Acute Inflammation GPPE

Inflammation

• Initial tissue reaction to wide range of injurious agents (Protective action)

• Complex reaction in tissues that consists mainly of responses of blood vessels and leukocytes

Type of inflammation

• Acute : Rapid, short duration

• Exudation of fluid and plasma proteins (edema)

• Emigration of leukocytes, mostly neutrophils

• Chronic : Slow, long duration

• Proliferation of blood vessels, fibrosis and tissue destruction

• Lymphocytes and macrophages

Causes of inflammation

• Infection : pyogenic bacteria & viruses

• Physical injury : trauma, burn & ionizing radiation

• Chemical injury : corrosives, acids & alkalis

• Immunologic injury

• Tissue necrosis (dead cells): myocardial infarction - inflammatory changes occur in viable tissue adjacent to necrotic tissue

Cardinal signs of acute inflammation

• Calor : heat caused by increased blood flow

• Rubor : redness due to dilatation of vessels

• Tumor : swelling due to an extravascular accumulation of fluid

• Dolor : pain due to increase pressure exerted by accumulation of interstitial fluid & to mediators

• Functio laesa : loss of function

Vascular response in acute inflammation

• Vasodilation : widening blood vessels

• Change in flow of blood

• Permeability of vessels

• Lymphatic vessel response : lymphatic vessels undergo pronounced enlargement in inflamed tissue and display increased leakiness, indicating reduced functionality

Changes in blood flow & caliber

1. First involves arteriole and then leads to opening of new capillaries beds in area

2. Increased blood flow

3. Heat and redness (erythema) at site of inflammation

4. Mediators: histamine, prostaglandin and nitric oxide (NO), on vascular smooth muscle

Increased vascular permeability (vascular leakage)

• Leading to escape of protein-rich exudate into extravascular tissue, causing edema

Mechanism

• Contraction of endothelial cells resulting in increased interendothelial spaces

• Endothelial injury, resulting in endothelial cell necrosis and detachment

• Leukocytes meditate vascular injury

• Increased transport of fluid and proteins, called transcytosis, through endothelial cell

Vascular leakage

• Exudation : escape of fluid, proteins, and blood cells from vascular system into interstitial tissue/body cavities

• Transudate :

1. Fluid with low protein content (mostly albumin)

2. Little/no cellular material

3. Low specific gravity

• Exudate :

1. Extravascular fluid that has high protein concentration

2. Due to increased vascular permeability

3. Cellular debris

4. High specific gravity

Cellular response in acute inflammation

• Recruitment from blood into extravascular tissue

• Recognition of microbes and necrotic tissues

• Removal of offending agents (by WBC)

Emigration

Passage of inflammatory leukocytes between endothelial cells into adjacent interstitial tissue

1. Margination: leukocytes localize to outer margin of blood flow adjacent to vascular endothelium

2. Pavementing : leukocytes line endothelial surface

3. Rolling: mediated by actions of endothelial selection loosely binding to leukocytes, producing “rolling” movement of leukocytes along endothelial surface

4. Adhesion : leukocytes adhere to endothelial surface and mediated by interaction of integrins on leukocytes binding to immunoglobulin-family adhesion protein on endothelium

Transmigration

Movement of leukocytes across endothelium and mediated by platelet endothelial cell adhesion molecule- I(PECAM-I) on both leukocytes and endothelium

Chemotaxis

• Process which leukocytes are attracted to and move towards an injury

• Mediated by diffusible chemical agents

• Chemotactic factors for neutrophils:

1. Products from bacteria

2. C5a

3. Arachidonic acid metabolites (leukotriene B4(LTB4)

Phagocytosis

Ingestion of particular material like tissue debris, living/dead bacteria and other foreign cells by phagocytic cells

1. Recognition and attachment: particle to be ingested by leukocyte

2. Engulfment: with formation of phagocytic vacuole

3. Killing/degradation: ingested material

Most important phagocytic cells:

• Neutrophils

• Monocytes-macrophages

Inflammatory mediators

Causing blood vessels to dilate, which increase blood flow to affected area. Leads to redness and warmth

Increase permeability of blood vessels, allowing (WBC) to enter

• Histamine

• Prostaglandin

• Nitric oxide (NO)

• Protein

• Peptides

• Glycoprotein

Cytokines

• Protein produced by many cell types

• Mostly activated lymphocytes, macrophages, endothelium, epithelium & connective cells at sites of tissue injury

• Regulate inflammatory response, ranging from initial changes in vascular permeability to resolution and restoration of tissue integrity

Types of inflammatory cells

Monocytes

• Macrophages in chronic inflammation

• Products of activated macrophages serve to eliminate injurious agents; microbes & initiate process of repair

• Other cell types: lymphocytes, plasma cells, eosinophils & mast cells

Lymphocytes

• Most prominent inflammatory cells in many viral infection: influenza, mumps, rubella & bacterial infections like whooping cough & tuberculosis

• Chronic inflammation

Plasma cell

• Associated with antibody synthesis

• Derived from B lymphocytes

• Chronic inflammation

Local effects of inflammation

• Heat

• Redness

• Sweeling

• Pain

• Loss of function

Systemic effect of inflammation

Changes are reaction to cytokines whose production is stimulated by bacterial products (LPS)

• Fever

• Sepsis

• Leukocytosis

• C-reactive protein (CRP)

• Increased pulse and blood pressure

• Anorexia

• Malaise

Systemic effect

Production is stimulated by bacteria products (LPS)

Fever

• Elevation of body temperature

• Pyrogens act by stimulating prostaglandin synthesis in vascular & perivascular cells of hypothalamus

• LPS stimulate leukocytes to release cytokines such as IL-I & TNF increase enzymes (cyclooxygenase) that convert AA into prostaglandin

Sepsis

• Severe bacterial infection

• Large amounts of organisms and LPS in blood stimulate production of several cytokines (TNF&IL-I): cause disseminated intravascular coagulation, cardiovascular failure & metabolic disturbance, which prescribed as septic shock

Leukocytosis

• Increased number of WBC in blood

• Accelerated release of cells from bone marrow, caused by cytokines (TNF&IL-L)

C-reactive protein ( CRP)

• Plasma concentration: may increase several hundred-fold as part of responses to inflammatory stimuli

• Fibrinogen

• Serum amyloid A(SAA) protein

Outcomes of acute inflammation

1. Resolution of tissue structure and function often occurs if injurious agent is eliminated (tissue back to normal)

2. Tissue destruction & persistent acute inflammation

• Abscess: localized collection of purulent exudate. Cavity filled pus (neutrophils, monocytes & liquefied cellular debris)

• Ulcer : loss of surface epithelium (peptic ulcer, ulcers of skin)

• Fistula : abnormal communication between 2 organs or between organ and surface

• Scar : tissue destruction, with resultant distortion of structure

  3.Conversion to chronic inflammation