inflammation and wound healing Flashcards
what is inflammation
local physiological response to tissue injury in vascularised connective tissue involving reaction of blood vessels which lead to accumulation of fluid and leucocytes in extravascular tissue
what type of response is inflammation
protective
what would happen without inflammation
Wounds and injured organs would never heal
Infections would go unchecked
in what cases can inflammation be harmful
- Life-threatening hypersensitivity reactions
- Chronic inflammatory diseases eg
rheumatoid arthritis and Crohn’s disease - Repair by fibrosis may lead to problems such as
disfiguring scars
what are the 2 types of inflammation
acute and chronic
what is acute inflammatioin
the initial rapid and often short lived series of tissue reactions to injury
what is chronic inflammation
the subsequent and often prolonged tissue reactions
following the initial response
what are the principle causes of acute inflammation
- infections e.g viruses, bacteria like ecoli
- hypersensitivity reactions e.g reactions to parasites
- Physical agents
eg physical trauma, uv light, thermal injury (burns or frostbite) - Irritant and Corrosive chemicals
eg acids, alkalis, infecting agents releasing chemical irritants - Foreign bodies
eg splinters, dirt, sutures, restorative materials
physical characteristics of inflammation
redness (rubor) - acute inflamed tissue appears red due to dilation of small blood vessels
heat (calor) - increase temp of tissue due to increases blood flow thorugh region
swelling (tumor) - accumulation of fluid in extravascular space
pain (dolor) - due to stretching and distortion of tissues caused by increased fluid
loss of function - movement inhibited by pain
describe the processes of acute inflammation
- vascular phase
- vasodilation (results in precapillary sphincter opening = increased blood flow therefor heat and redness)
- increased permeability of blood vessels ( brought about by chemical mediators like histamine and bradykinin)
- Exudative and cellular phase
- Fluid and cells escape from permeable venules
IDEK = Leakage of fluid is confined to POST CAPILLARY VENULES
Gaps in venules are largely intercellular
Endothelial cells contain contractile proteins, when stimulated by chemical
mediators they pull open transient pores
Endothelial cells are NOT damaged in this process
what is the net increase of extravascular fluid called
oedema
Explain the fluid exudate
what is the diagnostic feature of acute inflammation
neutrophil accumulation in the extracellular space
functions of neutrophils
kill microorganisms
ingest offending agents
degrade necrotic tissue
produce chemical mediators
produce toxic oxygen radicals
produce tissue damaging enzymes
how does a neutrophil reach the site of an inflammatory stimulus
chemotaxis = locomotion orientated along a chemical gradient
by a combination of different processes that involving adhesion of circulating leucocytes to endothelial cells and subsequent migration through endothelium
what are the 3 stages in the neutrophils reaching the site of inflammatory stimulus
- Migration - normally blood cells flowing centre of the lumen, the area adjacent to blood vessel wall carries only plasma / loss of intravascular fluid and increased plasma viscosity slows flow allowing neutrophils to flow in the plasmatic zone (ONLY OCCURS IN VENULES)
- Adhesion - increased neutrophils adhesion results from interaction between adhesion molecules on its surface and the endothelial surfaces
- Transendothelial migration - once firm adhesion to the endothelium has been achieved, neutrophils insert pseudopodia into the junctions between endothelial cells. they then cross through the basement membrane and into the extravascular space
what compounds do chemotactics for neutrophils include
- bacterial products
- complements components
- cytokines
- Products produced by neutrophils themselves
what is the definition of phagocytosis
complex process by which phagocytes such as neutrophils and macrophages engulf and ingest microorganisms or other cells and foreign particles
what are the 3 steps in phagocytosis
- recognitions and attachment
- engulfment -
- killing and degradation
what is opsonization
process of coating a particle to target it for phagocytosis
what is the role of Opsonins
they bind specifically to receptors on leucocytes and greatly enhance phagocytosis
describe the process of phagocytosis
- recognitions and attachment - initiated by recognition of
particles by leucocyte surface receptors - engulfment - Attachment of a particle to a phagocyte receptor initiates the process of active phagocytosis. Engulfment involves cytoplasmic extensions to flow around the particle
resulting in complete ‘engulfment’ of the particle within a phagosome
made by the cell membrane
This phagosome membrane then fuses with lysosomal membrane,
resulting in discharge of the lysosome content into the phagolysosome - killing and degradation = Killing of infectious agents occurs by 2 types of mechanism:
i. Oxygen-dependent
Phagocytosis results in products of oxygen reduction which cause
intracellular killing of micro-organisms
ii. Oxygen-independent
Via the action of substances in leucocyte granules
eg Lysozyme which attacks bacterial coat
Defensins that are cytotoxic to microbes
Acidic pH inside phagocytic vacuoles
After killing, acid hydrolase from lysosomes degrade the
microorganisms inside the phagolysosome
During activation and phagocytosis, leucocyte products are released
into the EXTRACELLULAR SPACE as well as into phagolysosome
what are the effects of lysosomal product release
products may cause endothelial and tissue damage
1. Activates coagulation factor XII
2. Attracts other leucocytes into the area
