Lecture 19/20: Pathophysiology of Bone Flashcards
PTH acts on target tissues to elevate ___ an decrease ___
Ca; phosphate
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
B. Active 1,25-(OH)2-D3
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. Inactive 24,25-(OH)2-D3
How does 1,25(OH)2-Vit D3 affect GI (major effect)?
How does it affect kidney (weak effect)?
GI: Increases absorption of plasma calcium and phosphate
Kidney: Decreases Ca and phosphate excretion
True or False: Hyperparathyroidism and Hypercalcemia can be caused by enlarged parathyroid
True - usually an adenoma
What are the two classical presenting symptoms of hyperparathyroidism and hypercalcemia?
Bone fracture
Kidney stone pain
Which of the following is usually asymptomatic and characterized by EXCESS production of PTH and EXCESS Calcium?
A. Secondary Hyperparathyroidism
B. Primary Hyperparathyroidism
B. Primary Hyperparathyroidism
How does elevated PTH in the plasma (as in primary hyperparathyroidism) affect osteoclasts and plasma calcium?
Elevated PTH => osteoclast hyperactivation => elevated Ca
- Negative feedback broken
What’s the normal relationship between plasma calcium and PTH?
Increase calcium leads to decreased PTH
What are the three skeletal effects seen with primary hyperparathyroidism?
- Osteoporosis
- Brown Tumors
- OFC (osteosis fibrosia cystica)
True or False: Decreased excitability of neurons, as well as muscles and cardiac cells is a global effect of primary hyperparathyroidism
True
What are three renal effects of primary hyperparathyroidism?
- Urinary tract stone
- Caclification of tubules/interstitium
- Calcification of organs
True or False: Primary hyperparathyroidism is a compensatory overactivation of parathyroid glands in response to chronic hypocalcemia
False - secondary hyperparathyroidism
Inadequate Ca intake, calcium malabsorption, severe Vit D3 deficiency, or chronic kidney disease can lead to ____ hyperparathyroidism
secondary
How do you treat primary hyperparathyroidism? secondary?
Primary = surgery
Secondary = address disease dysfunction
True or False: Parathyroid-dependent hypercalcemia is usually symptomatic while hypercalcemia associated with malignancies is usually asymptomatic
False - Parathyroid-dependent hypercalcemia is usually ASYMPTOMATIC while hypercalcemia associated with malignancies are usually SYMPTOMATIC
Hypercalcemia mneumonic?
Myelomas secrete ____ while malignancies of bone release cytokines, which induce bone ____
PTH-related peptide; resorption
In the case of malignancy induced hypercalcemia, do you expect levels of PTH from parathyroid gland to be within normal range, elevated, or decreased?
Decreased
- Base on negative feedback by high Calcium
What are serum PTH and calcium like in malignancies?
Ca elevated, while PTH is decreased
Which conditions is associated with inadequate release of PTH and hypocalcemia?
A. Hyperthyroidism
B. Hypoparathyroidism
C. Hypothyroidism
B. Hypoparathyroidism
What typically causes hypoparathyroidism?
Damage to parathyroid during thyroidectomy
What are serum PTH and calcium concentrations like in hypoparathyroidism?
Low Ca and PTH
In hypocalcemia, there is low PTH, Ca, which leads to membrane HYPERexcitability. What are the four major effects of this?
1.Dental hypoplasia
2. Skin Tetany (Trousseau or Chvostek Sign)
3. Prolonged QT Intervals
4. Neurological
What induces hyperphosphatemia?
Hypoparathyroidism
- Leads to tissue calcification
What are the 4 primary causes of hyperphosphatemia?
- Chronic renal failure
- Hypoparathyroidism (low plasma PTH -> low PO3 urine -> high PO3 in plasma)
- Vit D Intox (increased gut absorption and kidney reabsorption)
- Acidosis (PO3 moves from cytosol to ECF to bind H)
Insulin infusion, urinary loss, or decreased Vit D3/malabsorption can result in
A. Hyperphosphatemia
B. Hypophosphatemia
B. Hypophosphatemia
Which of the following calcium aggregates are important for osteocytic osteolysis and have FAST exchange with ECF?
A. Amorphous Crystals
B. Hydroxyapatite Crystals
A. Amorphous Crystals
Which of the following calcium aggregates are important for SLOW exchange of ECF and bone resorption?
A. Amorphous Crystals
B. Hydroxyapatite Crystals
B. Hydroxyapatite Crystals
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. Osteoblasts
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
B. Osteocytes
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
C. Osyteoclasts
Where are calcified matrix hydroxyapatite crystals found?
Osteoid
____ promotes maturation of preosteoblast
PTH
PTH stimulates mature osteoblast to secrete which two molecules?
M-CSF and OPG
After RANK and M-CSF bind, pre-osteoclasts become ____
osteoclasts
____ chew bone and release calcium and phosphate, which enter the plasma
Osteoclasts
____ detect worn out bone, secrete RANKL, and attracts osteoclasts
OsteoCYTES
Which molecule prevents RANK from binding to RANKL?
Osteoprotegerin
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. PTH
True or False: Vit D stimulates PTH receptors on osteocytes to release RANKL
False - PTH does this
Which of the following stimulates osteoblast to release -CSF and RANK and is permissive to PTH?
Vit D
RANKL comes from ____ while OPG from ___
osteocytes; activated osteoblasts
___ binds to RANKL, reduces osteoclast formation/maturation, and reduces lifespan of osteoclast
OPG
True or False: RANKL prolongs lifespan of osteoclasts and increases maturation of osteoclast precursors
True
Low peak bone mass and increased bone reabsorption leads to ____
osteoporosis
How does one lose bone during immobilization?
True or False: Thyrotoxicosis and other endocrine disorders can lead to hyperactivation of osteoclasts by T3
True
How do GC affect bone health?
Where does most bone damage occur in osteoporosis?
Trabecular bone
- inner part of bone
____ is an antiresorption drug that inactivates and induces apoptosis of osteoclasts
Bisphosphonates
_____: Bone formed during remodeling is undermineralized
___ In kids, new bone forming at growth plates is undermineralized
Osteomalacia
Rickets
Renal osteodystrophy?
____: A condition characterized by disorganized increase in bone mass, which leads to bone fragility
Paget Disease
Infection of osteoclast precursors with measles may make one more prone to develop _____
Paget Disease
Juvenile Paget was linked to mutations activating ___ or inactivating ___
RANK; OPG
Three phases of Paget Disease?
Osteolytic
Mixed
Osteosclerotic
True or False: Infarction of bone and bone marrow is a feature of osteonecrosis
True
Trauma, ETOH abuse, GC, and Bisphosphonates can cause which conditions?
A. Paget Disease
B. Osteonecrosis
C. Osteoporosis
B. Osteonecrosis
If osteonecrosis happens in subchondral bone with limited blood flow, poor perfusion leads to ___
angiogenesis
-infarct + angiogenesis = dead bone
What pathogen typically causes pyogenic osteomyelitis?
S. aureus
Which mutations is associated with brachydactyl?
HOXD13
Achondroplasia, common cause of dwarfism, is due to mutation in ____
FGF23 R3
True or False: Osteopetrosis is due to mutation in RANKL
True
Which collagen is defect in Osteogenesis Imperfecta?
Collagen Type 1
- CA2
- Proton Pump
