Inflammation Notes | Course Paper

Inflammation

Definition: Inflammation is a localized defensive immune reaction of the organism which tries to

localize and eliminate the pathogenic agent. Inflammatory response is a defense mechanism that

protect organisms from infection and injury.

– Part of the innate immune response (physically, chemically and cellular defences against pathogen,

does not include the white blood cells.)

– Comprises of vascular, metabolic, cellular changes, triggered by the entry of pathogen into healthy

tissues of the body

Etiology (the cause)

– Exogenous causes

• Physical agents (burns)

• Chemical agents (toxic gases, acids, bases)

• Biological agents (bacteria, virus, parasites)

– Endogenous causes

• Circulation disorders (thrombosis, infarction (inadequate blood supply to the affected area),

hemorrhage (bleeding or blood loss))

• Enzymes activation (acute pancreatitis)

• Metabolic products deposals or disposal (uric acid, urea)

Cardinal Inflammation signs (Primary or major symptom)

– Rubor (redness)

– Tumor (swelling)

– Calor (heat)

– Dolor (pain)

– May or may not be followed by functio laesa, or loss of function (fifth sign of acute inflammation

by Galen)

Classes of inflammation

– Acute (Intense)

• Severe, intense, but usually short in duration

• Most can be treated at home

• Patients dies because of shortage of nurses

• May suffer sickness, vomiting or acute pain, but they do not die.

• E.g. Boil by S. Aureus

– Chronic (Recurring)

• Continual and recurring

• Happen with chronic diabetes or arterial disease

• Chronic pain can exacerbate (increase severity) or prolong the function disability of the

patients

• Chronic atrial fibrillation is associated with an increased risk of death.

• If left untreated, the condition may become chronic

• E.g. Tuberculosis by M. tuberculosis

Characteristics of inflammations

– Acute

• Cause – Single injury

• Duration – Takes up to hours or days

• Presentative symptom – Increase permeability, exudation (fluid emitted by organisms through

pores or wound)

• Main components – Liquid, proteins/proteases and antiproteases/ PMN leucocytes,

macrophages

• Connecting reaction – Thrombosis

– Chronic

• Causes – Permanent present of the causing agent or bacteria, etc.

• Duration – Weeks, months, years (depending on the causing agent)

• Presentative symptom – Proliferative fibroblasts (contribute connective tissue proteins for

wound repair), no exudation

• Main components – Macrophage, Lymphocytes, Eosinophyl, granulocytes, connective tissue

hiperplasy (group of fibrous connective tissue lesions/injury)

• Connecting reactions – immune response

Microscopic changes

– Dilation of vessels

– Sludging of red blood cells

– Fluid leaks into interstitium (a contiguous/in close proximity fluid-filled space between cells)

– Implies increased permeability of vessels (to protein, not water)

– Cells move into interstitium

Function of inflammation

– Localize and destroy injuries agent and by products

– Confining (enclose or stay in one area) effects of damage where total elimination is not possible

– Repair and replace damaged tissues

Part 1: Fluid Definitions

– A transudate has a low protein content usually caused by alterations in hydrostatic or oncotic

pressure. (colloid osmotic pressure, induced by protein or albumin) Implies a hydrostatic (pressure)

problem.

• Occurs due to increased hydrostatic pressure or low plasma oncotic pressure.

• E.g. Cirrhosis (complication of liver diseases like hepatitis and chronic alcoholism), nephrotic

syndrome (kidney disorder, damages small blood vessels that filter waste and excess water

causes body pass too much protein in urine), hypoalbuminemia (level of albumin in blood is

low)

– An exudate has a high protein content, caused by increased vascular permeability. Implies an

inflammatory process.