3. Damages local tissues
4. Increases vascular permeability
5. Pyrogens producing systemic fever
what do neutrophils undergo after phagocytosis
apoptosis
what is the role of chemical mediators of acute inflammation
endogenous chemical mediators that drive the process of inflammation
what do chemical mediators cause
- Vasodilatation
- Emigration of neutrophils
- Chemotaxis
- Increased vascular permeability
- Itching and pain
what chemical mediators of inflammation are released
- Histamine
- Lysosomal compounds
- Serotonin
- Chemokines
- Leukotrienes
- Prostaglandins
what factors does the plasma do in inflammation
it contains 4 enzymatic cascade systems which mediate various aspects of inflammation
1. Complement system
2. Coagulation system
3. Kinin system
4. Fibrinolytic system
what are the beneficial effects of acute inflammation
- Dilution of toxins- can be carried away by lymphatics
- Entry of antibodies- due to increased vascular permeability
- Stimulation of the immune response- fluid exudate containing
antigens reaches local lymph nodes - Fibrin Formation – impedes movement of micro-organisms
- Delivery of nutrients and oxygen - aided by blood flow
- Transport of drugs – eg antibiotics
what are the harmful effects of acute inflammation
- Digestion of normal tissues
- Swelling – eg laryngeal oedema, brain swelling
- Inappropriate inflammatory response – eg type I hypersensitivity
what are the systemic effects of acute inflammation
- Fever
- Constitutional Symptoms
- Weight Loss
- Reactive Hyperplasia of the Reticuloendothelial System
- Haematological Changes
what factors favour progression from acute to chronic inflammation
- Indigestible substances such as glass and suture material
- Deep seated suppurative inflammation in which drainage is delayed or inadequate will
result in a thick abscess wall composed of fibrous/granulation tissue - Recurrent episodes of acute inflammation and healing may eventually result in the
clinicopathological entity of chronic inflammation
what are 6 examples of chronic inflammation
- Resistance of infective agent to phagocytosis and intracellular killing eg Tuberculosis,
leprosy, viral infections - Foreign body reactions to endogenous materials eg gout (may be acute or
chronic) - Foreign body reactions to exogenous materials eg asbestos
- Some autoimmune diseases eg. Rheumatoid arthritis
- Specific diseases of unknown aetiology eg ulcerative colitis
- Primary granulomatous diseases eg sarcoidosis
what are the cells that are most predominant in chronic inflammation
lymphocytes, plasma cells and macrophages
A few eosinophils may be present but neutrophil polymorphs are scarce
what cells can be replaced if lost
ONLY labile and stable
what can cells be divided into
labile - (multiply continually throughout life)
eg GI Tract, Bone Marrow
stable - (only multiply when receive stimulus to do so)
eg Hepatocytes, Endothelium
permanent populations- Permanent (cannot multiply)
eg Neurones, Skeletal Muscle
what is meant by the term restitution
complete restoration of the tissue to normal after an episode of acute inflammation
what factors favour restitution
- Minimal cell death and tissue damage
- Occurrence in an organ or tissue with regenerative capacity
eg liver - Rapid destruction of the causal agent
- Rapid removal of fluid and debris by good local vascular drainage
describe repair by connective tissue fibrosis
Tissue destruction includes loss of parenchymal cells
and the associated stromal framework
Non-regenerated parenchymal cells replaced by connective tissue
(granulation tissue) which in time produces fibrosis and scarring
what does repair by connective tissue fibrosis involve
- Angiogenesis- formation of new blood vessels
- Migration and proliferation of fibroblasts
- Deposition of collagen
- Maturation and organisation of fibrous tissue - remodelling
what is organisation of tissues
replacement by granulation tissue
what factors favour organisation
- Large amounts of fibrin formed
- Substantial necrosis
- Exudate and debris cannot be removed or discharged
describe repair with scarring and the contrast between first and second intention
First Intention -
Surgical scar -
Closely apposed edges
Minimal granulation tissue
Minimal fibrosis
Second Intention -
Ulcerated surface -
Edges widely separated
Prominent granulation tissue
Prominent fibrosis
what are the local factors that influence wound healing
- Infection – single most important cause of delay in healing
- Mechanical factors – ie early motion of wounds delays healing
- Foreign bodies – ie sutures or glass
- Size, location and type of wound – wounds heal better in richly
vascularised areas
what are the systemic factors that influence wound healing
- Nutrition – wound healing profoundly influenced by ability to
synthesise protein and collagen - Metabolic status – diabetes is associated with delayed healing
- Circulatory status – an adequate vascular supply is essential for
normal cellular function (hypoxia, reduced local nutrition) - Hormones – glucocorticoids are anti-inflammatory but impair
collagen synthesis
what are the pathological aspects of wound repair
- Deficient scar formation – wound dehiscence/ulceration
- Excessive formation of repair components – keloid scar
- Formation of contractures – exaggerated contraction
results in deformity of the wound and surrounding tissues
In summary wound healing is a complex but orderly
phenomenon involving a number of processes:
* Induction of acute inflammatory response
* Regeneration of parenchymal cells (if possible!)
* Migration and proliferation of parenchymal and connective tissue
cells
* Synthesis of collagen
* Remodelling/organisation of connective tissue and parenchymal
components
