Lecture:Lecture:

ChronicChronic Inflammation.Inflammation.

InflammationInflammation is a is a complex reaction in complex reaction in

vascularized tissues. Itvascularized tissues. It is is a protective response to a protective response to

injury, which dilutes, injury, which dilutes, destroys, or isolates the destroys, or isolates the

causative agent.causative agent.

Inflammation Inflammation

Inflammation is a reaction of the Inflammation is a reaction of the microcirculation characterized by microcirculation characterized by movement of fluid and leukocytes movement of fluid and leukocytes from the blood into the extravascular from the blood into the extravascular tissues. tissues. This is frequently an This is frequently an expression of the host's attempt to expression of the host's attempt to localize and eliminate metabolically localize and eliminate metabolically altered cells, foreign particles, altered cells, foreign particles, microorganisms, or antigens.microorganisms, or antigens.

InflammationInflammation is is classified according to classified according to

duration:duration:- acute inflammation, acute inflammation, - chronic inflammation.chronic inflammation.

InflammationInflammation Chronic inflammation Chronic inflammation may present in three may present in three

histological forms: histological forms: granulomasgranulomas Chronic inflammation Chronic inflammation characterized by characterized by

mononuclear cell infiltrations mononuclear cell infiltrations that may be that may be diffusediffuse or or focalfocal; ;

production of production of connective tissue - fibrosisconnective tissue - fibrosis;; formation of new blood vessels formation of new blood vessels – angiogenesis– angiogenesis.. These reaction patterns are often interrelated and These reaction patterns are often interrelated and

may coexist. Infiltrates of chronic inflammation are may coexist. Infiltrates of chronic inflammation are composed of lymphocytes, plasma cells and composed of lymphocytes, plasma cells and macrophages in various proportions. macrophages in various proportions.

Persistent tissue damage is repaired continuously Persistent tissue damage is repaired continuously by fibroblasts and related by fibroblasts and related connective tissue connective tissue cells.cells.

Inflammation has three major Inflammation has three major components (or stages):components (or stages):

1.1. Alteration Alteration of vascular caliber and of vascular caliber and structural changes in microvasculature.structural changes in microvasculature.

2.2. Exudation, Exudation, increased vascular increased vascular permeability, emigration of leucocytes permeability, emigration of leucocytes from microcirculation to the focus of from microcirculation to the focus of injury.injury.

3.3. Proliferation Proliferation of connective tissue cells of connective tissue cells and cells of parenchyma to restore injury.and cells of parenchyma to restore injury.

Chronic inflammation.Chronic inflammation.

granulation tissuegranulation tissue

InflammationInflammationChronic inflammation. Lymphocytes, plasma cells (arrows), and a few macrophages are present.

InflammationInflammation Specific inflammatory mediators produced at the Specific inflammatory mediators produced at the

sites of injury regulate this response of the sites of injury regulate this response of the vasculature to injuryvasculature to injury..

Mediators of the inflamatory response

InflammationInflammation

no yes

Chronic inflammation.Chronic inflammation.

granulation tissuegranulation tissue

Chronic inflammation.Chronic inflammation. Proliferation of

connective tissue cells & cells derived from some leucocytes emigrated due to exudation proliferative inflammation.

Chronic inflammation.Chronic inflammation.

macrophamacrophagege

Classification of proliferative Classification of proliferative (chronic) inflammation.(chronic) inflammation.

1. 1. Interstitial inflammation Interstitial inflammation .. 2. 2. Granulomatous inflammation Granulomatous inflammation .. 3. 3. Hypertrophic proliferative inflammation with Hypertrophic proliferative inflammation with

formation of polyps & condylomasformation of polyps & condylomas.. 4. 4. Proliferative inflammation around parasitesProliferative inflammation around parasites..

Interstitial inflammationInterstitial inflammation Lymphoid infiltration in Lymphoid infiltration in

the stromathe stroma;; Diffuse;Diffuse; Fibrosis and sclerosisFibrosis and sclerosis. .

Granulomatous Granulomatous inflammationinflammation Granulomatous inflammation is a Granulomatous inflammation is a

distinctive morphologic pattern of distinctive morphologic pattern of inflammatory reaction encountered in inflammatory reaction encountered in relatively few diseases. Tuberculosis relatively few diseases. Tuberculosis is the archetype of the granulomatous is the archetype of the granulomatous diseases, but also included are diseases, but also included are syphilis, sarcoidosis, cat-scratch syphilis, sarcoidosis, cat-scratch fever, leprosy, brucellosis.fever, leprosy, brucellosis.

GranulomaGranuloma

A granuloma consists of a microscopic A granuloma consists of a microscopic aggregation of plump fibroblasts or aggregation of plump fibroblasts or histiocytes that have been transformed into histiocytes that have been transformed into epithelial-like cells, designated there for epithelial-like cells, designated there for epithelioid cells, surrounded by a collar of epithelioid cells, surrounded by a collar of mononuclear leukocytes, principally mononuclear leukocytes, principally lymphocytes and Occasionally plasma cells. lymphocytes and Occasionally plasma cells. Frequently, but not invariably, large giant Frequently, but not invariably, large giant cells are found in the periphery or sometimes cells are found in the periphery or sometimes in the center of granulomas. These giant cells in the center of granulomas. These giant cells may achieve diameters of 40 to 50 microns.may achieve diameters of 40 to 50 microns.

GranulomaGranuloma Certain variation in the granulomatous pattern is Certain variation in the granulomatous pattern is

encountered among the reactions of various encountered among the reactions of various etiologies. The granuloma of tuberculosis classically etiologies. The granuloma of tuberculosis classically has central caseous necrosis. The fusion of many has central caseous necrosis. The fusion of many caseating granulomas may give rise to large caseating granulomas may give rise to large macroscopic lesions of caseous necrosis.macroscopic lesions of caseous necrosis.

