Inflammation

Question 1

List the common causes of acute inflammation

Answer 1

Infection due to:
• bacteria: exotoxins & endotoxins, enzymes
• viruses: intracellular replication causing cell damage
• parasites

Trauma

Physical & chemical agents

Tissue necrosis (death of part of tissue)
• Usually occurs due to lack of blood supply

Foreign bodies:
• splinters, dirt, sutures

Immune reactions (hypersensitivity

Question 2

•Describe the clinical features of acute inflammation

Answer 2

Red

Hot

Swollen

Pain

Loss of function

Question 3

•List and explain the main features of the acute inflammatory
response

Answer 3

Arterioles vasoconstrict - area becomes white (Local axon reflex)

arteriolar, capillary and venule dilation allows all the immune cells and chemical mediators to arrive- area becomes red and warm (Histamine,
serotonin, nitric
oxide,
prostaglandins)

Increased vascular permeability - causes swelling due to oedema (Histamine, C3a &
C5a, leukotrienes) (increases in spaces between endothelial cells so white cell can get to the tissues in emigration - which causes swelling)

vascular stasis - loss of fluid due to decreases in blood concentration as everything is in the tissues now, slows the blood flow

Question 4

What 3 functions does inflammation have?

Answer 4

• Protective
  • Destroy, wall off or dilute injurious agent
  • Initiate repair

Question 5

What are the differences in acute and chronic inflammation?

Answer 5

Acute
• Onset: immediate
• Short lived
• Usually single episode
• Neutrophils and other
granulocytes

Chronic
• Gradual onset
• Prolonged
• Frustrated healing
• Macrophages and
lymphocytes

Question 6

what are some examples of acute inflammation in the oral cavity?

Answer 6

• Abscess
• Acute pulpitis - response to bacteria
• Lacerations
• Acute herpetic gingivostomatitis - caused by Herpes simplex virus
• Parotitis - bacterial infection due to parotid gland stones
• Reactions to piercings

Question 7

What does increased vascular permeability occur as a result of? (3 things)

Answer 7

1. Retraction of endothelial cells.
2. Endothelial injury
3. Increased transport of fluid and proteins through
   endothelial cells, known as transcytosis.

Question 8

What type of fluid is seen in oedema of inflammation?

Answer 8

Exudate: Extravascular fluid with a high protein

content. This is what we see in inflammation

Question 9

What is transudate?

Answer 9

Extravascular fluid with low protein content - increase in pressure of vessel but no spaces between endothelial cells , can’t get white blood cells out but fluid gets out

Question 10

What is the role of oedema (excess fluid in the tissues) in acute inflammation?

Answer 10

1. contains complement - proteins (membrane receptors) found in the plasma - normally inactivated, when activated form pathway, each protein turns into enzyme and amplifies itself down the pathway - enzyme cascade
   - protylysis of c3 important
2. may contain antibodies which act as an opsonin and aids phagocytosis as the white cells have a receptor which can bind to that antibody
3. contains clotting cascade - fibrin forms a barrier to spread of infection (fibrinogen
   converted to fibrin by thrombin).
   • Coagulation may also promote inflammation
4. Contains Kininogens: these are converted to kinins by
   proteases (e.g.thrombin). Bradykinin- similar effect to
   histamine (vasodilation)
5. Dilutes bacterial & other toxins

Question 11

Which molecule is a key molecule in vasodilation and how is it stimulated?

Answer 11

trauma, complements and cytokines act on mast cells which release histamine - key molecule in vasodilation

also serotonin and nitric oxide

Question 12

What is transcytosis?

Answer 12

Increased transport of fluid and proteins through

endothelial cells

Question 13

What are the 3 pathways of complements linked to oedema?

Answer 13

Classical pathway - c1 activated by normal antibodies binding to antigen
alternative pathway
- pathogen produces LPS that activated c1
Lectin pathway - Lectin activates c1

Question 14

What is the membrane attack complex?

Answer 14

series of c5-c9 proteins that punch holes in cells

MAC forms
transmembrane
channels. These disrupt
the phospholipid bilayer
= cell lysis and death

Question 15

What does c3a stimulate?

