Test 3 - Schricker Flashcards
Major causes of Hypercalcemia
- Primary hyperparathyroidism
- Malignant disease
- Latrogenic Vitamin D
Major treatments for Hypercalcemia
Treatment with bisphosphonates (inhibit osteoclast activity)
What is an indication of hyperparathyroidism?
Intact parathyroid hormone
What is the primary cause of hypercalcemia?
Parathyroid Hormone-Related Protein
What is PTHrP produced by?
Tumors
What are common tumors that produce PTHrP?
Breast, Lung, Kidney, Other Solid Tumors
Major causes of Hypocalcemia?
Drop in Serum Albumin (adjusted calcium levels)
Major treatments of Hypocalcemia
Activate osteoclast activity
T/F: There is an abnormal metabolism of Vitamin D associated with Hypocalcemia?
True
Osteoporosis
- What is it?
- Risk factors?
- Treatment
- Loss of mineral density with age (peak density at 30), increase fractures,
- Risk factors: female, smoke, excessive exercise, no exercise, too much caffeine, poor diet
- Treatment: estrogen, biphosphates, calcitonin, PTH
Paget’s Disease
- Characteristics
- Symptoms
- Cause
- Treatments
- Large, numerous Osteoclasts. Many Osteoblasts and an increase in alkaline phosphatase.
- Symptoms: Large, misshapen bones, less dense/brittle - high serum content of hydroxyproline, pyridinolines, and telopeptides
- Cause is unknown. Maybe genetic or early childhood viral infection.
- Treatments: Bisphosphonates and calcitonin
Osteomalacis
- What does it cause?
- Associated issue
- Defects in Hydroxyapatite formation due to vitamin D deficiency
- Rickets
What is Rickets?
Bone and Muscle weakness/skeletal deformity. Due to inhibited Vitamin D metabolism
Noticed during the industrial revolution - lack of sunlight due to pollution and narrow alleys
Treatment - Cod Liver Oil
What will you notice on teeth because of Rickets?
The dentin will have “gaps” since it does not remodel like bone
What is the mineral component of bone?
Hydroxyapatite C10[PO4]6[OH]2; 50-60%
What is the primary protein component of bone?
Collagen
How do the remodeling cycle and serum calcium levels affect one another
Decreases bone mass/ increase bone reabsorption = increase calcium in serum
Where else is calcium found?
Bound to Albumin
How is calcium distributed in the serum?
Ionized Calcium - 50%
Protein Bound (Albumin) Calcium - 40%
Citrate or Phosphate Bound Calcium - 10%
What Factors Regulate the Bone Remodeling Cycle?
Serum calcium, hormones, and cytokines
What cells are involved in bone remodeling?
Osteoblasts Build Bone
Osteoclasts Resorb Bone
How do RANK, RANKL, OPG, and Estrogen regulate osteoclasts?
Estrogen is a precursor for Osteoprogenerin (OPG).
OPG can bind to RANKL which inhibits it from binding to RANK (this inhibits osteoclasts)
RANKL and RANK binding together will stimulate osteoclasts
How do osteoblasts regulate osteoclasts?
Osteoblast release RANKL ligand that stimulate RANK receptor and stimulates osteoclast formation
What are the major consequences of increased PTH?
- Increases serum calcium and decreases serum phosphate
- Increases calcium reabsorption in the kidneys
- Stimulates osteoclasts
- Increases absorption in the small intestine
What regulates PTH production?
Triggered by low plasma Ca levels
What are the consequences of increased Vitamin D?
Increases serum calcium, increases bone adsorption
What regulates Vitamin D Production?
Sunlight → precursors synthesized in the skin
Liver = Stores Vitamin D
Kidney = Conversion of Vitamin D to active form occurs
1alpha-hydroxylase is the point of regulation
