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PR3154 > IC10 - MSK Pathophysiology > Flashcards

IC10 - MSK Pathophysiology Flashcards

1
Q

What are the functions of skeleton?

A
  1. Stores calcium and phosphorus (regulates mineral balance between blood and bone)
  2. Form, support, stability, movement
  3. Bone, ligament, muscle, tendon, cartilage, other connective tissue
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2
Q

What is the function of the red bone marrow?

A

Hematopoeisis

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3
Q

What is the purpose of the yellow bone marrow?

A

Store fats that can be used during starvation

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4
Q

What are the functions of the muscles?

A
  1. Keep bones in place
  2. Movement
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5
Q

Skletal muscles are ____ to the bones.

A

attached

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6
Q

Skeletal muscles are arranged in ______ groups around joints.

A

opposing

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7
Q

Muscles are _____.

A

innervated

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8
Q

What type of tissues are the tendons made of?

A

Fibrous connective tissue

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9
Q

Which two parts do the tendons connect?

A

Muscles and bones

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10
Q

What connects the ends of bones to form a joint?

A

Ligaments

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11
Q

What is the purpose of ligament?

A

Limit joint dislocation and restrict improper hyperextension and hyperflexion.

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12
Q

What are Bursae for?

A

Provide cushions between bones and tendons and/or muscles around joints

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13
Q

What is the cause for inflammation?

A

DAMPS (damage associated molecular patterns)

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14
Q

What happens during inflammation when neutrophils are recruited within hours?

A
  1. Recruitment of neutrophils via CXCL8
  2. Secretion of inflammatory cytokines e.g. IL-1
  3. Cytokines activate tissue stem cell
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15
Q

What is the purpose of DAMPs during initial immune response?

A
  1. Activate tissue macrophages
  2. Secrete inflammatory cytokines
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16
Q

What happens on the 1st to 3rd day after muscle injury?

A
  1. Monocytes are recruited via CCL2
  2. Combines with IFN-y TNF-a, IL-1 to give inflammatory macrophages
  3. Inflammatory macrophages combines with IL-4, 10, 13 to become tissue repair macrophages
  4. Tissue repair macrophages release growth factors, PDGF, VEGF and IGF-1, leading to angionesis, cell proliferation and differentiation.
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17
Q

Explain how impaired healing, scarring and fibrosis can occur during healing phase.

A
  1. Inflammatory macrophages become pro-fibrotic macrophages when coupled with IL-4
  2. Production of profibrotic MMPs, TIMPs which are deposited in extracellular matrix
  3. Scar forming myofibroblast is formed from pro-fbrotic macrophages via TGF-B and PDGF
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18
Q

What occurs during regeneration of injured muscles?

A
  1. In presence of IL-10 from TH2 and regulatory T cells, anti-inflammatory anti-fibrotic macrophage is formed.
  2. This inhibits scarring.
  3. y-deltaT cell release IGF-1 to give stem/progenitor cell
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19
Q

What is arthritis?

A

A condition with swelling and tenderness of one or more joints, accompanied with inflammation, joint pain, stiffness and worsen with age

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20
Q

List 5 causes of arthritis.

A
  1. Wear and tear
  2. Autoimmune injuries
  3. Degeneration
  4. Repeated overuse
  5. Obesity
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21
Q

What is osteoarthritis?

A

A condition which occurs due to overuse of joints which deteriorates more with aging

22
Q

List three risk factors of osteoarthritis.

A
  1. Physical or sports injuries
  2. Heavy weight
23
Q

Describe the progression of orteoarthritis.

A
  1. Release of PRRs and DAMPs (e.g. alarmins) and pro inflammatory cytokines aand complements
  2. Result in synovitis and chondrocytes activation
  3. End result is cartilage remodeling and repair as well as thinckened subchondral bone
24
Q

What are the non medical treatments for OA?

A
  1. PT/OT/Transcutaneous electrical nerves stimulation
  2. Synovectomy
  3. Tendon repair
  4. Religning bones
  5. Joint fusion
  6. Total Joint replacement
25
Q

How is rheumatoid arthritis diagnosised?

