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Sem 2 Physiology > Week 3 - Bone Physiology and Calcium > Flashcards

Week 3 - Bone Physiology and Calcium Flashcards

1
Q

What are some of the functions of bone?

A

Support, storage of minerals, fat and 99% of the body’s calcium, protection (cranial/thoracic regions), haematopoiesis and leverage

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2
Q

What are the two components of bone?

A

Cellular and ECM

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3
Q

What % of ECM is hydroxyapatite and is it inorganic or organic?

A

67%

Inorganic

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4
Q

What makes up the organic component of ECM?

What % is it?

A

33% is organic
28% is collagen
5% is noncollagenous proteins

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5
Q

What’s the hydroxyapatite:calcium ratio?

A

1.3-2.0

Changes through life

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6
Q

Describe the organic matrix and the importance of its two main components

A

90-95% is collagen 1
Remainder is proteoglycans - gelatinous ground substance including chondroitin sulfate and hyaluronic acid.
These give sugars help the proteoglycans mis with collagen to give a 3-D matrix –> this bit gets calcified and turned into bone

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7
Q

What are the bone precursor cells? Where do you find them and what do they turn onto?

A
  • Osteoprogenitors
  • Start as stem cells (mitotic)
  • Located in inner cellular layer or periosteum, endosteum and lining the osteonic canals
  • Turn into Osteoblasts
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8
Q

When are osteoprogenitor cells most active?

A

During bone growth
But
A large number are reactivated in adult life in repair of fracture

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9
Q

What is an Osteoblast? Where is it found?

A

An osteoblast is a cell that begins to form bone. They’re derived from osteoprogenitor cells and synthesize the organic components of the bone matrix
Located on the surface of bone tissue, and appear cuboidal when active

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10
Q

What do Osteoblasts turn into?

A

Osteocytes - mature bone cells

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11
Q

Describe the structures surrounding an osteocyte?

A

Osteocytes sit in lacunae - cytoplasmic processes - connected by canaliculi.
The cells are trapped as the surrounding ECM has become calcified.

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12
Q

What is the purpose of canaliculi?

A

They carry extracellular fluid containing nutrients to nourish the osteocytyes

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13
Q

How to osteocytes communicate?

A

Through gap junctions - these connect adjacent cells and allow ions and small molecules to travel from cell to cell

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14
Q

What are osteoclasts?

A

Large, motile, multinucleated, bone-resorbing cells derived from monocytes.

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15
Q

Where would you find an osteoclast?

A

They occupy depressions in bone matrix

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16
Q

How does bone resorption occur?

A

Osteoclasts adhere tightly to established bone matrix, acidify the bone surface using Hydrogen ATP-ases, and exocytose lysosomal enzymes
Degraded mineral and organic components are endocytosed by the osteoclasts, and delivered to nearby capillaries to enter the circulation

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17
Q

Why are osteoclasts so important?

A

Provide a large source of free calcium into the circulation

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18
Q

What is the pathway of an osteoprogenitor cell?

A

Osteoprogenitor –> osteoblast –> osteocyte

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19
Q

What is the annual bone turnover?

A

10-20%

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20
Q

Where does linear and width growth in a bone occur?

A

Linear - growth at an epiphyseal plate

Width - at the periosteum

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21
Q

Describe bone formation

A

Active osteoblasts synthesize and extrude collagen.
Collagen fibrils form an organic matrix - this is osteoid
Mineralization occurs - calcium phosphate is deposited in the osteoid and forms hydroxyapatite

22
Q

What happens in bone formation if there’t not enough calcium?

A

Hydroxyapatite cannot be formed

23
Q

What are the five steps of bone remodelling?

A
  1. Activation of osteoclasts
  2. Resorption of bone
  3. Reversal phase - occurs because after osteoclasts eliminate enough calcium to wake the osteoblasts up
  4. Formation of bone
  5. Resting
24
Q

What are some of the functions of calcium in the body?

A 
Nervous system function - release of neurotransmitters
Clottng
Bones
Muscle contraction
Endocrine system
Cardiovascular system
Intracellular signalling
What are consequences of hypercalcaemia?
25
Q

What are consequences of hypercalcaemia?

A

Depression of neuromuscular activity as sodium channels get blocked. This causes bathmotropy - increases membrane potential needed for an action potential. This ends up shutting down the nervous and muscular system
Kidney stones

26
Q

What are some consequences of hypocalcaemia?

A

Potentiates neuromuscular activity, causing positive bathmotropy. This results in tetanic contraction
There’s also impaired clotting

27
Q

What are the changes in calcium plasma concentrations that causes clinical signs?