This chest radiograph reveals a miliary pattern in all lung fields. Note the stippled

appearance throughout.

Miliary tuberculosis of Miliary tuberculosis of lungs.lungs.

Tuberculous granuloma. Tuberculous granuloma.

Granulomatous Granulomatous inflammationinflammation

Giant multinucleated cells comprise a large mass of Giant multinucleated cells comprise a large mass of cytoplasm containing numerous (20 or more) small nuclei. cytoplasm containing numerous (20 or more) small nuclei. Two types of giant cells are encountered. The Pirogov-Two types of giant cells are encountered. The Pirogov-Langhans type is said to be characteristic of tuberculosis, Langhans type is said to be characteristic of tuberculosis, but in reality it may be found in some of granulomatous but in reality it may be found in some of granulomatous reactions. The nuclei in this form tend to be arranged about reactions. The nuclei in this form tend to be arranged about the periphery of the cell, sometimes encircling the the periphery of the cell, sometimes encircling the circumference, and at other times producing horse shoe circumference, and at other times producing horse shoe patterns. The foreign body type giant cell differs in that the patterns. The foreign body type giant cell differs in that the numerous nuclei are scattered throughout the cytoplasm in numerous nuclei are scattered throughout the cytoplasm in no distinctive pattern.no distinctive pattern.

Granulomatous Granulomatous inflammationinflammation

Granulomatous inflammation.Granulomatous inflammation.Tuberculous granuloma. Tuberculous granuloma.

Granulomatous Granulomatous inflammation.inflammation.

Tuberculous granuloma. Tuberculous granuloma.

At high magnification, the granuloma demonstrates that the epithelioid macrophages are elongated with long, pale nuclei and pink cytoplasm. The macrophages organize into committees called giant cells. The typical giant cell for infectious granulomas is called a Langhans giant cell and has the nuclei lined up along one edge of the cell. The process of granulomatous inflammation takes place over months to years.

There is a small tan-yellow subpleural granuloma in the mid-lung field on the right. In the hilum is a small yellow tan granuloma in a hilar lymph node next to a bronchus. This is the "Ghon complex" that is the characteristic gross appearance with primary tuberculosis. In most persons, the granulomatous disease will not progress. Over time, the granulomas decrease in size and can calcify, leaving a focal calcified spot on a chest radiograph that suggests remote granulomatous disease.

Granulomatous Granulomatous inflammation.inflammation.Tuberculous Tuberculous granulomagranuloma..

Giant multinucleated Giant multinucleated cells of Pirogov-cells of Pirogov-LanghansLanghans

Granulomatous Granulomatous inflammation.inflammation.

Tuberculous granuloma. Tuberculous granuloma.

Granulomatous Granulomatous inflammation.inflammation.

Tuberculous granuloma. Tuberculous granuloma.

Syphilitic mesaortitisSyphilitic mesaortitis

Syphilis produces gummatous necrosis in the center of its granuloma. Gummatous necrosis tends to have a rubbery consistency, firmer than the soft cheesy texture of the tuberculous reaction.

ActinomycosisActinomycosis

ActinomycosisActinomycosis

Granulomatous Granulomatous inflammation. Rheumatic inflammation. Rheumatic

fever.fever.

Granulomatous inflammation.Granulomatous inflammation.

In contrast, sarcoidosis almost never produces central necrosis, and so the sarcoid granuloma is often called a "hard tubercule", while the tuberculosis granuloma is often referred to as a "soft tubercule".Epithelioid cells (ЭК), lymphocytes (Л), giant cells (ГК), asteroid bodies (АТ). Zone of fibrosis (ЗФ).

A fungus ball composed of blue-staining hyphal elements of Aspergillus is seen here in a bronchus. Fungus balls may also form when fungi colonize cavitary lesions of tuberculosis.

Branching, septate hyphae are close-packed here and radiating outward in this aspergilloma.

The hyphae of Aspergillus are seen more clearly here. Aspergillus has a propensity to invade into blood vessels.

Fungal InfectionsFungal Infections

CoccidioidomycosisCoccidioidomycosis

Coccidioidomycosis, which is caused Coccidioidomycosis, which is caused by inhalation of the spores of by inhalation of the spores of Coccidioides immitis, is widely spread Coccidioides immitis, is widely spread through the southwestern part of the through the southwestern part of the United States, sharing many of the United States, sharing many of the clinical and pathologic features of clinical and pathologic features of histoplasmosis and tuberculosis. histoplasmosis and tuberculosis.

This well-formed granuloma has a large Langhans giant cell in the center. Two small spherules of Coccidioides immitis are seen in the giant cell.

Fungal InfectionsFungal Infections

CoccidioidomycosisCoccidioidomycosis

In most instances, the lesions are limited to In most instances, the lesions are limited to a peripheral parenchymal granuloma, with a peripheral parenchymal granuloma, with or without lymph node granulomas. In a few or without lymph node granulomas. In a few instances, however, the lesion is progressive, instances, however, the lesion is progressive, although the rate of progression is slow. although the rate of progression is slow. Immunocompromised patients may Immunocompromised patients may experience rapid progression of the disease.experience rapid progression of the disease.

At higher magnification, the thick wall of the C. immitis spherule is seen in a giant cell in the center of the photomicrograph. The spherule contains endospores. In the United States, C. immitis is endemic to the southwest.

Condyloma of penis.Condyloma of penis.

Proliferative Proliferative inflammation around inflammation around

parasites. parasites. Echinococcosis Echinococcosis of liver.of liver.

DirofillariosisDirofillariosis

Eosinophilic leukocytes Eosinophilic leukocytes in the infiltrate.in the infiltrate.

Chronic abscess of lung.

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