Lecture 4; Cell injury, inflammation and healing. Part 2. Flashcards
What are some basic principles of inflammation?
- Bodys response to tissue injury
- Dynamic process, evolves over time
What are triggers of acute inflammation?
- Infections and microbial toxins
- Trauma
- Physical and chemical agents
- Tissue necrosis
- Foreign bodies
- Immune reactions
Describe how acute inflammation is a dynamic process;
Following tissue injury;
1) Pro-inflam cytokines are released
2) Resident tissue macrophages are activated
3) Endothelial cells are activated to alter blood flow.
In acute inflammation what does endothelial cell activation result in? What are the messangers?
Activated endothelial cells produce;
- Inflam cytokines
- Prostoglandins
- NO
= Vasodilation and increased permeability
Describe blood flow changes in inflammation and what happens;
- Hyperaemia -> Protein rich exudate in tissue (Oedema)
Whats found in protein rich exudate / oedema?
Inflammatory cells (Generic)
- Antibodies
- Fibroninogen
- Compliment proteins
- Kinin and plasmin
What does the loss of fluid from vessels during inflammation do to blood flow dynamics and what does this allow?
Loss of fluid increases viscosity = Stasis
Stasis results in leukocytes found nearer edge of blood vessels (Margination) i.e post capillary venules.
Margination (1/4); Describe cell adhesion molecules in the margination process:
During inflammation the expression of cell adhesion molecules on the endothelial surface is increased.
- Endothelial SELECTIN molecule expression is increased and these slow neutrophil. (Selectins bind glycoproteins) (remember margination has occured and stasis)
- Neutrophils increase INTEGRINS which bind ligands known as addressins on endothelial cells (Causes neutrophils to firmly stop and adhere)
Margination (2/4); Describe how endothelial cells migrate;
Move between endothelial cells in a process known as diapaedesis. (Moving between endothelial cells and then basement membrane into the extra vascular space)
Margination (3/4); Describe how neutrophils become activated;
Neutrophils become activated by multiple signals including;
- Chemokines
- IL1
- TNF-Alpha
- Bacterial products that bind toll like receptors
Margination (4/4); Describe what makes the neutrophils move towards the site of inflammation.
Moving up the gradient of chemotactic factors (Chemotaxis), Filopedia extended during this.
These factors include;
- Exogenous substances i.e bacterial products
- Endogenous substances i.e Compliments, leukotrienes, chemokines i.e IL8
When is acute inflammation terminated?
- Offending agent is eliminated.
- Secreted mediators of inflammation are broken down or eliminated
- Active anti-inflammatory mechanisms are present. (Prevent excessive damage to the tissue)
What are the local clinical manifestations of inflammation?
- Redness (Rubor)
- Swelling (Tumor)
- Heat (Calor)
- Pain (Dalor)
- Loss of function
What are the systemic effects of inflammation?
- Pyrexia (IL1, TNFa)
- Leukocytosis
- Acute Phase Proteins (increased production from liver)
- Endocrine changes i.e increased glucocorticoid steroid hormones.
Why is controlling inflammation important?
Inflammatory and repair processes that follow them can be harmful if they occur inappropriately or are not adequately controlled.
