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Morphologic Patterns
Defect in leukocyte function
Complement deficiency
Systemic manifestation
Acute Inflammation
CELLULAR EVENTS:
LEUKOCYTE EXTRAVASATION AND PHAGOCYTOSIS
Vasodilation
Role of Mediators
in Different
Reactions of
Inflammation
Increased vascular
permeability
Chemotaxis, leukocyte
recruitment and activation
Fever
Pain
Tissue damage
Prostaglandins
Histamine
Nitric oxide
Vasoactive amines
Bradykinin
Leukotrienes C4, D4, E4
PAF
Substance P
C5a
Leukotriene B4
Chemokines
IL-1, TNF
Bacterial products
IL-1, TNF
Prostaglandins
Prostaglandins
Bradykinin
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
Complement deficiency
Systemic manifestation
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Patterns of Acute Inflammation
Outcomes of Acute Inflammation
Patterns of chronic Inflammation
Defect in leukocyte function
Complement deficiency
Systemic manifestation
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Several types of inflammation vary in their
morphology and clinical correlates. Why?
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The severity of the reaction
specific cause
the particular tissue
site involved
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SEROUS INFLAMMATION
FIBRINOUS INFLAMMATION
SUPPURATIVE OR PURULENT
INFLAMMATION
ULCERS
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SEROUS INFLAMMATION:
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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FIBRINOUS INFLAMMATION
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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 INFLAMMATION
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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 and
thus lead to scarring (organization)
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 (pusproducing) bacteria
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Suppurative inflammation. A, A subcutaneous bacterial abscess with
collections 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
Localized liquefactive necrosis liver abscess
Removal of the
dead tissue
leaves behind a
scar
ULCERS

An ulcer is a local defect of the surface of an
organ or tissue that is produced by the
sloughing (shedding) of inflammatory
necrotic tissue
ULCERS
encountered in:
1) inflammatory necrosis of the mucosa of the mouth,
stomach, intestines, or genitourinary tract
2)
subcutaneous inflammation of the lower
extremities in older persons who have circulatory
disturbances
Ulceration can occur only when tissue necrosis and
resultant inflammation exist on or near a surface
Epithelial Defect
Necrotic base
Fibrinopurulent exudates
Granulation tissue
Fibrosis
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Patterns of Acute Inflammation
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Outcomes of Acute Inflammation
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Patterns of chronic Inflammation
Defect in leukocyte function
Complement deficiency
Systemic manifestation
Acute inflammation may have one of the four
outcomes:
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Complete resolution
Healing by connective tissue replacement (fibrosis)
Progression of the tissue response to chronic
inflammation
Abcess formation
Complete resolution
When?
1) the injury is limited or short-lived
2) there has been little tissue destruction
3) the damaged parenchymal cells can
regenerate
Complete resolution
Mechanism:
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Neutralization and removal of chemical mediators
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Normalization of vascular permeability
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halting of leukocyte emigration
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Clearance of edema (lymphatic drainage) ,
inflammatory cells and necrotic debris
(macrophages).
Events in the resolution of
inflammation
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Healing by connective tissue replacement
(fibrosis):
This occurs after substantial tissue destruction
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the inflammatory injury involves tissues that are incapable of
regeneration
there is abundant fibrin exudation.
The destroyed tissue is resaorbed and eventually
replaced by fibrosis.
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Progression of the tissue response to chronic
inflammation:
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occurs when the acute inflammatory response
cannot be resolved WHY?
Due to: 1. the persistence of the injurious agent
2. some interference with the normal
process of healing
A 36-year-old man has had midepigastric
abdominal pain for the past 3 months. An
upper gastrointestinal endoscopy shows a 2cm, sharply demarcated, shallow ulceration
of the gastric antrum. A biopsy specimen of
the ulcer base shows angiogenesis, fibrosis,
and mononuclear cell infiltrates with
lymphocytes, macrophages, and plasma
cells. Which of the following terms best
describes this pathologic process?
(A) Acute inflammation
(B) Serous inflammation
(C) Granulomatous inflammation
(D) Fibrinous inflammation
(E) Chronic inflammation
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Patterns of Acute Inflammation
Outcomes of Acute Inflammation
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Patterns of chronic Inflammation
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Defect in leukocyte function
Complement deficiency
Systemic manifestation
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inflammation of prolonged duration
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weeks or months
Mixture of active inflammation, tissue destruction, and
attempts at repair
it may follow:
1.
acute inflammation
or
2.
begins insidiously,
as a low-grade,
often asymptomatic
response.
