Bones Flashcards
1
Q
What is the amount of calcium consumption in the general population vs in lactose intolerant population?
A
- general pop. - 800-830mg
- lactose intolerant - 200-560mg
2
Q
Osteoporosis
A
- reduction in bone mineral density (decrease in bone quantity)
- changes in bone structure (decrease in bone quality)
- results in increased risk of fractures
3
Q
Can calcium be synthesized by the body?
A
no, all calcium is provided through the diet
4
Q
where is most calcium stored?
A
bone and teeth
5
Q
How is extracellular fluid calcium regulated?
A
hormones
6
Q
what is the homeostatic set point/range for calcium?
A
9-10.5mg/dL
7
Q
Absorption
A
- occurs in the small intestine
- increases dietary calcium uptake
8
Q
Reabsorption
A
- occurs in the kidney
- calcium can be excreted in the urine OR reabsorbed back into the blood
9
Q
Resorption
A
- occurs in the bone
- dissolves bone structure to release calcium stored in bone into bloodstream
10
Q
Parathyroid hormone
A
- 1st response to low blood calcium
- serves to INCREASE blood calcium
- stiumulates production of calcitriol in kidney (activates 1a-hydroxylase enzyme)
- stimulates resorption of bone
- maximizes tubular reabsorption of calcium in kidney
11
Q
Calcitriol
A
- 2nd response to low blood calcium
- serves to INCREASE blood calcium
- stimulates resorption of bone
- facilitates absorption of calcium from small intestine (short term response)
- maximizes tubular reabsorption of calcium in kidney (short term response)
12
Q
Calcitonin
A
- response to high blood calcium
- serves to DECREASE blood calcium
- suppresses tubular reabsorption of calcium in kidney
- inhibits bone resorption and facilitates remineralization
- longer term response to improve bone density
13
Q
What is the active form of vitamin D?
A
1,25-dihydroxycholecalciferol = calcitriol
14
Q
Howdoes calcitriol influence disease processes?
A
- decreases adaptive immune system activation
- calcitriol is lipid soluble - can pass freely across plasma membranes and can function as a transcription factor
- binds to MAARS receptor -> activates second messengers, kinases and various signaling pathways
15
Q
How can calcium be absorbed across the apical membrane?
A
- passive diffusion: paracellular transport - active when high calcium
- calcium channel TRPV6
16
Q
How is calcium transported across the basolateral membrane?
A
- sodium calcium exchanger (3Na+ in / 1 Ca2+ out)
- calcium pump (Ca2+ out, H+ in)
17
Q
What stimulates gene expression and protein synthesis of Ca2+ apical and basolateral transporters and calbindin?
A
Calcitriol
18
Q
Calbindin
A
transports calcium to and from intracellular stores in the mitochondria and ER to help maintain intestinal Ca2+ levels and contribute to blood Ca2+ levels
19
Q
Does PTH inhibit or promote bone forming reactions? What reactions specifically?
A
- inhibit
- type 1 collagen formation
- osteocalcin production in osteoblasts
20
Q
What mechanism is in place for when a rapid PTH response is needed for low blood Ca2+?
A
- pre-pro PTH stored in vesicles
- pre-pro form transcribed in ribosome
- signal sequence cleaved and moves to ER
- pro sequence cleaved and PTH is activated
21
Q
CaSR
A
- calcium sensing receptor
- stops PTH release from vesicles when blood calcium is high
- Ca2+ binds to the CaSR and activates a signaling pathway to stop PTH release
22
Q
Familial hypercalcemic hypocalciuria
A
- due to mutations in CaSR (not responsive to changes in blood Ca2+ levels - body perceives lack of Ca2+ levels and sustains PTH secretion
- hypercalcemia: high/increased blood Ca2+ levels in blood sustained by bone resorption
- hypocalciuric: low levels of Ca2+ in the urine -> development of kidney stones because Ca2+ stays trapped in the kidney and is neither lost in the urine or reabsorbed into the blood
23
Q
What are the two types of bone?
