Acute Inflammation

The immediate and easy response to injury designed to deliver leukocytes to the site of injury is called inflammation. It is the manifestation of a disease which can be beneficial but can also cause harm.

There are two types of inflammation- acute and chronic. Acute inflammation is the initial and often transient series of tissue reactions to injury. Chronic inflammation is the subsequent and often prolonged tissue response following the initial response.

The causes of inflammation in the human body is:-

1. Microbial infection- bacteria and viruses
2. Hypersensitivity reaction- excessive immune response causing tissue damage
3. Physical agents- trauma, radiation or heat injury
4. Chemicals- corrosives, acids or bacterial toxins
5. Tissue necrosis- secondary to ischaemia

There are a few ways microbes can cause inflammation in the human body:-

1. Bacterial exotoxins- chemicals released by bacteria which stimulate inflammation
2. Bacterial endotoxins- associated with bacterial cell walls, also stimulate inflammation
3. Viral intracellular multiplication- leading to cell death, debris then stimulates inflammation.
4. Organisms can also cause hypersensitivity reactions- some parasitic infections can cause inflammation.

When cells undergo necrosis, they release cellular contents into the extracellular space. These contents include pro-inflammatory mediators such as cytokines, chemokines, and damage-associated molecular patterns (DAMPs). DAMPs act as danger signals that alert the immune system to the presence of cell damage. They can activate nearby immune cells and trigger an inflammatory response.

The signs of inflammation are:-

1. Redness (rubor)- vasodilation
2. Heat (calor)- increased blood flow brings heat to the surface.
3. Swelling (tumour)- accumulation of fluid due to increase in inflammatory cells migrating to the area.
4. Pain (dolor)- Due to physical distortion of tissue and due to the release of some chemical mediators (prostaglandins, bradykinin)
5. Loss of function

The stages of inflammation:-

1. Release of chemical mediators
2. Vasodilation
3. Increased vascular permeability
4. Fluid accumulation
5. Cellular recruitment
6. Phagocytosis

The two major components of early acute inflammation are:-

1. Vascular changes- change in vessel calibre, increase in vascular permeability- increased net flow of fluid out of vessels called exudation.
2. Cellular events- Formation of cellular exudate- accumulation of neutrophil polymorphs.

As a part of the cellular events within inflammation:-

1. Stasis- Blood flow slows as a result of vasodilation
2. Margination- Slowed blood flow enables WBCs to accumulate near the blood vessel wall- Neutrophils are the main cell of acute inflammation
3. Rolling- Selectins stimulate WBCs to roll along cell wall
4. Adhesions- (a)Endothelial expression of cell adhesion molecules (ICAM and VCAM). (b) Adhesion molecules also expressed on WBCs - integrins, selectins (c) Low affinity initially - affinity increased by proteoglycans + prostaglandins (VCAMs and ICAMs) and histamine + thrombin (selectins)
5. Transendothelial migration (a) WBCs able to move through vascular endothelium (leaky) (i)Caused by endothelial contraction, mediated by histamine, bradykinin, substance n and leukotrienes (ii)Direct damage (b) Pass through junctions - diapedesis, transcytosis

1. Histamine
2. Lysosomal compounds
3. Leukotrienes
4. Prostaglandins
5. Serotonin
6. Chemokines

1. Recognition and attachment- Opsonins
2. Engulfment
3. Killing and degradation- (a)Reactive oxygen species - NADPH oxidase (b) Reactive nitrogen species - nitric oxide synthase

Histamine causes vascular dilation and permeability. It is released mainly by mast cells (an immune cell that lives in connective tissue until activation).

The lysosomal compounds are released by neutrophils and have lots of different functions such as vascular permeability. Some can also stimulate release of histamine from mast cells.

Leukotrienes are a family of inflammatory mediators produced in neutrophils by the oxidation of arachidonic acid. It has vasoactive properties.

Prostaglandins are derived from arachidonic acid. It is released by lots of cell types. They cause increased vascular permeability and platelet aggregation. I

Serotonin causes vasoconstriction and it is released by platelets.

Chemokines are a family of chemicals which attract more white blood cells to site of inflammation. e.g. IL-8 attracts neutrophils.

1. Coagulation system- converts soluble fibrinogen into fibrin.
2. Kinins- activated by coagulation factor XII, bradykinin is an important peptide in mediating vasodilation, pain.
3. Fibrinolytic system
4. Complement system

The complement system can be activated by:-

1. Enzymes released from dying cells
2. Formation of antigen-antibody complexes
3. Products of fibrinolytic and kinin systems

1. C5a, C3a- chemotaxis of neutrophils and mast cells, histamine release from mast cells, increased vascular permeability
2. C567- chemotaxis of neutrophils
3. Membrane attack complex/ C56789- Cytolytic activity
4. C4b, 2a, 3b- Opsonisation of bacteria

1. Dilution of toxins
2. Entry of antibodies
3. Transport of drugs
4. Fibrin formation
5. Delivery of nutrients and oxygen
6. Stimulation of immune response

1. Digestion of normal tissue
2. Swelling
3. Inappropriate inflammatory response e.g. anaphylaxis