Acute Inflammation Flashcards
What is acute inflammation?
(Acute) Inflammation “Response of living tissue to injury”
Innate, immediate and early, stereotyped
Short duration – minutes/hours/few days
“initiated to limit the tissue damage”
What is acute inflammation controlled by and what can it lead to?
- Vascular and cellular reactions
Accumulation of fluid exudate and neutrophils in tissues - Controlled by a variety of chemical
- Protective, but can lead to local mediators derived from plasma or cells complications and systemic effects
What are the causes of acute inflammation?
- Microbial Infections – e.g. pyogenic organisms
- Hypersensitivity reactions (acute phase)
- Physical agents
- Chemicals
- Tissue necrosis
What are the clinical features of acute inflammation?
Main clinical signs: – RUBOR = redness – TUMOR = swelling – CALOR = heat – DOLOR = pain & loss of function
What are the changes in tissues in acute inflammation?
Changes in tissues : 1. Changes in blood flow 2. Exudation of fluid into tissues 3. Infiltration of inflammatory cells Inflammatory mediators of each step
What are the changes in blood flow in the vascular phase of acute inflammation?
- Transient vasoconstriction of arterioles (few secs)
- Vasodilatation of arterioles and then capillaries
- –> increase in blood flow (heat and redness) - prolonged to last for the duration of the process - Increased permeability of blood vessels
- –> exudation of (protein – rich) fluid into tissues
- –> slowing of circulation (swelling) - (Concentration of RBCs in small vessels and
increased viscosity of blood = STASIS)
In the vascular phase of acute inflammation, describe the response of the chemical mediators
1) Immediate early response (1/2 hr)
• HISTAMINE
– Released from mast cells, basophils and platelets
– In response to many stimuli: e.g. physical
damage, immunologic reactions, C3a, C5a, IL-1, factors from neutrophils and platelets
causes:
vascular dilatation, transient increase in vascular permeability, pain
Persistent response:
• Many and varied chemical mediators, interlinked and of varying importance
• Incompletely understood
e.g. leukotrienes, bradykinin
Phase ii. Exudation of fluid into tissues
What is the fluid flow across vessel walls determined by?
• Fluid flow across vessel walls is determined by the
balance of hydrostatic and colloid osmotic pressure
comparing plasma and interstitial fluid:-
– Increased hydrostatic pressure -> increased fluid flow out of vessel
– Increased colloid osmotic pressure of interstitium -> increase fluid flow out of vessel
What leads to the net outflow of fluid in vessels?
• Acute inflammation -
– arteriolar dilatation leads to increase in hydrostatic pressure
– increased permeability of vessel walls leads to loss of protein into interstitium
Therefore Net flow of fluid out of vessel -> OEDEMA (increased fluid in tissue spaces)
What are the consequences of vascular leakage?
Consequences of Vascular Leakage = Oedema
• Oedema = excess of fluid in interstitium
• Can be transudate or exudate
• Oedema leads to increased lymphatic drainage
Define exudate and transudate
- Fluid loss in inflammation is an EXUDATE = high protein content - more protein content than plasma
- Fluid loss due to hydrostatic pressure imbalance only is a TRANSUDATE = low protein content (e.g. cardiac failure or venous outflow obstruction) - same protein content as plasma
What are the mechanisms of vascular leakage?
• Endothelial contraction -->gaps – histamine, leukotrienes • Cytoskeletal reorganisation --> gaps – Cytokines IL-1 and TNF • Direct injury - toxic burns, chemicals • Leukocyte dependent injury – toxic oxygen species and enzymes from leucocytes • Increased transcytosis - channels across endothelial cytoplasm – VEGF
What is the purpose of exudation?
Delivery of plasma proteins e.g. fibrin to the site on injury
In the cellular phase o acute inflammation, what is the primary type of white blood cell involved in inflammation?
Neutrophil leucocyte
• The primary type of white blood cell involved in
inflammation. Neutrophils are a type of granulocyte,
also known as a polymorphonuclear leucocyte
N.B. Neutrophil = polymorph (multi lobed nucleus)
What are the stages in the infiltration of neutrophils?
- Stasis causes neutrophils to line up at the edge of
blood vessels along the endothelium = MARGINATION (RBCs stay in the middle) - Neutrophils then roll along endothelium, sticking to it intermittently = ROLLING
- Then stick more avidly = ADHESION
- Followed by EMIGRATION of neutrophils through blood vessel wall
How do neutrophils escape from vessels?
- Relaxation of inter-endothelial cell junctions
- Digestion of vascular basement membrane
- Movement
How do neutrophils move?
How do neutrophils move? Diapedesis and Emigration; Chemotaxis.
Chemotaxis = movement along concentration gradients of chemoattractants
• Chemotaxins - C5a, LTB4, bacterial peptides
• Receptor-ligand binding
• Rearrangement of cytoskeleton
• Production of pseudopod
What is phagocytosis?
Neutrophils engulf pathogens contact, Recognition, Internalisation facilitated by opsonins (Fc and C3b) cytoskeletal changes phagosomes fuse with lysosomes to produce secondary lysosomes
Opsonins attach to debris for which polymorphs have receptors eg F.C. (immunoglobulin) and c3b - part of complement cascade
Overlap of immunity and inflammation
What are the 2 types of killing mechanisms?
O2 dependent
– Produces superoxide and hydrogen peroxide.
– H2O2-Myeloperoxidase-halide system - produces HOCl.
O2 independent
– Lysozyme & hydrolases
– Bactericidal Permeability Increasing Protein (BPI)
– Cationic proteins (‘Defensins’)
- important in infarction (necrosis secondary to ischaemia) where there is hypoxia
What are the chemical mediators of acute inflammation?
• Proteases (plasma proteins, produced in liver)
– Kinins
– Complement system C3a, C5a
– Coagulation / fibrinolytic system
• Prostaglandins / Leukotrienes
– Metabolites of arachidonic acid
• Cytokines / chemokines (produced by wbc’s)
– Many and varied! Interleukins, TNF alpha
What are the effects of chemical mediators of acute inflammation?
- Increased blood flow : histamine, prostaglandins
- Vascular permeability : histamine, leukotrienes
- Neutrophil chemotaxis : C5a, LTB4, bacterial peptides
- Phagocytosis : C3b
What are the 2 “hallmarks” of acute inflammation?
- exudate of oedema
- infiltrate of inflammatory cells
How does exudation of fluid combat injury?
1. Exudation of fluid Delivers plasma proteins to area of injury - Immunoglobulins - Inflammatory mediators - Fibrinogen
Dilutes toxins
Increases lymphatic drainage
- Delivers micro-organisms to phagocytes and antigens to immune system
- any cause of oedema increases lymphatic drainage
Other than exudation of fluid, what other changes can combat injury?
- Infiltration of Cells
Removes pathogenic organisms, necrotic debris - Vasodilatation
Increases delivery, increases temperature - Pain and loss of function
Enforces rest, reduces chance of further traumatic
damage.
