- reaction of vascularized living tissue to injury, characterized by movement of fluid and leukocytes from the blood into the extravascular space

- destroys, dilutes, or walls off injurious agents

- begins process of healing and repair

- Acute, Chronic or Granulomatous

Inflammation

- Rapid onset, usually short duration (may persist)

- predominantly neutrophils in protein-rich exudates (fibrin)

- monocyte/macrophages, platelets

- associated with necrosis and pyogenic bacteria

Acute Inflammation

- usually long duration

- may follow acute, have insidious onset, or primary response to some injuries (viral infections)

- predominantly "mononuclear cells" (lymphocytes, plasma cells, monocyte/macrophage/histiocytes)

- evidence of healing (fibrosis, fibroblasts)

- associated with immune system, viral, intracellular organisms or non-degradable substances

Chronic Inflammation

- hallmark is nodular collections of modified macrophage/histiocytes called "granulomas"

- collection of "activated" macrophages

- Epithelioid cells & Multinucleated (histiocytic) giant cells

- caseating or non-caseating granulomas

- dependent on indigestible material, organisms or idiopathic

Granulomatous Inflammation

- Two common forms of these

- Langhans giant cells (nuclei on periphery)

- Foreign body giant cells (nuclei cluster or randomly distributed)

Multinucleated (histiocytic) giant cells

- defining cells of granulomatous inflammation

- may both be present or just one in order to be called a granuloma

Epithelioid cells or Histiocytic giant cells

- Tuberculosis (caseating)

- Bacterial dx's (leprosy, syphilis, Cat scratch dx)

- Fungi (Coccidioides, Histoplasma, Cryptococcus)

- Parasites (Schistosomiasis)

Inciting (indigestible) organisms that cause granulomas

1. Most neutrophils

2. Mostly lymphocytes

3. Epithelioid or histiocytic giant cells

4. Neutrophils & Lymphocytes

Acute, Chronic, Granulomatous, "Mixed" Inflammation

- Rubor (redness) due to vasodilation w/ increased flow

- Calor (heat) due to increased vasodilation w/ flow

- Tumor (swelling) due to edema w/ increased vascular permeability

- Dolor (pain) due to stimulation of nerve endings

Four Cardinal Signs of Localized Inflammation

- physiologic response of the body to inflammation

- fever, leukocytosis, elevated "acute phase proteins", increased ACTH/glucose, decreased appetite, sleep

- lymphadenopathy (localized or generalized)

- lymphangitis, lymphadenitis (inflammation of lymphatic vessels

Systemic "Acute Phase Response" to Inflammation

- Vascular Events --> Increased Vascular Permeability --> Leukocyte Recruitment & Activation --> Killing/Degradation (Digestion) --> Release of Leukocyte Products

Steps in Acute Inflammation

- vascular dilation

- major, fundamental event in the process

- dilating pre-capillary arterioles result in enlarging microvascular bed, increased bllod flow, transudation

Vascular Events of Acute Inflammation

- caused by endothelial cell contraction increasing gaps in the junctions between endothelial cells (reversible)

- OR caused by disruption of cell-cell junctions due to conformational changes in adhesion molecules (reversible)

- OR caused by endothelial cell damage due to loss of endothelial cells leads to denudation of BM (irreversible)

- Results in Exudation, Edema, slowing of circulation, WBC margination

Increased Vascular Permeability in Response to Acute Inflammation

- outflow of protein-rich fluid (included in the proteins are inflammatory mediators, fibrinogen, and antibodies)

Exudation

- stagnation disrupts laminar blood flow, WBCs fall out

- come to rest on the surface of the endothelial cells

WBC Margination

- Adhesion, Emigration/Chemotaxis, Phagocytosi

Leukocyte Recruitment & Activation in response to Acute Inflammation

- involves interaction between adhesion molecules on both WBC and endothelial cell surfaces

Adhesion

- WBCs move between endothelial cells, cross the BM to enter the interstitial space (diapedesis)

- Granuloctyes, monocytes, and lymphocytes all respond to chemotactic stimuli

- first neutrophils, then monocyte/macrophages (48 hrs)

Emigration/Chemotaxis during Leukocyte Recruitment & Activation

- recognize and attach to substances with "opsonin" help

- use ligant-receptor complex, G-protein mediated messengers, increased cytoplasmic calcium

- pseudopods flow around object, form a phagosome, forms phagolysosome (degranulation)

Phagocytosis in Acute Inflammation Response

- oxygen-dependent or independent

- "burst" of oxygen consumption and production of oxygen radicals

- H2O2-Myeloperoxidase-Halide System

- NADPH, superoxide dismutase, Myeloperoxidase (H2O2 into HOCL), HOCL is potent bactericidal agent

- found in neutrophils and macrophages

- Defensins (cationic protein), Lysosyme (neutrophil granules), Lactoferrin (neutrophils granules w/ iron), Major basic protein (eosinophils)

Killing/Degradation (Digestion) during Acute Inflammation response

- Amplifies inflammation by releasing chemical mediators that stimulate inflammation

- lysosomal enzymes & oxygen radicals produce localized tissue damage

- "regurgitation during feeding" where enzymes leak into ECF if lysosome fuses before phagosome is completed closed

- "frustrated phagocytosis, reversed endocytosis" where object is too big to engulf, products released into phagosome

- cell dies, releasing its contents

Release of Leukocyte Products in Acute Inflammation Response

- most important in the acute response, first to arrive

- inflammatory cells in "pus"

- short lived (6 hrs), best at killing pyogenic organisms (use myeloperoxidase)

Neutrophils

- classic cell of chronic inflammation, but also present w/ acute

- very important for antigen processing and presentation (IL-1 and TNF)

- w/ granulomas, these activate to become epithelioid cells and/or giant cells

Macrophages/Monocytes

- contain virtually all of the histamine in the body

- histamine is major contributor to inflammation by inducing vascular permeability & arteriolar vasodilation

Mast cell/Basophil

- function in hemostasis and contain multiple mediators of inflammation & healing, stimulating both vascular & cellular changes

- important in repair, by stimulating fibroblasts

- contain serotonin and platelet derived growth factor

Platelets

- associated with allergic reactions, parasitic infections, and chronic inflammation

- modulate mast cell mediated reactions (neutralizing damaging effects of degranulation)

- contain lysosomes with major basic protein

Eosinophils

- scar

Cicatrix

- pus in a body cavity, especially the pleural spaces

Empyema

- exudate with lots of mucus (nasal discharge)

Catarrhal exudate

- granuloma associated with syphilis; non-caseating but with central necrosis

Gumma

- process of forming pus

Suppuration

- inflammation of veins

Phlebitis

- inflammation of testis

Orchitis

- inflammation of the mouth

Stomatitis

- inflammation of the salivary gland

Sialadenitis

- inflammation of bile duct

Cholangitis

- inflammation of tendon sheath

Tenosynovitis

- inflammation of subcutaneous adipose tissue

Panniculitis

- inflammation of CT

cellulitis

- inflammation of the breast

Mastitis