

What three hormones are involved in the regulation of calcium phosphate?

A
  • Parathyroid Hormone (PTH)
  • Calcitriol (1,25 dihydroxycholecalciferol) tells us how many times it has been hydroxylated. This is the hormonally active metabolite of vitamin D whcih has three hydroxyl groups. (GOOGLE)
  • Calcitonin (produced by C cells in the thyroid gland)
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8
Q

How is parathyroid hormone synthesised?

A
  • PTH has no serum binding protein
  • Straight chain polypeptide hormone -pro-pre-hormone (115AA long) clesved to 84AA
  • Synthesis is regulated both at transcriptional and post transcriptional lecel
    • Low serum calcium up-regulate gene transcription
    • High serum calcium down-regulates
    • Low serum calcium prolongs survival of mRNA (mechanism not known)
  • Half time is 4 minutes and released PTH cleaved in liver
  • PTH continually synthesised but little store
    • Chief cells degrade hormone as well as synthesis it
    • Cleavage of PTH in chief cells accelerate by high serum calcium levels.
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9
Q

What organs does PTH target and what are its physiological effects?

A
  • Kidney
    • Decreases loss to urine (ionined Ca)
  • Gut
    • Activates Vitamin D and hence increases transcellular uptake from GI tranct
  • Bone
    • Increease resorption.
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10
Q

What is the action of PTH in the gut?

A

PTH stimulates conversion of vit D to its active form which increases the uptake of Ca2+ from the gut.

Dietary intake of calcium is typically 1000mg/d

  • Only 30% of which is absorbed by a paracellular uptake effective when Ca2+ is not limited
  • Absorbtion is significantly increases by vitamin D via a transcellular uptake.
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11
Q

What role does Ca2+ play in the bone?

A

Skeleton has two primary functions:

Structural has two primary functions Sturctural support and maintaining serum Ca2+ conc.

  • The maintenance of serum calcium conc is priorty
    • Diseases in bone that affect structural integrity have consequences for serum calcium conc. and visa verse
  • Calcium phosphate crystals found within collagen fibrils
    • Ca+Pi = hydrixyapetite crystals

Bone deposition

  • Osteoblasts produce collagen matrix which is mineralized by hydroxyapetite

Boenreabsorbtion

  • Osteoclasts produce acoid micro-environment hydorxyapatite dissolves

Bone is dynamic

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12
Q

What are the actions of PTH on the bone?

A

1-2 hours PTH stimullates osteolysis

  • PTH induces osteoblastic cells to synthesise and secrtee cytokines on cell surface
  • Cytokines stimulate differentiation and activity in osteoclasts and protect them from apoptosis
  • PTH decreases osteoblast activity exposing bony surface to osteoclasts
  • Reabsorbtion of miniralised bone and release of Pi and Ca2+ into extracellular fluid
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13
Q

How is vitimin D made into its active form?

A
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14
Q

How is vitamin D like a hormone?

A
  • Each of the forms of Vit D is hydrophobic
  • Transported in circulation bound to carrier proteins: act through a nuclear receptor
  • 25-hydroxyvitamin D in the liver has a half life of about 2 weeks whereas the active form only has a half life of 5 hours
  • Pre-vitamin bound to carrier small enough to be filtered by the glomerulus and enter the PCT where the comversion to active form takes place by enzyme 1a-hydroxylase
  • The active form of the hormone is released from the kidney
  • C-1 hydroxylation is under negative feedback to serum calcium levels, elevated calcium prevents C-1 hydroxylation.
  • Elevated PTH stimulates C-1 hydroxylation to form Calcitriol, 1,25-dyhydroxycholecalciferol
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15
Q

What role does calcitriol play?

A

It raises calcium.

  • Active uptake and extrusion of Ca2+ ions
  • Transcellulae transport
  • Endocytosis and exocytosis of Ca-CaBP complex

Is responsible for longer term control.

It is the active form of vitamin D3

It acts on bone, gut and kidney

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16
Q

What is calcitonin?

A
  • Made by C cells in the thyroid gland
  • In animals, it lowers serum calcium.
    • But, in human, if remove thyroid, this doesn’t dysregulate the serum calcium levels.
    • Maybe role in pregnancy?
  • Can be used clinically to lower serum calcium.
17
Q

What happens if there is an increase in plasma calcium?

