4 - Inflammation Flashcards
What is inflammation?
Reaction of living vascularised tissue to sub-lethal cellular injury
What is the function of inflammation?
Remove cause of injury and initiate repair.
Types of inflammation
acute (hours/days)
chronic (weeks/months)
Different cell types and mechanisms
BUT NOTE – inflammation can also have harmful effects – Can cause tissue destruction
Causes of inflammation
Infection… BUT inflammation is NOT JUST caused by infectious organisms…
Foreign body
Tissue destruction – mechanical trauma, chemical injury, radiation injury, endogenous (autoimmune reaction, crystal deposition)
What are the inflammatory cells?
Neutrophils
Macrophages
Lymphocytes
What are the vascular changes involved with inflammation?
Immediate supply of cells and soluble factors
Extracellular matrix and resolution or repair
What are neutrophils and what is their role?
Produced in bone marrow
Circulate in blood
Contain cytoplasmic granules
ROLE
Phagocytosis (gobble up) of organisms, debris.
Degranulation (release contents of granules)
Enzymes
Free radicals
Soluble mediators
What are monocytes/macrophages and what do they do?
Monocytes in blood
Once in tissue give rise to macrophages
ROLE
Phagocytosis
Control many other inflammatory cells
Release cytokines
What do Eosinophils do?
Seen in allergic and parasitic causes of inflammation
What do mast cells do?
Also seen in allergic diseases
What are the vascular changes involved in inflammation? Explained…
Vascular calibre and flow increased REDNESS & HEAT
Dilatation and increased blood flow to injured area enables rapid delivery of inflammatory cells and mediators
Adhesion molecules expressed on endothelium
Inflammatory cells stick to vessel wall
Vascular permeability -> SWELLING
Leaky capillaries allow cells and mediators to enter tissue – EXUDATE
What is exudate?
What comes out of leaky vessels – fluids, cells, proteins (fibrin, antibodies, small molecules involved in cell signaling)
- Purulent
- Serous
- Haemorrhagic
- Fibrinous
How do white cells change during inflammation?
Leave blood and enter tissue
Migrate through tissue to injured site (chemotaxis)
Become activated
Ingest organisms/cell debris (phagocytosis)
Secrete soluble mediators that aid inflammatory process
How do cells get to the sight of injury?
Chemotaxis…
Move towards injured area
Exogenous and endogenous compounds attract cells.
Activation…
Phagocytosis
What is inside the phagosome?
Oxygen Independent cell killing Bactericidal permeability increasing protein – “does what is says on the tin” Lysozyme Lactoferrin Major basic protein Defensins
What soluble factors are in exudate?
-Factors produced locally by cells
-Vasoactive amines
Released from mast cells, basophils and platelets
Histamine
Causes increased vascular permeability
e.g. Acute asthmatic reactions
Other Factors
Platelet Activating Factor
Clotting factors
Nitric oxide
CYTOKINES – proteins produced by many cell types (lymphocytes, macrophages, endothelial cells, etc) that modulate function of other cells – IL1 and Tumour necrosis factor (TNF).
-Circulating plasma proteins
-Antibodies
Clinical features of acute inflammation.
LOCAL
RUBOR – redness
TUMOUR – swelling (oedema)
CALOR – heat
DOLOR – pain
Loss of function
Clinical features of acute inflammation.
SYSTEMIC
Fever
shock
Summary of acute inflammation
Acute co-ordinated response: vessels, cells and soluble mediators
Neutrophil is main cell
Exudate formed
Variety of outcomes
Outcome of acute inflammation
RESOLUTION
Tissue returns to normal
Only occurs if :-
Tissue contains cells that can regenerate to replace lost cells
Little structural damage done – cells need a framework to build on.
Classic example – Pneumococcal pneumonia
Outcome of acute inflammation
REPAIR
Tissue loss too great, and cells unable to regenerate
Replace normal tissue with fibrous scar tissue
Fibroblasts – produce collagen
Collagen – strong “scar” type collagen
Remodelling – reorientation of collagen fibres for maximal tensile strength
Abscess
What hinders repair?
GENERAL
Poor nutrition…
Protein needed for collagen production and energy needed for cell function.
Vitamin deficiency
Vitamin C – needed by fibroblasts to make collagen
Vitamin A- required for epithelial regeneration
Mineral deficiency
e.g. Zinc
Suppressed inflammation…
e.g. By steroids
Old age
Diabetes
What hinders repair?
LOCAL
Poor blood supply
Persistent foreign body
Movement e.g across a fracture site, hence the need for a cast.
What hinders repair?
COMPLICATIONS
Keloid (area of irregular fibrous tissue formed at the site of a scar or injury) formation
Excess collagen deposition
Contractures (shortening and hardening of muscles, tendons, or other tissue, often leading to deformity and rigidity of joints)
Fibrous scar tissue contracts as it matures. If scarring occurs across a joint it can cause poor joint mobility.
Impaired function
e.g. fibrous scars in the myocardium after a heart attack
