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Inflammation

Inflammation: refers to your body’s process of fighting against things that harm it, such as infections, injuries, and toxins, in an attempt to heal itself. When something damages your cells, your body releases chemicals that trigger a response from your immune system.

This response includes the release of antibodies and proteins, as well as increased blood flow to the damaged area. The whole process usually lasts for a few hours or days in the case of acute inflammation.

Chronic inflammation happens when this response lingers, leaving your body in a constant state of alert. Over time, chronic inflammation may have a negative impact on your tissues and organs. Some researchTrusted Source suggests that chronic inflammation could also play a role in a range of conditions, from cancer to asthma.

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Inflammation:

A protective response involving host cells, blood vessels and proteins

Goals are:

Eliminate the initial cause of cell injury
Remove necrotic cells and tissues
Initiate the process of repair

ALSO A POTENTIALLY HARMFUL PROCESS:

Components of inflammation that are capable of

destroying can also injury bystander normal tissue

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Etiology

The causes of inflammation are many and varied:

Exogenous causes:

Physical agents

Mechanic agents: fractures, foreign corps, sand, etc.
Thermal agents: burns, freezing

Chemical agents: toxic gases, acids, bases
Biological agents: bacteria, viruses, parasites

Endogenous causes:

Circulation disorders: thrombosis, infarction, hemorrhage
Enzymes activation – e.g. acute pancreatitis
Metabolic products deposals – uric acid, urea

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FEATURES

Tissue damage

Cellular – vascular - cellular response

Metabolic Changes

Tissue Repair

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Cells involved in Inflammation

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Types

Acute

Swine Erysipelas

Atopic Dermatitis, Dog

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Chronic

MCF, COLON

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1 Vasodilation

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2.Vascular leakage and Edema

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Acute inflammation - sequence of events

Transient vasoconstriction
Vasodilation
Increased blood flow
Increased vascular permeability
Hemoconcentration and slowing of flow or stasis
Leukocyte trafficking

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Normal State:

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Transient vasoconstriction

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Vasodilation

Increased Blood Flow

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Plasma fluid

Increased vascular permeability
Hemoconcentration and slowing of flow or stasis
Leukocyte margination
Leukocyte firm adhesion and extravascular emigration

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1. Capture

2. Rolling

4. Arrest

7. Transcellular

Migration

8. Paracellular

Migration

Adapted from Ley et.al. Nature Reviews Immunol 7:678-689, 2007

Activation

Overview of leukocyte trafficking in

acute inflammation

1.c Capture

1.capture

2.rolling

3.Slow rolling

4. Arrest

5. Adhesion

Strengthening

spreading

6. Intravascular

crawling

7. Transcellular

Migration

8. Paracellular

Migration

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Soluble mediators involved in acute

inflammation

Sources of soluble mediators

Plasma Protein

Cells

Etc.

Sources

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Mast cell

Vasoactive amines

- HISTAMINE

Preformed within cytoplasmic granules of mast cells and basophils
Promotes venodilation and increased vascular permeability
Promotes endothelial activation
Can mediate all symptoms of acute inflammation
Important mediator of Type I hypersensitivity reactions
Released during mast cell activation

C5a

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Preformed in granules of platelets
Released during platelet activation
Promotes venodilation and increased vascular permeability
Can mediate all symptoms of acute inflammation
Promotes endothelial activation
Binding to serotonin receptors located on local sensory nerves produces sensation of pain

Vasoactive amines

- SEROTONIN

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Nitric Oxide

Produced constitutively by endothelial cells
Causes smooth muscle relaxation
Also produced by infiltrating leukocytes in inflamed tissues

From Robbins Pathologic Basis of Disease 6^th Edition, 1999

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Plasma Proteases

1. The complement system

2. The clotting system

3. The kinin system

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Role of complement components

in acute inflammation

C5a

C3a

Activate mast cells (histamine release)

a. vasodilation

b. increased vascular permeability

Leukocyte chemotaxis,

activation and adhesion,

leukotriene production

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Cytokines and chemokines

Small molecular weight proteins (8 to 30 Kd)
Produced by most all nucleated cells
Major mechanism of cell – cell communication
A specialized subset of chemotactic cytokines are known as “chemokines”
Cytokines have complex and overlapping functions in vivo
In order for a cell to respond to a cytokine it must express the appropriate receptor
Cytokines may be either pro or anti-inflammatory
A given cell may produce a variety of pro and anti-inflammatory cytokines
A target cell may express multiple cytokine receptors
The cytokines present at a site of inflammation also serve to define the TYPES of leukocytes recruited

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Clinical features of fluids in Acute Inflammation

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Acute Inflammation: Examples

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CHRONIC INFLAMMATION

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Chronic Inflammation

Persistent or resistant infections that can resist either phagocytosis or (if phagocytosed) resist intracellular killing

Bacteria- eg Mycobacterium, Nocardia
Fungi- eg Blastomyces, Histoplasma
Protozoa- eg Trypanosoma, Leishmania
Parasites

Prolonged exposure to stimuli

Infections “hidden” from immune responses. Some bacteria such as Streptococcus and Staphlyococcus are not resistant to phagocytosis or digestion but can hide within the large amount of degenerate neutrophils and necrotic debris (pus) that they are associated with

Inert material- Plants, minerals, some suture/ surgical material (“foreign bodies”)

Some immune-mediated/autoimmune diseases

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Pathogens and Stimuli associated with Chronic Inflammation

Bacteria with special cell walls

Mycobacterium, Nocardia

Fungi

Blastomyces, Histoplasma, Aspergillus

Protozoa

Leishmania, Trypanosoma, Entamoeba, Encephalitozoon

Parasites

Demodex, migrating nematodes, Ostertagia, trematodes

Foreign Bodies

Suture material, hair, plant awns, splinters, sand/dirt

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Types of Chronic Inflammation�based on Histology

Granuloma/Granulomatous
Abscess
Fistula
Pyogranuloma/Pyogranulomatous
Eosinophilic granuloma

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Granuloma

Main cell type: macrophages

Macrophage, histiocyte, > epithelioid macrophages, syncytial cells, > giant cells

Lymphocytes

T and B cells (plasma cells)

Polymorphonuclear cells ±

Eosinophils, basophils, neutrophils

Fibroblasts/fibrocytes

Other: debris, pathogens, angiogenesis, etc

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Granulomatous inflammation with large macrophages

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Granulomas/pyogranulomas

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Feline Infectious Peritonitis

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Abscess

http://davidgilchrist.info/catabscess.html

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Abscesses with Fistulas

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Rhesus monkey- Pulmonary blastomycosis

Courtesy Wake Forest University and Armed Forces Institute of Pathology

Granulomatous pneumonia with Blastomyces

Fungal Infections

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H&E

Shows morphology

PAS

Stains fungus purple

Granulomatous sinusitis with fungus (yeast form) (Cat)

Granulomatous encephalitis with fungus(hyphae) (Dog)

Fungal Granulomatous Inflammation

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Examples of Autoimmune Diseases

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Sebaceous Adenitis

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Pemphigus �foliaceous

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@VET HELP