PMI03-2012 Flashcards
Define inflammation.
Complex response of vascularised tissues to infections and tissue damage
Involves cells and molecules of host defence from the circulation
How long does acute inflammation take to develop?
Minutes to hours
How do acute and chronic inflammation differ?
Tissue composition
CAN OCCUR SIMULTANEOUSLY
What is the purpose of acute inflammation?
Destroy/contain noxious stimuli by dilution and phagocytosis
Initiate repair and return function by fibrin formation and nutrient transport
What agents can cause damage?
Physical = trauma, thermal, radiation
Chemical = CO, cigarette smoke, ethanol
Infectious = toxins, metabolic products, lysis, DNA damage
O2 deprivation = hypoxia, ischaemia
Immunologic = autoimmunity
What vascular events take place in inflammation?
Vasodilatation
Increased vascular permeability
Which mediators are responsible for the vascular events that occur in inflammation?
Histamine
Prostaglandins
Platelet activating factor
Kinins
Leukotrienes
What is the purpose of vasodilatation in inflammation?
Decreased flow rate so cells pack/vascular congestion and escape vessels more easily
What is the purpose of increased vascular permeability in inflammation?
Allows exudation of fluid, molecules and immune cells
Which cell is predominant in acute inflammation?
Neutrophil/polymorphonuclear leukocyte (PMN)
How do neutrophils reach the site of injury/infection from the blood?
Margination at site where vascular events have occurred
Receptors detect endothelial ligands (and vice versa) = rolling adhesion with selectins
Arrest of rolling with integrins (PMN) and ICAM-1 (endothelial)
Transmigration/diapedesis
Chemotaxis
Describe the process of rolling adhesion of neutrophils in acute inflammation.
L-selectin of neutrophils weakly binds P-selectin of endothelial cells
Attaching and detaching = rolling
Which molecules upregulate selectins?
IL-1
TNF
(released following tissue damage)
What molecules can contribute to chemotaxis of neutrophils?
Bacterial products
Chemokines
C5a/anaphylatoxins
Leukotriene B4
What are the three types of exudate?
Serous
Fibrinous/fibrin
Purulent/suppurative
Describe serous exudate.
Least common type of exudate
Cell-poor
Found in mucosal or skin blisters
Feature of certain viral infections
Describe fibrinous exudate.
Pinky-orange with H&E
Occurs where there has been significant vascular damage
Fibrinogen leaks out to form fibrin
Describe purulent exudate.
Cell-rich - usually with neutrophils
Found commonly in abscesses
Especially common in pyogenic bacterial infections (Staphylococcus)
Give some examples of plasma-derived mediators.
Kinins
Complement
Fibrin
Give some examples of inflammatory cell-derived mediators.
Histamine
Serotonin
Prostaglandins
Leukotrienes
Nitric oxide
Platelet activating factor
Describe how neutrophils carry out their actions.
- Adherence and ingestion with extension of pseudopodia into a phagosome - aided by opsonisation
- Phagosome fuses with lysosome to form phagolysosome
- Digestion
- Residual body is discharged or sequestered
How are the killing species/compounds created for digestion in a neutrophil?
Reduction of NADP+ to NADPH in formation of superoxide anion (ROS)
ROS converted to hydrogen peroxide
Myeloperoxidase converts H2O2 to hypochlorite in the presence of Cl-
What are the cardinal signs of inflammation?
Heat/calor
Redness/rubor
Swelling/tumor
Pain/dolor
Loss of function/functio laesa
What causes heat in inflammation?
Vasodilatation
Increased blood flow
What causes redness in inflammation?
Vasodilatation
Increased blood flow
What causes swelling in inflammation?
Exudation (increased vascular permeability)
What causes pain in inflammation?
Release of mediators
Exudation
Inflammatory cell influx
What are the beneficial effects of acute inflammation?
Dilution of toxins
Entry of antibodies and immune cells
Nutrient and drug transport
Fibrin formation
What are the adverse effects of acute inflammation?
Tissue damage
Swelling
Pyrexia
(Asthma and autoimmunity)
