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Pharmacy BSI > BSI Lecture 47-48 Bone Physiology > Flashcards

BSI Lecture 47-48 Bone Physiology Flashcards

1
Q

What is bone remodeling?

A

The process of breaking down and replacing bone tissue

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2
Q

What is the purpose of bone remodeling?

A
  1. Renew bone before it deteriorates
  2. Redistributes bone matrix along lines of stress
  3. Repairs injured bone
  4. Calcium and phosphate homeostasis
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3
Q

What does BMU stand for?

A

Bone multicellular unit

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4
Q

What is the BMU composed of?

A

Osteoblasts and osteoclasts

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5
Q

What do osteoclasts do?

A

They break down bone and carve small tunnels in the bone

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6
Q

What is the purpose of the ruffled border of osteoclast?

A

It forms a seal with bone surface

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7
Q

What are the catabolic substances that breaks down bone within Osteoclasts?

A

Lysosome enzymes and acid

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8
Q

What do the lysosomes inside the osteoclast do?

A

They digest proteins in the matrix

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9
Q

What does the acid inside the osteoclast do?

A

Breaks down calcified mineral salts

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10
Q

How is bone resorption or bone turnover measured?

A
  1. Collagen breakdown products have pyridinoline structures which can be measured in the urine as an index of rate of bone resorption.
  2. Serum bone-specific alkaline phosphatase levels are sometimes used in the index of bone turnover.
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11
Q

______ re-build bone.

A

Osteoblasts

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12
Q

What does osteoblast secrete?

A

Organic matrix (aka osteoid) and alkaline phosphatase

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13
Q

What are osteoid most made of?

A

Collagen

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14
Q

What does alkaline phosphatase do?

A

Initiate calcification of mineral salts

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15
Q

How much of bone mass is being remodeled at any one time?

A

About 5% by ~2 million BMUs

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16
Q

How do the BMU’s communicate?

A

By using RANK/RANKL/OPG

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17
Q

Where are RANKL (Receptor Activated of NF-kB ligand) expressed?

A

In the membrane of osteoblasts and some immune cells

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18
Q

What does RANKL bind to?

A

RANK on osteoclast precursor cells and osteoclasts to stimulate their activity.

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19
Q

What does binding of RANKL to RANK on osteoclast precursor cells stimulate?

A

Osteoclastogenesis

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20
Q

What is Osteoclastogenesis?

A

The formation of new osteolclast

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21
Q

Which BMU produces Osteoprotegerin (OPG)?

A

Osteoblast and various immune cells

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22
Q

What does OPG do?

A

Inhibits osteoclastogenesis by binding to RANKL, which prevents them from binding to RANK.

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23
Q

The balance of ______/_______ expression apprears to control the remodeling process.

A

RANKL/OPG

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24
Q

Name some hormones or cytokines that regulate RANKL/RANK/OPG system?

A
  1. PTH (Parathyroid hormone)
  2. IL-6
  3. Estrogen
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25
Q

What does PTH do?

A

Increases RANKL expression and suppresses OPG expression in osteoblasts and some immune cells. (increases bone resorption)

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26
Q

What does IL-6 do?

A

Increases RANKL expression and suppresses OPG. (increases bone resorption)

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27
Q

What does estrogen do?

A

Stimulates OPG expression and suppresses RANKL expression. (Decreases bone resorption)

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28
Q

What is bone resorption?

A

The process by which osteoclasts break down the tissue in bones and release the minerals, resulting in a transfer of calcium from bone tissue to the blood.

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29
Q

Bone is a major reservoir for ____ and _____.

A

Calcium; phosphate

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30
Q

99% of ______ is stored in the skeleton.

A

Calcium

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31
Q

Where is the 1% of calcium that is not in the skeleton?

A

In the plasma

32
Q

What are glucocorticoids and what do they do?

A

They are steroid hormones that increases resorption. (Used in organ transplants that suppress immune system)

33
Q

What is the biologically active form of Calcium?

A

Ionized-not bound to anything

34
Q

What are the inactive forms of Calcium?

A

Bound form (to albumin (41%) and anions(9%)

35
Q

Why is calcium important?

A

Important in

  1. Blood clotting
  2. Muscle contractions
  3. Nerve Function
36
Q

What are the signs and symptoms of hypocalcemia?

A
  1. Spontaneous action potentials due to increased Na permeability
  2. Paresthesias (tingling)
  3. Tetany (first see in hands, wrists; occur in laryngeal muscles which can kill you)
  4. Cardiac arrythmias
  5. Seizures.
37
Q

What are the signs and symptoms of more severe hypercalcemia?

A
  1. Nervous system depression
  2. Sluggish reflexes
  3. Muscle weakness
  4. Lethargy and fatigue
  5. Constipation
  6. Decreased appetite
  7. Nausea and vomiting
  8. Frequent urination (polyuria)
  9. Excessive thirst (polydipsia)
38
Q

What is polyuria?

A

Production of abnormally large volume of dilute urine. Kidneys become insensitive to ADH (Anti-Diuretic Hormone(from pituitary gland)) which causes excess urination.

