Pathology: Acute Inflammation

Question 1

What is acute inflammation ?

Answer 1

The immediate and early response to injury, designed to deliver leukocytes to the site of injury
Can be beneficial but also harmful

Question 2

What are the two types of inflammation ?

Answer 2

Acute
-Initial and often transient series of tissue reactions to injury

Chronic
-Subsequent and often prolonged tissue response following initial acute response

Question 3

What are causes of inflammation ?

Answer 3

Microbial infections
-E.g. bacteria & viruses

Hypersensitivity reactions
-Excessive immune response leading to tissue damage

Physical agents
-Trauma, radiation or heat injury

Chemicals
-Corrosives, acids or bacterial toxins

Tissue necrosis
-e.g. secondary to ischaemia
-lots of acute inflammatory infiltrate seen in necrotic tissue

virtually identical to causes of injury

Question 4

How can microbrial infections stimulate inflammation ?

Answer 4

Bacterial
-Exotoxins; chemicals released by bacteria
-Endotoxins; associated with bacterial cells walls

Virus
-Intracellular multiplication; leads to cell death, debris stimualtes inflammation

Organisms can also cause hypersensitivity reactions
e.g. some parasitic infections and TB

Question 5

What is hypersensitivity ?

Answer 5

Excess immune response due to altered state of immunological responsiveness

Question 6

How do Physical Agents and Chemicals cause inflammation ?

Answer 6

Cause tissue damage (see previous lecture)
Presence of damaged/dead tissue provokes inflammatory response

Question 7

How does tissue necrosis cause inflammation ?

Answer 7

Dead tissue releases peptides
Triggers acute inflammatory response

Question 8

What are the cardinal signs of inflammation ?

Answer 8

Redness (rubor)
-Bc vessel dilation

Heat (calor)
-Bc increase blood flow

Swelling (tumor)
-Bc accumulation of fluid and increase in inflammatory cells migrating to the area

Pain (dolor)
-Bc physical distortion of tissue and due to release of some chemical mediators (prostaglandins, bradykinin)

Loss of function of inflammed area (functio laesa)

Question 9

What are the stages of inflammation

Answer 9

Rough order
1) Release of chemical mediators
2) Vasodilatation
3) Increased vascular permeability (lets cells move through)
4) Fluid accumulation
5) Cellular recruitment
6) Phagocytosis

Neutrophil diapedesis, moves down chemotacctic gradient, phagocytosis

chemotacctic gradient is a chemical gradient

Question 10

What are the two major components in early inflammation ?

Answer 10

Vascular changes
-Change in vessel calibre
-Increase in vascular permeability

Cellular events
-Formation of cellular exudate

Question 11

Describe changes in vessel calibre in early inflammation

Answer 11

There is initial transient constriction
-Often as injury response, minimise blood loss

Then vasodilation
-Can last from 15 mins up to several hours
-Gets more neutrophils in

Question 12

Describe the purpose of increased vascular permeability in early inflammation ?

Answer 12

Allows for increased net flow of fluid out of vessels - “exudation”
-lets fluid into injured tissue, can dilute toxins in injured/poisoned areas

Question 13

Describe formation of cellular exudate in early inflammation

Answer 13

Involves accumulation of neutrophil polymorphs
-Nuetrophils are characteristic cell of acute inflammatory response

Neutrophils move out of vessel into tissue by diapedesis

Question 14

Why are neutrophils so amazing?

Answer 14

Motile
-Move by calcium depedent cytoplasmic microtubule contraction or chemotaxis
-By contracting cytoplasmic microtubules; dependent on calcium ions
-e.g. chemotaxis in response to inflammatory chemicals

Can stick to opsonised microbes
-Once bacteria have encountered immunoglobulins or complement components, neutrophils can bind to them

Phagocytosis
-Can gobble up particles e.g. cellular debris
-Can gobble up microbes and kill them
-Variety of intracellular methods to produce microbicidal agents E.g. producing hydrogen peroxidase, to react with cytoplasmic myeloperoxidase

Question 15

How do neutrophils move into damaged/infected tissues?

