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Y2 Pathology > Inflammation and healing > Flashcards

Inflammation and healing Flashcards

1
Q

Define inflammation

A

A protective response to healing
- a complex response to injurious agents such as microbes and damaged cells that consists of vascular responses, migration, activation of leukocytes and systemic reactions

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2
Q

Give examples of when inflammation would be a response

A
  • infectious agents
  • mechanical trauma
  • heat/cold stress
  • radiation
  • cancerous cells
  • necrotic cells
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3
Q

Give some characteristic signs of inflammation

A
  • Heat
  • Redness
  • Swelling
  • Pain
  • Loss of function
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4
Q

What are the 2 overall main roles of inflammation?

A
  • Destruction, dilution or walling off infectious agents/injured tissue
  • Induction of healing and repair of affected tissue
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5
Q

In what tissue type does inflammation occur?

A

Vascularised tissue

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6
Q

What does inflammation lead to the accumulation of?

A

Fluid and leukocytes

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7
Q

Which plasma components are involved in inflammation?

A
  • Clotting factors
  • Fibrinogen
  • Kininogens
  • Complement components
  • Fluid
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8
Q

How do blood vessels change during inflammation?

A

Change to allow inflammatory cells to leave blood vessels

- in normal situations they prevent fluid leaving and cells from leaving

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9
Q

Where are mast cells found?

A

Surrounding blood vessels

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10
Q

What makes up the extracellular matrix?

A

Locally secreted proteins which assemble into networks in spaces surrounding cells forming connective tissue

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11
Q

What are the 3 main components of the extracellular matrix?

A
  • Fibrous components e.g. collagen, elastin
  • Adhesive glycoproteins
  • Proteoglycans
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12
Q

What are the 3 main functions of the extracellular matrix?

A
  • Sequestration of water
  • Reservoir for growth factors
  • Surface for cells to adhere to, migrate and proliferate within
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13
Q

What is produced by fibroblasts?

A

Collagen

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14
Q

What are the main characteristics of acute inflammation

A
  • short duration
  • oedema
  • neutrophils
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15
Q

What are the main characteristic of chronic inflammation?

A
  • Longer duration
  • Macrophages and lymphocytes
  • Proliferation of blood vessels
  • Fibrosis
  • Necrosis/degeneration
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16
Q

What is exudation?

A

Escape of fluid, proteins and blood cells from the vascular system into interstitial tissues or body cavities

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17
Q

What is pus?

A

Inflammatory exudate rich in leukocytes and cell debris

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18
Q

Give a definition of acute inflammation

A

Immediate and early response to an injurious agent and or to cell injury
Dominated by vascular changes

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19
Q

Describe the vascular changes that take place during acute inflammation

A
  • Increased blood flow
  • Leakage of plasma, plasma proteins and margination of leukocytes = increased vascular permeability
  • Accumulation of leukocytes at the site
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20
Q

What acts as a vascular signalling mechanism of inflammation?

A
  • Slowing circulation leads to stasis due to a loss of fluid and increased blood viscosity
  • With stasis comes the onset of cellular events as it allows WBCs to come into contact with epithelial cells
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21
Q

What are the 3 reasons for increased vascular permeability?

A
  • Endothelium mediated vascular leakage
  • Protein leakage across venules
  • Increased hydrostatic pressure in capillary bed
22
Q

What are the 3 mechanisms involved in endothelium mediated vascular leakage which leads to an increased vascular permeability?

A
  1. Response to chemical mediators or cytokines which both cause gap formation between cells
  2. Fluid escapes because of necrosis or epithelial cells caused by burns and some bacterial infections
  3. Sometimes the inflammatory response can be harmful to the individual - WBCs can damage host cells
23
Q

What are the 5 stages of extravasation?

A
  1. Rolling of leukocytes on endothelium
  2. Activation of leukocytes
  3. Stable adherence of leukocytes to endothelium
  4. Transmigration of leukocytes through the vessel wall
  5. Leukocyte migration in interstitial tissues towards a chemotactic stimulus
24
Q

What are expressed on the epithelial surface to select for WBCs during extravasation?

A

Selectins and integrins

25
Q

What is produced to activate the endothelium during extravasation?