39
Q

__________ is a monoclonal antibody that binds to the RANKL (acts similary to OPG)

A

Denosumab

40
Q

What does ADH (Anti-Diuretic Hormones (from pituitary gland)) do?

A

It causes the kidneys to reabsorb water to be put back into the blood.

41
Q

What are the signs and symptoms of most severe hypercalcemia?

A

a. Nervous system depression
b. Sluggish reflexes
c. Muscle weakness
d. Lethargy and fatigue
e. Constipation
f. Decreased appetite
g. Nausea and vomiting
h. Frequent urination (polyuria)
i. Excessive thirst (polydipsia)
j. Kidney stones

42
Q

What are the symptoms of hypophosphatemia?

A

a. Muscle dysfunction and weakness
b. Mental status change, from irritability to gross confusion, delirium and coma.
c. Instability of cell membranes due to low ATP levels; this may cause rhabdomyolysis and hemolytic anemia.

43
Q

What is a major sign of hyperphosphatemia?

A

Calcium levels will be lowered due to precipitation of phosphate with the calcium in tissues.

44
Q

What is ectopic calcification?

A

A pathological deposition of calcium salts in tissues or bone growth in soft tissues.

45
Q

85-90% of _______ is stored in the skeleton?

A

Phosphate

46
Q

2/3 of plasma phosphate is in _______ compounds.

A

Organic

47
Q

1/3 of plasma phosphate as _______ phosphate.

A

Inorganic (Pi)

48
Q

PTH _______ plasma calcium and ______ plasma phosphate.

A

Increases; decreases

49
Q

What stimulates PTH release from the parathyroid gland?

A

Low plasma calcium levels

50
Q

What can act directly on the parathyroid glands and decrease PTH secretion?

A

1,25 hydroxyvitamin D3 (1,25(OH)2D3 )

51
Q

PTH _________ bone resorption.

A

Increases

52
Q

T or F? PTH decreases intestinal absorption of calcium and phosphate via activation of vitamin D.

A

False, increases

53
Q

PTH increases activity of 1-alpha-OHase in the ________

A

Kidneys

54
Q

PTH increases the reabsorption of _____ by the kidneys

A

Calcium

55
Q

How does PTH decrease blood phosphate levels?

A

By decreasing reabsorption by the kidneys

56
Q

Calcitonin __________ plasma calcium and phosphate.

A

Decreases

57
Q

Where is calcitonin secreted from?

A

Parafollicular cells of thyroid gland

58
Q

What causes stimulation of calcitonin release?

A

High plasma calcium levels

59
Q

Does calcitonin increase or decrease bone resorption?

A

Decrease

60
Q

T or F? Calcitonin decreases reabsorption of calcium and phosphate by the kidneys?

A

True, the body gets rid of it in the urine

61
Q

Vitamin D _________ plasma calcium and phosphate.

A

Increases

62
Q

What effect does Vitamin D have on intestinal absorption of calcium and phosphate?

A

It increases intestinal absorption

63
Q

What minor effect does vitamin D have on kidneys?

A

Increases reabsorption of calcium and phosphate

64
Q

How is vitamin D metabolized?

A

It is converted in the liver by Vitamin D-25-hydroxylase to 25-hydroxyvitamin D3 [25(OH)D3]

65
Q

Where does vitamin D2 and D3 come from?

A

From the coversion of 7-dehydrocholesterol in the skin by solar ultraviolet B radiation of from dietary sources.

66
Q

What is the major circulating form of vitamin D in the blood that is measured to assess vitamin D status of an individual?

A

[25(OH)D3]

67
Q

25(OH)D3 is an inactive form of Vitamin D that must be converted in the ____________.

A

Kidneys

68
Q

How is 1,25 hydroxyvitamin D3 formed?

A

It is formed by the the enzyme 25-hydroxyvitaminD-1-alphahydroxylase(1-alpha-OHase)

69
Q

What is another name for 1,25 hydroxyvitamin D3?

A

Calcitriol

70
Q

T or F? PTH stimulates activity of 1-alpha-OHase in the liver and therefore is integral in the activation of vitamin D

A

False, kidney

71
Q

The renal production of 1,25(OH)2D3 is used for regulating ________ and _________ metabolism.

A

Calcium; phosphorous

72
Q

T or F? There appears to be a hierarchy in utilization of vitamin D in the body.

A

True

73
Q

What are the hierarchy levels of calcium?

A
  1. Vitamin D maintains plasma calcium levels primary by increasing intestinal calcium absorption.
  2. Only when extracellular ionized calcium requirement is met will 25(OH)D3 be used by other tissues and be converted locally to 1,25(OH)2D3
74
Q

What does Vitamin D reduce?

A

a. Risk of variety of cancers
b. Hypertension
c. Heart disease
d. Infectious disease
e. mmultiple sclerosis
f. rheumatoid arthritis
g. asthma
h. depression
i, type 1 diabetes
j. metabolic syndrome

75
Q

How has vitamin D been linked to the aging process?

A

Higher vitamin D levels associated with longer telomeres.

76
Q

T or F? HIgher vitamin D levels has been associated with greater weight loss in dieting individuals.

A

True

77
Q

T or F? More the 50% of population gets insufficient vitamin D.

A

True

Pharmacy BSI (58 decks)

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