Patho: Exam 2: Bone Flashcards
Cortical bone
Cortical bone
Describe the Cortical bone?
hard outer layer- compact bone tissue- forms a cortx ( outside) of most bones
how poris is Cortical bone?
Porosity 5-30%
What percent of the total bone mass is made up by cortical bone?
80% of the total bone mass
Cortical bone also contains what type of canals?
Contains Haversian and osteons
Trabecular bone (cancellous or spongy bone)
Trabecular bone (cancellous or spongy bone)
What is the function of Trabecular bone ?
Allows room for blood vessels and marrow
What percent of bone mass does Trabecular bone account for?
20% of bone mass(10x surface area of compact bone)
how poris is Trabecular bone ?
Porosity 0f 30-90%
Changes in the rate of bone turnover are manifested principally in what bone?
The Trabecular bone or cancellous bone
All bones contain what type of bone?
cancellous & cortical elements but the proportions differ
Femur: the shaft is cortical bone and morrow is fat, the ends are thing cortx with course cancellous (Treabecular) benign prominent. Therefore you have bone turn over in the ends.
The skeletal system is vital during life, it has an essential role in what? (1-5)
1: Mineral homeostasis: this is where we can store and retain minerals such as Ca+.
2: Houses hematopoietic elements: this changes with age
3: Mechanical support for movement
4: Protects Viscera: Internal organs
5: Determines body size and shape
Epiphysis
Extends from subarticular bone plate to the base of the growth plate
Metaphysis
coarse cancellous bone: Important in hematogenous infections tumors and skeletal malfomations.
Diaphysis
Body or shaft of the bone ( zone between 2 metaphysis)
Despite its stony hard structure, the bone is a dynamic tissue that is continuosly what?
Resorbed
Renewed
Remodeled
Resorption, what does this mean in regards to drug therapy, if a drug increases resorption?
Drugs that are antiresorptive?
Increase the osteoclast activity so you are breaking down bone
Block the break down of bone, stop osteoclast from breaking down bone.
The process of reprobation, renewal, and remolding is carried out by several different types of one cells that are regulated by what?
Transcription factors
Cytokines
Growth factors
There are Four types of cells:
Osteoprogenitor cells
Osteoblast
Osteocyte
Osteoclast
Components of bone
- Cells
- Mineralized phase: a lot of calcium, phosphate ect.
- Organic matter- Hydroxyapatite, Other proteins, Osteocalcin, Osteopontin.
How are Osteoblast stimulated?
o With the stimulation of RunX2 and CBFA1 transcription factors Osteopogentor cells undergo final differentiation and become osteoblast
o WNT ( from the Osteoprogentor cells) binds to the LRP 5/6 LDL receptor related portien 6 and 5receptors and allows for Beta Catenin to be the anchor into the laminar bone area and and prdoduce hydroxiappitiate to make matrix
• With out WNT, beta catenin will become proliferated and destroyed.
o BMP- Bone Morphogenic protein- stimulates the osteoblast even more, proliferates like crazy.
• In 2002 the used BMP was approved for use in spinal fusions, they would use a collagen sponge (called Infuze) and infuse it with BMP, and when it gets inserted it stimulates bone growth.
• Now in 2012 they found that BMP actually can lead to cord stenosis and cancer.
The Osteopogentor cells can also produce surface osteoblast that can get triggered to produce cytokines or become to become activated. The cytokines that are produced actually activate osteoclast. This allows for continuous building and breaking.
what is the function of osteoblast?
Osteoblast are located on the surface of the bones. These cells synthesize, transport and arrange the many proteins of the matrix and initiate the process of mineralization.
Osteoblast have receptors that bind regulatory hormones such as:
regulatory hormones ( parathyroid hormone, Vit D, Leptin and estrogen)
What do Cytoblast produce to make the matrix
Hydroxyapatite
Osteoblast produce Hydroxyapatite, what is it?
A combination of calcium, phosphate and hydroxide ( OH-)
Osteoblast also produce Type I collagen what is that?
Can determine the strength of the bone, it will be wolven fist and then it will turn into lamellar bone
Osteoblast also produce Osteocalcin, what is that?
maker for osteoblast activity, used clinically in patients who have osteoperosis, if you give them a medication that is suppose to increase osteoblast activity. It will take 2 years to see a change on a bone density scan, so you can order an osteoalcin lab to see if the medication is working.
