W7 - Exercise & Inflammation Flashcards

1
Q

What are the functions of the inflammatory response?

A
  • Protect against injury and infection
  • Initiated when there is physical damage (external objects, unaccustomed exercise)
  • Infections (viruses, bacteria, fungal, parasitic)
  • Exposure to toxins, pollutants or industrial chemicals, radiation, high levels of FFA
  • Stimulate repair of damaged tissues
  • Cytokines(signalling molecules, like the hormones of the immune system) and other mediators released from immune cells and damaged
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2
Q

What are the features of acute inflammation?

A
  • immune cells destroy affected cells
  • inflammatory proteins stimulate tissue repair
  • rapid, short-lived response (mins, days. hours)
    Without acute inflammation: would end up with sepsis
    • Acute = short lasting
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3
Q

What are the features of chronic inflammation?

A
  • Immune cells keep trying to repair
  • low level, continuous release of inflammatory proteins
  • common causes: unhealthy lifestyle, autoimmune disease
  • long-lasting (months, years)
    Chronic - is stimulated when the stimulus remains in the blood e.g.: high levels of alcohol
    • Immune system turns on its own tissues
      Low level of pro-inflammatory mediators into the blood, lasts months & years
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4
Q

Provide some examples of acute and chronic inflammatory illnesses

A

Acute:
* Common cold
* A splinter
* Muscle damage - does not lead to any long term health issues
* Radiation exposure
Chronic:
* Obesity
* Autoimmune disease
* Long-term smoking

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5
Q

What are the 5 cardinal signs of acute inflammation?

A

Heat –> Redness –> Swelling –> Pain –> Loss of Function

Heat happens particularly in the extremities
Redness - from scratching
- Start of 20th century(vechal) - loss of function

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6
Q

Describe each of the cardinal signs:

A
  • Heat & Redness - Increased blood flow due to vascular dilatation gives redness and heat - first 2 to appear
  • Swelling - Increased vascular permeability allows fluid and immune cells to move into the damaged area, causing swelling - endothelial cells retract, the cells shrink and this makes the gaps bigger
  • Pain - Certain chemical mediators stimulate sensory nerve endings giving pain
  • Nerves are also stimulated via stretch receptors due to swelling - can also cause pain
    • Pain and swelling result in loss of function
    • Protects, to stop further damage being caused
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7
Q

What is the difference between monocytes and macrophages?

A
  • Monocytes will respond the same way no matter the infection
    Monocytes - in the blood
  • Macrophages - in the interstitial fluid and out of the blood(mature tissue version
    Of monocytes)
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8
Q

What are granulocytes?

A

Granulocytes - cytoplasm had granules in it, granules are cytotoxic(killing) enzymes
* Both these cell types are phagocytic (wrap themselves around it to engulf it)

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9
Q

What happens in the acute inflammatory response?

A

1) Initiation of acute inflammatory response
2) Vascular dilation and increased vascular permeability
3) Margination
4) Neutrophils arrive rapidly
5) phagocytosis of damaged tissue
6) Termination of acute inflammatory response

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10
Q

Describe the first step of: initiation of acute inflammatory response

A

1) Injury/presence of pathogen
2) LPS & complement proteins
3) recognised by the resident phagocytic immune cells (macrophages & neutrophils)
4) These secrete soluble mediators
e.g.: cytokines, prostaglandins, nitric oxide

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11
Q

Describe step 2: vascular dilation and increased vascular permeability

What is the impact of vascular dilation & increased vascular permeability?

A

1) activated neutrophils and macrophages
2) These release IL-6 and TNF-a cytokines
3) These cytokines along with Csa activate mast cells
4) the mast cells release: histamine, bradykinin, leukotrienes, PAF, prostaglandins, cytokines
5) bradykinin along with leukotrienes & PAF increase vascular permeability
6) Activated neutrophils and macrophages release prostaglandins, this along with nitric oxide causes vascular dilation

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12
Q

Explain step 3: margination - the process of leukocytes migrating from the blood vessel to tissue

A

1) Rolling - the neutrophils with adhesion molecules on its surface rolls slowly
2) Tight Binding - These adhesion molecules then stick to the adhesion molecules on the surface of the blood vessel
3) Diapedesis - neutrophils move through the vessel wall via diapedesis into the interstitial space

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13
Q

What is the impact of increased vascular permeability and vascular dilation

A

1) blood flow increases to the area
2) leakage of fluid into the interstitial space(oedema/swelling)
3) Blood gets thicker - more viscous
4) slow down blood flow
5) clotting leukocyte- margination

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14
Q

What is margination helped by?
explain it

A

Chemotaxis
* chemically induced movement
* directed migration of cells in response to concentration gradients of secreted cytokines known as ‘chemokines’
* e.g. interleukin‐8 (IL‐8), (potent neutrophil chemokine released by macrophages and mast cells
- Like magnets to move neutrophils into tissues from the blood

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15
Q

Describe step 4: neutrophils arrive rapidly

A

Main cell recruited in acute inflammation
are neutrophils
- swelling in the local area

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16
Q

Explain step 5: time to remove the damaged tissue, phagocytosis

A

Once engulfed becomes a phagosome
- Lysosome fuses with phagosome
- combining killing enzymes with target(phagolysosome)
- Neutrophils have extracellular material that create nets for the debris that prevents it from infecting more cells

17
Q

Explain step 6: the resolution, termination of the acute inflammatory response

A
  • neutrophils self-destruct
  • switch from releasing pro-inflammatory mediators to pro-resolving mediators (e.g.: resolvers)
  • these stop further neutrophil recruitment and signal to apoptotic neutrophils and macrophages
18
Q

How do inflammatory cytokines effect the liver?

A

insulin resistance, sustained acute phase, protein release

19
Q

How do inflammatory cytokines effect adipose tissue?

A

adipokine production, immune cell infiltration
- In adipose tissue - stimulates - leptin(inflammatory)

20
Q

How do inflammatory cytokines effect endothelial cells?

A

endothelial dysfunction, atherosclerosis

21
Q

How do inflammatory cytokines effect skeletal muscle?

A

sarcopenia, insulin resistance

22
Q

How do inflammatory cytokines effect bone?

A

bone remodelling, osteoporosis

23
Q

how does weight loss impact inflammation?

A

Q1 - least active
Q4 - most active, these had the lowest biomarkers
If adipose tissue is large reservoir, losing the source of inflammatory cells (cytokines) been lost through weight loss

  • Some activity is better than no activity
24
Q

What is the result of physical inactivity and positive energy balance?

What cell increases cause this?

A

subcutaneous and visceral fat accumulation
‐ leading to chronic
inflammation and risk of
cardiometabolic disease, type 2 diabetes
- reduced longevity
- reduced functional capacity

  • Pro-inflammatory cytokines
  • Triglycerides
  • LDL
  • free fatty acids
  • TLR expression