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Biochem 6200 Furci > SCHRICKER Exam 4 Bone Stuff > Flashcards

SCHRICKER Exam 4 Bone Stuff Flashcards

1
Q

What are the 2 main causes of Hypercalcemia?

A
  1. Primary hyperthyroidism (bones and stones)
  2. Malignant disease (tumors)
  3. Iatrogenic Vitamin D (overexposure)
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2
Q

Symptoms of hypercalcemia

A
  1. Dehydration
  2. Vomiting
  3. Reduced renal perfusion
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3
Q

Treatment of Hypercalcemia

A

Bisphosphonates because they inhibit osteoclasts

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4
Q

Hypercalcemia detection with Intact Parathyroid Hormone

A
  • Primary cause of hypercalcemia is from parathyroid hormone-releated protein (PTHrP)
  • PTHrP has sequence homology with PTH
  • Intact PTH diagnoses hyperthyroidism
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5
Q

Tumor Production of PTHrP (where?)

A

PTHrP produced by tumors of breast, lung, kidney and other solid tumors. Less commonly by hematologic, gastrointestinal, and head and neck tumors

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6
Q

What are the 4 main causes of Hypocalcemia?

A
  1. Hypoparathyroid (usually result of parathyroid gland – surgery, tumor, disease)
  2. Non-parathyroid (disease, Vit D deficiency/resistance, malabsorption of Ca)
  3. PTH resistance
  4. Drop in Albumin and changes in ionized calcium from pH change
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7
Q

Describe 2 factors resulting in PTH resistance

A
  1. Increase in PTH, end organ resistance to PTH, usually genetic Defect in G-protein***???
  2. Hypomagnesemia - need Mg for PTH to bind to excretory granules
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8
Q

Symptoms of Hypocalcemia

A

Neuromuscular irritability, Chveostek’s sign, Trousseau’s Sign, numbness, tingling, cramps, tetany, seizures

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9
Q

Abnormal metabolism of Vitamin D can lead to Hypocalcemia…what are the 3 main causes of abnormal metabolism of Vit D

A
  1. Vitamin D deficiency
  2. Tissue resistance to Vitamin D
  3. Clinical Conditions
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10
Q

What are 3 causes of Vit D deficiency (that can lead to Hypocalcemia)

A
  1. Reduced exposure to sunlight
  2. Poor dietary Intake
  3. Malabsorption
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11
Q

What clinical conditions can result in abnormal metabolism of vitamin D?

A
  1. Liver disease

2. Renal failure

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12
Q

Hyperthyroidism (HPT) is a factor causing Hypothyroidism….how does this occur?

A
  • Increased production in parathyroidism
  • Diagnosed by bones, stones, and abdominal groans
  • 80-85% caused by Adenoma
  • HPT increases bone remodeling, results in opseopenia, most bone density back to normal 6 months after surgery
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13
Q

Describe the cause of Osteoporosis

A
  • Loss of mineral density with age

- Relative rates of bone synthesis and and resorbtion change

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14
Q

At what age does bone density peak?

A

30

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15
Q

What is the major risk associated with osteoporosis?

A

Increased risk of bone fracture

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16
Q

Name the 4 most common treatments for osteoporosis

A
  1. Estrogen (hormone replacement therapy)
  2. Bisphosphates
  3. Calcitonin
  4. PTH (1-34 Amino Acid Sequence)
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17
Q

Describe the pathology associated with Paget’s Disease

A
  • Large numerous multinucleate Osteoclasts
  • Large number of osteoblasts
  • Increase in alkaline phosphatase
  • High serum content of hydroproline, pyridolines, and telopeptides
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18
Q

What are the physical manifestations of Paget’s disease?

A
  • Large, misshapen bones

- Bones less dense, more brittle

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19
Q

What is the cause of Osteomalacia?

A

Defects in HA formation due to Vitamin D deficiency

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20
Q

Rickets is the result of what disease?

A

Osteomalacia

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21
Q

What are the symptoms of rickets?

A
  • Bone and Skeletal weakness

- Skeletal deformity (large head, spinal curvature)

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22
Q

What is a common cure for rickets?

A

Cod Liver oil

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23
Q

What is the cause of osteogenesis imperfecta?

A

Caused by mutations in Type 1 Collagen

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24
Q

What genes are most commonly affected by osteogenesis imperfecta?

A

COLIA1, COLIA1, and CRTAP

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25
Q

Much like some fillings, bone is ______

A

Composite

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26
Q

What is the mineral content of bone?

A

HA (strong but not tough), 50-60% HA plates.

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27
Q

What is the primary protein component?

