CHRONIC INFLAMMATIONS - Semmelweis...

Botond TIMÁR

CHRONIC INFLAMMATIONS

05.10.2017

Chronic inflammation

OUTCOMES OF ACUTE INFLAMMATION

Healing (Elimination) – restitutio ad integrumResolution of tissue structure and function with elimination of stimulus Tissues with regenerating capabilities

Tissue destruction and persisiting inflamation withAbscess formationUlcerationsFistulesScarring

Chronic inflammation (Persistent) Replacement of neutrophils with monocytes and lymphocytes, plasmacells and macrophagesAccompanied by proliferation of fibroblasts and new vessels with scarring

• Persistent infections• Organisms usually of low toxicity that invoke delayed

hypersensitivity reaction• M. tuberculosis and T. pallidum causes granulomatous reaction

• Prolonged exposure to potentially toxic agents• Exogenous agents include silica which causes silicosis• Endogenous causes include atherosclerosis caused by toxic

plasma lipid components • Autoimmunity

• Auto-antigens provoke self-perpetuating immune responses that cause chronic inflammatory diseases like RA, MS

• Responses against common environmental substances cause chronic allergic diseases, such as bronchial asthma

Causes of persistence (chronic inflammation)


Components of chronic inflammation

- Mononuclear Cells (Macrophages, Lymphocytes, Plasmacells)- Tissue damage via immune mediated processes- Reparation (Angiogenesis), Fibroblasts (Fibrosis)


Primary chronic Inflammations

From the beginning progressing as a chronic inflammation with lymphocytedominance and without purulent components like:

Etiology/Pathogenesis

- Immunological inflammation process with cytotoxic lymphocytes and/orantigene-antibody reaction against foreign bodies or autoantigenes

- Asbestos, Quarz etc..

- Certain specific microorganisms like Mycobacterium tuberculosis, Treponema(Syphilis) etc.

Secondary chronic inflammations

Acute inflammation progresses into a chronic process

e.g. chronic ulceration, chronic bronchitis, chronic pleuritis/pericarditischronic hepatitis etc.


Secondary chronic inflammations


Chronic fibrous pleuritis

Cave!!!Fibrinous ≠ Fibrous

Chronic fibrous inflammationsChronic inflammation

Acute fibrinous pleuritis

Chronic inflammationsChronic inflammation

Acut fibrinous pericarditis(see details in previous lecture)

Chronic fibrous pericarditis

Fibrotic adhesionsCalcification „Panzerherz”

Focal, chronic inflammations with non-specific reactions with characteristic granulation tissue formation.

Morphology of the granulation tissue is trizonal:

Chronic inflammation with granulation tissueChronic inflammation

The combination of proliferating fibroblasts, loose connective tissue, new blood vessels and scattered chronic inflammatory cells, forms a type of tissue that is unique to healing wounds and is called granulation tissue.

Chronic ulcer of the stomach

I.

II.III.

Etiology: Helicobacter pylori

Chronic inflammation with granulation tissueChronic inflammation

Complications:BleedingPerforationMalignant transformation

Round, oval, sharply punched-out defectBase is clean, smooth

Chronic liver abscess with pyogenic membrane

Secondary chronic inflammationsChronic inflammation

VIGYÁZAT! VIGYÁZAT!

Granulocyta leukocyta (neutrophil, eosinophil vagy basophil

granulatios szövet fibroblastok + érújdonképződés + kötőszövet

Granuloma körülírt, specifikus krónikus gyulladás

Fibrin fibrinogénből képződik (thrombus vagy exsudatum)

Fibroblast kötőszöveti sejt többféle funkcióval

Fibrosis kötőszövet felszaporodás (főleg I-es kollagén)

Primary chronic Inflammations

Primary chronic inflammationsChronic inflammation

Components / Cells: - Lymphocytes- Macrophages (main role)- Giant cells- Fibroblasts

In the blood : MonocytesIn tissues: Histiocytes, Alveolar macrophages, Kupfer Cells, Osteoclasts, Microglia

Half life: 1 TagPhagocytic activity

Epitheloid cells:Specialised, modified macrophages which are specialised to secrete proteases and activating cytokines. They can cluster in order to increase efficiency to secrete these enzymes. (therefore their name – clustering, epithel-like: Epitheloid cells!)

Macrophages

Multinucleate giant cells: Fusion of macrophages and epitheloid cells.

Primary chronic inflammationsChronic inflammation

Granuloma: Microscopic aggregation of macrophages that are transformed into epithelioid cells, surrounded by a collar of lymphocytes and occasionally plasma cells

Granulomatous inflammation is a form of chronic inflammation characterized by collections of activated macrophages, often with T lymphocytes, and sometimesassociated with central necrosis.

