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Pathophysiology > Lecture 19/20: Pathophysiology of Bone > Flashcards

Lecture 19/20: Pathophysiology of Bone Flashcards

1
Q

PTH acts on target tissues to elevate ___ an decrease ___

A

Ca; phosphate

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2
Q

Phosphate, Vit D, Ca, and1,25-(OH)2-D3 deficiency AND elevated PTH lead to…
A. Inactive 24,25-(OH)2-D3
B. Active 1,25-(OH)2-D3

A

B. Active 1,25-(OH)2-D3

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3
Q

Vit D sufficiency, Normo/Hypercalcemia, and Normo/Hyperphosphatemia lead to…
A. Inactive 24,25-(OH)2-D3
B. Active 1,25-(OH)2-D3

A

A. Inactive 24,25-(OH)2-D3

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4
Q

How does 1,25(OH)2-Vit D3 affect GI (major effect)?

How does it affect kidney (weak effect)?

A

GI: Increases absorption of plasma calcium and phosphate

Kidney: Decreases Ca and phosphate excretion

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5
Q

True or False: Hyperparathyroidism and Hypercalcemia can be caused by enlarged parathyroid

A

True - usually an adenoma

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6
Q

What are the two classical presenting symptoms of hyperparathyroidism and hypercalcemia?

A

Bone fracture
Kidney stone pain

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7
Q

Which of the following is usually asymptomatic and characterized by EXCESS production of PTH and EXCESS Calcium?
A. Secondary Hyperparathyroidism
B. Primary Hyperparathyroidism

A

B. Primary Hyperparathyroidism

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8
Q

How does elevated PTH in the plasma (as in primary hyperparathyroidism) affect osteoclasts and plasma calcium?

A

Elevated PTH => osteoclast hyperactivation => elevated Ca

  • Negative feedback broken
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9
Q

What’s the normal relationship between plasma calcium and PTH?

A

Increase calcium leads to decreased PTH

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10
Q

What are the three skeletal effects seen with primary hyperparathyroidism?

A
  1. Osteoporosis
  2. Brown Tumors
  3. OFC (osteosis fibrosia cystica)
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11
Q

True or False: Decreased excitability of neurons, as well as muscles and cardiac cells is a global effect of primary hyperparathyroidism

A

True

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12
Q

What are three renal effects of primary hyperparathyroidism?

A
  1. Urinary tract stone
  2. Caclification of tubules/interstitium
  3. Calcification of organs
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13
Q

True or False: Primary hyperparathyroidism is a compensatory overactivation of parathyroid glands in response to chronic hypocalcemia

A

False - secondary hyperparathyroidism

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14
Q

Inadequate Ca intake, calcium malabsorption, severe Vit D3 deficiency, or chronic kidney disease can lead to ____ hyperparathyroidism

A

secondary

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15
Q

How do you treat primary hyperparathyroidism? secondary?

A

Primary = surgery
Secondary = address disease dysfunction

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16
Q

True or False: Parathyroid-dependent hypercalcemia is usually symptomatic while hypercalcemia associated with malignancies is usually asymptomatic

A

False - Parathyroid-dependent hypercalcemia is usually ASYMPTOMATIC while hypercalcemia associated with malignancies are usually SYMPTOMATIC

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17
Q

Hypercalcemia mneumonic?

A
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18
Q

Myelomas secrete ____ while malignancies of bone release cytokines, which induce bone ____

A

PTH-related peptide; resorption

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19
Q

In the case of malignancy induced hypercalcemia, do you expect levels of PTH from parathyroid gland to be within normal range, elevated, or decreased?

A

Decreased
- Base on negative feedback by high Calcium

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20
Q

What are serum PTH and calcium like in malignancies?

A

Ca elevated, while PTH is decreased

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21
Q

Which conditions is associated with inadequate release of PTH and hypocalcemia?
A. Hyperthyroidism
B. Hypoparathyroidism
C. Hypothyroidism

A

B. Hypoparathyroidism

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22
Q

What typically causes hypoparathyroidism?

A

Damage to parathyroid during thyroidectomy

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23
Q

What are serum PTH and calcium concentrations like in hypoparathyroidism?

A

Low Ca and PTH

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24
Q

In hypocalcemia, there is low PTH, Ca, which leads to membrane HYPERexcitability. What are the four major effects of this?

A

1.Dental hypoplasia
2. Skin Tetany (Trousseau or Chvostek Sign)
3. Prolonged QT Intervals
4. Neurological

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25
Q

What induces hyperphosphatemia?

A

Hypoparathyroidism
- Leads to tissue calcification

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26
Q

What are the 4 primary causes of hyperphosphatemia?

