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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
Much like some fillings, bone is ______
Composite
26
What is the mineral content of bone?
HA (strong but not tough), 50-60% HA plates.
27
What is the primary protein component?
Collagen (tough but not strong)
28
Describe tooth structure
- Enamel = matrix is amelogenin and 90% HA | - Dentin = matrix is collagen and 67% HA
29
Compare bone to Teeth
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
Bone is the major _____ reserve
Bone is the major CALCIUM reserve
31
Describe the pathway of bone synthesis to bone resorption
Bone synthesis --> Increase in Bone Mass --> Decrease in Serum Ca --> Bone Resorption
32
Describe the pathway of Bone Resorption to Bone Synthesis
Bone resorption --> Decrease in bone mass --> Increase in Serum Ca --> Bone synthesis
33
Where is calcium found?
~99% of Ca is contained in mineralized tissue | -The remaining is circulated in a bound ionic form
34
How is Ca Distributed in the serum?
- Ionized Calcium = 50% - Protein bound Calcium=40% (bound to albumin) - Citrate or phosphate bound Calcium = 10%
35
Bone is a _____ structure; constantly building and resorbing bone
Bone is a DYNAMIC structure; constantly building and resorbing
36
What factors regulate the remodeling cycle?
1. Serum calcium 2. Hormones 3. Cytokines
37
What cells are involved in the Bone Remodeling Cycle?
1. Osteoblasts build bone | 2. Osteoclasts resorb bone
38
Osteoblasts and osteoclasts are from _____ lineages
DIFFERENT LINEAGES
39
_______ complex bind together to activate osteoclasts to help _____ bone
RANK/RANKL complex bind together to activate osteoclast to help RESORB bone
40
How does OPG impact resorption?
OPG INHIBITS the resorption process by binding RANK in place of RANKL so it cannot proceed
41
What does RANKL do to bone?
Bone THICKENING....critical for remodeling cycle
42
Estrogen _______ osteoclast formation
Estrogen SUPPRESSES osteoclast formation
43
_____ prepares osteoclasts to resorb bone
RANK prepares osteoclasts to resorb bone
44
RANK binds the cytokine _____
RANKL
45
The binding of RANK to RANKL can be blocked by ______
blocked by OPG
46
_____ and _____ control the differentiation and activation of osteoclasts
RANKL and OPG control the differentiation and activation of osteoclasts
47
______ stimulates bone resorption
RANKL stimulates bone resorption
48
______ inhibits bone resorption
OPG inhibits bone resorption
49
Estrogen induces _____ synthesis
Estrogen induces OPG synthesis
50
Disruption of OPG in mice results in _____
Osteoporosis
51
RANKL knockout mice lack _______, resulting in osteoPETrosis
Osteoclasts
52
Osteopetrosis results in excessively _____ bone
Thickened
53
How do osteoblasts regulate osteoclasts?
Osteoblasts produce OSTEOPROTEGRIN and RANK ligand the regulate osteoclasts
54
What are the major consequences of increased PTH?
Effect on bone -- HPT increases bone remodeling resulting in OSTEOPENIA
55
Longer than ____ AA in length means an intact PTH and presence of ________
Longer that 24 AA in length means an intact PTH and presence of HYPERPARATHYROIDISM
56
What regulates PTH production?
Regulation is through serum calcium levels in a negative feedback loop
57
______ plays an important role in calcium regulation
Vitamin D plays an important role in calcium regulation
58
What are the 3 ways in which Vitamin D regulates calcium levels
1. Increases serum calcium 2. Increases gut absorption of calcium 3. Increases bone absorption
59
What is a major consequence of increased vitamin D?
Vitamin D is the 3rd leading cause of hepercalcemia
60
Describe regulation of Vitamin D production
- 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
In calcium metabolism, the driving force is to maintain stable ______ levels
SERUM CALCIUM
62
Calcium is important for ______, _____, ______
Calcium is important for Clotting, Muscle Contraction, Cardiovascular Function
63
Bone acts as a store for _____
Calcium
64
Serum calcium levels trigger production of ________
regulatory hormomes
65
_____, _____, and ____ are the primary regulators of Calcium metabolism
Parathyroid hormone, Calcitonin and Vitamin D are primary regulators

Biochem 6200 Furci (8 decks)

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