Inflammation Flashcards
Inflammation is a complex reaction of what type of tissue?
Vascularised connective tissue
Give 2 pros of inflammation
without inflammation:
1- wounds and injured organs would never heal
2-infections would go unchecked
Give 3 cons of inflammation
inflammation can be dangerous because:
1- life threatening hypersensitivity reactions
2- chronic inflammatory diseases; rheumatoid arthritis
3- repair by fibrosis may lead to problems; disfiguring scars
What are the 2 types of inflammation?
Acute - initial rapid and often short-lived series of tissue reactions to injury
Chronic - the subsequent and often prolonged tissue reactions following the initial response
What are the 5 principal causes of acute inflammation?
1- infections 2-hypersensitivity reactions 3-physical agents (trauma) 4-irritant and corrosive chemicals 5- foreign bodies
What are the 5 physical characteristics of inflammation?
1- Rubor 2-Calor 3-Tumor 4-Dolor 5-loss of function
What are the phases of acute inflammation?
1- vascular phase –> i)vasodilation, ii) increased permeability of blood vessels
2- exudative and cellular phase –> i) fluid exudate, ii) cellular component
Explain and describe the vascular phase of acute inflammation
i) vasodilation = results in increased blood flow, thus rubor and calor
ii) increased vascular permeability= brought about by chemical mediators histamine and bradykinin, forms gaps in venules, leakage of fluid confined to POST-CAPILLARY VENULES.
Explain and describe the exudative and cellular phase of acute inflammation
i) the fluid exudate = contains fibrin, proteins and white blood cells. fluid exudate escapes from the permeable venules, and is continually removed by lymphatics then replaced. Net increase in extravascular fluid is called ODEMEA.
ii) the cellular component = diagnostic feature of acute inflammation is neutrophil accumulation in the extracellular space.
What are neutrophils?
Neutrophils are white blood cells (leukocytes) which move from the blood stream and into a wound to engulf and digest contaminants.
What are the 6 functions of neutrophils?
1- kill microorganisms 2-ingest offending agents 3-degrade necrotic tissue 4-produce chemical mediators 5-produce toxic oxygen radicals 6-produce tissue damaging enzymes
What is the first step in order for neutrophils to reach the site of inflammatory stimulus?
MARGINATION = loss of plasma and increased plasma viscosity slows down blood flow and allows neutrophils (white blood cells which usually flow in the lumen of the blood vessel) to flow in the plasmatic zone [ONLY OCCURS IN VENULES]
What is the second step in order for neutrophils to reach the site of inflammatory stimulus?
ADHESION = neutrophils adhere to endothelial cell wall (interaction between adhesion molecules on neutrophil surface and the endothelial wall)
What is the third step in order for neutrophils to reach the site of inflammatory stimulus?
TRANSENDOTHELIAL MIGRATION = after successful adhesion to endothelium, neutrophils insert pseudopodia (arm-like projections of cytoplasm) into the junctions between endothelial cells. Then cross through basement membrane into extravascular space.
What is this 3 step process of neutrophil migration to the site of inflammatory stimulus termed as?
Chemotaxis
Give the 4 compounds which direct neutrophils in chemotaxis (chemotactic compounds)
1- bacterial products
2- complement components
3- cytokines
4- products produced by neutrophils themselves
What happen once the neutrophil has reached the wound debris, it must attach to the micro-organism (debris), but what process must happen first?
OPONISATION -
a particle is first “coated” in OPSONINS (antibodies which attach to antigens on particle) in order to be better targeted in phagocytosis.
What is phagocytosis?
Phagocytosis is the complex process by which phagocytes such as neutrophils and macrophages engulf and ingest micro-organisms or other cells and foreign particles
What is the first step of phagocytosis?
RECOGNITION AND ATTACHMENT = typical but not absolute requirement - leucocyte surface receptors recognise particles.
What is the second step of phagocytosis?
ENGULFMENT = cytoplasmic extensions flow around the particle and completely engulf particle - phagosome
Phagosome membrane fuses with lysosomal (vesicles in cytoplasm) membrane to create phagolysosome - discharge lysosomal content (digestive enzymes) into phagolysosome
What is the third step of phagocytosis?
KILLING AND DEGRADATION = Killing in 2 ways: Oxygen dependent, Oxygen independent Degradation: acid hydrolase from lysosomes degrade microorganism inside the phagolysosome
What may occur when leucocyte products are released into extracellular space and into phagolysosome?
May cause tissue and endothelial damage
What process do neutrophils undergo after phagocytosis?
