Inflammation

Question 1

What is inflammation?

Answer 1

The response of vascularised tissue that brings cells and molecules of host defences from circulation to site where they are needed, to eliminate offending agents.

Question 2

What are 4 main causes of inflammation?

Answer 2

1) Infection
2) Tissue necrosis (eg. Ischaemia, Trauma, Chemical injury)
3) Foreign bodies
4) Immune rxns (eg. Autoimmunity, Hypersensitivity)

Question 3

What are the differences between acute and chronic infection?

Answer 3

Acute:
- quick onset: mins - hrs
- mainly neutrophils
- mild and self-limiting injury and fibrosis
- prominent local and systemic signs

Chronic:
- slow onset: days
- monocytes/macrophages, lymphocytes
- severe and progressive injury and fibrosis
- less sever local and systemic signs

Question 4

What are the 5 cardinal signs of (local) inflammation?

Answer 4

1) Redness
2) Warmth
3) Swelling
4) Pain
5) Loss of function

Question 5

What are 3 systemic signs of inflammation?

Answer 5

1) Fever (via IL-1, TNF)
2) Loss of appetite
3) Loss of weight

Question 6

What are the steps of acute inflammation?

Answer 6

1) Foreign Ag detected by mast cells and macrophages

2) Mast cells secrete histamines and prostaglandins → vasodilation → Redness and warmth

3) Exudate containing plasma, cells and proteins (including kinins → bradykinins)

4) Bradykinins + Prostaglandins (from macrophages) → stimulate free nerve endings → Pain

5) INF-α, IL-1ß from macrophages → Fever

6) Slower blood flow + endothelial selectins → margination of neutrophils → roll and adhere with integrins → transmigration into site of injury via chemokine gradient

Question 7

What is the difference between exudate and transudate?

Answer 7

Exudate is caused by inflammation has a much higher protein and cells.

Transudate is caused by ↑hydrostatic pressure but ↓colloid (proteins) osmotic pressure.

Question 8

What chemicals do mast cells produce?

Answer 8

Prostaglandins and histamines

Question 9

What chemicals do Macrophages produce?

Answer 9

Prostaglandins, IL-1ß, TNF-α

Question 10

Which chemicals cause vasodilation?

Answer 10

Prostaglandins and Histamine

Question 11

Which chemicals cause pain?

Answer 11

Prostaglandins and Bradykinins (activated kinins from exudate)

Question 12

Which chemicals cause fever?

Answer 12

IL-1ß and TNF-α → hypothalamus

Question 13

What causes the loss of function?

Answer 13

Pain and swelling → voluntary loss of function
Tissue injury → involuntary loss of function

Question 14

What enables the extravasation of neutrophils?

Answer 14

1) Vasodilation → ↓ speed of blood flow
2) Endothelial selectins slow neutrophils
3) Adherence by integrins
4) Transmigration through basal lamina into adventitia down the chemokine gradient

Question 15

Which chemicals increase vascular permeability?

Answer 15

Histamine, c3a, c5a, Leukotrienes

Question 16

Where do complements responsible for increased vascular permeability come from?

Answer 16

Blood plasma

Question 17

What are the consequences of inflammation?

Answer 17

1) Resolution
2) Abscess formation
3) Fibrosis
4) Chronic inflammation

Question 18

What are some determinants of resolution?

Answer 18

1) Tissue type (labile, stable, permanent)
2) Injury duration
3) Extent of tissue destruction
4) Nature of agent (eg. bacteria → abscess)

Question 19

What are the 4 general patterns of acute inflammation?

Answer 19

1) Serous
2) Fibrinous (fibrosis)
3) Suppurative (pus → neutrophils, necrotic debris, bacteria)
4) Ulcer (defect in epithelial surface)

Question 20

What are the components of pus?

Answer 20

Dead neutrophils, necrotic debris, bacteria

Question 21

What forms when suppuration is localised?

Answer 21

Abscess

Question 22

What is the difference between systemic inflammation and systemic effects of inflammation?

Answer 22

Systemic effects of inflammation are caused by local release of cytokines into circulation.
Systemic inflammation is associated with Sepsis.

Question 23

What are 6 systemic effects of infection?

Answer 23

1) Pyrexia
2) Constitutional symptoms (malaise, lethargy, anorexia)
3) Weight loss
4) Reactive hyperplasia of reticuloendothelial system (lymph node swelling)
5) Haematological changes (eg. Anaemia, Leukocytosis, ↑ESR)
6) Amyloidosis (deposition of serum amyloid A in tissues)

Question 24

What are the benefits and drawbacks of inflammation?

Answer 24

Benefits:
- toxin dilution
- Ab entry
- drug transport
- fibrin formation
- O2 and nutrient delivery
- stimulation of immune response

Drawbacks:
- Digestion of normal tissue
- swelling
- inappropriate response (eg. autoimmunity, atopy)
- can lead to abscess formation, chronic inflammation or fibrosis

Question 25

How does acute inflammation progress to chronic inflammation?

Answer 25

Persistent actue inflammation

Question 26

What are the 3 main causes of chronic inflammation?

Answer 26

1) Persistent infections
2) Hypersensitivity (including autoimmunity)
3) Prolonged exposure to toxic agents

Question 27

What are the 3 components/mechanisms of chronic inflammation?

Answer 27

1) Inflammation
- Mononuclear cells → Plasma cells, M1 activate Lymphocytes; Th1/17 promote macrophages
- Eosinophils
- Mast cells

2) Repair
- attempts at fibrosis and angiogenesis

3) Tissue injury
- by persisting offending agents & inflammatory cells

Question 28

What is the 1 special case of chronic inflammation we need to know?

Answer 28

Granulomatous inflammation

Question 29

What is granulomatous inflammation?

Answer 29

A special type of chronic inflammation characterised by the presence of granulomas

Question 30

What are the components of a granuloma?

Answer 30

1) Epithelioid histiocytes (macrophages from the stroma that have undergone frustrated phagocytosis)
2) Multinucleated giant cells
3) Central caseous necrosis
4) CD4+ Th cells

Question 31

What are some causes of granulomatous inflammation?

Answer 31

1) Specific infections
(eg. mycobacterium, parasites, fungi)

2) Materials resisting digestion
(eg. keratin, necrotic bone, cholesterol synthesis, talc, silica, suture material, oils, silicone)

3) Chemicals
(eg. Beryllium)

4) Drugs
(eg. Allopurinol, Sulfonamide → hepatic granuloma)

5) Others
(eg. Sarcoidosis, Crohn’s disease, Wegener granulomatosis)

Question 32

What colour is characteristic of inflammation on histology?

Answer 32

Pink (high protein content of exudate)

Question 33

What is a carbuncle?

Answer 33

An infection of the hair follicle(s) that extends into the surrounding skin and deep underlying subcutaneous tissue

Question 34

What are foamy histiocytes/macrophages indicative of?

Answer 34

Prolonged chronic inflammation

Question 35

Would pus be present in chronic inflammation?

Answer 35

If no underlying acute inflammation, no