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Reg Phys and Pharm > Calcium Homeostasis > Flashcards

Calcium Homeostasis Flashcards

1
Q

Describe the biological functions of calcium

A
  • skeletal rigidity - hydroxyapatite and calcium phosphate
  • component of connective tissue and teeth
  • haemostasis (blood clotting) - intrinsic and extrinsic cascades
  • excitation-contraction coupling - smooth and striated muscle
  • stimulus-secretion coupling - ACh from the NMJ
  • cell-to-cell adhesion - cadherins
  • second messenger for enzymatic activity (calmodulin)
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2
Q

What hormones regulate extracellular calcium levels

A

Parathyroid hormone,1,25-dihydroxyvitamin D, Calcitonin

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3
Q

Origin and function of 1,25-dihydroxyvitamin D

A

Kidneys; increases small intestine ability to intake calcium in diet

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4
Q

Origin and function of PTH

A

Cheif cells of parathyroid glands; acts on bones to increase release of calcium, increases reaborption of calcium from filtrate, facilitates conversion of vit D -> 1,25-dihydroxyvitamin D (biologically active

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5
Q

Functions of calcitonin

A
  • respond to hypercalcemia
  • stores calcium in skeleton
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6
Q

Stimuli for secretion of PTH

A

Hypocalcaemia

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7
Q

Action of PTH on bones to induce hypercalcemia

A

PTH stimulates cytokines that recruit osteoblasts, which induce osteoclasts (bone resorption)

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8
Q

Action of PTH on GI tract to induce hypercalcemia

A

Activates synthesis of 1,25-dihydroxyvitamin D (kidney) and increases trancellular uptake of Ca from the small intestine

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9
Q

Action of PTH on kidneys to induce hypercalcemia

A

Increase calcium reabsoprtion by increasing activity of calcium channels and pumps. Synthesis of 1,25-dihydroxyvitamin D

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10
Q

How is free calcium sensed

A

Calcium-sensing receptors (CaSR)

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11
Q

Synthesis of PTH in hypercalcemia

A

Negative feedback pathway suppresses PTH secretion

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12
Q

PTH action on 1,25-dihydroxyvitamin D

A

increases formation by increasing hydroxylation to 1,25-dihydroxyvitamin D in the kidney

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13
Q

The role of 1,25-dihydroxyvitamin D on the small intestine

A
  • diffuses into enterocytes and binds to vitamin D receptor (VDR) and increases gene expression
  • increases calcium transport across the enterocyte membrane by increased expression of apical calcium channels and basolateral calcium transporters
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14
Q

The role of 1,25-dihydroxyvitamin D on the kidneys

A

Increases expression of Na-Pi cotransporter and improves PTH-mediated calcium absorption

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15
Q

Role of 1,25-dihydroxyvitamin D on the bones

A

Increases number of osteoclasts

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16
Q

Stages of 1,25-dihydroxyvitamin D hydroxylation

A
  • 1st occurs in skin where UV light converts 7-dehydrocholesterol into cholecalciferol (vitamin D3)
  • 2nd occurs in the liver where cholecalciferol is converted to biologically inactive 25-hydroxycholecalciferol
  • Final reaction occurs in kidneys where it is converted to 1,25-dihydroxyvitamin D, which aids absorption across the intestinal wall
17
Q

How is the second hydroxylation of 1,25-dihydroxyvitamin D regulated

A
  • increased GH
  • increased prolactin
  • increased oestrogen
  • decreased FGF23
  • decreased 1,25-dihydroxyvitamin D
18
Q

What action does increased 1,25-diOH-D3 in kidneys have on PTH

A

Inhibitory

19
Q

Heterozygous CaSR and Galpha11 gain-of-function mutation in ADH

A

Causes high urinary excretion of calcium even in normal extracellular calcium concentrations (hypocalcemia)

20
Q

Heterozygous inactivating mutation in the calcium-sensing receptor (CaSR) results in

A

Hypercalcemia -> no inhibition of PTH secretion even when plasma calcium concentration is high

21
Q

Origin and function of calcitonin

A

Clear cells of the thyroid glands; responds to hypercalcaemia (function is limited in healthy individuals)
- PRIMARY STIMULUS FOR THE RELEASE OF PTH

22
Q

Calcitonin is secreted in response to

A

High plasma calcium concentration

23
Q

Action of STIM1

A
  • Responds to calcium store depletion by oligomerising and translocating to the plasma membrane
  • Bind to Orai and open calcium channels to replenish intracellular calcium
24
Q

Inhibitor of STIM1

A

Calmodulin

25
Q

Symptoms of hypercalcemia

A

(bones, stones, groans and psychiatric overtones)
- lethargy
- depression
- constipation
- renal calculi
- frequent urination
- nausea
- arrhythmias

26
Q

Symptoms of hypoclacemia

A
  • pins and needles
  • muscle spasms
  • paralysis
  • convulsions
27
Q

How sex hormones influence calcium homeostasis

A

Oestrogen is repsonsible fo bone maturation and testosterone maintains bone density

28
Q

How glucocorticoids maintain calcium homeostasis

A

Regulate bone density and intestinal calcium absorption

29
Q

How parathyroid hormone-related protein (PTHrP) influences calcium homeostasis

A

mimics action of PTH in bones and kdineys -> produces outside of parathyroid glands
- induces hypercalcemia mostly by paracrine rather than endocrine signalling

Reg Phys and Pharm (16 decks)

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