CSB520 - Inflammation & Repair

What form of cell death causes an inflammatory response?

Necrosis stimulates an acute inflammatory response

What are the 3 microscopic features of acute inflammation?

Hyperaemia, oedema (exudate) & the recruitment of neutrophils

After a transient reflexive period of vasoconstriction, vasodilation leads to hyperaemia. The increased permeability of the vessels allows serum & proteins to enter the affected tissue forming oedema which because of its high protein content can be referred to as exudate. Neutrophils are activated and are attracted to the acutely inflamed tissue, migrating through the vessel walls.

Neutrophils are phagocytic and the primary cell to associate with acute inflammation, however they have a short lifespan and will be aided my macrophages that will finish the job of neutrophils as well as remove apoptotic neutrophils.

What type of oedema is observed in acute inflammation and how does it occur?

Exudate, which is an oedematous fluid which is high in proteins or pus which has proteins, cellular debris/necrotic cells, white blood cells and sometimes microorganisms. 

In acute inflammation the hyperaemia results in increased hydrostatic pressure which forces fluid from the vessels into the tissue (transudate) but there is also increased vascular permeability which allows plasma proteins to also enter the tissue with the fluid hence why we get an exudate.

What are the 3 main components of granulation tissue & their role/purpose in repair?

Granulation tissue is composed of:

1.    Fibroblasts secreting collagen protein.

2.    Macrophages coordinating events & cleaning up debris

3.    Angiogenesis, the formation of new blood vessels to provide nutrients and blood gases during the repair process.

Once the dead tissue is removed and the space filled with collagen, the fibroblasts and macrophages migrate away leaving the largely acellular protein (collagen) scar. Because of the acellular nature of the scar, the new vessels regress through apoptosis and the collagen fibers contract as it matures.

What are the consequences of healing through organisation?

Granulation tissue is the immature scar, the tissue that forms the scar and so will occur in acute inflammation that heals through organization and it will always be present in chronic inflammation as part of the repeated attempts at repair.

Scarring allows repair & fills in the tissue deficits so we can survive but it lacks the properties of the tissue that it replaces. In addition, scar tissue contracts over time pulling surrounding tissue with it which can distort the surrounding parenchyma.

Specifically, in the heart the scar represents a weak point that can form an aneurysm & is pro- rather than anti-coagulant predisposing towards thrombus formation. Scar tissue lacks the strength of the normal cardiac muscle & will not relay electrical impulses in the same way as the normal heart muscle.

What are the 3 main causes of chronic inflammation?

1. Unresolved acute, so for example when the stimulus causing the acute response remains.

2. Repeated acute

“Special” cases where there is little/no acute response preceding the chronic inflammation which includes some infections and autoimmune reactions.

Define the 3 general features of chronic inflammation?

1. Ongoing tissue injury and destruction

2. Lymphocytes

3. Repeated attempts at repair through the formation of granulation tissue and, when occurring in stable/labile tissues, proliferation of parenchymal cells.

Describe the possible negative consequences of chronic inflammation.

the increased proliferation of epithelial cells (hyperplasia) and oxidative stress as a result of chronic inflammation has led to the development of cancer.

It is when cells are dividing & copying their DNA that they are most vulnerable to errors occurring. If you make the cells divide more, during to inflammation then there is greater risk for mutation and for that mutation to be passed onto daughter cells. In addition, to proliferation, during inflammation there is often increased levels of oxidants & other mediators capable of damaging DNA

What is meant by sterile & non-sterile sites in the human body?

In the human body, "sterile sites" are areas where microorganisms are not present, whereas "non-sterile sites" are areas that harbor resident or transient microbial flora

Understand the main differences between the innate & adaptive systems.

Have a basic understanding of what autoimmune & hypersensitivity responses are.

Hypersensitivity responses are an over-reaction of the acquired/adaptive immune system to an antigen/target.

Auto means self, so autoimmune diseases involve the adaptive/acquired immune system targeting something normal in our bodies. Autoimmune diseases do not always cause chronic inflammation, some cause apoptosis of our cells so that we experience a loss of function but not inflammation (e.g. type 1 diabetes). Others cause necrosis so that we lose the functional cells as well as experience chronic inflammation (e.g. chronic inflammatory bowel disease and rheumatoid arthritis).

Have a basic understanding of what is meant by the term immune-compromised & the patients at risk.

Please note that people with autoimmune and hypersensitivity disorders are not immune compromised, they have strong immune systems it is just they are over-reacting or targeting something that they should not. Those of you doing drug-based units will learn that some of the treatments for these conditions aim to dampen down the immune response.

People that are immune compromised have a weakened immune system and or impaired innate defenses, leaving them open to opportunistic infections, i.e. infections caused by microbes of low virulence which do not usually cause disease unless our immune system is weakened.

What factors may prevent complete repair from occuring?

Resolution is the term for healing without scarring. Permanent tissues like the brain and heart will never heal by resolution as neurons, skeletal and cardiac myocytes do not divide. In labile/stable tissues resolution is not possible when a lot of tissue has been lost or when there is overlying infection, poor immunity, poor nutrition or interruption of healing.