A

Cytokines (TFN, IL-1) produced by macrophages

26
Q

Describe the events of cytokines acting on P-selectin

A
  • Onset of inflammation: activation of endothelium by cytokines leads to tethering of leukocytes and rolling of selectins
  • Once activated the endothelium starts expressing proteins (P-selectin)
  • Leukocytes then start having increased contact with epithelial cells
27
Q

What molecule is involved in the stable adherence of leukocytes to the endothelium?

A

Integrin ligand - binds to WBCs once they have been activated by P-selectin

28
Q

Describe how a leukocytes migrates through the endothelium?

A

Transmigration through the endothelial lines vessel

Chemotaxis - movement through tissue to the site of injury

29
Q

Which molecules are dominant in acute inflammation during:
6-24hours?
24-48 hours?

A 
6-24 = neutrophils 
24-48 = neutrophils are replaced by macrophages
30
Q

What are the reasons for the molecules dominating acute inflammation changing?

A
  • Change in adhesion molecule and chemokine patterns with time
  • Neutrophils have a short life
  • Change in endothelial cell adhesion molecule patterns over time
31
Q

What forms a chemical gradient to allow chemotaxis?

A

Chemoattractants

32
Q

Give some endogenous and exogenous examples of chemoattractants

A 
Endogenous:
- Components of the complement system
- Cytokines (chemokines)
Exogenous:
- Bacterial products
33
Q

What are the different effects of chemokines?

A
  • Chemotaxis of leukocytes
  • Angiogenesis (growth of blood vessels)
  • Collagen production
  • Proliferation of haematopoietic precursors
34
Q

Describe the physical leukocyte movement that enables that to get to the site of injury

A
  • Binding of a chemoattractant to a cell receptor -> mobilisation of calcium from intracellular stores -> increased cytosolic calcium -> assembly of the contractile elements
  • Extension of a pseudopod which pulls the remainder of the cell into the direction of the extension
35
Q

Which process takes place when leukocytes get to the site of injury?

A

Phagocytosis

36
Q

What are the two major phagocytes?

A

Neutrophils and macrophages

37
Q

What are the 3 overall steps of phagocytosis?

A
  • Recognition and attachment
  • Engulfment
  • Killing or degranulation
38
Q

What increases the efficiency of phagocytosis?

A

Opsinisation of microbes

  • Fc fragment of IgG, binding to receptor on phagocyte
  • C3b of C3
39
Q

What are PAMPs?

A

Involved in the recognition and attachment during phagocytosis
Pathogen associated molecular patterns

40
Q

Microbial killing is often by .. ?

A

Oxygen dependant mechanisms e.g. free radicals; reactive oxygen species

41
Q

Give examples of oxygen independent killing mechanisms

A
  • Lysozyme
  • Bacterial permeability increasing protein
  • Lactoferrin
  • Defensins
  • Enzymes
42
Q

What is degradation?

A

Acid hydrolases in granules of neutrophils and lysosomal granules of monocytes degrade bacteria at a low pH

43
Q

What are neutrophil extracellular traps?

A
  • Extracellular fibrillar networks
  • High conc of antimicrobial substances
  • Prevent spread of microbes
44
Q

During engulfment what are the particles enclosed within, at different stages?

A

A phagosome, which fused with a lysosome, forming a phagolysosome, where degranulation occurs

45
Q

Give some examples of chemical mediators of inflammation

A
  • Histamine
  • Serotonin
  • Cytokines
  • Chemokines
  • Complement
46
Q

Which chemical mediator of inflammation is a component of cell membrane phospholipids?

A

Arachidonic acid

47
Q

What is the role of arachidonic acid?

A

Can mediate all steps of inflammation

Important therapeutic targets

48
Q

What are the signs of an acute phase response?

A
  • Fever
  • Increased BP
  • Shivering, chills
  • Malaise
  • Nausea
  • Photophobia
49
Q

Where are acute phase proteins synthesised?

A

In the liver

50
Q

What is leucocytosis?

A

Increased WBC in blood

51
Q

Define the following:

  1. Neutrophilia

2. Neutrophilia with left shift

A
  1. increased neutrophils in blood

2. increased immature neutrophils in blood

52
Q

What are the two neutrophilia signalling factors?

A

TNF-a

IL-1

Y2 Pathology (33 decks)

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