Extra Martin Skeletel Path Flashcards
(30 cards)
Two histologic forms of bone and 3 features of each?
Woven: produced quick, less structural integrity, used in fetal development and fracture repair
Lamellar: strong, parallel collagen and slow production
Explain what an osteoclast is and what do they secrete to break down bone?
What is an osteocyte and what is their main function?
Multi nucleated macrophages
Secrete MMPs to break down bone
Inactivated osteoblast that controls calcium and phosphate levels
Talk about what she wanted us to know about bone peak bone mass?
Peak bone mass occurs about 30 and then in the 4h decade, resorption is now greater than formation for the rest of our life and we begin to lose skeletal mass.
Talk about the dynamic between RANK and RANKL in breaking down bone?
RANK is a receptor that activates the NF Kappa beta pathway on osteoclasts.
RANKL is the ligand found on the osteoblast that then activates RANK, turning on NFKB pathway and breaking down bone.
What is the role of OPG?
This is a decoy receptor on osteoblasts that can bind RANKL and prevent it from interacting with RANK and activated osteoclasts. So it is pro build.
What is the role of the WNT/B cat pathway with regulation of bone breakdown and building?
What inhibits the WNT pathway?
Activating the WNT/B cat pathway leads to production of OPG in the osteoblast, which eventually leads to pro build.
Sclerostin
Balance between net bone formation and break down is modulated by what two main things?
RANK and WNT
3 things she mentioned encourage build?
3 things she mentioned encourage breakdown?
Estrogen, testosterone and Vit D
PTH, IL1 and gluco
MCSF stimulate generation of what?
What is the signaling mechanism osteoclasts and osteoblasts use between one another?
Osteoclasts
paracrine
What type of mutations are we dealing with in developments disorders of bone?
Inherited mutations
What is the mutated gene for the following bone disorders? Brachydactyly D and E? Clefdocranial dysplasia? Achondroplasia? Thanatopphoric dysplasia? Achondrogensis Type 2? Osteopetrosis?
HoxD13 RUNX2 FGFR3 FGFR3 COL2A1 CA2
Clinical features of the following bone disorders to know? Brachydactyly D and E? Clefdocranial Dysplasia? Thanatophoric Dysplasia? Achondrogenesis Type 2?
Short, fat terminal phalanges of first digit
Abnormal clavicles and Wormian bodies (extra bones within cranial sutures)
Severe limb shortening and bowing
Short trunk
Thanatophoric Dysplasia is the most common cause of what?
What is the biochemical cause?
2 clinical features?
What happens to these patients at birth?
This is like achondroplasia but some differences.
Most common lethal form of dwarfism.
Different gain of function mutation in FGFR3
Small chest cavity
Die at birth
Mutations in LPR5 receptor can lead to two bone disorders?
Mutations in RANKL would lead to what problem?
Osteoporosis or osteopetrosis
Problems with osteoclast
What is the difference between osteogenesis type 1 and type 2?
Type 1: normal life span with childhood fractures that decrease with time. Collagen is normal, just less of it. Autosomal dominant
Type 2: usually fatal in utero with multiple intrauterine fractures and respiratory failure. Collagen is not normal. Autosomal recessive
Put the 4 types of OI in order of severity?
Which ones have blue sclera and which one has white sclera?
1,4,3, and 2.
123 have blue and 4 has white.
What are the two forms of osteopetrosis, what are their inheritance patterns, and what patient population do they affect most commonly?
Severe infantile type, AR, children of Mediterranean and Arab especially.
Mild type more in teens and adults, AD.
What is a sign on x ray of bones in a person with osteopetrosis?
The ends of the bones look like an Erlenmeye flask
What is going on with MPS and how does this affect bone?
Lysosomal storage diseases caused by a deficiency in enzymes, mostly acid hydrolase enzymes, to break down mucopolysacharides. These guys build in cells and tissues and cause various health problems. In bone and cartilage, they can cause apoptosis and destroy it.
How do we define osteopenia and osteoporosis as far as bone density levels?
What event signifies osteoporosis?
1-2.5 SD below the mean
At least 2.5 SD below the mean
Atraumatic or vertebral compression fracture signifies it.
5 major factors in the development of osteoperosis?
Age, exercise, genetic factors, calcium state, hormonal influences
2 ways low estrogen accelerates bone loss?
Stimulates osteoclast activity via RANKL
Stimulates inflammatory cytokines IL6, TNFA, and IL1
Characteristic morph change of osteoporotic vertebral bodies?
Decreases horizontal trabeculae and increased vertical trabeculae
Explain the progression of the trabeculae and cortex in osteoporosis?
Tracbulae thins first and quicker. The cortex will thin too but it takes longer.
