Inflammation Flashcards
Define inflammation
Reactions of living vascularised tissue to sub- lethal injury
What are the three types of inflammation?
Acute
Chronic
Granulomatous (type of chronic inflammation)
What triggers histamine release and what effect do histamines have?
Binding of IgE to the Fc receptor on mast cells - Antigens bind to the IgE and cause cross-linking and mast cell degranulation Histamines cause: vasodilation + increased vascular permeability
What is an exudate?
Fluid with high protein content and cellular debris, which leaves vessels and deposits in tissues or on tissue surfaces, usually as a result of inflammation
What is a transudate?
Fluid escape from vessels due to disturbances in hydrostatic and colloid osmotic pressure – NOT CAUSED BY INFLAMMATION
What is the most important difference between exudates and transudates?
Exudates are associated with inflammation transudates are not
What are the three types of exudates and how do they differ?
Serous – fluid filled – lowest protein content of the three exudates
Fibrinous – high fibrin content – more due to traumatic injury
Purulent – pus filled – fibrin, inflammatory cells, debris and fluid
What is the main histological feature of acute inflammation?
Lots of neutrophils
What are the three main cell types involved in chronic inflammation?
Macrophages
Lymphocytes
Plasma Cells
What is an important difference between acute and chronic inflammation?
Acute inflammation produces an exudate whereas chronic inflammation doesn’t
What are the histological features of granulomatous inflammation?
Granuloma – collection of macrophages
You get a collection of macrophages in the middle and they may appear to have fused together
There will be lymphocytes and plasma cells around the outside
What is the good outcome of inflammation?
Resolution – healing of tissue damage to preserve integrity and function
What is ‘Repair’ in terms of wound healing?
Replacing normal tissue with scar tissue
Give an example of resolution and how it takes place.
Pneumococcul lobar pneumonia
Inititally you get exudation
Then you get red hepatisation (erythrocytes move into the alveolar cells)
Grey hepatisation – erythrocytes break down
Provided the basement membrane is still there – the body can remove the problem
What are three main complications of repair? Describe each of them
Keloids – excess collagen deposition
Contractures – scar tissue contracts after a while, if the scar tissue is over a joint it can affect joint mobility
Organ Function – if normal functional tissue is replaced with scar tissue
what are features of acute inflammation?
- Transient and early response to injury
- Hours/few days
- Involves release of chemical mediators
- Typical vascular and leucocyte response
- NOT the same as infection
what are features of chronic inflammation?
- Inflammation of prolonged duration
- Weeks/months/years
- Usually due to persistent injury causing agent
what is Granulomatous Inflammation?
Specialised form of chronic inflammation
what are the cells of the inflammatory response and healing?
- neutrophils
- macrophages
- lymphocytes
- eosinophils
- mast cells
what are the soluble factors of inflammatory response and healing?
- antibodies
- cytokines
- complement system
- coagulation system
what are the cardinal signs of inflammation?
- rubor - redness
- calor - heat
- tumour - swelling
- dolor - pain
- functio laesa - loss of function
what is calor caused by?
histamine mediated vasodilation
what is tumor caused by?
- Oedema - increased fluid in interstitial fluid
- Caused by histamine mediated increase in permeability of vessels
what is rubor caused by?
- blood flow isn’t as fast so you get redness
what is loss of function caused by?
- due to swelling and pain
what is histamine?
- vasoactive amine
- produced by mast cells
- packaged into granules inside mast cells
- when an antigen binds to the IgE on the surface of mast cells it causes degranulation
- leading to vasodilation and vascular permeability
how to target
- histamine
- prostaglandins
- IL- 1 and TNF
- anti histamines
- aspirin
- anti TNF antibodies
how do vessels become leaky?
- consists of two factors
- hydrostatic pressure and colloid osmotic pressure
- hydrostatic pressure is the pressure exerted forcing water out of the vessels
- colloid osmotic pressure is the osmotic pressure pulling water into the vessels
- hydrostatic pressure > colloid osmotic pressure
what does the exudate consist of?
what is the function of the exudate?
- fluid, cells, proteins (fibrin)
- fluid purpose
dilutes pathogen and allows soluble mediators to spread - fibrin purpose
stops the pathogen from spreading and gives the inflammatory cells substrate to hold onto
what are the types of exudate ?
serous - fluid filled (blisters) fibrinous - high fibrin content due to trauma purulent- pus filled (Combination of fibrin, inflammatory cells, debris and fluid)
what is the action of neutrophils in acute inflammation?
- Enter tissue
- Migrate to site of cell injury - chemotaxis
- Become activated
- Carry out their designated role - e.g. phagocytosis
- Interact with other cell types - release of soluble mediators
what is the main role of neutrophils?