A
- cortical / compact: most of bone mass - provides strength for weight bearing
- Trabecular / spongy: composed of osteoblasts and osteoclasts - undergoes constant turnover of synthesization and resorption
24
Q
Osteoblasts
A
- bone forming cells
- ossification / bone deposition
- secrete organic matrix
25
Osteoclasts
bone resorbing cells (breakdown)
26
Osteocytes
* old osteoblasts embedded in bone matrix
* sense mechanical stress on bone and secrete growth factors that stimulate new osteoblasts and bone formation
27
What are the two major components of bone?
1. Organic Matrix (majority is type 1 collagen fibers)
2. Bone Salts (major crystalline salt is hydroxyapatite
28
How does bone deposition occur? What are the major players?
* osteoblasts deposit proteins to form the organic matrix
* type 1 collagen -> hardened by hydroxyapatite deposits
* osteocalcin -> strongly binds Ca2+ and hydroxyapatite
* Osteonectin -> binds to hydroxyapatite and collagen fiber -> forms lattice work holding organic matrix and bone salts together
29
How do osteoblasts regulate the activation on osteoclasts?
* RANK-L secreted or expressed on cell surface by osteoblasts bind RANK on the surface of osteoclast progenitor cells
* RANK-L binding to RANK stimulates cell to mature into a functional osteoclast
30
What stimulates the secretion/expressionof RANKL by osteoblasts?
* calcitriol
* PTH
* inflammatory cytokines (TNFa, IL-6)
* Prostaglandin E2 (derived from n-6 PUFA)
31
Osteoprotegerin
* RANK-L antagonist
* binds to RANK-L and forms a complex that cannot bind to the RANK receptor
* inhibits osteoclast maturation
* secretion stimulated by estrogen and IL-4
32
M-CSF
* macrophage colony stimulating factor
* stimulates the expression of RANK in osteoclasts
33
What is the mechanism of bone resorption by osteoclasts?
* osteoclasts send out villus-like projections toward the bone, forming a "ruffled border" - increases SA of cell membrane in contact w the bone surface
* secrete proteolytic enzymes that are stored in lysosomes to digest the organic matrix of the bone (type 1 collagen, osteonectin, osteocalcin)
* secrete citric acid to dissolve hydroxyapatite and help digest the bone matrix
34
Integrin and Vitronectin proteins
seal the osteoclast against the bone (integrin on osteoclast, vitronectin on bone)
35
TRAP proteins
allow osteoclast to move along the bone surface and continue to breakdown bone
36
What are the stimulators of bone resorption?
* inflammatory cytokines (TNFa, IL-6)
* lipid mediators (PGE2)
* Growth factors (epidermal growth factor)
* **RANK-L bound to RANK**
* **PTH**
37
What are the inhibitors of bone resorption?
* cytokines - IL-4, IFNy
* calcitonin
38
What are the stimulators of bone formation?
* insulin-like growth factor
* BMP
* Estrogen
39
Are there higher levels of bone formation in post- or pre-menopausal females? Why?
* postmenopausal
* because of interventions like calcium supplements etc.
40
T score
Compares BMD to a reference mean for a 30 y/o male or female
41
What does a T score of -2.5 indicate?
osteoporosis
42
What does a T score of -1 to -2.5 indicate
osteopenia
43
What does a T score of 0 indicate?
peak BMD
44
What are the mechanisms connecting exercise to bone health?
* increase OPG secretion by osteoblast
* Decrease RANKL expression by osteoblast
45
What is the ideal dietary ratio of n-6:n-3 PUFA?
4:1
46
What does a very low BMI increase risk for in terms of osteoporosis?
increased risk of fragility-related fractures
47
What does a high BMI increase risk for in terms of osteoporosis?
* site-specific increased risk of fractures + inflammation driven increases in bone resorption (TNFa and IL-6)
