W22 Inflammation

What is the effect of inflammation?

Mechanism of disease- can trigger/cause tissue damage/cellular death and can either occur systemically or on a localised level

What is inflammation?

A localised response to cellular injury with an overall aim of removing the harmful stimuli and initiating healing

What is the function of inflammation?

• Removes dead tissue and cells

• Protects against local and spread of infection

• Sets up pathway to wound healing requiring white blood cells and cell mediators

What is acute inflammation?

Fast and relatively non-specific (minutes- days)

What is chronic inflammation?

Simultaneous destruction and healing of tissues resulting in prolonged tissue stress or malfunction (weeks-months-years)

What are the 5 cardinal signs of inflammation?

• Pain

• Heat

• Redness

• Swelling

• Loss of function

What occurs in a normal capillary?

Blood flow is smooth, surrounding tissue is interstitial tissue and occasional lymphocyte/macrophage and blood stays in vessels

What happens to capillaries when inflammation occurs?

Increased blood flow, prompting vasodilation and localised heat- thus causing redness. Leakage of plasma proteins causes edema and hence the cardinal signs of swelling. Neutrophil emigration to site of swelling, hence the pain

What are causes of inflammation?

• Trauma

• Chemical injury

• Radiation

• Burns/frostbite

• Reduction in blood flow

• Infection

• Overactive immune system

What is meningitis?

Inflammation of the surface membranes surrounding the brain and spinal cord- this swelling can lead to bursting of blood vessels and can be fatal

What is vasculitis?

Inflammation of a blood vessel- an artery blockage may result in inflammation but it can also be caused by infection, autoimmune disease or cancer

What are examples of superficial inflammation of the cornea?

• Punctuate epithelial erosion (PEE)

• Punctuate epithelial keratitis (PEK)

• Sub epithelial infiltrates

• Superficial punctuate keratitis (SPK)

What is harmful inflammation of the cornea?

Deep infiltrates which go through the epithelial and attacking stroma and descement membrane, causing ulceration, melting and vascularisation (vessels growing where they shouldn’t be)

What are corneal infiltrates?

Build up of white blood cells

What’s the pathogenesis of inflammation?

• Injury (can be anything)

• Cell gives off chemical mediators

• This causes increased blood flow (hence redness, heat) and vasodilation (pain, swelling)

What is chemotaxis?

Movement of chemicals generated by chemical mediators

What changes do chemical mediators bring?

Vasodilation and increased vessel permeability

Where can cell mediators derive from in acute inflammation?

Cells or blood plasma

How do mediators come from cells?

They can either be secreted or synthesised: histamine from mast cells are a powerful vasodilator and increase vessel permeability

Where do mediators come from in the blood plasma?

Inactive precursors already in circulation- examples include complement proteins and kinins

What is the benefit of increasing blood flow?

Brings more nutrients and oxygen to the area, increases metabolic rate of tissue cells, leading to healing

What’s the benefit of leaky capillaries and edema (fluid in tissue places?)

As clotting proteins enter the area, this causes fibrin barrier, causing healing

How does white blood cell emigration stimulate healing?

Removal of damaged/dead tissue cells and pathogens from area

How do we get leakage from blood vessels?

Gap junctions between endothelial cells increase

How do we study inflammation to test for leaky vessels?

Inject blue dye into blood vessels, dye leaks out of tissues if there’s been trauma

What’s the immediate transient response?

Histamine is commonly cell mediator- amount of dye in interstitial tissue peaks and then falls at 15 mins

What’s the delayed persistent response?

Cell mediators prostaglandins and kinins- delay time since trauma

What’s the immediate persistent response?

Amount of dye in tissue will remain/ not go down eventually from endothelial cell damage

What is the cellular inflammatory response?

Invasion of phagocytes and blood cells- neutrophils are one of the the first cells to arrive at the site of injury, phagocytes arrive several hours after the neutrophils

What’s the first step in the response of neutrophils for acute inflammation?

Marination and adhesion- neutrophils enter blood from bone marrow and roll along vessel wall and sticks to endothelial wall of blood vessel

What happens after margination and adhesion?

Diapadesis- neutrophils leave blood vessels to enter tissue

What happens after diapedesis?

Positive chemotaxis- neutrophil moves to site of inflammation as inflammatory chemicals diffused from inflamed site acting as chemotactic agents

What happens after positive chemotaxis?

Phagocytosis- phagocytes take up any dead cells

How does phagocytosis occur?

Monocytes mature into macrophages as they follow neutrophils to site of injury via positive chemotaxis

What happens to a severe infection?

Pus is formed- these are dead neutrophils, broken down tissue cells as well as any living/dead pathogens