09-acute inflammation.morphology, pptx

8/13/2019 09-Acute Inflammation.morphology, Pptx

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Morphologic PatternsDefect in leukocyte function

Complement deficiency

Systemic manifestation


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Acute InflammationCELLULAR EVENTS:

LEUKOCYTE EXTRAVASATION AND PHAGOCYTOSIS


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Role of Mediators

in Different

React ions of

Inf lammation

Vasodilation

Prostaglandins

Histamine

Nitric oxide

Increased vascular

permeability

Vasoactive amines

BradykininLeukotrienes C4, D4, E4

PAFSubstance P

Chemotaxis, leukocyte

recruitment and activation

C5a

Leukotriene B4Chemokines

IL-1, TNF

Bacterial productsFever IL-1, TNF

ProstaglandinsPain Prostaglandins

Bradykinin

Tissue damage

Neutrophil and macrophage

lysosomal enzymes

Oxygen metabolites

Nitric oxide


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Patterns of Acute Inflammation

Outcomes of Acute Inflammation

Patterns of chronic Inflammation

Defect in leukocyte function




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Patterns of Acute Inflammation Outcomes of Acute Inflammation






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Several types of inflammation vary in their

morphology and clinical correlates. Why? The severity of the reaction

specific cause

the particular tissue

site involved


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SEROUS INFLAMMATION

FIBRINOUS INFLAMMATION

SUPPURATIVE OR PURULENTINFLAMMATION

ULCERS


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SEROUSINFLAMMATION:

Serous inflammation is marked by the

outpouring of a thin fluid

e.g. the skin blister resulting from a burn or

viral infection represents a large

accumulation of serous fluid


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more severe injuries and more greater vascular

permeability, larger molecules such as fibrinogen

pass the vascular barrier, and fibrin is formed and

deposited


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A fibrinous exudate is characteristic of inflammation in the

lining of body cavities, such as the meninges,

pericardium and pleura


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Fibrinous exudates may be removed by fibrinolysis

But when the fibrin is not removed, it may stimulate

the ingrowth of fibroblasts and blood vessels andthus lead to scarring (organization)


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characterized by the production of large

amounts of pus or purulent exudate

consisting of neutrophils, necrotic cells,and edema fluid

Certain bacteria (e.g., staphylococci)

produce this localized suppuration and are

therefore referred to as pyogenic (pus-producing) bacteria


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Suppurative inflammation. A, A subcutaneous bacterial abscess withcollections of pus. B, The abscess contains neutrophils, edema fluid, and

cellular debris.


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Abscesses : localized collections of

purulent inflammatory tissue caused by

suppuration buried in a tissue, an

organ, or a confined space


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Localized liquefactive necrosis liver abscess

Removal of thedead tissueleaves behind a

scar


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ULCERS

An ulcer is a local defect of the surface of an

organ or tissue that is produced by thesloughing (shedding) of inflammatorynecrotic tissue


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ULCERS

encountered in:

1) inflammatory necrosis of the mucosa of the mouth,stomach, intestines, or genitourinary tract

2) subcutaneous inflammation of the lowerextremities in older persons who have circulatorydisturbances


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Acute inflammation may have one of the four

outcomes: Complete resolution

Healing by connective tissue replacement (fibrosis)

Progression of the tissue response to chronic

inflammation

Abcess formation


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Complete resolution

When?

1) the injury is limited or short-lived

2) there has been little tissue destruction

3) the damaged parenchymal cells canregenerate


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Complete resolution

Mechanism:

Neutralization and removal of chemical mediators Normalization of vascular permeability

halting of leukocyte emigration

Clearance of edema (lymphatic drainage) ,inflammatory cells and necrotic debris(macrophages).


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Events in the resolution of

inflammation


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Healing by connective tissue replacement

(fibrosis):

This occurs after substantial tissue destruction

the inflammatory injury involves tissues that are incapable ofregeneration

there is abundant fibrin exudation.

The destroyed tissue is resaorbed and eventually

replaced by fibrosis.


