ic10 msk pathophysiology Flashcards
different bone marrows and their function
red: hematopoeisis
yellow: fatty connection tissue used in times of starvation
skeleton function
storage of calcium and phosphate to regulate mineral balance in blood stream.
form support stability movement
muscle characteristics
connected to bones, arranged in opposing groups around joints = keep bones in place, plays a role in movement
muscles are innervated - CNS = contraction
what is a tendon
tough flexible band made of fibous connective tissue
connect muscle to bones.
what are DAMPS
damage-associated molecular patterns
e.g.
ATP, S100, HMGB1,
IL-1alpha (most common),
HSP70 (circulation)
histones, PRR…
released during various types of cell death/stressed cells
recognised by tissue macrophages = release inflammatory cytokines
High mobility group box 1 protein, Heat shock protein 70
brief overview of initial immune response to tissue injury
neutrophils recruited first (hours; by CXCL8) > monocytes/macrophages (1-3days; by CCL2) > T cells (1-2 weeks)….
what are the inflammatory cytokines and the following mechanism
IL1, IL6
IFN-Y,
TNF alpha
IL17
….
activates inflammatory macrophages (M(IFN-y)) = differentiate to tissue repair macrophages
why is tissue healing impaired/has scarring or fibrosis occurred during the immune response
inflammatory macrophage M(IFN-y) stimulate T cells (Th and CD8+) in positive. feedback loop
= inhibit tissue stem cells
M(IFN-y) may also differentiate to pro-fibrotic macrophage M(IL-4)-like to increase ECM protein deposition and subsequent fibrosis (scarring)
also release TGF-beta and PDGF to cause differentiation of pericytes to scar forming myofibroblasts
what is secreted for fibrosis
profibrotic MMP TIMPS
adaptive immune cytokines
IL2, IL6, IL12, IL23, TGF beta (differentiate CD4+ helper cells)
immunosuppressive/regulatory inflammatory cytokines
IL10
TGF beta
IL 7
GM-CSF
overview of tissue regeneration
M(IL10)-like activate regulatory T helper cells by secreting anti-inflammatory cytokines like IL10
which inturn secrete growth factors PDGF, VEGF, IGF-1…
OA description
caused by the overuse of joints (including physical or sports injury, weight bearing) = deterioration
OA pathophysiology
articular cartilage damage = chondrocyte activity to remove and repair damage (become hypertrophic) = aberrant chondrocytes = more breakdown
cartilage loss (due to MMP, vasoactive peptide release from subchondral bone = collagen breakdown) and apoptosis of chondrocytes
STIMULATE PATHOLOGIC CHANGE (release of inflammatory cytokines)
= form fibrillation in cartilage + cartilage shards
= subchondral bones rub against each other + sclerosis, microfracture, osteophyte formation
how do chondrocytes cause tissue degeneration in OA
chondrocytes release DAMPS that bind to PRR = release of cytokines eg IL1, IL6, TNF-alpha= hypertrophy = NFKB activation, upregulation of NO, PGE2, activation of complement/adaptive immune system (B, T cells) = progressive synovitis = effusion, synovial thickening