Answer 15

Margination
-Loss of intravascular fluid which slows flow to site allows them to sow down and move to side of vessel

Adhesion (aka pavementing)
-Neutrophils adhere to vascular endothelium
-Caused by interaction between paired adhesion molecules on the neutrophil and endothelial surfaces

Emigration
-Pass between endothelial cells, through basal lamina and into adventitia and tissue

Adventita in capillaries here means surrounding tissue and mass

Question 16

What are the components of the inflammatory response ?

Answer 16

Cells and chemical agents

Question 17

What are the cellular components of the inflammtory response ?

Answer 17

Endothelial and inflammatory cells (e.g. naeutrophils)

Question 18

What are the chemical agents component of the inflammtory response ?

Answer 18

Cytokines
Complement
Histamine
Prostaglandins
Lysosomal Compounds
Leukotrienes
Seratonin
Chemokines
Plasma factors

Question 19

Describe the role of chemical mediators in early chemical events

Answer 19

Histamine and thromin released by original inflammatory stimulus
-Cause up regulation of P-selectin and platelet activating factor (PAF) onendothelial cells

Neutrophils start to roll along endothelial wall
-Ligands on the neutrophil surface engage with the P-selectin onendothelial cells

PAF docks with corresponding receptor on neutrophil and promotes expression of other molecules (LFA-1, MAC-1)
-overall end result is firm neutrophil adhesion to endothelial surface

Question 20

What is histamine ?

Answer 20

Is a chemical mediator released from a cell
-Causes vascular dilation and permeability
-Released mainly by mast cells (an immune cell that lives in connective tissue, waiting to be activated)
-Also plays a role in neutrophil adhesion to endothelium

Question 21

What are Lysosomal compounds ?

Answer 21

Chemical mediator of acute inflammatory response
-Lots of different functions, such as vascular permeability
-Some can stimulate histamine release from mast cells
-Released by neutrophils

Question 22

What are leukotrienes ?

Answer 22

Chemical mediator of acute inflammatory response
-Vasoactive properties
-Often made in neutrophils from arachidonic acid

Question 23

What are prostoglandins ?

Answer 23

Chemical mediator of acute inflammatory response
-Derived from arachidonic acid
-Some cause increased vacular permeability
-Some cause platelet aggregation
-Released by lots of cell types

Question 24

What is seratonin ?

Answer 24

Chemical mediator of acute inflammatory response
-Vasoconstrictor
-Released by platelets
-Immediate after injury

Question 25

What are chemokines ?

Answer 25

Chemical mediator of acute inflammatory response -Family of chemicals which attract more white blood cells to site of inflammation -Eg IL-8 attracts neutrophils -Are a type of cytokine

Question 26

What are plasma factors ?

Answer 26

Chemical mediator of acute inflammatory response Four enzyme cascade systems within plasma: Coagulation system -Converts soluble fibrinogen into fibrin Kinins -Activated by coagulation factor XII -Bradykinin important peptide in mediating vasodilation and pain (it is a peptide) Fibrinolytic system Complement system

Question 27

What is the compliment system ?

Answer 27

Chemical mediator of acute inflammatory response Products of complement important in acute inflammation: Can be activated by: -Enzymes released from dying cells -Formation of antigen-antibody complexes -Products of fibrinolytic and kinin systems

Question 28

Give examples of products of the complement system which are important in acute inflammation:

Answer 28

C5a, C3a -Chemotaxis of neutrophils -Histamine release from mast cells -Increased vascular permeability C567 -Chemotaxis of neutrophils Membrane attack complex/C56789 -Cytolytic activity C4b, 2a, 3b -Opsonisation of bacteria

Question 29

What are benefits of inflammation ?

Answer 29

Dilution of toxins -by cellular exudate Entry of antibodies Facilitates transport of drugs Fibrin formation Delivery of nutrients & oxygen -by increased vascular permeability Stimulation of immune response

Question 30

What are harmful effects of inflammation ?

Answer 30

Digestion of normal tissue Swelling -E.g. in airway is bad Inappropriate inflammatory response -E.g. anaphylaxis | Swelling from cellular exudate, toxin dilution, neutrophils