A
  1. High CRP (inflammation)
  2. Rheumatoid factor
  3. Anticyclic citrullinated peptide (anti-CCP) antibodies
  4. Inflammation in joints
26
Q

Describe the pathophysiology in rheumatoid arthritis using TNF.

A
  1. TNF activates more macrophages which in turn increase IL-1
  2. TNF and IL1 release GM-CSF, IL6, 8 and MMP respectively
  3. Leads to cartilage and bone destruction
27
Q

What are the medications used for RA?

A
  1. NSAIDS
  2. Glucocorticoids
  3. DMARDS (disease modifying antirheumatic drugs) and biologics
28
Q

Explain how gout occurs through activation of signal 1.

A

Signal 1: Activated to transcript and transcribe inflammasome compents in nucleus of cells

29
Q

Explain how gout occurs through activation of signal 2.

A

Signal 2:
1. Activation of inflammasone pathway through monosodium urate crystals
2. Build up of inflammasome.
3. Pro-IL1B activates to IL-1B and is released through pyroptoic pore
4. Gasdermin D becomes N-terminal cleavage product and causes pyrotosis

30
Q

What happens to potassium in the cell during IL1 production in gout?

A

Leaves the cells

31
Q

Describe what will happen after IL-1B leaves the cells in gout

A
  1. React with IL-1R responsive cells (endothelial cells and synoviocytes)
  2. Undergoes phosphorylation to p65 and p50 which leads to release of cytokines and chemokines from nucleus
  3. This increases the inflammatory cascades and neutrophil influx
32
Q

List two IL1 inhibitors used for gout.

A
  1. Canakinumab (IL1b inhibitor)
  2. Anakinra (IL1R inhibitor)
33
Q

What is one compound that can be used to block K+ efflux in gout?

A

beta-hydroxybutyrate

34
Q

What is the molecule that can inhibit mitochondrial ROS?

A

Epigallocatechin gallate

35
Q

Name 2 NLRP3 inflammasone inhibitors.

A
  1. Colchicine
  2. MCC950
36
Q

List 2 IL-1B processing inhibitors.

A
  1. VX-765 (Inhibits caspaase-1)
  2. AAT-FC (Inhibits serine proteases)
37
Q

What is osteoporosis?

A

A condition where bone loss is faster than bone generation, leading to weak and brittle bones and stooped posture, back pain.

38
Q

Where are osteoblasts derived from?

A

Mesenchymal stem cells

39
Q

What is the function of osteoblasts?

A

Bone matrix synthesis and its subsequent mineralization

40
Q

What are the function of osteocytes?

A
  1. Respond to changes in physical forces upon bone
  2. Transduce messages to cells on the bone surface, directing them to initiate formation or resorption responses.
41
Q

Osteoclasts are _______ cells from hematopoietic lineage.

A

large multinucleated

42
Q

What are the functions of osteoclasts?

A

Resorption of mineralized tissue

43
Q

What are the four processes of bone remodelling and renewal?

A
  1. Activation and resoprtion
  2. Reversal
  3. Formation
  4. Quiescence
44
Q

What happens during activation and resorption?

A
  1. Sitmulation of preosteoclasts
  2. Differentiate to matue osteoclasts under influence of cytokines and growth factors
  3. Digestion of mineral matrix (old bones)
45
Q

What happens during reversal?

A

Resoprtion ends

46
Q

What happpens during formation?

A

Osteoblasts synthesise new bone matrix

47
Q

What happens during quiescence?

A

Osteoblasts become resting bone lining cells on newly formed bone surface

48
Q

What is one class of drugs that can cause secondary osteoporosis?

A

Glucocorticoids

49
Q

What do glucocorticoids do to the major bone cells?

A
  1. Induces the decrease in osteoblast differentitation
  2. Increase death of both osteoblasts and osteocytes
50
Q

List 2 ways in which osteoporosis can be prevented.

A
  1. Nutrition - Calcium and vitamin D
  2. Exercise guidelines

PR3154 (16 decks)

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