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A 36-year-old man has had midepigastricabdominal pain for the past 3 months. Anupper gastrointestinal endoscopy shows a 2-

cm, sharply demarcated, shallow ulcerationof the gastric antrum. A biopsy specimen ofthe ulcer base shows angiogenesis, fibrosis,and mononuclear cell infiltrates withlymphocytes, macrophages, and plasmacells. Which of the following terms bestdescribes this pathologic process?

(A) Acute inflammation

(B) Serous inflammation(C) Granulomatous inflammation(D) Fibrinous inflammation(E) Chronic inflammation


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Defect in leukocyte function Complement deficiency



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inflammation of prolonged duration

weeks or months

Mixture of active inflammation, tissue destruction, and

attempts at repair

it may follow:1. acute inflammation

2. begins insidiously,

as a low-grade,

often asymptomatic

response.

This is the cause of tissue

damage in some of the mostcommon and disabling human

diseases, such as rheumatoid

arthritis, atherosclerosis,

tuberculosis, and chronic lung

diseases

or


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1. Viral infection

2. Persistent infections by certain microorganisms,e.g. tubercle bacilli, Treponema pallidum, fungi, and parasites.

3. Prolonged exposure to potentially toxic agents, either

exogenous or endogenous

e.g. of exogenous agent is particulate silica, when inhaled forprolonged periods, results in silicosis

e.g. of endogenous agent is atherosclerosis (a chronic inflammatory

process of the arterial wall induced by endogenous toxic plasma

lipid components)

4. Autoimmunity:immune reactions develop against the

individual's own tissues

In these diseases, autoantigens evoke immune reaction that

results in chronic tissue damage and inflammation e.g.

rheumatoid arthritis and lupus erythematosus


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1. Infiltration with mononuclear cells include Macrophages

Lymphocytes

Plasma cells

Eosinophils

2. Tissue destruction induced by the persistent offending agent or by

the inflammatory cells.

3. Healing by connective tissue replacement of damaged

tissue, accomplished by proliferation of smallblood vessels (angiogenesis) and, in particular,

fibrosis


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MONONUCLEAR CELL INFILTRATION

Macrophages

the dominant cellular player in chronic inflammation

The mononuclear phagocyte system (sometimescalled reticuloendothelial system) consists of closelyrelated cells of bone marrow origin, including bloodmonocytes and tissue macrophages

mononuclear phagocyte system


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mononuclear phagocyte system

monocytes begin to emigrate into extravascular tissues quite early inacute inflammation and within 48 hours they may constitute the

predominant cell type


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Macrophages may be activatedby a variety of stimuli,including cytokines (e.g., IFN-) secreted by sensitized T lymphocytes and

by NK cells

bacterial endotoxins

other chemical mediators Activation results in

increased cell size

increased levels of lysosomal enzymes

more active metabolism

greater ability to phagocytose and kill ingested microbes.

Activated macrophages secrete a wide variety ofbiologically active productsthat, if unchecked, result inthe tissue injury and fibrosis


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.

Products of macrophages

1.Acid and neutral proteases

2.Chemotactic factors

3.Reactive oxygen metabolites

4.Complement components

5. Coagulation factors6.Growth promoting factors for fibroblasts, blood

vessels and myeloid progenitor cells

7.Cytokines : IL-1, TNF

8.Other biologic active agents ( PAF, interferon,

AA metabolites) to eliminate injurious agents such as

microbes

to initiate the process of repair

It is responsible for much of the

tissue injury in chronic inflammation

Function?!!..


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The roles of activated macrophages in chronic inflammation.

Acute&

Chronic inflam.persist


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In chronic inflammation, macrophage accumulation

persists, this is mediated by different mechanisms:

1. Recruitment of monocytes from the circulation, which resultsfrom the expression of adhesion molecules and chemotacticfactors

2. Local proliferation of macrophagesafter their emigration fromthe bloodstream

3. Immobilization of macrophageswithin the site of inflammation


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Lymphocy tes Both T & BLymphocytesmigrates into inflammation

site

Lymphocytes and macrophages interact in a bidirectional way and


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Activated lymphocytes and macrophages influence each other and also

release inflammatory mediators that affect other cells.

