Acute Inflammation Flashcards
Define ‘inflammation’
A reaction to injury or infection involving cells such as neutrophils and macrophages
In what two instances is inflammation good
- Infection
2. Injury
In what two instances is inflammation bad
- Autoimmunity
2. Over-reaction to a stimulus
In what two ways is inflammation classified as?
Acute and Chronic
Three characteristics of an acute condition
- Sudden Onset
- Short Duration
- Usually resolves
Three characteristics of chronic inflammation
- Slow onset or sequel to acute
- Long Duration
- May never resolve
Name five cells involved in inflammation
- Neutrophil Polymorphs
- Macrophages
- Lymphocyte
- Endothelial Cell
- Fibroblasts
How long do macrophages survive for
Weeks to months
Role of macrophages (3)
- Ingest bacteria and debris
- Carry debris away
- Present antigen to lymphocyte
How long do lymphocytes last
Years (almost as long as we can do!)
Role of lymphocyte
Produce chemicals which attract in other inflammatory cells
Immunological memory
What lymphocyte produces antibodies
Plasma cells
What lymphocyte produces cytokines
T-cells
Where are endothelial cells found
Lining capillary blood vessels in areas of inflammation
What happens to endothelial cells in areas of inflammation (3)
- Become sticky so inflammatory cells adhere to them
- Become porous to allow inflammatory cells to pass into tissues
- Grow into areas of damage to form new capillary vessels
What is produced by fibroblasts and under what condition is this produced
Collagen in areas of chronic inflammation and repair
Give an example of an acute inflammation
Acute Appendicitis
What causes acute appendicitis
Unknown why it happens
Name four things that happen when acute inflammation takes place
- Neutrophils appear
- Blood Vessels Dilate
- Inflammation of serosal surface occurs
- Pain felt
Give an example of chronic inflammation
Tuberculosis
At what point during TB does inflammation occur
Later on - does not appear initially
What four things occur during chronic inflammation
- Mycobacteria ingested by macrophages
- Lymphocytes appear
- Macrophages appear
- Fibrosis
( Macrophages often fail to kill kill mycobacteria)
When does acute inflammation occur
Initial tissue reaction to injury
What two things happen during acute inflammation
- Vascular component: Dilatation of vessels
2. Exudative component: Vascular leakage of protein-rich fluid
How long does acute inflammation last
Few hours to a few days
What suffix is given to conditions caused by inflammation
-itis
5 causes of acute inflammation
- Microbial Infections
- Hypersensitivity reactions
- Physical Agents
- Chemicals (acids and alkalis)
- Tissue necrosis
What is the most common cause of inflammation
Microbial infection
How are microbial infections caused
- Bacteria release specific exotoxins which initiate inflammation or endotoxins which are associated to the cell walls
What is a hypersensitivity reaction
An excess immune reaction that damages tissues
What physical agents cause acute inflammation
UV Lights and ionising radiation
How do irritants cause acute inflammation
By tissue damage or directly releasing specific chemical irritants
How does tissue necrosis cause acute inflammation
Death of tissues from lack of oxygen or nutrients
What factors are indications of acute inflammation
Redness Heat Swelling (oedema) Pain (stretching of tissues) Loss of function
What are the early stages of acute inflammation
Odema fluid accumulates in extracellular space
What is the cellular component of oedema fluid called
Neutrophil polymorph
What happens to the microcirculation during acute inflammation
- Smooth muscle of arteriolar walls form pre capillary sphincters which regulate blood flow through the capillary bed.
- Flow through some capillaries shut down
Where are blood cells located in the capillary
Centre of the lumen (axial flow)
Where does plasma flow along the capillaries
The plasmatic zone (outer part of the lumen)
Why does axial flow exist
Keeps blood cells away from and adhering to the blood wall
What are fenestrations
Areas of the capillaries where the wall gets thinner than the rest of the vessel
What happens to vascular permeability during acute inflammation
- High colloidal osmotic pressure causes fluid to be ejected into extravascular space.
- Colloidal proteins also pushed into extracellular fluid which increases oncotic pressure at venule end (exudation).
- Less fluid re-enters capillary at venule end
What can be found in fluid exudate
Immunoglobulins
Coagulation factors
What are acutely inflamed organ surfaces covered by
Fibrin
Are endothelial cells damaged during inflammation
No
Why are endothelial cells not damaged during inflammation
They contain a protein called actin which causes contraction of endothelial cells, opening transient pores when stimulated by inflammatory mediators
Example of an inflammatory mediator
Histamine
How do chemicals like x-rays contribute to inflammation
By delaying prolonged leakage which CAN damage endothelial cells
How does tissue sensitivity impact inflammation
Tissues in different parts of the body respond to inflammatory mediators in different ways (e..g those in the CNS are very insensitive to them)
What is the diagnostic histological feature of acute inflammation
Accumulation of neutrophil polymorphs
What happens to neutrophils during inflammation
- Margination of neutrophils
- Adhesion of neutrophils
- Neutrophil emigration
- Diapedesis
What is the margination of neutrophils
Cells usually confined to axial flow end app in plasmatic zone near to endothelium due to loss of fluid
What is the adhesion of neutrophils
Neutrophils adhere to endothelium which doesn’t normally happen
Do neutrophils make contact with the endothelial walls normally
Yes, randomly but don’t adhere to it
Along with neutrophils what other cell adheres to endothelial walls
Leucocytes
What is neutrophil emigration
They move through opened pores formed by endothelial cells (the actin contractions in response to inflammatory mediator) through basal lamina into adventitia.
