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MNSR > Lecture 6 > Flashcards

Lecture 6 Flashcards

1
Q

What are the different roles of calcium in the body?

A
  • Structural
    In bones and teeth
  • Signalling
    Constriction and relaxation of blood vessels, nerve impulse transmission, muscle contraction, secretion of hormones (e.g. insulin), mechanism of vision, taste and smell
  • Co-factor in proteins and enzymes
    Clotting/coagulation of blood in association with vitamin K dependent proteins
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2
Q

What are the factors affecting calcium absorption in the body?

A

Absorption enhanced by:
Vitamin D, which promotes the production of a calcium binding protein in intestinal cells. Vitamin D deficiency can lead to rickets.

Lactose, other sugars and proteins keep calcium in a soluble form

Absorption inhibited by:
Oxalic acid binds to calcium and makes it insoluble

High fat diet results in unabsorbed fats, which will form soaps with calcium preventing absorption

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3
Q

Where does calcium absorption primarily occur, and why?

A

In the duodenum, since it has a low pH

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4
Q

What is the source of calcium for the human body?

A
  • Plants
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5
Q

What are the two ways that calcium can be absorbed?

A
  • Active transport

- Passive diffusion

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6
Q

When does calcium’s solubility increase?

A
  • When the pH decreases

Calcium enters the body as a salt, which is not soluble in water, but it becomes more soluble with a decrease in the pH

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7
Q

Two types of bone?

A

Cortical bone (Compact bone) and Trabecular bone (Cancellous bone)

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8
Q

Cortical bone (Compact bone)?

A

Dense, low porosity, found in the shaft and forms outer shell around cancellous bone

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9
Q

Trabecular bone (Cancellous bone)?

A

Low density, high porosity, forms insides of the bones. The spaces between the bone are filled with fluid bone marrow cells

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10
Q

What are the two type of chemical components of bone?

A

Two types:
Organic (protein) matrix and Inorganic minerals

-Bone is composed of collagen stiffened by crystals of calcium hydroxyapatite

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11
Q

Organic (protein) matrix?

A
  • Comprises mainly type 1 collagen (highly cross-linked triple helical protein structure)
  • Also found in cartilage
  • Osteocalcin
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12
Q

Inorganic minerals?

A
  • Major minerals are calcium and phosphate

- Found as calcium hydroxyapatite which has a molecular formula: Ca5(PO4)3(OH)

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13
Q

How much of human bone is mineralised?

A

About 60%

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14
Q

What is the mineral component of human bones?

A

Calcium hydroxyapatite

Ca5(PO4)3(OH)

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15
Q

What happens if you increase the mineral component of bones (calcium hydroxyapatite)?

A
  • Increases stiffness
  • Reduces flexibility

Ex: Auditory ossicles

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16
Q

What happens if you increase the mineral component of bones (calcium hydroxyapatite)?

A
  • Decrease stiffness
  • Increase flexibility
    (Can absorb energy without breaking)
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17
Q

What are the 3 types of cells only found in the bone?

A
  • Osteoclasts: responsible for degrading bone (resorption), and come from bone marrow
  • Osteoblasts: cells that form new bone, and come from bone marrow
  • Osteocytes: sense bone deformation and signal then the need for adaptive remodelling of bone size/shape, and they come from osteoblasts, once they become trapped in the matrix they secrete
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18
Q

Osteoid?

A
  • New bone produced by the osteoblasts, which is made of collagen and other protein
  • They control calcium and mineral deposition
19
Q

Bone modeling?

A

Produces a change in the size and shape of bone, when new bone is deposited without previous bone resorption

20
Q

Bone remodeling?

A
  • Resorption by osteoclasts precedes bone formation by osteoblasts
  • Coupling of osteoblast and osteoclast activities
  • Need to remove bone to build it up again
21
Q

Remodeling of bone (more in depth)?

A
  1. Osteocytes release local factors that attract cells from blood and marrow into the remodeling compartment
  2. Osteoclasts resorb matrix and microcrack, then successive teams of osteoblasts deposit new bone
22
Q

Production of extracellular organic matrix?

A

The first step in bone formation (osteogenesis):

Consists of type 1 collagen and osteocalcin (non-collagenous protein)
- In bone, collagen formed of tropocollagen subunits

23
Q

Tropocollagen molecule?

