ic10 msk pathophysiology Flashcards

1
Q

different bone marrows and their function

A

red: hematopoeisis
yellow: fatty connection tissue used in times of starvation

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
2
Q

skeleton function

A

storage of calcium and phosphate to regulate mineral balance in blood stream.

form support stability movement

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
3
Q

muscle characteristics

A

connected to bones, arranged in opposing groups around joints = keep bones in place, plays a role in movement

muscles are innervated - CNS = contraction

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
4
Q

what is a tendon

A

tough flexible band made of fibous connective tissue
connect muscle to bones.

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
5
Q

what are DAMPS

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
6
Q

brief overview of initial immune response to tissue injury

A

neutrophils recruited first (hours; by CXCL8) > monocytes/macrophages (1-3days; by CCL2) > T cells (1-2 weeks)….

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
7
Q

what are the inflammatory cytokines and the following mechanism

A

IL1, IL6
IFN-Y,
TNF alpha
IL17
….
activates inflammatory macrophages (M(IFN-y)) = differentiate to tissue repair macrophages

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
8
Q

why is tissue healing impaired/has scarring or fibrosis occurred during the immune response

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
9
Q

what is secreted for fibrosis

A

profibrotic MMP TIMPS

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
10
Q

adaptive immune cytokines

A

IL2, IL6, IL12, IL23, TGF beta (differentiate CD4+ helper cells)

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
11
Q

immunosuppressive/regulatory inflammatory cytokines

A

IL10
TGF beta
IL 7
GM-CSF

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
12
Q

overview of tissue regeneration

A

M(IL10)-like activate regulatory T helper cells by secreting anti-inflammatory cytokines like IL10
which inturn secrete growth factors PDGF, VEGF, IGF-1…

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
13
Q

OA description

A

caused by the overuse of joints (including physical or sports injury, weight bearing) = deterioration

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
14
Q

OA pathophysiology

A

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 well did you know this?
1
Not at all
2
3
4
5
Perfectly
15
Q

how do chondrocytes cause tissue degeneration in OA

A

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

How well did you know this?
1
Not at all
2
3
4
5
Perfectly
16
Q

what causes pain in RA

A

pain caused by distension of the synovial capsule

activation of nociceptive nerve endings

17
Q

non-medical tx for OA

A

physical, occupational therapy
transcutaneous electrical nerve stimulation (TENS)
synovectomy
tendon repair
realigning bones
joint fusion
total joint replacement

18
Q

pathophysiology of rA

A

genetic predisposition + immunologic trigger
= t cell mediated immune response
= inflammation
= recruitment of inflammatory cells
= release of protease, prostaglandins,
= destruction of articular cartilage, underlying bone

inflmm also associated w angiogenesis in synovium = synovial cell proliferation/activation = pannus activation

ALSO, release of inflammatory cytokines = activation of osteoclasts = bone breakdown

19
Q

gout causes

A

1) overproduction of uric acid
= primary: inborn errors of metabolism
= secondary: conditions increasing cell turnover and purine generation

2) underexcretion of uric acid

20
Q

gout patho

A

glutamine + PRPP = NUCLEIC ACID in body tissues
breaks down to guanine, adenine, then hypoxanthine
(xanthine oxidase)
= xanthine = uric acid

21
Q

role of PRPP

A

phosphorobosyl pyrophosphate
salvage pathway

reuse guanine and hypoxanthine to form nucleic acids

22
Q

how do MSU crystals cause pain and inflammation

A

MSU crystals = formation and activation of inflammasome complexes
= Caspase-1 activation
= IL-1 beta (through pyrotopic pores)
= DAMPS immune response activation (on endothelial cells, synoviocytes)
= increase cytokine, chemokines
= activate inflammatory cascade, neutorphil influx

*inflammasome also causes formation of ROS via potassium efflux

23
Q

how are inflammasomes produced

A

stimulation of TLR (receptors) causes production of NF-KB transcription factors = formation of inflammasome components.

24
Q

what is anakinra

A

recombinant IL1- RA
4-6 hours t1/2
SC administration

canakinumab is human anti-IL-1beta monoclonal antibody

25
Q

what are osteoblasts

A

derived from mesenchymal stem cells

for bone matrix synthesis and mineralisation

26
Q

what are osteocytes

A

osteoblasts that become incorporate into the newly formed osteoid = calcified bone

1) respond to changes in physical forces upon bone
2) transduce message to cells on the bone surface = initiate formation/resorption

27
Q

what are osteoclasts

A

large multinucleated cells attached to bone surface/
derived from hematopoietic lineage

resorption of mineralised tissue

28
Q

what is the process of bone remodelling and renewal?

A

1) activation and resorption
- preosteoclast stimulated = differentiate (cytokines, growth factors) = mature osteoclast = resorption

2) reversal
- end of resorption

3) formation
- osteoblast synthesis new bone matrix

4) quiescence
- osteoblast become resting bone lining cells

29
Q

how do GC cause 2º osteoporosis

A

1) decrease differentiation of osteoblast.
2) increase death of osteoblast and osteocytes.