PTH dematerializes things, why is the receptor on the osteoblast
to produce the cytokines to stimulated osetoclast to break down bone
What is the effect of Leptin receptors on the osteoclast?
there is increased lepin causes increased stimulation of osteopbalst
What effect does increased tension or weight on the bone have on bone growth?
in obese people, the more weight you put in the bones is sensed by osteocytes which stimulate the osteoblast to build more ( this is why weight lifting is good for osteoperosis.)
What do osteoblast have to do with the stimulation of Osteoclast?
express factors regulating differentiation & function of osteoclasts- trigger osteoclast to break down bone
osteoclast
transform into osteocytes. Osteocytes communicate with each other and with cells on the bone surface via intricate network of cytoplamic processes that transverse tunnels in the matrix know as Canaliculi . Osteocytes help to control calcium and phosphate levels in the microenvironment and detect mechanical forces and translate them into biologic activity, this process is called Mechanotranstction.
What are osteocytes surround by?
Osteoblasts surrounded by deposited organic matrix
What is the function of osteocytes ?
Responsible for mechanotransduction: detect mechanical forces and translating them into biologic activity
Osteoclasts
Osteoclasts
What are osteoclast derived form?
Derived from monocyte/macrophage lineage
Mature multinucleated osteoclasts contain how many nuclei?
6-12 nuclei- again precursor form macrophages
Regulation of osteoclast differentiation and maturation is through what?
M-CSF, IL-1, TNF (ODP) ( monocyte colony stimulating factor)
Where does MCSF come from?
It is a cytokine produced by the osteoblast.
How are osteoclast produced?
o So the Osteoblast will produce the M-CSF which will bind to a M-CSF receptor found on an osteoclast precursor (which is actually a immature monocyte)
o In addition you also need a RANK ligand (which is expressed on the surface of the osteoblast cell) has to bind to the RANK receptor on the osteoclast cell
o Which will cause differentiation which will make the osteoclast activated.
How is this system regulated so there is not continuous degeneration.
Osteoprotegrin is produced by the osteoblast cells so the cells are not consiantly activated, it is a molecule that binds to the RANK lignad on the osteoblast cell preventing the binding to the osteoclast cell.
This is a great place for medications, like oseoperosis where the osteoclast are overactive, you can stop them by giving a durg similar to what?
Osteoprotegrin ( which will block the RANK ligand)
Where are Osteoclasts found?
In small depressions celled Howship Lacunae.
what effect does HRT (estrogen) have to inhibit bone demineralization?
actually increased production of osteoprotefrin to prevent RANK binding, also decreased the production of RANK ligand in general.
What affect does PTH have on bone demineralization?
Osteobast become activated which will build bone and also priduce the RANK ligand and decreased the amount of osteoprotegrin so you have break down of bone predominant and Ca+ goes back into the circulation.
Estrogen- pulls Ca+ back into the bone
PTH: puts Ca+ back into ciculation.
Bone Resorption Mechanism
Ruffled border of the osteoclast overlying the resorption pit ( Howshop lacunae) will generate an acidic environment (PH 4.0-5.0) which will denature the proteins and break down bone. Acid digests organic components
What are the three essentials for osteoclastogensis?
TNF related receptor RANK
Tumor necrosis factor- when RANK is active it causes Necrosis
RANK ligand
M-CSF
What happends biochemically when RANK bings to the RANK receptor?
It activates NF Kappabeta which signals increasing osteoclastogeneiss
What blocks the macrophage from becoming an osteoclast
Osteoprotegrin blocks osteoclastogenesis
What is the Functional unit of the bone called:
basic multicellualr unit
what is the basic multicellular unit made up of
Composed of osteocytes, osteoblasts, and osteoclasts- Control bone formation and resorption
What is dominant early in life, what is dominant later in line?
Early in live: bone formation is dominate ( osteoblast dominate)
Later in life: Remodeling occurs
What percent of you skeleton remodels in one year?
10% of skeleton remodeled/year
when do you have peak bone mass?
Peak bone mass achieved in early adulthood
Define Modeling:
bone resorption and formation occur on separate surfaces- break down some place and building some other place
define Remodeling:
replacement of old bone with new bone mass.
What are the two types of bone?
Woven bone: haphazard organization of collagen fibers
Lamellar bone: regular-parallels alignment of collagen into sheets
When will you see wolven bone?
Seen in fetal skeletal and growth place, seen a few days after fractures.
What type of bone is always abnormal in adults?
Wolven bones