A
  1. Chronic renal failure
  2. Hypoparathyroidism (low plasma PTH -> low PO3 urine -> high PO3 in plasma)
  3. Vit D Intox (increased gut absorption and kidney reabsorption)
  4. Acidosis (PO3 moves from cytosol to ECF to bind H)
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27
Q

Insulin infusion, urinary loss, or decreased Vit D3/malabsorption can result in
A. Hyperphosphatemia
B. Hypophosphatemia

A

B. Hypophosphatemia

28
Q

Which of the following calcium aggregates are important for osteocytic osteolysis and have FAST exchange with ECF?
A. Amorphous Crystals
B. Hydroxyapatite Crystals

A

A. Amorphous Crystals

29
Q

Which of the following calcium aggregates are important for SLOW exchange of ECF and bone resorption?
A. Amorphous Crystals
B. Hydroxyapatite Crystals

A

B. Hydroxyapatite Crystals

30
Q

Which of the following make the proteins of the osteoid matrix, secrete alk phos, mineralize collagen, and exocytoses Ca and PO3
A. Osteoblasts
B. Osteocytes
C. Osyteoclasts

A

A. Osteoblasts

31
Q

Which of the following is trapped in mineralize bone, where it transfers Ca from amorphous crystal to ECF; it is also involved in: osteocytic osteolysis?
A. Osteoblasts
B. Osteocytes
C. Osyteoclasts

A

B. Osteocytes

32
Q

Which of the following is a multi-nucleated cell that secretes H+ to dissolve hydroxyapatite and collagenases to degrade collagen?
A. Osteoblasts
B. Osteocytes
C. Osyteoclasts

A

C. Osyteoclasts

33
Q

Where are calcified matrix hydroxyapatite crystals found?

A

Osteoid

34
Q

____ promotes maturation of preosteoblast

A

PTH

35
Q

PTH stimulates mature osteoblast to secrete which two molecules?

A

M-CSF and OPG

36
Q

After RANK and M-CSF bind, pre-osteoclasts become ____

A

osteoclasts

37
Q

____ chew bone and release calcium and phosphate, which enter the plasma

A

Osteoclasts

38
Q

____ detect worn out bone, secrete RANKL, and attracts osteoclasts

A

OsteoCYTES

39
Q

Which molecule prevents RANK from binding to RANKL?

A

Osteoprotegerin

40
Q

Which of the following promoters maturation of pro-osteoblasts to osteoblasts AND stimulates PTH receptors on osteoblasts to release M-CSH and OPG / PTH receptors on osteocytes to release RANKL
A. PTH
B. Vit D

A

A. PTH

41
Q

True or False: Vit D stimulates PTH receptors on osteocytes to release RANKL

A

False - PTH does this

42
Q

Which of the following stimulates osteoblast to release -CSF and RANK and is permissive to PTH?

A

Vit D

43
Q

RANKL comes from ____ while OPG from ___

A

osteocytes; activated osteoblasts

44
Q

___ binds to RANKL, reduces osteoclast formation/maturation, and reduces lifespan of osteoclast

A

OPG

45
Q

True or False: RANKL prolongs lifespan of osteoclasts and increases maturation of osteoclast precursors

A

True

46
Q

Low peak bone mass and increased bone reabsorption leads to ____

A

osteoporosis

47
Q

How does one lose bone during immobilization?

A
48
Q

True or False: Thyrotoxicosis and other endocrine disorders can lead to hyperactivation of osteoclasts by T3

A

True

49
Q

How do GC affect bone health?

A
50
Q

Where does most bone damage occur in osteoporosis?

A

Trabecular bone
- inner part of bone

51
Q

____ is an antiresorption drug that inactivates and induces apoptosis of osteoclasts

A

Bisphosphonates

52
Q

_____: Bone formed during remodeling is undermineralized

___ In kids, new bone forming at growth plates is undermineralized

A

Osteomalacia
Rickets

53
Q

Renal osteodystrophy?

A
54
Q

____: A condition characterized by disorganized increase in bone mass, which leads to bone fragility

A

Paget Disease

55
Q

Infection of osteoclast precursors with measles may make one more prone to develop _____

A

Paget Disease

56
Q

Juvenile Paget was linked to mutations activating ___ or inactivating ___

A

RANK; OPG

57
Q

Three phases of Paget Disease?

A

Osteolytic
Mixed
Osteosclerotic

58
Q

True or False: Infarction of bone and bone marrow is a feature of osteonecrosis

A

True

59
Q

Trauma, ETOH abuse, GC, and Bisphosphonates can cause which conditions?
A. Paget Disease
B. Osteonecrosis
C. Osteoporosis

A

B. Osteonecrosis

60
Q

If osteonecrosis happens in subchondral bone with limited blood flow, poor perfusion leads to ___

A

angiogenesis

-infarct + angiogenesis = dead bone

61
Q

What pathogen typically causes pyogenic osteomyelitis?

A

S. aureus

62
Q

Which mutations is associated with brachydactyl?

A

HOXD13

63
Q

Achondroplasia, common cause of dwarfism, is due to mutation in ____

A

FGF23 R3

64
Q

True or False: Osteopetrosis is due to mutation in RANKL

A

True

65
Q

Which collagen is defect in Osteogenesis Imperfecta?

A

Collagen Type 1

  • CA2
  • Proton Pump

Pathophysiology (26 decks)

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