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Physiology 3003 > Lecture 13 ---Calcium homeostasis > Flashcards

Lecture 13 ---Calcium homeostasis Flashcards

1
Q

What is the distribution of Ca2+ throughout the body?

A

> 99% skeleton
1% soft tissue (cells)
0.1% ECF

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2
Q

Where is Ca2+ found inside cells?

A

MITOCHONDRIA & ER

[Ca2+] in cytoplasm = very low

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3
Q

What is the distribution of Ca2+ in the ECF?

A

(1) IONISED CALCIUM = 50%
(2) COMPLEXED TO ANIONS = 9%
(3) BOUND TO PROTEINS (esp albumin) = 41%

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4
Q

What is the BIOLOGICALLY ACTIVE form of Ca2+ in the ECF?

A

IONISED CALCIUM is biologically active

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5
Q

What anions does Ca2+ typically complex to?

A

Citrate
Phosphate
Sulfate

Ca2+ complexed to anions= Biologically INACTIVE

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6
Q

How much Ca2+ is in the body?

?? (male)
?? (female)

A

1200g (male)

1000g (female)

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7
Q

What is the importance of Ca2+ in the body (7)

A
  • *(1) BONE & TEETH (increases compressible strength)
  • *(2) BLOOD CLOTTING (activates blood clotting factors 9/10, prothrombin, thrombin)
  • *(3) MUSCLE CONTRACTION (skeleton = binds to troponin, allows myosin/actin binding….smooth= binds to calmodulin = activates myosin kinase)
  • *(4) NERVOUS SYSTEM (Ca2+ entry at terminal causes vesicles to fuse with membrane & neurotransmitter is released)
  • *(5) ENDOCRINE SYSTEM (processes involving exocytosis (e.g. insulin release))
  • (6) CARDIOVASCULAR SYSTEM (L-type Ca2+ channels responsible for plateau phase in CV contraction)
  • *(7) BIOLOGICAL PROPERTIES OF MEMBRANES (makes biological membranes more IMPERMEABLE to Na+ …B/C Ca2+ binds to protein of Na+ channel on activation gate = conformational change = blocks Na+ entry…(hypercalcaemia, hypocalcaemia)
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8
Q

What blood clotting factors does Ca2+ activate?

A

Factors 9 & 10
Thrombin
Prothrombin

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9
Q

What effect does HYPERcalcaemia & HYPOcalcaemia have on neuromuscular activity?

A

HYPERcalcaemia (too much Ca2+): depresses NM activity

HYPOcalcaemia (too little Ca2+): makes nerves/muscle hyper excitable

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10
Q

CALCIOSTAT SYSTEM

A

Mechanisms for maintaining plasma [Ca2+]
CALCIOSTAT SYSTEM (CaSR detect changes in ECF [Ca2+] and produce rapid response)
(1) KIDNEY–REABSORPTION
(2) INTESTINE–ABSORPTION
(3) BONES–RESORPTION

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11
Q

CaSR

A

Calcium Sensing Receptors detect changes in ECF [Ca2+]

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12
Q

KIDNEY–REABSORPTION of Ca2+

What regulates?

A

90% = obligate reabsorption (Proximal tubule/descending loop henley/distal tubule)

10% = SELECTIVE REABSORPTION depending on plasma [Ca2+] (distal tubule/Collecting duct)

Under control of PARATHYROID HORMONE (PTH)

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13
Q

What % of the circulating calcium is filtered by the kidneys? Why not 100%?

A

59% is filtered

50% ==Ionised Ca2+
9% ==bound to anions

The 41% bound to proteins is NOT FILTERED

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14
Q

INTESTINE–ABSORPTION of Ca2+

A

We absorb: 350mg/day ~30% of what we ingest, we absorb

  • *Vitamin D increases absorption of Ca2+ in intestine
  • *Ca2+ is very poorly absorbed due to it being a divalent cation
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15
Q

Recommended daily intake of Ca2+

A

1000mg/day

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16
Q

How much Ca2+ to we absorb from the diet every day?

How much Ca2+ to we excrete from the diet every day?

A

ABSORB: ~350mg (~30% of total absorption)

EXCRETE: ~900mg/day

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17
Q

How much Ca2+ is lost in gastric juices/slough mucousal cells per day?

A

~250mg/day

18
Q

BONES–RESORPTION of Ca2+

A

TWO PROCESSES:
(1) RAPID PHASE (minutes –> hours): OSTEOCYTIC OSTEOLYSIS

(2) SLOW PHASE (days–>weeks): Osteoclasts secrete H+ ions & acid phosphatase into a confined resorption bay (at the ruffled cell border)…
* *H+ combines with Cl- –> HCl which dissolves the bone tissue
* *Acid Phosphatase: hydrolyses the collagen matrix

19
Q

What is OSTEOCYTIC OSTEOLYSIS

A

The Rapid phase of bone resorption (minutes –> horus)

Osteocytes & osteoblasts are connected by OSTEOCYSTIC MEMBRANE SYSTEM (OMS) through channels filled with BONE FLUID

(1) ==>REDUCED [Ca2+] IN BONE FLUID–> stimulates SOLUBILISATION OF BONE –> mobilisation of Ca2+ to bf
(2) ==>REDUCED [Ca2+] IN BLOOD –> stimulates parathyroid hormone (PTH) secretion –> stimulates PTH receptors on OSTEOBLASTS –> INCREASES Ca2+ MEMBRANE PERMEABILITY => Ca2+ movement from bf –> ECF

20
Q

What is the SLOW PHASE of Ca2+ resorption by bones

A

(1) OSTEOCLASTS secrete H+ ions & Acid phosphatase

==> H+ combines with Cl- (=HCl) & dissolves the bone tissue
==> ACID PHOSPHATASE hydrolyses the collagen matrix fibres

21
Q

What are the hormones that control Ca2+ Homeostasis?

