7 - Inflammation (early events)

Question 1

Goal of inflammatory reaction

Answer 1

To bring leukocytes and plasma proteins normally circulating in blood to the site of infection of tissue damage, eliminate the causative agent an initiate healing

Question 2

Types of inflammation

Answer 2

Acute or chronic

Question 3

onset of acute and chronic inflammation

Answer 3

• Acute: Fast (minutes or hours)
• Chronic: Slow (days, months or years)

Question 4

Cells involved in acute and chronic inflammation

Answer 4

• Acute: Mainly neutrophils
• Chronic: Monocytes/macrophages, lymphocytes

Question 5

Tissue injury, fibrosis of acute and chronic inflammation

Answer 5

• Acute: Mildm self limited
• Chronic: Often severe, progressive

Question 6

Local and systemic signs of acute and chronic inflammation

Answer 6

• Acute: Prominent
• Chronic: less prominent

Question 7

Cardinal signs of inflammation

Answer 7

• Redness (increased blood flow)
• Heat (increased blood flow)
• Swelling (leakage of cells and fluid into tissues)
• Pain (increased nerve sensitivity due to chemical mediators)
• Loss of function

Question 8

Causes of inflammation

Answer 8

• Infective agents
• Foreign bodies (dirt, splinters, implants)
• Immune reactions (hypersensitivity & autoimmune)
• Tissue necrosis (death)
• Physical agents (trauma, heat, cold)
• Chemical agents (drugs, toxin)

Question 9

Inflammatory process

Answer 9

• Offending agent is recognised by Macrophages, dendritic cells and mast calls which then produce chemical mediators (cytokines)
• Leukocytes (neutrophil and monocytes) are recruited from the circulation to the site where the offending agent is located
• Leukocytes and proteins are activated to destroy and eliminate the offending substance
• The reaction is controlled and terminated
• The damaged tissue is repaired

Question 10

Two components of inflammatory responses

Answer 10

Vascular changes and cellular events

Question 11

Vascular changes

Answer 11

Maximise movement of proteins and leukocytes from circulation to site of infection/injury.

Question 12

Examples of vascular changes

Answer 12

Vasodilation, increased bloodflow and permeability

Question 13

Vasodialtion

Answer 13

• Action of mediators (histamine) on vascular smooth muscle
• Initial constriction (transient)
• Arterioles dilate followed by capillary bed expansion
• Increased blood flow → redness & heat

Question 14

Increased permeability

Answer 14

• Outpouring of protein rich fluid into extravascular tissues (exudate)
• causes swelling

Question 15

Two ways permeability is changed

Answer 15

1. Retraction of endothelial cells (gaps appear between endothelial cells)
2. Endothelial injury (Direct damage)

Question 16

End result of change permeability

Answer 16

• Fluid and proteins escape
• small molecules first, fibrinogen last
• ↑ osmotic pressure of tissue
• swelling

Question 17

Cellular events

Answer 17

• Leukocytes that are recruited to sites of inflammation eliminate the offending agents following their activation
• Most important leukocytes in typical inflammatory reactions are the ones
  capable of phagocytosis
• Neutrophils and macrophages (slower responders)

Question 18

Which cells produce growth factors that aid in repair

Answer 18

Macrophages, stay longer than other cells

Question 19

Role of cytokines in leukocyte emigration

Answer 19

TNF and IL-1 act on the endothelium of venules near the site of infection to initiate leukocyte emigration into tissues

Question 20

Role of chemokines in leukocyte emigration

Answer 20

Provide signals to leukocytes to help them traffic to the site of infection once they have migrated into
tissues (chemotaxis)

Question 21

TNF and IL-1 actions

Answer 21

Endothelial activation (pain, fever, metabolic abnormalities)

Question 22

Loose attachment and rolling of leukocytes

Answer 22

• In response to cytokines, endothelial cells upregulate expression of adhesion molecules called selectins
• selectins bind to surface carbohydrates on leukocytes
• repetitive process of leukocytes becoming tethered to the endothelium, flowing blood disrupting binding and bonds reforming downstream

Question 23

Firm adhesion

Answer 23

• in response to chemokines, integrins expressed on leukocytes assume a highaffinity state
• endothelial cells upregulate expression of adhesion molecules ICAM-1 and
  VCAM-1 that bind to integrins expressed by leukocytes
• firm binding of integrins to their ligands arrests the rolling, cytoskeleton of
  leukocytes is reorganised such that they spread out on the endothelial surface

Question 24

Leukocyte migration

Answer 24

• chemokines stimulate the motility of leukocytes, as do bacterial products and products of complement activation
• leukocytes begin to migrate between endothelial cells, through the vessel wall
  and along the concentration gradient of these chemoattractants

Question 25

Chemotaxis

Answer 25

Movement of leukocytes after emigration towards an increasing concentration of a chemotactic agent (usually a protein or polypeptide)

Question 26

Chemoattractants

Answer 26

Both exogenous and endogenous substances can act as chemoattractants (e.g. bacterial products, chemokines, complement components)

Question 27

Leukocyte activation

Answer 27

- Leukocytes require activation in order to perform functions - Neutrophils and macrophages can become activated - Induced by a variety of chemical mediators - Functions following activation include phagocytosis, lysis/killing of injurious particles and release of further chemical mediators

Question 28

Phagocytosis

Answer 28

The process by which neutrophils and macrophages ingest debris / foreign particles

Question 29

3 phases of phagocytosis

Answer 29

1. Recognition and attachment by receptors on surface of macrophages 2. Engulfment 3. Killing and degradation

Question 30

Phagocytosis engulfment

Answer 30

- Pseudopods form around organism - Foreign material incorporated within cell vacuole (phagosome) - Fusion with lysosomes and release of lysosomal contents

Question 31

phagocytosis killing and degradation

Answer 31

Reactive oxygen species, nitric oxide, lysosomal enzymes

Question 32

Resolution

Answer 32

Restoration of tissue to a completely normal state after acute inflammation or other tissue damage or death

Question 33

When is resolution most likely to occur

Answer 33

- when cell death and tissue damage is minimal - when damaged cells are capable of regeneration - when causative organism is rapidly eliminated - where local conditions favour removal of exudate

Question 34

Process of resolution

Answer 34

1. Return to normal permeability 2. Drainage of fluid & proteins into lymph 3. Pinocytosis into macrophages 4. Phagocytosis of apoptotic neutrophils 5. Phagocytosis of necrotic debris 6. Disposal of macrophages

Question 35

Serous inflammation

Answer 35

- Characterised by presence of thin, watery fluid in exudate - Commonly seen in blisters from burns or viral infections

Question 36

Purulent inflammation

Answer 36

- Large amounts of pus (dead leukocytes & bacteria), neutrophils, necrotic cells, edema fluid - Caused by pyogenic bacteria (staph spp.) - Central region of necrotic cells with infiltration of neutrophils

Question 37

Fibrinous inflammation

Answer 37

- Characterised by entry of fibrinogen (clotting factor) into tissues - Fibrinogen is cleaved to form fibrin and when not removed it can lead to scarring - Inflexible sheets of fibrin

Question 38

Ulcerative inflammation

Answer 38

- Excavation in tissue surface produced by shedding of necrotic inflammatory tissue - Commonly seen in mucosa of mouth, stomach and intestines