Lymphocytes and macrophages interact in a bidirectional way, and

these reactions play an important role in chronic inflammation


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Eosinophi lsare abundant in immune reactions mediated by IgE and inparasitic infections

respond to chemotactic agents derived largely from mast cellsGranules contain major basic protein: toxic to parasites and

lead to lysis of mammalian epithelial cells

Mast cells


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are widely distributed in connective tissues

express on their surface the receptor that binds theFc portion of IgE antibody ,

the cells degranulate and release mediators, such ashistamine and products of AA oxidation


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GRANULOMATOUS INFLAMMATION

Granulomatous inflammation is a distinctive

pattern of chronic inflammatory reaction

characterized by focal accumulations of

activated macrophages, which often develop an

epithelial-like (epithelioid) appearance


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Infections

Bacterial

Parasitic

Fungal

Inorganic dusts

Foreign bodeis

unknown

Examples of Diseases with Granulomatous Inflammations


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Disease Cause Tissue Reaction

Tuberculosis Mycobacterium

tuberculosis

Noncaseating tubercle

Caseating tubercles

Leprosy Mycobacterium leprae Acid-fast bacilli inmacrophages;noncaseating granulomas

Syphilis Treponema pallidum Gumma: wall of

histiocytes; plasma cell

Cat-scratch disease Gram-negative bacillus Rounded or stellategranuloma

Sarcoidosis Unknown etiology Noncaseating granulomas

Crohn disease Immune reactionagainst intestinalbacterial

dense chronic inflammatoryinfiltrate with noncaseatinggranulomas

Examples of Diseases with Granulomatous Inflammations


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Role of lymphatic and Lymph Nodes in

Inf lammat ionuRepresents a second line of defense

uDelivers antigens and lymphocytes to the

central lymph nodes

uLymph flow is increased in inflammation

uMay become involved by secondary

inflammation (lymphangitis, reactivelymphadenitis)


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1. Genetic

2. Acquired

lead to increased vulnerability to infections


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A. Defect in leukocyte adhesions:- Leukocyte adhesion deficiency 1

chain of CD11/CD18 integrins

- Leukocyte adhesion deficiency 2 Fucosyl transferase required for synthesis of sialylated

oligosaccharide (receptor for selectin)

B. Defect of phagocytosis (Chdiak-Higashi syndrome)An autosomal recessive condition characterized by neutropenia

(decreased numbers of neutrophils), defective degranulation, anddelayed microbial killing

C. Defect of bactericidal activity(Chronic granulomatous disease)Patients susceptible to recurrent bacterial infection. Chronicgranulomatous disease results from inherited defects in the

genes encoding several components of NADPH oxidase, whichgenerates superoxide.


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Thermal injury, diabetes, malignancy,sepsis, immunodeficiencies Chemotaxis

Hemodialysis, diabetes mellitus Adhesion

Leukemia, anemia, sepsis, diabetes,neonates, malnutrition

Phagocytosis and microbicidal activity


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Complement deficiency Systemic manifestation


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Complement deficiencyhereditary deficiency ofC3 results in anincreased susceptibility

to infection withpyogenic bacteria.

Inherited deficiencies of C1q, C2, and C4increase the risk of immune complex-

mediated disease (e.g., SLE)

Deficiencies of the late

components of theclassical complementpathway (C5-C8) resultin recurrent infections byNeisseria


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hereditary deficiency of complement components,

especially C3 (critical for both the classical andalternative pathways), results in an increasedsusceptibility to infection with pyogenic bacteria.

Inherited deficiencies of C1q, C2, and C4 do notmake individuals susceptible to infections, but theydo increase the risk of immune complex-mediateddisease (e.g., SLE), possibly by impairing theclearance of apoptotic cells or of antigen-antibodycomplexes from the circulation.

