Pathophys - Cartilage and Bone Flashcards
mesenchymal stem cell derivatives
- muscle cells
- adipocytes
- osteoblasts
- fibroblasts
- chondroblasts
what is unique about the derivation of osteoclasts?
they come from the monocyte cell line
fibroblasts secrete what?
components of connective tissue
define connective tissue
- tissue that connect, supports, binds, or separates other tissues or organs
- typically have relatively few cells embedded in an amorphous matrix
- often has collagen or other fibers like cartilagenous, fatty and elastic tissues
what is the most abundant protein in the body?
collagen
proteoglycans are precursor molecules for what?
collagen
function of proteoglycans
bind collagen fibrils, elastic fibers and reticular fibers together
where do elastic fibers predominate?
in blood vessels and ligaments
reticular fibers predominate where?
in lymphatic tissue and basement membranes
vitamin C is a cofactor for what process?
hydroxylation of proline and lysine
the deficiency of vitamin C causes what?
- scurvy
- poor wound healing
ehlers-danlos syndrome
- defective procollagen peptidase results in uncleaved procollagen or in lysyls hydroxylase
- so can’t hydroxylate lysine needed for staggered array of tropocollagen
- hyperelasticity, joint dislocations, vascular wall rupture
osteogenesis imperfecta
- point mutation in collagen gene resulting in reduction in type 1 collagen
- type 1 collagen is needed for normal ossification
- brittle bones and blue sclera
what are the two most important things to remember about osteogenesis imperfecta?
- type 1 collagen deficient
* blue sclera
goodpasture’s syndrome
- auto-antibodies to type IV collagen
- results in renal and or lung basement membrane thickening
marfans syndrome
- defect in fibrillin 1 gene, chromosome 15
- fibrillin surrounds elastic fiber core
- results in dilation of aorta, mitral prolapse, periosteal changes (elongation)
presentation of pt w/ marfan’s
- tall stature
- high arched palate
- myopia
- mitral valve prolapse
a mitral valve prolapse causes what heart sound?
systolic click
general overview of collagen production (in terms of cells)
- chondroblasts form chondrocytes
- chondrocytes make tropocollagen
- tropocollagen molecules overlap into collagen fibrils
- fibril bind together to form fibers
- fibers bind together to form tendons
structure of tropocollagen
3 alpha strand proteins arranged in alpha helix
functions of ECM
- cell adhesion
- cell-cell communication
- differentiation
ECM formation
- chondroblast form chondrocytes
- chondrocytes secrete ECM
- young collagen from ECM matures
ECM is primarily made of what two things?
- aggregan
- type II collagen
What is the significance of ECM being negatively charged?
it holds water
cartilage at the end of long bones is what?
articular cartilage
what is the the thickest cartilage of the human body and why
- the articular cartilage of the patella
- d/t the huge stress on the patella-femoral joint during resisted knee extension
characteristics of cartilage
- limited repair
- nutrition supplied by diffusion
- very slow turnover in ECM
what are the three types of cartilage
- hyaline
- elastic
- fibrocartilage
pathophys of osteoarthritis
- there are biomechanical and chemical processes involving the cartilage, synovium, bone and soft tissues surrounding the joint
- they can be sparked by a single traumatic event, repeated microtrauma or genetic, metabolic, or systemic factors affecting the integrity of cartilage
what is secreted by chondrocytes during osteoarthiritis progression?
-metalloproteinases (MMPs)
MMPs
- inclue collagenase, stromelysin and gelatinase
- degrade cartilage
what could make cartilage more susceptible to MMPs?
inappropriately low levels of tissue inhibitors of MMPs
what is a unique property of chondrocytes?
- chondrocytes secrete the things needed to build cartilage
- but also secrete the MMPs that break it down
during cartilage remodeling, what are the levels of matrix and protease/inhibitor ratio during a net increase?
- increased fibroblasts laying down matrix (matrix synthesis)
- decreased protease: inhibitor ratio (MMP)
during cartilage remodeling, what are the levels of matrix and protease/inhibitor ratio during a net decrease?
- decreased matrix synthesis
- increased protease: inhibitor ratio
what are the main findings in an XR of a joint w/ osteoarthirits?
- narrowing of joint space
- subchondral sclerosis
cell derivatives for bone formation
- mesenchymal stem cell –> osteoblasts
- bone marrow –> monocyte –> osteoclast
what type of bone growth grows on a cartilaginous template?
endochondrial
what are the two parts of endochondrial bone growth?
- osteoclast chase
- chondrocyte run
osteoclast chase
- osteoclasts (from monocytes) enlarge the bone marrow cavity
- creates an invading front of ossification
chondrocyte run
- calcification of the cartilage matrix surrounding hypertrophic chondrocytes
- proliferating chondrocytes away from the ossification front increase the length of the cartilage
Haversian system
- fundamental functional unit of much compact bone
- composed of an artery in the middle of an osteon which is filled with osteocytes
what signaling system is used by osteoblasts?
RANKL
RANKL signaling system
- macrophages are signaled on to make osteoclasts
- can be used to heal and remodel
intramembranous bone growth
-bone grows directly by connective tissue basement membrane developing into bone
intramembranous bone growth is important for what two things?
- fracture healing
- development of the skill
mechanism of intramembranous bone growth
- mesenchymal stem cells –> osteoblasts and osteocytes
- secrete type I collagen (osteoid)
- lay down mineralization
content of bone
- 50-70% mineral
- 20-40% organic matrix
- 5-10% water
- <3% lipids
minerals contained in bone
Ca, Pi, PPi, Mg, K, hydroxyapatitie, and others
increase in extracellular PPi has what effect on hydroxyappetite?
decrease
decrease in extracellualr PPi has what effect on hydroxyappetite?
increase (i.e increased mineralization)
hydroxyapatite function
storage unite for Ca and phosphorus
what hormones regulate the mineralization of bone?
- PTH
- Vit. D
describe bone remodeling (aka bone metabolism)
- lifelong process
- mature bone tissue is removed from skeleton (bone resporption)
- new bone tissue is formed (ossification)
- control fracture repair and micro damage
what is the main hormone in bone remodeling?
PTH
PTH is secreted by the?
parathyroid gland
PTH regulates what?
serum Ca
PTH is primarily secreted in response to what?
lowered serum Ca
function of PTH
- decrease in serum Ca leads to:
- PTH acting on osteoblasts
- this indirectly activates osteoclasts to tear down bone and release Ca