Main Role:
• Kill bacteria and recruit more cells
• Phagocytosis
• Degranulation
what is cellular egress?
consists of :
margination
- cells are pushed to the edges of vessels
rolling and adhesion
- Once at the margin they can bind to endothelial cells through selectins on the neutrophil and endothelial cells
The selectin bonds are loose - the neutrophil rolls along the side of the blood vessel and is slowed down
As it slows down more permanent bonds are formed which fixes the
neutrophil to the vessel wall
transmigration
- Neutrophil dissolves basement
Enters interstitium
chemotaxis
- Follow chemical gradient to the site of inflammation
what does phagocytosis consist of?
- opsonisation
- opsonins attach to the bacteria
- ingestion
pathogen is phagocytosed - killing
destruction of phagocytosed material in vacuole
what are eosinophils necessary for?
they are important in allergic and parasitic causes of inflammation
what are mast cells important in?
allergic diseases
how long does the inflammation last and what controls the length?
Mediators and neutrophils have short half life
• Stimulus (e.g. bacteria) removed
• Mast cells and lymphocytes release anti-inflammatory products (lipoxins)
• Macrophages release anti-inflammatory products
what are the histological features of acute inflammation?
There are lots of Neutrophils
- There will also be mast cells and eosinophils
what is the evolution of acute inflammation to chronic inflammation?
- Breakdown of myofibres
- Fewer neutrophils in chronic
inflammation - Other cell types involved
define prolonged inflammation?
Inflammation of prolonged duration in which active inflammation, tissue destruction and attempts at repair occur simultaneously.
what is the cause of chronic inflammation?
- Persistent infection
- Prolonged exposure to toxic agent
- Autoimmunity
- Foreign body (e.g. splinter)
what are the cells involved in chronic inflammation?
Macrophages
Lymphocytes
Plasma Cells
what do monocytes and macrophages do?
- Live longer than neutrophils
- Phagocytosis
- Control many other inflammatory cells - by releasing cytokines
- Increase in viral and atypical bacterial infections
what are the histological features of chronic inflammation?
Macrophages, lymphocytes and plasma cells present
what is the histology of granulation tissue?
Lots of fibroblasts producing granulomatous tissue
what is the basic pathology of Lots of fibroblasts producing granulomatous tissue?
FORM OF CHRONIC INFLAMMATION - shows granuloma formation
• Clusters of macrophages
• Involves specific immune reaction T cells
what are the causes of granulomatous inflammation?
Infection
Foreign Material
Reaction to Tumours
Immune Diseases (e.g. Crohn’s)
what are the histological features of granulomatous Inflammation?
- Macrophages are in the middle and lymphocytes around the outside
- Horseshoe shaped nuclei and fused macrophages are seen at latter stages of
granulomatous inflammation
what are the main differences between acute and chronic inflammation?
acute
- neutrophils
- histamine
- necrosis
- lasts a few days
- complete resolution
chronic
- monocytes
- cytokines
- prominent scar tissue
- delayed onset
- scar tissue
what are the good outcomes of inflammation?
- removes the causative agent
- cessation of inflammatory reaction
- heals the tissue damage to preserve integrity and function
what are the bad effects of inflammation?
LOCAL:
• Excess local tissue damage/scarring
• Secondary effects on nearby tissue - e.g. bronchoconstriction in asthma
SYSTEMIC:
• Systemic inflammatory reaction
• Secondary multi-organ failure
eg. septic shock
what is resolution ?
what is repair?
RESOLUTION = regeneration of normal functional parenchymal cells
REPAIR = connective tissue and SCAR TISSUE formation
when does resolution happen?
Tissue contains cells that are capable of regeneration to replace lost cells:
• EXAMPLE: Liver cells
Little structural damage done
when does repair happen?
tissue loss is too great and cells are unable to regenerate
what happens when resolution happens? in Pneumococcal lobar pneumonia
Initially you get exudation
• Then you get red hepatisation - erythrocytes move into the alveolar cells
The erythrocytes break down causing grey hepatisation
• Provided that the underlying structure (BASEMENT MEMBRANE) is still there -
the body can remove the problem
what happens when repair happens?
- Fibroblasts - produce collagen
- Collagen - strong scar type collagen
- Remodelling - reorganisation of collagen fibres for maximal tensile strength
what hinders repair?
generally?
- Poor nutrition (protein needed for collagen production)
- Vitamin Deficiency (C needed by fibroblasts to make collagen, A needed for epithelial regeneration)
- Mineral Deficiency
- Suppressed Inflammation
what hinder repair locally?
- Poor blood supply
- Persistent foreign body (e.g. splinter)
- Movement (e.g. broken bones need casts to hold the bones in place
what are complications of repair?
- Keloid Formation
• Excess collagen deposition - Contractures
• Fibrous scar tissue contracts as part of its maturing process
-Impaired Organ Function
• Fibrous scars forming in organs will cause loss of functional tissue