Immun (non-infectious) granuloma (Type IV HSR – T-cell mediated immune response):Rheumatoid arthritis type = fibrinoid NecrosisRheumatic fever type = small granulomas with Aschoff nodes and Anitschkov-cells

Immun (Infectious) granulomas:SyphilisTuberkulosis Ttpe = central, cheesy appearing necrosisPseudotuberkulosis Type = e.g.: Fungal infections

Non-immun granulomas (foreign body granulomas) (no type 4 HSR):Foreign body type

Unknown etiology:Sarkoidosis Type

Types of granulomas:

Giant cells:

LanghansForeign bodyTouton

Granulomatous inflammationChronic inflammation

Granuloma formation is a cellular attempt to contain an offending agent that is difficult to eradicate. In this attempt there is often strong activation of T lymphocytes leading to macrophage activation, which can cause injury to normal tissues.

Giant cellsChronic inflammations

LANGHANS They are formed by the fusion of epithelioid cells (macrophages), and contain nuclei arranged in a horseshoe-shaped pattern in the cell periphery.

FOREIGN-BODY TYPE


The nuclei are arranged in a disorganized manner. The nuclei in this cell are centrally placed and overlap each other.

TOUTON TYPE

In:Fat necrosisXanthomaXanthogranuloma…

They contain a ring of nuclei surrounding a central homogeneous cytoplasm, while foamy cytoplasm surrounds the nuclei. The cytoplasm surrounded by the nuclei has been described as both amphophilic and eosinophilic, while the cytoplasm near the periphery of the cell is pale and foamy in appearance.


DiseasesInfectious granulomatous diseases:

TuberculosisLepraSyphilisToxoplasmosisBrucellosisTyphoid fever (Salmonella typhimurium)Tularaemia

Immun granulomas:SarcoidosisCrohn diseaseAschoff-nodules in rheumatic fever granulomas)Chronic polyarthritis (rheumatoid nodules)

Foreign body granulomas:Foreign-body reaction


Non-caseating granuloma (Sarkoidosis Type)

Langhans type giant cells

Epitheloid cell layer,

outer Lymphocytic infiltrate

SarcoidosisM.CrohnToxoplasmosisBerylliosis

Examples:


Sarcoidosis

SarcoidosisChronic inflammations

Lymphnode

Multisystem disease of unknown etiologycharacterized by noncaseating granulomatous inflammation in many tissues and organs.- >90% have lung involvement

Etiology/PathogenesisLargely unknown (!), disordered immune regulation in genetically predisposed individuals exposed to certain environmental agents.Process is driven by CD4+ T-cellsMorphologyInvolved organs show typical sarcoid type granulomas

Symptoms:Pain in the Thorax, Bilateral hilar expansion

SarcoidosisChronic inflammations

Inflammatory bowel diseases Crohn diseaseColitis ulcerosa (Ulcerative colitis)

Crohn disease:Crohn disease, also known as regional enteritis, may occur in any area of the gastrointestinal tract but the most common sites involved at presentation are the terminal ileum, ileocecal valve, and cecum.

extraintestinal Symptoms: Erythema nodusum, Uveitis, Arthritis, primary sclerosing cholangitis

Crohn disease

Crohn diseaseChronic inflammations

Morphology:

Aphtous ulerSkip lesionsCobblestione appearance (diseased tissue is depressed below the level of normal mucosa)Fissures

Fissure


Non-caseating granulomas may be present


Central foamy cells (Macrophages),

Foreign-body type giant cells

Lymphocytic wall

Foreign-body granuloma

AsbestosisSilikosisexogeneous foreign bodies(e.g. splinter)

Cholesterol crystalsUraMucus

Diseases:


Foreign-body granuloma

Silica

splinter


Rheumatic /rheumatoid „granuloma”nodules

fibrinoid nekrosis in the center,

Surrounded by histiocytes with owl-eye like nucleolus (Anitchkov cells),

Scattered giant cells

Myokarditis in rheumatic fever

Vorkommen:


Acute Rheumatic Fever

Pancarditis:

fibrinous pericarditis,

granulomatous myocarditis,

endocarditis

Etiology: acute,

immunologically mediated,

multisystem inflammatory

disease that

occurs after group

A β-hemolytic streptococcal

infections (usually

pharyngitis)

Chronic inflammationChronic inflammation

rheumatisches Granulom


Aschoff nodules with central fibrinoid necrosis! Anitchkov-Cells (spec. Histiocytes)

RAChronic inflammation

Rheumatoid Arthritis

Rheumaknoten

- RA a chronic inflammatory disorder of autoimmune origin that principally attacks the joints, producing a nonsuppurative proliferative and inflammatory synovitis

- W >> M, 40. – 50. Y, CD4+ Th cell mediated process- Autoantibody (IgM) against the Fc-Fragment of the IgG (Rheuma faktor)Pannus – synovial cell hyperplasia and proliferation with dense inflamm infiltrateRheumatoid nodules – subcutaneous tissue of forearm, elbows with granuloma-like lesions)

Pannus

Destruktion

GelenkdeformationenMorgensteifigkeitSchwellung

Characteristic features includediffuse osteopenia, marked loss of the joint spaces of the carpal, metacarpal,phalangeal, and interphalangeal joints, periarticular bony erosions, and ulnar drift of the fingers.

RAChronic inflammation

Granuloma with mixed infiltratese.g. necrotising granulomas

Mesenterial Lymphadenitis (Yersinia pseudotuberculosis)Lymphogranuloma venerum (Chlamydia trachomatis)Bilharziose (Schistosomiasis)Cat scratch disease (Bartonella henselae)

Diseases:


Cat scratch disease

Cat-scratch disease is a self-limited lymphadenitis caused by the bacterium Bartonella henselae.

primarily a disease of childhood; 90% are < 18 years of age.