Answer 15

Dilation and increased vascular permeability

Question 16

What does c3a and c5a stimulate?

Answer 16

Stimulate histamine release
promotes formation of leukotrienes (attracts neutrophils) and prostaglandins (vasodilation)

attracts phagocytes - neutrophils

Question 17

Which complement has a role in opsonisation?

Answer 17

c3b can bind to outside of pathogens and phagocytes have a c3b receptor with which to bind to this - phagocytose more easily

Question 18

What are the stages of the cellular response?

Answer 18

1. Margination- due to vascular stasis (blood vessels dilate and WBC drop to the edge of the vessels)
2. . Pavementation- neutrophils adhere to the endothelial cells using adhesion molecules on
   vessel wall known as selectins (bind lightly, roll and stop). Neutrophils then bind more
   strongly using integrins on their cell surface to ICAM (receptors) on endothelial
   cells (promoted by IL-1, TNF alpha)
3. Emigration- movement of neutrophils between endothelial cells via
   chemotaxis via chemotactic gradient (e.g. IL-8, C5a)
4. the cells aggregate in the tissues where needed
5. Phagocytosis- neutrophils and macrophages engulf and destroy
   microorganisms/necrotic tissue
   Pseudopodia (projection of their cytoplasm) surrounds microorganism to form phagosome, and
   destroyed by reactive oxygen species and hydrolytic enzymes in lysosomes - phagolysosome forms

Question 19

Why do white blood cells not adhere to endothelial cells all the time?

Answer 19

Don’t have ICAM receptors on endothelial cells all the time

cytokines - iL-1 and TMF -alpha promotes the process which isn’t always present

Question 20

What molecules attract the white blood cells to the tissues in emigration?

Answer 20

IL-8 and c5a

Question 21

What are the 3 methods of neutrophils to destroy pathogens?

Answer 21

Phagocytosis
• Degranulation (defensins,
lysozyme, lactoferrin)
• NETS (Neutrophil
extracellular traps)

Question 22

What type of inflammation is an abscess?

Answer 22

acute inflammation - neutrophils, dead/dying bacteria and cell debris

Question 23

What are NETs?

Answer 23

Neutrophile extracellular traps
CHROMATIN released as the neutrohpils die - attracts the enzymes and free ozygen radicals and pathogens
The DNA acts as a meshwork containing proteases

It increases the concentration of antimicrobials in an area - limits tissue damage in other area as they only gather in specifc area

Question 24

Why is there pain in acute inflammation? (2 reasons)

Answer 24

• Increase in tissue pressure due to oedema
  • Inflammatory mediators stimulate pain fibres e.g.
  bradykinin and prostaglandins

Question 25

What are the 3 outcomes of acute inflammation?

Answer 25

* Complete resolution - common response to trauma, bacteria gone, tissue goes back to normal, oedema drains away e.g. ulcer - cells turn over so quickly so heals well * Healing by fibrosis - common on skin and in specialised tissue e.g. heart and brain - cells don't turn over as quick, pathogen removed but granulation tissue depositis - (endothelial cells and fibroblasts) which matures to become dense scar tissue that has lots of collagen • Progression to chronic inflammation - • Acute inflammatory response fails to get rid of injurious agent e.g. foreign-body or there is an interference with normal healing e.g. neutropenia (low wbc) or radiotherapy e.g. dental abscess causes by bacteria in tooth, acute inflamm goes away but bacteria is still there so can progress to chronic - chronic perapical granuloma or radicular cyst

Question 26

List the common causes of chronic inflammation

Answer 26

Acute inflammation failed to resolve e.g. - chronic and low grade rom the outset usually in response to chronic low grade stimuli persistent injury viral infections chronic infections autoimmune diseases

Question 27

Describe the clinical features of chronic inflammation

Answer 27

• minimal vascular changes • infiltration by chronic inflamm cells -macrophages, lymphocytes and plasma cells • Repair- vascular granulation tissue (fibroblasts + endothelial cells)- may mature to give scarring • Continued tissue destruction inflammatory agent or inflammatory cells from host response and pathogen

Question 28

What is chronic inflammation?