A
18
Q

What happens if there is a decrease in plasma calcium?

A
19
Q

What is EDTA?

A

EDTA is a calcium chelator

20
Q

What is the role of citrate?

A

Citrate chelates calcium ions.

If you give over 5 units of blood, also give Ca2+ as levels will fall low.

21
Q

What are the causes of hypercalcaemia in hospitals?

A
  • Malignant osteolytic bone metastases
  • Multiple myeloma

Common cancers that metastastse to bone causing lytic lesions and hypercalcaemia:

  • Breast
  • Lung
  • Renal
  • Thyroid

Prostate cancer is a common cause of bone metastases. However, it causes osteoblastic metastases that to not cause hypercalaemia.

22
Q

What are common sites for metastases for prostate cancer?

A
  • Vertebrae
  • Pelvis
  • Proximal parts of the femur
  • Ribs
  • Proximal part of the humerus
  • Skull
23
Q

What is primary hyperparathyroidism?

A

One of the 4 parathyroid glands deelops an adenoma and secretes excessive parathyroid hormone, This causes serum calcium to rise and serum phosphate to fall

24
Q

What is secondary hyerparathyroidism?

A

All four parathyroud glands become hyperplastic.

This is seen is patients with vitamin D

Vitamin D deficiency can ce dietary / environmentsl or seen in chronic renal failure die to failure of the 25 hydroxylation of Vitamin D.

Vitamin D deficiency means that theur calcium absorbtion is low resulting in low serum calcium levels, that then causes PTH lecles to rise,

The raised PTH acticates oeseoclasts in order to mobilise calcium from bone in an attempt to maintain normal serum calcium.

From the patients perspective, the main problem is bone pain due to osteomalacia in the case of vitim D deficiency and in the case of chronic renal failure due to renal osteodystrophy.

25
Q

What are the symptoms of primary hyperparathyroidism?

A
  • Moans - tired, exhausted, depressed
  • Groans - constipation, peptic ulcers, pancreatitis
  • Stones - kidney stones. Also polyuria due to impaired sodium and water reabsorption
  • Bones - bones and muscle aches,

In recent years, patients are asymptomatic having had serum biochemistry for other reasons.

26
Q

What role does calcium have on neuronal activity?

A

CALCIUM RAISES THE THRESTHOLD FOR NERVE MEMBRANE DEPOLARISATION and therefore an action potential:

  • Hypercalcemia leads to supression of neuronal activity - lethargy, confusion, soma
  • Hypocalcemia leads to excitable nerves - tingling, muscle tetany and even epilepsy
27
Q

What are the symtoms of severe hypercalcaemia?

A

AT high calcium levles the polyuria can lead to dehydration which then exacerbates the hypercalcaemia. This can lead to:

  • Lethargy
  • Weakness
  • Confusion
  • Coma
  • Renal failure

Rehydration is the mainstay of treatment.

28
Q

What are the symptoms of hypocalcaemia?

A

Seen mostly in post total-thyroidectomy because of inadvertant removal / ischaemia of parathyroid glands.

  • Perioral tingling and tingling in the fingers
  • Carpopedal spasm

Hypocalcaemia can kill due to laryngeal muscle tetany, so needs treating quickly.

Symptoms can develop when serum calcium falls below 2.10 mmol/l and can start within 6 hours of thyroidectomy.

29
Q

What is the difference between osteomalacia and osteopotosis?

A

Osteoporosis = Decreased bone density with a normal ratio of mineral to matrix. Normal bone but not enough of it! It is a process that involves the degeneration of already constructed bone. Leads to brittle bones that are prone to fracture.

Osteomalacia = Ratio of mineral to matric is decreased (not enough mineral in bone). It is an abnormality that can affect bone building in children (rickets) or bone mineralisation in adults. It leads to soft bones that are prone to bending.

30
Q

What are the rIsk factors for osteoporosis?

A
  • Postmenocausal women
  • Low BMI
  • Long-term oral steroid use
  • Heavy drinking
  • Smoking
  • Low BMI
  • Prolonged inactivity, such as best rest
31
Q

What are the consequences of osteoporosis?

A
  • Hip fracture
  • Wrist fracture
  • Vertebral crush fracture

Sem 2 - MEH (22 decks)

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