A

Collagen (tough but not strong)

28
Q

Describe tooth structure

A
  • Enamel = matrix is amelogenin and 90% HA

- Dentin = matrix is collagen and 67% HA

29
Q

Compare bone to Teeth

A
  1. Bone has lower mineral content
  2. Bone is maintained and can heal, but enamel cannot heal and dentin can only MAYBE heal
  3. Bone is vascularized
30
Q

Bone is the major _____ reserve

A

Bone is the major CALCIUM reserve

31
Q

Describe the pathway of bone synthesis to bone resorption

A

Bone synthesis –> Increase in Bone Mass –> Decrease in Serum Ca –> Bone Resorption

32
Q

Describe the pathway of Bone Resorption to Bone Synthesis

A

Bone resorption –> Decrease in bone mass –> Increase in Serum Ca –> Bone synthesis

33
Q

Where is calcium found?

A

~99% of Ca is contained in mineralized tissue

-The remaining is circulated in a bound ionic form

34
Q

How is Ca Distributed in the serum?

A
  • Ionized Calcium = 50%
  • Protein bound Calcium=40% (bound to albumin)
  • Citrate or phosphate bound Calcium = 10%
35
Q

Bone is a _____ structure; constantly building and resorbing bone

A

Bone is a DYNAMIC structure; constantly building and resorbing

36
Q

What factors regulate the remodeling cycle?

A
  1. Serum calcium
  2. Hormones
  3. Cytokines
37
Q

What cells are involved in the Bone Remodeling Cycle?

A
  1. Osteoblasts build bone

2. Osteoclasts resorb bone

38
Q

Osteoblasts and osteoclasts are from _____ lineages

A

DIFFERENT LINEAGES

39
Q

_______ complex bind together to activate osteoclasts to help _____ bone

A

RANK/RANKL complex bind together to activate osteoclast to help RESORB bone

40
Q

How does OPG impact resorption?

A

OPG INHIBITS the resorption process by binding RANK in place of RANKL so it cannot proceed

41
Q

What does RANKL do to bone?

A

Bone THICKENING….critical for remodeling cycle

42
Q

Estrogen _______ osteoclast formation

A

Estrogen SUPPRESSES osteoclast formation

43
Q

_____ prepares osteoclasts to resorb bone

A

RANK prepares osteoclasts to resorb bone

44
Q

RANK binds the cytokine _____

A

RANKL

45
Q

The binding of RANK to RANKL can be blocked by ______

A

blocked by OPG

46
Q

_____ and _____ control the differentiation and activation of osteoclasts

A

RANKL and OPG control the differentiation and activation of osteoclasts

47
Q

______ stimulates bone resorption

A

RANKL stimulates bone resorption

48
Q

______ inhibits bone resorption

A

OPG inhibits bone resorption

49
Q

Estrogen induces _____ synthesis

A

Estrogen induces OPG synthesis

50
Q

Disruption of OPG in mice results in _____

A

Osteoporosis

51
Q

RANKL knockout mice lack _______, resulting in osteoPETrosis

A

Osteoclasts

52
Q

Osteopetrosis results in excessively _____ bone

A

Thickened

53
Q

How do osteoblasts regulate osteoclasts?

A

Osteoblasts produce OSTEOPROTEGRIN and RANK ligand the regulate osteoclasts

54
Q

What are the major consequences of increased PTH?

A

Effect on bone – HPT increases bone remodeling resulting in OSTEOPENIA

55
Q

Longer than ____ AA in length means an intact PTH and presence of ________

A

Longer that 24 AA in length means an intact PTH and presence of HYPERPARATHYROIDISM

56
Q

What regulates PTH production?

A

Regulation is through serum calcium levels in a negative feedback loop

57
Q

______ plays an important role in calcium regulation

A

Vitamin D plays an important role in calcium regulation

58
Q

What are the 3 ways in which Vitamin D regulates calcium levels

A
  1. Increases serum calcium
  2. Increases gut absorption of calcium
  3. Increases bone absorption
59
Q

What is a major consequence of increased vitamin D?

A

Vitamin D is the 3rd leading cause of hepercalcemia

60
Q

Describe regulation of Vitamin D production

A
  • Precursor is synthesized in the skin and stored in the liver
  • Converted to active form in the kidney and 1-alpha hydroxylase is point of regulation
61
Q

In calcium metabolism, the driving force is to maintain stable ______ levels

A

SERUM CALCIUM

62
Q

Calcium is important for ______, _____, ______

A

Calcium is important for Clotting, Muscle Contraction, Cardiovascular Function

63
Q

Bone acts as a store for _____

A

Calcium

64
Q

Serum calcium levels trigger production of ________

A

regulatory hormomes

65
Q

_____, _____, and ____ are the primary regulators of Calcium metabolism

A

Parathyroid hormone, Calcitonin and Vitamin D are primary regulators

Biochem 6200 Furci (8 decks)

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