Answer 28

Inflammation, repair and continued tissue destruction occur simultaneously Duration • Lasts weeks, months or years. ``` Systemic features (fever, general malaise) • Typically less in comparison to acute ```

Question 29

What are 3 examples of where acute inflammation fails to resolve?

Answer 29

``` foreign body, grit, retained sutures • Non-vital tooth causing continued chronic inflammation at the root apex • Poor healing due to inadequate blood supply e.g. osteoradionecrosis, areas of dead bone can't respond ```

Question 30

What are 3 examples of chronic and low grade inflammation from the outset?

Answer 30

• Certain micro-organisms such as mycobacteria responsible for tuberculosis • Prolonged exposure to toxins e.g. silica responsible for silicosis; atherosclerosisresponse to lipids in plasma • Autoimmune disease- body mounts an inflammatory reaction against a component of ‘self. e.g. rheumatoid arthritis

Question 31

What are 3 examples of chronic and low grade inflammation from the outset?

Answer 31

• Certain micro-organisms such as mycobacteria responsible for tuberculosis • Prolonged exposure to toxins e.g. silica responsible for silicosis in the lungs; atherosclerosis response to lipids in plasma • Autoimmune disease- body mounts an inflammatory reaction against a component of ‘self. e.g. rheumatoid arthritis

Question 32

What are the roles of the activated macrophages in chronic inflammation?

Answer 32

Antigen presentation stimulate immune response - activated T cells, then differentiates into cytotoxic T cells, T helper cells can activate B cells - plasma cells - antibodies, T cells activate macrophages (IFN-gamma) ``` produces growth factors. Stimulation of fibroblasts + endothelial cells to promote healing ``` Phagocytosis produces cytokines (activate lymphocytes) + chemokines attract inflammatory cells + regulate inflammatory response

Question 33

What are macrophages derived from?

Answer 33

Blood monocytes activated by IFN-gamma produced by T cells

Question 34

What colour cytoplasm so eosinophils contain?

Answer 34

Pink Major basic protein in granulues important in parasitic infections

Question 35

Why is there ongoing tissue destruction in chronic inflammation?

Answer 35

``` • Products of activated macrophages such as free oxygen, proteases • Necrotic tissue promotes further inflammation - further necrosis etc • Release of enzymes by neutrophils • Cytotoxic T cells • Products of micro-organisms ```

Question 36

What two mechanisms does repair occur via?

Answer 36

1. Regeneration: complete resolution to normal tissue - oral cavity 2. Connective tissue deposition and scar formation: occurs in tissues not capable of complete regeneration e.g. heart/brain or where there has been prolonged, severe damage e.g. periodontal disease

Question 37

What is granulation tissue made up of?

Answer 37

* Fibroblasts * Endothelial cells stimulated by growth factors from macrophages to come to the area

Question 38

What is granulomatous inflammation? - type of chronic inflammation

Answer 38

collections of macrophages and giant cells (lots of macrophages combined together multinucleated) in an area combine, surrounded by a rim of lymphocytes e.g. in TB, chron's diseases, orofacial granulomatism - epitheliod macrophages (round, big and pink) - multinucleate giant cell - lymphocytes

Question 39

What are the 2 types of multinucleate giant cells?

Answer 39

Foreign body type e.g. in response to stitches - nuclei randomly aranged in the cell Langhans type - nuclei in a horse shoe shape around edge

Question 40

What are the causes of Granulomatous inflammation?

Answer 40

• Certain micro-organisms- e.g. mycobacterium which causes tuberculosis, syphilis, leprosy • Certain immune reactions- e.g. Crohn’s disease; OFG • Response to foreign material e.g. sutures

Question 41

How is a granulomatous inflammation different to periapical granuloma and granulation tissue?

Answer 41

periapical granuloma - no collection of macrophages, granulation tissue and chronic inflammation granulation tissue is just granulation tissue

Question 42

What is a caseating granuloma?

Answer 42

There is some necrosis in the middle - specifically in Tb