Chapter 4. Inflammation

CHAPTER CONTENTS Introduction to inflammation Acute inflammation Chronic inflammation

INTRODUCTION TO INFLAMMATION CONCEPTION Inflammation is a complex reaction to injurious agents that consists of vascular response, cellular reaction, and systemic reactions. a defensive response fundamentally be divided into acute inflammation and chronic inflammation

INTRODUCTION TO INFLAMMATION CARDINAL CLINICAL SIGNS acute inflammation has 5 cardinal signs: redness (rubor) heat (calor) swelling pain (dolor) loss of function increased blood flow to the inflamed area accumulation of fluid release of chemicals that stimulate nerve endings a combination of factors

redness heat swelling pain

INTRODUCTION TO INFLAMMATION SYSTEMIC CLINICAL SIGNS in acute inflammation: A. fever B. changes in the peripheral white blood cell count neutrophils leukocytosis neutrophil nucleus shift to the left lymphocytosis neutropenia C. changes in plasma protein levels the levels of certain plasma proteins increase entry of pyrogens and release prostaglandins bone marrow release or production viral infection

neutrophil nucleus shift to the left immature mature neutrophil nucleus shift to the left

ACUTE INFLAMMATION the early response of a tissue to injury the first line of defense against injury nonspecific changes in the microcirculation: exudation of fluid emigration of leukocytes the causative factors (6 points)

MORPHOLOGIC AND FUNCTIONAL CHANGES the two main components of the acute inflammatory: the microcirculatory response the cellular response

The microcirculatory response vasodilation and stasis increased permeability exudation of fluid

The microcirculatory response A. vasodilation and stasis in the microcirculation a transient vasoconstriction (induced by action of mediators) dilation of arterioles, capillaries, and venules (hyperemia) stasis

The microcirculatory response B. increased permeability in venules and capillaries active contraction of actin filaments in endothelial cells direct damage to endothelial cells leukocyte-mediated endothelial injury transcytosis increased permeability increase (reversible)

The microcirculatory response B. increased permeability in venules and capillaries three phases of increased permeability in acute inflammation: (1) an immediate phase (2) a delayed response (3) a prolonged response these permeability changes are effected by various chemical mediators

The microcirculatory response C. exudation of fluid exudation: increased passage of fluid out of the microcirculation because of increased vascular permeability the composition of an exudate approaches that of plasma, but rich in proteins fibrinogen is converted to fibrin rapidly exudation should be distinguished from transudation

Grossly, fibrin is seen on an acute inflamed serosal surface that changes to a rough, yellowish bread and butter-like surface, covered by fibrin and coagulated proteins.

The microcirculatory response C. exudation of fluid the functions of exudation: (1) dilute the offending agent (2) cause increased lymphatic flow, conveying noxious agents to the draining lymph nodes to facilitating a protective immune response (3) flood the area with plasma, which contain numerous defensive proteins

The cellular response leukocyte infiltration plays an important role in limiting the spread of injury in defending the host tissue Acute inflammation is characterized by the active emigration of inflammatory cells from the blood into the area of injury.

The cellular response extravasation: the process of the leukocytes from the vessel lumen to the interstitial tissue. 3 steps of extravasation : (1) margination, rolling and adhesion to endothelium in the lumen (2) transmigration across the endothelium (3) migration toward the site of injury

A. types of cells involved The cellular response A. types of cells involved neutrophils (polymorphonuclear leukocytes) phagocytic cell of the macrophage system lymphocytes and plasma cells

The cellular response B. margination, adhesion and transmigration of neutrophils

The cellular response C. emigration of neutrophils take 2-10minutes intercellular junctions basement membrane

The cellular response D. chemotactic factors chemotaxis: In the interstitial tissue, neutrophils move toward the site of injury, oriented along a chemical gradient. chemotactic factors: Govern the active emigration of neutrophils and the direction in which they move.

The cellular response E. phagocytosis recognition opsonization: the agent has been coated with immunoglobulin or complement factor 3b (opsonins). engulfment the agent + opsonins phagosome microbial killing phagosome fuses with lysosomes, therefore the enzymes can access to the engulfed microorganism and kill them engulfment

Process of phagocytosis

The cellular response diapedesis F. erythrocyte the orderly flow of blood is disturbed in the dilated vessels erythrocyte form heavy aggregates and sludging erythrocyte enter an inflamed area passively diapedesis hemorrhagic inflammation

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MEDIATORS OF ACUTE INFLAMMATION A variety of endogenous chemical mediators play some important roles in the modulation of inflammatory response. originated from cells or plasma: cell-derived mediators: sequestered in intracellular granules and synthesized in response to a stimulus plasma-derived mediators: present in precursor form and activated by proteolytic cleavage

summary of inflammatory mediators Function Major mediators Vasodilation 5-HT,histamine, bradykinin ,PGE2 Permeability 5-HT,histamine, C3a, C5a, PAF Chemotaxis C5a, LTB4, cytokins Fever Cytokines( IL-1, 6, TNF), PG Pain PGE2 , bradykinin Tissue damage Lysosomal enzymes , NO

TYPES OF ACUTE INFLAMMATION A. serous inflammation B. fibrinous inflammation C. suppurative (purulent inflammation) D. hemorrhagic inflammation

TYPES OF ACUTE INFLAMMATION A. serous inflammation occur in skin, and in peritoneal, pleural and pericardial cavities accumulation of excessive clear watery fluid with a variable protein content Catarrhal inflammation is a mild exudative inflammation of a surface mucous membrance without apparent tissue destruction.

burn blisters

Serous inflammation of skin

TYPES OF ACUTE INFLAMMATION B. fibrinous inflammation large amounts of fibrinogen pass the vessel wall, and fibrins are formed in the extracellular spaces Pseudomembranous inflammation is the fibrinous inflammation occurred on a mucosal surface, and a membranous film consisting mainly of fibrin mixed with necrotic cells appears on the surface of the affected mucosa.