A

Up 30% = nerves and muscles unresponsive
Down by 35% causes convulsions
Down by 50% = death

28
Q

Describe the calcium %s in different body compartments

A

99% in bone matrix
1% in cells - mitochondria and ER (SR in muscle)
0.1% in ECF - normal plasma conc is 2.4 mM

29
Q

How is calcium ‘packaged’ in the ECF?

A

9% complexed to anions
50% ionized
41% protein bound

30
Q

Which form of calcium in the ECF is freely active calcium?

A

Ionized calcium

31
Q

What kind of proportion of calcium is absorbed from the GIT?

A

about 10%, we only get around 100mg/day

32
Q

How much calcium do we lose from our urine?

A

Approx 100mg/day

33
Q

Where does the calcium in the ECF move to?

A

Bones
Cells
Kidneys

34
Q

Describe the calciostat system?

A

When calcium drops below a certain threshold, the parathyroid hormone (PTH) is released
This moves through the body and activates osteoclasts, which degrade hydroxyapatite and releases calcium into plasma

35
Q

What is Vit D to PTH?

A

An agonist

36
Q

What is the action of Vit D on calcium? (3)

A

Causes an increase in plasma Ca concentration:

  1. principally by increasing the amount of calcium the duodenum is able to scavenge from food
  2. Reduces excretion of Ca in faeces and urine
  3. Increases Ca mobilization from the bones
37
Q

Which molecule acts as an antagonist to PTH?

A

Calcitonin

38
Q

How long does it take PTH to increase bone degradation?

A

About half a day

39
Q

What is the rapid action effect of PTH?

A

Stimulates osteocytes in bone to release all of the calcium they have stored in their mitochondria and endoplasmic reticulum, by increasing osteocyte permeability to calcium. This calcium is released as liquid into the ECF

40
Q

What are mechanisms of PTH for increasing plasma CA, excluding action on bone?

A
  1. Decreases renal excretion of calcium by upregulating Ca-ATPase and Na-Ca antiporters in the thick ascending limbs and distal tubule of the kidneys. this increases reabsorption up from 97% ish
41
Q

What is the general effect of Calcitonin?

A

A short term, fine-tuning antagonist of PTH, decreasing plasma levels

42
Q

In which diseases is insufficient PTH seen, and what does this cause?

A

Autoimmune disease and patients with thyroidectomy have insufficient PTH
Causes: muscle hypocalcaemia (

43
Q

What are some consequences of hyperthyroidism i.e. chronically elevated PTH?

A 
Excessive bone demineralization
Hypercalcaemia
Depression of CNS/PNS
Muscle weakness
Kidney stones
Coma
44
Q

Where is calcitonin secreted from, and why is it secreted?

A

Secreted from parafollicular cells of the thyroid gland, in response to increases in plasma Ca concentration

45
Q

How does Calcitonin have an effect on plasma calcium levels?

A

Acts through the calcitonin receptor, which has a cAMP mechanism.
Inhibits activity of osteoclasts, reducing bone turnover and inhibiting osteoclast formation
This is only a minor effect
Also decreases kidney Ca reabsorption

46
Q

How important is Calcitonin on Ca plasma regulation?

A

Has a very minor role - thyroid removal has no effect on plasma Ca conc in vivo

47
Q

How does PTH have a direct effect on Vit D?

A

Active PTh stimulates the conversion of inactive D3 to active D3

48
Q

How does calcium move from the lumen of the duodenum to the blood?

A

The calcium channel CAT1 moves it from the lumen into the enterocyte.
Calcium is then bound to Calbindin and moves through the cell
Calcium moves out of the cell and into the blood through the Calcium ATPase antiporter

49
Q

How does Vit D specifically affect the process of calcium moving from duodenum to the blood?

A

CAT1 is VitD responsive - activated by Vit D. This increases how much calcium gets into an enterocyte
Vit D also increases concentration of calcium binding protein (Calbindin), creating a gradient for calcium to enter the cell, by lowering the intracellular gradient (as the more calcium bound to calbindin, the faster it gets into the blood)

50
Q

What is Vit D’s effect on the kidneys?

A

Basically the same as that on the liver cell - increases calcium absorption

51
Q

What is Rickets, and what is it a result of?

A

Rickets is a result of low calcium levels, leading to impaired ossification of the newly created osteoid. This leads to soft and pliable bones

52
Q

Describe the two types of Rickets

A

Type 1 - mainly due to Vit D deficiency, either from lack of solar exposure or dietary deficiency
Type 2 - Vit D receptor mutation

Sem 2 Physiology (3 decks)

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