• Occurs due to inflammation and increased capillary permeability

• E.g. Pneumonia (inflammation in air sacs of lungs), cancer, tuberculosis (Infection in lungs),

viral infection, autoimmune (disease where own immune system attacking own body)

Changes that combat injury

– Vasodilation (Increases delivery, temperature and removes toxins)

– Exudate (Delivers immunoglobulins, dilutes toxins, deliver fibrinogen, increases lymphatic

drainage)

– Increased lymphatic drainage (Delivers bugs to phagocytes and antigens to immune system)

– Cells (Removes pathogenic organisms, necrotic debris (premature death of cells), etc.)

– Pain and loss of function (Enforces rest, reduces chance of further traumatic damage)

Mechanisms (Chemical Mediators)

Three phases:

1) Immediate early response (30mins)

– Histamine

• Released from mast cells (tissue cells of immune system and present in connective tissue),

basophils and platelets.

• In response to many stimuli: Physical damage, immunologic reactions, anaphylatoxins

such as C3A and C5A, interleukin-1 (IL1), Factors from neutrophils and platelets

• Effects: Largely vascular, pain, and not chemotactic (exhibiting chemotaxis – the

movement of organism in response to chemical stimulus)

2) Immediate sustained response

– Not always seen

– Due to direct damage to endothelial cells

3) Delayed response (Peaks about 3 hours)

– Many and varied chemical mediators, interlinked and of varying importance.

– Incompletely understood

– Important because possibility of therapeutic intervention.

Tissue damage

– The inflammatory reaction takes place at microcirculation (circulation of blood in smallest vessels)

level and it is composed by the following changes:

• Tissue damage

• Cellular – vascular and cellular response

• Metabolic changes

• Tissue repair

– Following injury:

• Huge interplay of acute phase proteins responsible for initiation of process

• Mediators responsible for the following events of inflammation are released

• E.g. Tissue macrophages, monocytes, mast cells, platelets, and endothelial cells are able to

produce a multitude of cytokines. Cytokines tissue Necrosis Factor-A (TNF-A) and Interleukin-

1 (IL1) are released first and initiate several cascades reaction.

➢ Inflammatory mediators, TNF-A and IL-1

❖ Responsible for the synthesis of IL-6, IL-8, and interferon gamma.

❖ The proinflammatory interleukins either function directly on tissue or work via

secondary mediators to activate the coagulation cascade, complement cascade, and

the release of nitric oxide, platelet-activating factor, prostaglandins, and leukotrienes.

❖ Cytokines, especially IL-6, stimulate the release of acute-phase reactants

(inflammation markers) such as C-reactive protein (CRP)

❖ Induce fever and the release of stress hormones (norepinephrine, vasopressin,

activation of the renin-angiotensin-aldosterone system).

Vasodilation and increased permeability of blood vessels

– Following tissue damage, blood vessels dilate in the area of damage.

– Vasodilation (dilation of blood vessels which causes blood flow increase).

• Chemical like inflammatory mediators released by damaged cells.

• Associated with redness and heat.

– Increased permeability permits defensive substances from the blood to enter the injured area.

• Allows fluid movement and results in edema

• Pain may cause by nerve damage, toxin irritation and edema pressure.

Types of inflammatory

mediators (contribute to

the event of inflammation)

Characteristics of inflammatory mediators

Prostaglandins

– Ubiquitous (present everywhere)

– lipid soluble molecules which contribute to vasodilation, capillary

permeability, and the pain and fever that accompany

inflammation.

– Prostaglandins PGE1 and PGE2 induce inflammation and

potentiate (increase) the effects of histamine and other

inflammatory mediators.

– Vasodilation of precapillary arterioles (edema), lower blood

pressure, modulates (adjust) receptors activity and affect

phagocytic activity of leukocytes

Leukotrienes

– Produced by mast cells and basophils

– Increase permeability of the blood vessels, stimulates the

chemotaxis and extravascularization (formation outside blood

vessels) of neutrophils, eosinophils, and monocytes

– Assist in attachment of phagocytes to pathogens

and is an important inflammatory mediator in bronchial asthma

and anaphylaxis.

contraction of endothelial cells and dilation of postcapillary

venules)