Fibrinous pericarditis

Fibrinous pericarditis

pseudo-membranous inflammation bacillary dysentery

pseudo-membranous inflammation diphtheria

TYPES OF ACUTE INFLAMMATION C. suppurative (purulent inflammation) the formation of purulent exudates or pus Pus is made up of neutrophils, necrotic cells and edema fluid. Abscess is a localized collection of purulent inflammation accompanied by liquefactive necrosis.

Abscess of kidney

Abscess of brain

Abscess of kidney Abscess of liver

TYPES OF ACUTE INFLAMMATION D. hemorrhagic inflammation marked hemorrhage is the predominant pathological change

COURSE OF ACUTE INFLAMMATION A. resolution B. repair C. suppuration D. chronic inflammation

DIAGNOSIS OF ACUTE INFLAMMATION surface structures local cardinal signs permit diagnosis internal organs systemic changes may first manifest rarely, examine a fluid exudates or tissue sample

CHRONIC INFLAMMATION the sum of the responses mounted by tissue against a persistent injurious agent commonly show A. immune response B. phagocytosis C. necrosis D. repair

CHRONIC INFLAMMATION the main features include (1) mononuclear cell infiltration macrophages play dominant rolls (2) tissue destruction (3) granulation tissue formation and fibrosis be distinguished from acute inflammation

CHRONIC INFLAMMATION IN RESPONSE TO ANTIGENIC INJURIOUS AGENTS mechanisms injurious agent antigens tissue damage self antigens some days chemotactic factors accumulation of chronic inflammatory cells activated T lymphocytes, plasma cells, macrophages

CHRONIC INFLAMMATION IN RESPONSE TO ANTIGENIC INJURIOUS AGENTS morphologic types A. granulomatous chronic inflammation B. nongranulomatous chronic inflammation

granulomatous chronic inflammation a special type of chronic inflammation character: the formation of granuloma granuloma: an aggregate of macrophages two types: epithelioid cell granuloma foreign body granuloma

granulomatous chronic inflammation characteristic features: the formation of epithelioid cell granuloma epithelioid cell: activated macrophages that appear as large cells with abundant pale, foamy cytoplasm langhans-type giant cell: derived from fusion of macrophages and characterized by 10-50 nuclei around the periphery of the cell

epithelioid cell granuloma langhans-type giant cell epithelioid cell

granulomatous chronic inflammation Granulomas are usually surrounded by lymphocytes, plasma cells, fibroblasts, and collagen.

granulomatous chronic inflammation causes (1) When macrophages have successfully phagocytosed the injurious agent but it survives inside them (2) When an active T lymphocyte-mediated cellular immune response occurs

granulomatous chronic inflammation changes in affected tissues: granulomas expand and fuse with adjacent granulomas to form large masses

granulomatous chronic inflammation changes in affected tissues: in many infectious granulomas, central caseous necrosis is a common feature

granulomatous chronic inflammation caseous necrosis: gross: yellowish-white and resembles crumbly cheese microscopic: finely granular, pink, and amorphous

nongranulomatous chronic inflammation characteristic features: The accumulation of sensitized lymphocytes, plasma cells, and macrophages in the injured area. These cells are scattered diffusely throughout the tissue. Scattered tissue necrosis and fibrosis are common.

nongranulomatous chronic inflammation causes and changes in affected tissues: A. chronic viral infections B. chronic autoimmune diseases C. chronic chemical intoxications D. chronic nonviral infections E. allergic inflammation and metazoal infections

CHRONIC INFLAMMATION IN RESPONSE TO NONANTIGENIC INJURIOUS AGENTS characteristic features: the formation of foreign body granuloma foreign body giant cells: numerous nuclei dispersed throughout the cell foreign material is usually identifiable in the center of the granuloma tissue necrosis is not an associated feature (figure 4-19)

Foreign body granuloma

FUNCTION AND RESULT OF CHRONIC INFLAMMATION function of chronic inflammation serves to contain and remove an injurious agent that is not easily eradicated by the body dependent on immunologic reactivity: (1) direct killing by activated lymphocytes (2) interaction with antibodies (3) activation of macrophages

FUNCTION AND RESULT OF CHRONIC INFLAMMATION associated with tissue necrosis and implies serious illness associated fibrosis: a repair mechanism and perhaps another side effect

MIXED ACUTE AND CHRONIC INFLAMMATION chronic inflammation may follow acute inflammation or result from repeated bouts of acute inflammation features of both types of inflammation may coexist in certain circumstances

CHRONIC SUPPURATIVE INFLAMMATION It is difficult to remove the large amounts of pus associated with chronic suppurative inflammation. The surrounding viable tissue responds with a longstanding inflammatory process in which areas of suppuration alternate with areas of chronic inflammation and fibrosis.

CHRONIC SUPPURATIVE INFLAMMATION The difference between an acute and chronic abscess lies in the thickness of the fibrous wall; both form are filled with pus.

Abscess of liver

RECURRENT ACUTE INFLAMMATION if there is predisposing cause, repeated attacks of acute inflammation may occur Each attack of acute inflammation is follwed by incomplete resolution that leads to a progressively increasing number of chronic inflammatory calls and fibrosis. subacute inflammation acute-on-chronic inflammation

CLINICAL AND PATHOLOGIC DIAGNOSIS difficult Precise diagnosis usually requires recourse to a full range of clinical and pathologic studies. table 4-9