unit 5 pathophys Flashcards
endochondral ossifcation
- Forms bones inferior to the skull excluding the clavicle
- After week 8 in embryonic development
1. Occurs at the primary ossification centre
2. Perichondrium becomes vascularised
3. Mesenchymal stem cells become vascularised and nutrients supplied to them
4. Mesenchymal stem cells differentiate into osteoblasts which secrete osteoid and line up on the diaphysis and deposit osteoid
5. Forms the bone collar
6. Formation of the bone collar causes chondrocytes to enlarge and cartilage matrix to calcify in central cavity
7. Calcified matrix becomes impermeable to nutrients and a vascular and die
8. Central clearing occurs
9. Healthy chondrocytes continue to elongate the epiphyseal ends
10. Periostea’s bud forms and supplies arteries, veins, nerves, lymphatics and osteoclastic cells
11. Osteoclasts will erode the central zone of calcified matrix and form empty space
12. Osteoblasts will deposit new spongy bone
13. Bone continues to elongate dismally
14. Primary ossification centre enlarges
15. Osteoclasts will erode the newly deposited trabeculae bone
16. Forms medullary cavity
17. Osteoblasts will replace with cortical Bone on diaphyseal surfaces
18. Secondary ossification centre will form but won’t develop until birth
19. Cartilage at epiphseal ends will become hyaline articulating cartilage
intramembranous ossification
- Forms bones of the skull and the clavicle
- Before week 8 in utero
1. Mesenchymal stem cells form the embryonic mesenchyme will cluster and proliferate
2. Differentiate into osteoblasts
3. Osteoblasts begin secreting osteoid and then cluster to form primary ossification centre
4. Peripherally mesenchymal stem cells continue to differentiate
5. Osteoblasts secrete osteoid towards the ossification centre
6. Osteoblasts become trapped
7. These differentiate into osteocytes
8. Osteoid calcifies after several days and forms hardened bone matrix
9. Osteoblasts begin to secrete osteoid around the embryonic vessels and forms trabeculae bone
10. Mesenchyme differentiates into the perichondrium
11. Compact bone replaces woven bone at edge
12. Internal spongy bone remains the same
post natal bone development
- Resting zone: chondrocytes aren’t dividing, maturing or proliferating. Hyaline articular cartilage
- Proliferating zone: rapid mitosis, stacking of chondrocytes, pushes diaphysis away from epiphysis
- Hypertrophy: maturation of older chondrocytes, cartilaginous matrix hardens
- Calcification: calcified matrix into the diaphysis
- Ossification zone: osteoclasts erode cartilage and the osteoblasts deposit osteoid
interstitial cartilage growth
Interstitial cartilage growth:
- Mesenchymal stem cells congregate and form chondrification centres
- Kartogenin influences cells in the chondrification centres to differentiate into chondroblasts
- Secrete cartilage matrix and entrap in the lacunae
- When surrounded by the matrix they become chondrocytes
- Chondrocytes then divide by mitosis
appositional cartialge growth
Appositional cartilage growth:
- Outer layer: spindle shaped cells, cluster in the perichondrium
- Inner chondrogenic layer: cells differentiate into chondroblasts and secrete type 2 collagen
action potential
- Action potential
- Axon terminal of somatic motor neuron, neuromuscular junction
- Action potential arrives at the axon terminal and causes the exocytosis of neurotransmitter acetylcholine vesicles
- Acetylcholine in the synaptic cleft will bind to the receptors on the sarcolemma
- High concentration of Na+ in the ECF so sodium enters through channels
- Causes influx of Na+ = depolarisation
- Action potential propagates down the sarcolemma
- Na+ opens the voltage gated calcium channels
- Generates action potential which propagates down the T tubule
- Calcium moves from the terminal cistern to the T tubule
sliding filament mechanism
- Calcium binds to troponin C on the actin filament
- Causes tropomyosin to move and expose the myosin binding site
- ATP binds to myosin head
- Breaks down into ADP, Phosphate and releases energy
- Causes myosin to move into position
- Myosin head binds to actin head
- ADP and phosphate release
- Causes a power shift, contraction
- Myosin pulls actin filament towards the M line
- Only releases actin when new molecule of ATP binds
terminating adaptive immune response
- Terminate the adaptive immune response: regulatory cell function, remove effector cells, long term maintenance of memory cells
- Turn off T cells as without co-stimulation they wll change phenotype or die
- When responding to antigen they’ll switch to TH2 antiinflammatory, anergy, exhaustion or activation induced cell death
- Same time will generate nTreg and iTreg which both have CD4, CD25, FoxP3 and nTreg have CD62L
- iTreg: from Naïve t cells, reduce activation signals from DC, sequester Il-12 and release Il-10 and TGF-beta
resolving inflammation
remove effectors, return tissue resident cells to inactive state, resolve pro-inflammatory mediators
- M2 macrophages
- Apoptotic neutrophils: secrete signals to attract macrophages, macrophages bind to phosphatidylserine on membrane during apoptosis, efferocytosis of neurtrophil, phenotype change of macrophage to produce anti-inflammatory, TGFbeta nduced T cells become T reg
- Il-10 and TGF beta
- Specific: lipids (lipoxins, increase phagocyte exit, stop neutrophil and eosinophil infiltration), protein/peptide (reduce or stop mediators, annexin A1), gaseous (anti-inflammatory, carbon monoxide), neuromodulators (block pain signals to brain)
wound healign and repair
replace damaged cells, replace tissue matrix
m1 macrophages
pro-infammatory, activated by PAMPS and DAMPS, NO for bacterial killing, secrete pro-inflam
m2 macrophages
anti-inflammatory, exposure to Th2 cytokines IL-13 and 4, angiogenesis, secrete IL-10 , MMP’s and VEGF
apoptotic macrophages
efferocytosis, secrewte TGF-beta, VEGF, IL-10, angiogenesis
TGf-beta
pleotropic cytokine, changes its function depending on its surroundings