What are their 1/2 lives?

A

(1) PARATHYROID HORMONE (PTH) -20-30min
(2) VITAMIN D-days-weeks
(3) CALCITONIN-10 min

22
Q

What is the 1/2 life of Parathyroid hormone (PTH)

A

20-30minutes

23
Q

Role of PARATHRYOID HORONE in Ca2+ homeostasis)

A
  • ->1/2 life = 20-30 minutes
  • ->Triggered by CaSR (calcium sensing receptors) on the surface of the parathyroid gland
  • **HIGH Ca2+ –> REDUCTION in PTH secretion/production
  • **LOW Ca2+ –> INCREASE in PTH secretion/production
  • -> Acts on KIDNEY ((1) increase reabsorption and (2) Increase activation of vitamin D3)
  • -> Acts on BONE (osteoblasts (CaSR)–> increases permeability to Ca2+)
24
Q

How is PTH regulated?

A

NEGATIVE FEEDBACK (High Ca2+ act on CaSr on PT surface cells = reduce PTH production and secretion)

25
Q

What is the 1/2 life of vitamin D3 (1,2 5 dihydroxycholecaliferol)

A

days–weeks

26
Q

Source of vitamin D3?

A

(1) Synthesised by iradiation of 7-dehydrocholesterol to cholecalciferol in the skin
(2) Diet (eggs/fish)

27
Q

What step of vitamin D3 synthesis is under control of PTH?

A

The final hydroxylation step (in the kidney) is under PTH control: PTH increases the biosynthesis of the enzyme 1A HYDROXYLASE which converts vitamin D to the ACTIVE form in the kidneys

28
Q

1A HYDROXYLASE

A

biosynthesis of 1A HYDROXYLASE is under control of PTH

1A HYDROXYLASE converts vitamin D to the ACTIVE FORM in the kidneys

29
Q

How does vitamin D function in Ca2+ homeostasis?

A

(1) Increases ABSORPTION in the intestines = increase in plasma [Ca2+]
(2) Increases REABSORPTION in the kidney= increase in plasma [ca2+]
(3) Increases CALCIFICATION (Uses Ca2+ to lay down bone) = small reduction in plasma [Ca2+]

30
Q

How is vitamin D3 regulated?

A

(1) 25 hydroxycholecaliferol inhibits conversion of cholecaliferol–>25hydroxycholecaliferol in the liver to consider vitamin D stores in the body

31
Q

CALCITONIN

A
  • ->Secreted by the PARAFOLLCULAR ‘C’ CELLS in the THYROID gland
  • ->1/2 life = 10 minutes
  • ->Stimulated by increased [Ca2+]
  • -> Cause Plasma [Ca2+] to decrease by
    (1) Inhibiting bone resorption (decrease Ca2+ release)
    (2) Increasing Ca2+ excretion
32
Q

HYPOCALCAEMIA

A

too little Ca2+

makes nerves/muscle hyperexcitable

33
Q

HYPOPARATHRYOIDISM

A

=> Insufficient PTH secretion
Leads to=> HYPOCALCAEMIA
Caused by=>(1) Autoimmune disease of PT (2) Loss of PT during Thyroid removal

34
Q

RICKETS & OSTEOMALACIA

A

=VITAMIN DEFICIENCY
Rickets = condition in children
=====>RICKETS TYPE 2: mutation in vitamin D receptor = activation of vitamin D doesn’t work.

Osteomalacia= condition in adults

Causes:

(1) lack of solar exposure
(2) Dietary Deficiency

35
Q

What causes rickets type 2?

A

Mutation in vitamin D receptor=activation of vitamin D doesn’t work!

36
Q

HYPERPARATHYROIDISM

A
  • *Leads to HYPERCALCAEMIA (>12-15mg/dL)
  • *CAUSE: (1) tumour in PT gland =over secretion PTH
  • *Consequences: excessive demineralisation of bone
37
Q

What blood Ca2+ levels are classified as HYPERcalcaemia?

A

> 12-15mg/dL

38
Q

at what [Ca2+] does plasma Ca2+ start to precipitate out as _______ in the ECF?

A

> 70mg/dL

CaCO (Calcium carbonate)

39
Q

PRIMARY (1’) and SECONDARY (2’) HYPERPARATHYROIDISM

A

1’: depression of CNS/PNS, muscle weakness, constipation, kidney stones, coma

2’: Increases PTH in response to hypocalcaemia (overshooting)

40
Q

More Ca2+ is needed for…

A

(1) GROWTH (w/out Ca2+ bone density is reduced & longitudinal growth is stunted)
(2) PREGNANCY/BREAST FEEDING
(3) MENOPAUSE (w/out protective effects of oestrogen menopausal women are prone to fractures)

41
Q

What changes are made during PREGNANCY/BREAST FEEDING to increase Ca2+ stores

A

Pregnancy hormones increase

(1) Vitamin D levels = increase absorption of Ca2+
(2) CALCITONIN levels increase = inhibit bone resorption = pregnant women incorporate more Ca2+ into bone as a store for the growing foetus to be drawn on in the 3rd trimester)

Physiology 3003 (15 decks)

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