A
  • Each molecule contains three helices
    of protein chains wound around each other to form a helical rod 3000 Å long and 15 Å in diameter
  • The three protein chains are linked together by hydrogen bonds, which can be formed bc some amino acids in tropocollagen are oxidised
24
Q

What is the purpose of the 400 Å gaps between the tropocollagen subunits?

A

Serve as nucleation sites for the deposition of long, hard, fine crystals of the mineral component (hydroxyapatite)

25
Q

What does a collagen fibre consist of?

A

A staggered array of tropocollagen molecules

26
Q

What causes scurvy?

A
  • A lack of vitamin C

Bc since some amino acids in tropocollagen are oxidised, and that oxidation requires vitamin C, if there is a lack of that vitamin then the body will be unable to make collagen

27
Q

Mineralisation?

A
  • Calcium and phosphate are derived from blood plasma
  • Mineralisation occurs soon after deposition of extracellular organic matrix
  • Mineral crystals form along the collagen fibrils and osteocalcin chains
28
Q

Osteocalcin?

A

It contains carboxyl groups (COO-) for binding calcium Ca2+

29
Q

What contributes to bone strength?

A
  • Renewal of bone
  • Remodeling causes increase in bone density up to 25 yrs
  • Bone mass and density are stable until 45 yrs
  • > 45 yrs bone mass starts to decrease
  • In women bone loss starts a few years before menopause
30
Q

Postmenopausal Osteoporosis?

A

Low estrogen levels in menopausal women can lead to increased bone resorption and accelerated bone loss

31
Q

Osteoporosis?

A
  • Bone disease in which the amount of bone reduces significantly, causing them to become weaker
  • Structural integrity of trabecular bone is impaired and the cortical bone becomes more porous and thinner
32
Q

What do strong and dense bones result from?

A

A balance between bone resorption and bone formation

33
Q

What happens if the balance between bone resorption and bone formation is disturbed?

A
  • Activity of bone-degrading osteoclast cells becomes greater than activity of bone-building osteoblast cells
  • Bone resorption become more important than bone formation and results in weak bones that are prone to fracture
34
Q

What are the most important risk factors for osteoporosis?

A
  • Female gender
  • Increased age
  • Estrogen deficiency
  • Smoking
35
Q

How to treat osteoporosis?

A
  • Use a type of drug called antiresorptive agents
  • Prevent further bone loss but also inhibit new bone formation, as the activities of osteoblast and osteoclast are coupled
36
Q

Classes of antiresorptive agents?

A
  • Estrogens and selective estrogen-receptor modulators
  • Peptide hormone (calcitonin)
  • Bisphosphonates
37
Q

Estrogen-Replacement Therapy?

A
  • To treat osteoporosis by slowing bone resorption by blocking signaling to the osteoclasts

Pros:

  • Relief of menopausal symptoms
  • Prevention of bone loss and fractures

Cons:

  • Risk of endometrial carcinoma (cancer)
  • Risk of breast carcinoma (cancer)
38
Q

Selective estrogen-receptor modulator?

A
  • To treat osteoporosis by slowing bone resorption by blocking signaling to the osteoclasts

Pros:

  • Reduce the rate of bone turnover
  • Prevention of bone loss and fractures
39
Q

Calcitonin?

A
  • To treat osteoporosis by rapidly inhibiting the action of osteoclasts

Pros:
- Therapy results in an increase in bone mineral density

Cons:

  • Expensive, must be given by injection or nasal spray
  • Some patients become resistant to its action during long-term use
40
Q

Bisphosphonates?

A
  • Most widely prescribed antiresorptive agents
  • first-line therapy for the treatment of post-menopausal osteoporosis
  • Block bone resorption with immediate effect
  • Bisphosphonates reside in the bones for long period: resorption still inhibited after discontinuation of the therapy
41
Q

Mode of action of non N-containing bisphosphonates?

A
  • Bind to bone mineral when they are administered and are then slowly released as bone is resorbed by osteoclasts
  • Suppress resorption by inhibiting the attachment of osteoclasts to bone matrix
  • Enhance osteoclast apoptosis (cell death)
42
Q

Mode of action of N-containing bisphosphonates?

A
  • Inhibit modification of proteins required for signaling

- Block signals important for osteoclast activity

43
Q

What percentage of calcium in your food is going to be absorbed?

A

10-40%

44
Q

What causes rickets?

A

A lack of vitamin D, which causes the skeleton to be weak

MNSR (12 decks)

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