What is diapedesis
Red blood cells escape passively through vessels due to hydrostatic pressure.
When does diapedesis occur
Major damage to blood vessels
What happens to neutrophils in later stages of acute inflammation
Chemotaxis
What is chemotaxis
Neutrophil polymorphs are attracted to chemical substances in solution
What two substances early in the inflammatory response are released by inflammatory stimulus
Histamine and Thrombin
Role of thrombin and histamine in inflammation
Up-regulation of adhesion molecules on surface of endothelial cells
What is the result of adhesion molecules increasing on surface of endothelial cells to neutrophils
They have a firm adhesion to the endothelial surface
Role of Histamine
- Vascular dilatation
2. transient phase of increased vascular permeability
Where are histamines stored
Mast Cells
What components stimulate the release of histamine
C3a and C5a
Lysosomal proteins released from neutrophils
Serotonin
Chemokines
How many cascade systems are in place in the plasma flow to produce chemical mediators
4: Kinin Fibrinolytic Coagulation Complement
What factor activates the kinin, fibrinolytic and coagulation systems
Hageman factor (XII)
What are the most important cytokines that stimulate inflammation due to injury
- IL-1
2. TNF - alpha
When do IL-1 and TNF-alpha have an effect
Following histamine and thrombin’s effects
What is E-selectin
An adhesion molecule that binds + activates neutrophils
Role of IL-8
Chemotaxins for neutrophil polymorphs
What is the effect of IL-8 and TNF-alpha on endothelial cells
Cause secretion of MCP-1 which is chemotactic for neutrophil polymorphs
What is the role of lymphatics in inflammation
- Channels become dilated as they drain fluid away from inflamed site.
- Limits oedema collection in tissues
What is the role of neutrophil polymorph
- Movement
- Adhesion to microorganisms
- Phagocytosis
How do neutrophil polymorphs cause movement
Contraction of cytoplasmic microtubules bring about amoeboid movement allowing chemotaxis
What does the amoeboid movement of neutrophil polymorphs depend on
Calcium ions and intracellular concentrations of cyclic nucleotides
define chemotaxis
Movement of a compound in one direction in response to inflammation
How are microorganisms opsonised
By immunoglobulins or complement compounds
How do neutrophils carry out phagocytosis
Phagocytes become pseudopodia shaped
:
1. Neutrophils produce H2O2 which reacts with myeloperoxidase in cytoplasmic granules
2. Produces microbicidal agent
Why are lysosomal products released from neutrophils
- Damages local tissues by proteolysis
- Activates coagulation factor XII
- Attracts leucocytes in the area
Role of mast cells in acute inflammation
Metabolise arachidonic acid to inflammatory mediators
What are mast cells stimulated by
C3a/C5a complement factors
Why is inflammation beneficial (6)
- Dilution of toxins
- Entry of antibodies due to increased intravascular permeability
- Transport of antibiotics
- Fibrin formation traps microbes facilitating phagocytosis
- Delivery of nutrients and oxygen
- Stimulation of immune response by drainage of this fluid into lymphatics allows soluble antigens to reach local lymph nodes
What other cells drive at the site of inflammation
Blood macrophages
What happens to blood macrophages upon leaving the blood vessels
Transform into macrophages by becoming more metabolically active
Role of macrophages
Clearing away tissue debris and damaged cells
Three harmful effects of inflammation
- Digestion of normal tissues (by collagenases and proteases)
- Swelling in certain areas
- OTT inflammatory response
What happens during resolution of acute inflammation
- Minimal cell death + tissue damage
- Occurrence in an organ that has regenerative capacity
- Rapid destruction of causal agent
- Rapid removal of fluid + debris
What are the three sequence of events that lead to resolution
- Phagocytosis of bacteria by neutrophils
- Fibrinolysis
- Phagocytosis of debris by macrophages
- Carry debris through lymphatics
- Disappearance of vascular dilatation
What is Suppuration
Formation of Pus (mixture of living, dying and dead neutrophils and bacteria)
What must happen in order for suppurating to occur
Causative stimulus must be persistent and always caused by an infective agent (pyogenic bacteria)
Describe Suppuration process
- Puss accumulates in tissue
- Puss surrounded by pyogenic membrane consisting of sprouting capillaries, neutrophils and fibroblasts
- Forms an abscess
What is problematic about an abscess
Bacteria within abscess are inaccessible to antibodies and antibiotics
How does an abscess close up
- It bursts
- Cavity collapses
- Cavity obliterated by organisation and fibrosis
- Scar formation
What happens if pus accumulates inside a hollow viscus
Mucosal layers of the outflow tract are covered by fibrin resulting in an empyema
Where is pus from an abscess discharged
Into the sinus tract
What is the sinus tract
A layer between the abscess and skin or mucosal surface
When does a fistula form
When sinus tract pus connects two mucosal surfaces together
What is organisation
Replacement by granulation tissue as part of repair
What three circumstances favour this outcome
- Large amounts of fibrin are formed which can’t be removed by fibrinolytic enzymes
- Large volumes of tissues become necrotic
- Exudate and debris can’t be removed
Describe organisation
- New capillaries grow into the inert material, macrophages migrate into the zone
- Fibroblasts proliferate under the influence of TGF-beta resulting in fibrosis
Where does organisation typically occur
lung parenchyma
What is the consequence of fibrin not being easily removed
Capillaries grow into fibrin
What stage follows on from suppuration
Organisation