Apoptosis
What are chemical mediators in inflammation?
Chemicals which mediate the inflammatory response, stimulated by the foreign microorganism
Give a few results of chemical mediator activity
Vasodilation, itching and pain, emigrations of neutrophils, chemotaxis, increasing vascular permeability.
Give a few examples of some CELL DERIVED chemical mediators
Histamines Serotonin Leukotrienes Lysosomal compounds chemokines prostaglandins
Give a few examples of some PLASMA DERIVED chemical mediator cascades
Kinin system - bradykinin
Fibrinolytic system
Complement system
Coagulation system
What are the beneficial effects of acute inflammation?
1 - dilution of toxins 2 - entry of antibodies 3 - stimulation of immune response 4 - firkin formation to impede microorganism movement 5 - delivery of nutrients 6 - transport of drugs (antibiotics)
What are the harmful effects of acute inflammation?
1 - digestion of normal tissues
2 - swelling - laryngeal oedema, brain swelling
3 - inappropriate inflammatory response - type 1 hypersensitivity
What are the systemic effects of acute inflammation?
1 - fever
2 - weight loss
3 - increased pulse and blood pressure
4 - reactive hyperplasia (enlargement of organs)
What are the outcomes of acute inflammation?
1- restitution (i.e complete restoration)
2- access formation
3 - chronic inflammation
4 - healing with scar formation by repair
What is chronic inflammation?
inflammation which either 1) follows on from acute or 2)primary chronic inflammation which is characterised by the cellular reaction
What factors favour acute to chronic inflammation?
if agent causing acute is not removed because:
1) indigestible material e.g. glass, suture
2) suppurative inflammation i.e. PUS due to inadequate/delayed drainage
3) recurrent episodes of acute appears as chronic clinically
What factors favour primary chronic inflammation?
1) Specific diseases of unknown aetiology e.g. ulcerative colitis
2) Some autoimmune diseases e.g. rheumatoid arthritis
3) Resistance of infectious agent to phagocytosis
4) foreign body reaction to exogenous and endogenous materials
5) primary granulomatous diseases
What are the main characteristics of chronic inflammation compared to acute inflammation?
LESS odemea and LESS change in blood flow, infiltration of tissues by MACROPHAGES, LYMPHOCYTES and PLASMA CELLS (neutrophils are scarce)
What is chronic inflammation almost uniformly accompanied by?
Tissue destruction and consequent attempts at healing by fibrosis
What are macrophages?
large white blood cell
capable of phagocytosis but DOESN’T DIE afterwards
activated by T cells
can fuse together to form multinucleated GIANT CELL
can release a number of proteolytic enzymes –> degradation of ECM –> tissue damage
What are the classification of cell types important to inflammation and wound healing?
LIABLE = multiply continually through life e.g. GI tract, bone marrow STABLE = multiply when receive stimulus e.g. hepatocytes, endothelium PERMANENT = cannot multiple e.g. neurones, skeletal muscle
Which cells can be replaced if lost?
Liable and Stable cells as they can multiply
What is not reconstructed in wound healing?
Complex tissue architecture
When does repair occur?
When there is tissue LOSS
When does connective tissue fibrosis occur?
when tissue destruction included = parenchymal cells AND associated stromal cells
What occurs in connective tissue fibrosis?
1) new blood cell formation
2) migration and proliferation of fibroblasts
3) deposition of collagen
4) maturation and organisation of fibrous tissue
What is organisation of tissue?
Organisation is tissue replacement by granulation issue , occurs if large amounts of fibrin are formed, if there is substantial necrosis and if fluid exudate cannot be removed
What is restitution?
the complete restoration of the tissues to normal after an episode of acute inflammation
When does recitation normally occur?
When there is:
1) minimal cell death & tissue damage
2) in an organ with regenerative capacity (liver)
3) rapid destruction of causal agent
4) good vascular drainage = rapid removal of fluid and debris
Compare scarring by first and second intention
1) First intention is surgical, second intention is ulcerated
2) First intention has closely posed edges, second intention edges widely separated
3) first intention = minimal granulation tissue, second intention = prominent granulation tissue
4) first intention = minimal fibrosis, second intention = prominent fibrosis
What are the local factors which influence wound healing
1) infection
2) early motion of wound
3) foreign bodies
4) size/location/type
What are the systemic factors which influence wound healing
1) nutrition
2) metabolic status (diabetics heal more slowly)
3) circulatory status (vast. supply must be good!)
4) hormones
What are a few types of scars gone wrong?
keloid scars = too much
contractures = looks too tight
ulceration