Deficiencies of the late components of the classicalcomplement pathway (C5-C8) result in recurrent

infections by Neisseria(gonococci, meningococci)but not by other microbes.


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Lack of the regulatory protein C1inhibitor allows C1 activation, with thegeneration of down-stream vasoactive

complement mediators The result is hereditary angioedema,

characterized by recurrent episodes oflocalized edema affecting the skin and/or

mucous membranes.


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Acute phasereaction/response

- IL-1 and TNF

- Fever

- Malaise

- Anorexia

Bone marrow

- leukocytosis- IL-1 + TNF

Lymphoid organs

Liver-IL-6, IL-1, TNF-Acute phase

proteins

C-reactive protein Lipopolysaccharide

binding protein Serum amyloid A a-2 macroglobulin

Haptoglobin Ceruloplasmin fibrinogen


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Feveris produced in response to Pyrogens What arepyrogens?

act by stimulating prostaglandin synthesis in the

vascular and perivascular cells of the

hypothalamus.

Bacterial products (called exogenous

pyrogens), stimulate leukocytes to release

cytokines such as IL-1 and TNF (called

endogenous pyrogens) that increase the

enzymes (cyclooxygenases) that convertAA into prostaglandins.

Fever


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In the hypothalamus, the

prostaglandins, especially PGE2,

stimulate the production of

neurotransmitters such as cyclicAMP, which function to reset the

temperature set-point at a higher

level.

NSAIDs, including aspirin , reducefever by inhibiting cyclooxygenase

and thus blocking prostaglandin

synthesis.

fever may induce heat shockproteins that enhance lymphocyte

responses to microbial antigens.

Fever

Increased erythrocyte sedimentation rate


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Increased erythrocyte sedimentation rate during inflammation

(ESR)

Rapid agglutination of erythrocytes

Hepatic synthesis of some plasma proteins

most notably fibrinogen

IL-6

IL-1

TNF

The rise in fibrinogen causes erythrocytes to form stacks (rouleaux) thatsediment more rapidly at unit gravity than do individual erythrocytes. This is thebasis for measuring the erythrocyte sedimentation rate (ESR)as a simple test

for the systemic inflammatory response,

Inflammation


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InflammationSystemic ManifestationsLeukocytosis:

WBC count climbs to 15,000 or 20,000 cells/l

most bacterial infectionLymphocytosis:

Infectious mononucleosis, mumps,German measles

Eosinophilia: bronchial asthma,hay fever, parasitic infestations

Leukopenia: typhoid fever,infection with rickettsiae/protozoa


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An experiment introduces bacteria into a


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An experiment introduces bacteria into aperfused tissue preparation. Leukocytesthen leave the vasculature and migrateto the site of bacterial inoculation. Themovement of these leukocytes is mostlikely to be mediated by which of the

following substances?

(A) Bradykinin(B) Chemokines

(C) Histamine(D) Prostaglandins(E)Complement C3a

A 32-year-old woman has had a chronic cough


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A 32-year-old woman has had a chronic coughwith fever for the past month. On physicalexamination, she has a temperature of 37.5C,and on auscultation of the chest, crackles areheard in all lung fields. A chest radiographshows many small, ill-defined nodular opacitiesin all lung fields. A transbronchial biopsyspecimen shows interstitial infiltrates withlymphocytes, plasma cells, and epithelioid

macrophages. Which of the following infectiousagents is the most likely cause of thisappearance?

(A)Staphylococcus aureus

(B) Plasmodium falciparurn(C) Candida albi cans(D) Mycobacteriurn tuberculosis(E) Klebsiella pneumo nine(F)Cytomegalovirus


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Time 4-6 hours to 3-5

days Vascular involvement

Active hyperemia

Edema, occ.fibrin thrombi

Neutrophils Cardinal signs of

inflammation

Lymphatics Role to remove exudate

Can lead to inflammation.

Lymphangitis

Lymphadenitis

09-acute inflammation.morphology, pptx

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