Manifests with regional lymphadenopathy, most frequently in the axilla and the neck. The nodalenlargement appears approximately 2 weeks after a felinescratch or, less commonly, after a splinter or thorn injury.

An inflammatory nodule, vesicle, or eschar is sometimes visible at the site of the skin injury.

In most patients the lymph node enlargement regresses during a period of 2 to4 months.

Rarely, encephalitis, osteomyelitis, or thrombocytopenia may develop in patients.

Micro: Lymphadenitis with rounded or stellate granuloma containing central granular debrisand recognizable neutrophils; giant cells uncommon.

Felinosis


Caseating granulomatousinflammation (Tuberculosis-Type)

Cell free cheesy necrosis in the middle,

Langhans-giant cells,

Epitheloid cell wall,

Lymphocytic infiltrate in the surrounding area

Syphilis (Treponema pallidum)Tuberculosis (Mycobacterium tuberculosis)

Tuberkuloid form of Lepra (Mycobacterium leprae), Wegener granulomatosis

Diseases:

Granulomatous inflammationsChronic inflammation

SyphilisChronische Entzündungen

The usual source of infection is contact with a cutaneous or mucosal lesion in a sexual partner in the early (primary or secondary) stages of syphilis.

!transplacental transmission!

Syphilis (lues)

Treponema pallidum, is a spiral form bacterium of the spirochete groups.

G-Primary syphilis. Several weeks after infection (mean, 21 days), a primary lesion, termed a chancre, appears at thepoint of spirochete entry.


Secondary syphilis.

The chancre of primary syphilis resolvesspontaneously over a period of 4 to 6 weeks and is followed in approximately 25% of untreated patients by the development of secondary syphilis.

The manifestations of secondary syphilis, include generalized lymphadenopathy and mucocutaneouslesions.

The mucocutaneous lesions of both primary and secondary syphilis are teeming with spirochetesand are highly infectious!!!!

Tertiary syphilis. Patients with untreated syphilis next enter an asymptomatic, late latent phase of the illness, defined as being more than 1 year after the initial infection.

In about one third of cases, new symptoms develop over the next 5 to 20 years.


Aneurysm on the aortic arch

Mesoaortitis luetica

LeprosyChronic inflammation

The infections are without symptoms and typically remain this way for 5 to 20 years.

Symptoms that develop include granulomas of the nerves, respiratory tract, skin, and eyes.

This may result in a lack of ability to feel pain, thus loss of parts of extremities due to repeated injuries or infection due to unnoticed wounds.

Tuberculoid/lepromatous types

Leprosy - (Hansen’s disease) Gerhard Armauer Hansen in 1873


Lepra lepromatosa tuberosa:

facies leontina (leprosa)


Lepra tuberculoides maculoanaesthetica:

With Leprids and nerve symptoms

TuberculosisChronic inflammation

Tuberculosis

Tuberculosis is a chronic granulomatous disease caused by Mycobacterium tuberculosis. It usually involves the lungs but may affect any organ or tissue in the body.

Infection with M. tuberculosis typically leads to the development of delayed hypersensitivity, which can be detected by the tuberculin (Mantoux) test.

Mycobacteria are slender rods that are acid-fast (i.e., they have a high content of complex lipids that readily bind the Ziehl-Neelsen [carbol fuchsin] stain and subsequently stubbornly resist decolorization)

The pathologic features of tuberculosis, such as caseating granulomas and cavitation, are the result of the destructive tissue hypersensitivity that is part of the host immune response.

The sequence of events are as follows:1. Entry into macrophages.2. Replication in macrophages.3. Development of cell-mediated immunity.4. T cell–mediated macrophage activation and killing of bacteria.5. Granulomatous inflammation and tissue damage.

Primary tuberculosis is the form of disease that develops in a previously unexposed and therefore unsensitized patient. About 5% of those newly infected acquire significant disease.

- primary lung involvement (inhalation)- primary enteral (through infected mild - very rare these days)

Primary Tuberculosis

Inhaled bacilli usually implant in the distal air spaces of the lower part of the upper lobe or in the upper part of the lower lobe. (close to the pleura)

1-cm to 1.5-cm area of gray-white inflammatory consolidation emerges. (Ghon focus).

This focus undergoes caseous necrosis.

Tubercle bacilli, either free or within phagocytes, travel via the lymphatic vessels to the regional lymph nodes, which also often caseate.

This combination of parenchymal and nodal lesions is called the Ghon complex.


Ziehl-Neelsen Staining


http://rds.yahoo.com/_ylt=A0WTb_pgjoRMplcA75CjzbkF/SIG=13tepi4k2/EXP=1283842016/**http:/upload.wikimedia.org/wikipedia/commons/9/9b/Mycobacterium_tuberculosis_Ziehl-Neelsen_stain_640.jpg

Thanks for your attention

Based among others on the book: Robbins: Basic pathology 9th, 10th editions

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