Acute and Chronic Inflammation Flashcards
What are the causes of acute inflammation?
- Physical agents, e.g. trauma, heat/cold, UV light, radiation.
- Irritant and corrosive chemical substances, e.g. acids and alkalis.
- Microbial infections, e.g. pyogenic bacteria.
- Immune-mediated hypersensitivity reactions, e.g. immune-mediated vasculitis, seasonal allergic rhinitis.
- Tissue nerosis, e.g. ischaemia resulting in an MI.
What are the causes of chronic inflammation?
Chronic inflammation usually develops as a primary response to:
- Microorganisms resistant to phagocytosis or intracellular killing mechanisms e.g. tuberculosis, leprosy.
- Foreign bodies, which can be endogenous (e.g. bone, adipose tissue, uric acid crystals) or exogenous (e.g. silica, suture materials, implanted prostheses).
- Some autoimmune diseases, e.g. Hashimoto’s thyroiditis, rheumatoid arthritis, contact hypersensitivity reactions.
- Primary granulomatous diseases, e.g. Crohn’s disease, sarcoidosis.
Inflammation becomes chronic when it occurs over a long period of time with simultaneous tissue destruction and attempted repair.
It may occur secondary to acute inflammation due to the persistence of the causative agent.
What are the classic signs of acute inflammation?
- Redness (rubor)
- Heat (calor)
- Swelling (tumour)
- Pain (dolour)
- Loss of function
These are produced by rapid vascular response and cellular events characteristic of acute inflammation.
What is the main function of the events of acute inflammation?
To bring elements of the immune system to the site of injury and prevent further tissue damage.
What is the difference between acute and chronic inflammation with respect to type of immunity?
- Acute inflammation - innate immunity.
- Chronic inflammation - cell-mediated immunity.
What are the prominent cell types in acute and chronic inflammation?
-
Acute inflammation
- Neutrophil
-
Chronic inflammation
- Lymphocytes
- Plasma cells
- Macrophages
What is the vascular response in acute inflammation?
- Blood flow to the capillary bed is normally limited by precapillary sphincters.
- In acute inflammation, vasodilation occurs when the arterioles and precapillary sphincters relax.
- This results in increased blood flow to the injured area.
- Increased vascular permeability - endothelial intracellular proteins contract under the influence of chemical inflammatory mediators, such as histamine, bradykinin, NO and leukotriene B4.
- Endothelial contraction results in:
- Increased fenestrations between endothelial cells.
- Increased permeability of vessels to plasma proteins.
- Proteins leak out of the plasma into the interstitial spaes, leading to a decrease in the plasma oncotic pressure. It includes circulating components such as immunoglobulins and coagulation factors.
What is inflammatory oedema?
The combined increase in hydrostatic pressure and the decreased oncotic pressure (from leakage of proteins into interstitial spaces) causes net fluid movement from plasma into tissues; this is inflammatory oedema.
What are the advantages of inflammatory oedema?
- Fluid increase in the dammages tissue dilutes and modifies the action of toxins.
- Protein levels increase in the tissue - these include protective antibodies and fibrin.
- Non-specific antibodies act as opsonins for neutrophil-mediated phagocytosis and function to neutralise toxins.
- The formation of a fibrin net acts as a scaffold for inflammatory cells, preventing the spread of microorganisms.
- Circulation of the exudate into the lymphatic system assists in antigen presentation and helps mount a specific immune response.
What is extravasation?
The movement of leucocytes out of the vessel lumen.
What are the 5 stages of extravasation?
- Margination of the plasmatic zone. This is assisted by the slowing of the blood.
- ‘Rolling’ of leucocytes due to the repeated formation and destruction of transient adhesions with endothelium.
- Adhesion (‘pavementing’) - leucocytes, eventually firmly adhere to the vascular endothelium, due to the interaction of paired molecules on the leucocyte and endothelial surface.
- Transmigration (diapedesis) - leucocytes pass between the enodthelial cell junctions, through the vessel wall into tissue spaces.
- Chemotaxis - neutrophils migrate towards, and are possibly activated by, chemical substances (chemotaxins) released at sites of tissue injury. These chemotaxins are thought to be leukotrienes, complement components and bacterial products.
What is bradykinin?
- Kinins are small, vasoactive peptides and bradykinin is the most well-known.
- It exerts its effects by increasing vascular permeability and producing pain.
- Both effects are cardinal features of acute inflammation.
- The kinin system is stimulated by activated coagulation factor XII (the Hageman factor).
What is histamine?
A vasoactive amine
What are cytokines?
Give examples.
- Cytokines are a family of chemical messengers that act over short distances by binding specific receptors on target cell surfaces. They include:
- Interleukins - cytokines that act between leucocytes.
- Interferons - inhibit replication of viruses within cells and activate macrophages and natural killer cells.
- Growth factors.
- Tumour necrosis factors - kill tumour cells but also stimulate adipose and muscle catabolism ledading to weight loss.
- Tumour necrosis factor alpha (TNFα) and interleukin 1 (IL1) are key cytokines in acute inflammation.
Describe the role of nitric oxide in inflammation.
- NO is a potent vasodilator which is released from endothelial cells and macrophages.
- NO acts as a regulator of inflammation, actively reducing the effect of other proinflammatory mediators.