This is the cause of tissue
damage in some of the most
common and disabling human
diseases, such as rheumatoid
arthritis, atherosclerosis,
tuberculosis, and chronic lung
diseases
1.
2.
Viral infection
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 for
prolonged 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
1.
Infiltration with mononuclear cells include
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2.
Tissue destruction
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3.
Macrophages
Lymphocytes
Plasma cells
Eosinophils
induced by the persistent offending agent or by
the inflammatory cells.
Healing
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by connective tissue replacement of damaged
tissue, accomplished by proliferation of small
blood vessels (angiogenesis) and, in particular,
fibrosis
MONONUCLEAR CELL INFILTRATION
Macrophages
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the dominant cellular player in chronic inflammation
The mononuclear phagocyte system (sometimes
called reticuloendothelial system) consists of closely
related cells of bone marrow origin, including blood
monocytes and tissue macrophages
mononuclear phagocyte system
–monocytes begin to emigrate into extravascular tissues quite early in
acute inflammation and within 48 hours they may constitute the
predominant cell type
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Macrophages may be activated by a variety of stimuli,
including
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Activation results in
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cytokines (e.g., IFN-γ) secreted by sensitized T lymphocytes and
by NK cells
bacterial endotoxins
other chemical mediators
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 of
biologically active products that, if unchecked, result in
the tissue injury and fibrosis
.
Products of macrophages
1.Acid and neutral proteases
2.Chemotactic factors
3.Reactive oxygen metabolites
4.Complement components
5. Coagulation factors
6.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
Function?!!..  to initiate the process of repair
 It is responsible for much of the
tissue injury in chronic inflammation
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 results
from the expression of adhesion molecules and chemotactic
factors
2.
Local proliferation of macrophages after their emigration from
the bloodstream
3.
Immobilization of macrophages within the site of inflammation
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Lymphocytes
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Both T & B Lymphocytes migrates into inflammation
site
–Lymphocytes and macrophages interact in a bidirectional way, and
these reactions play an important role in chronic inflammation
Activated lymphocytes and macrophages influence each other and also
release inflammatory mediators that affect other cells.
•Eosinophils
are abundant in immune reactions mediated by IgE and in
parasitic infections
• respond to chemotactic agents derived largely from mast cells
• Granules contain major basic protein: toxic to parasites and
lead to lysis of mammalian epithelial cells
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Mast cells
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are widely distributed in connective tissues
express on their surface the receptor that binds the
Fc portion of IgE antibody ,
 the cells degranulate and release mediators, such as
histamine and products of AA oxidation
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GRANULOMATOUS INFLAMMATION
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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
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Bacterial
Parasitic
Fungal
Inorganic dusts
Foreign bodeis
unknown
Examples of Diseases with Granulomatous Inflammations
Disease
Cause
Tissue Reaction
Tuberculosis
Mycobacterium
tuberculosis
Noncaseating tubercle
Caseating tubercles
Leprosy
Mycobacterium leprae
Acid-fast bacilli in
macrophages;
noncaseating granulomas
Syphilis
Treponema pallidum
Gumma: wall of
histiocytes; plasma cell
Cat-scratch disease Gram-negative bacillus Rounded or stellate
granuloma
Sarcoidosis
Unknown etiology
Noncaseating granulomas
Crohn disease
Immune reaction
against intestinal
bacterial
dense chronic inflammatory
infiltrate with noncaseating
granulomas
Role of lymphatic and Lymph Nodes in
Inflammation
u Represents a second line of defense
u Delivers antigens and lymphocytes to the
central lymph nodes
u Lymph flow is increased in inflammation
u May become involved by secondary
inflammation (lymphangitis, reactive
lymphadenitis)
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Patterns of Acute Inflammation
Outcomes of Acute Inflammation
Patterns of chronic Inflammation
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Defect in leukocyte function
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Complement deficiency
Systemic manifestation
1.
2.
Genetic
Acquired
lead to increased vulnerability to infections
A. Defect in leukocyte adhesions:
- Leukocyte adhesion deficiency 1
β chain of CD11/CD18 integrins
- Leukocyte adhesion deficiency 2
 Fucosyl transferase required for synthesis of sialylated
oligosaccharide (receptor for selectin)

B. Defect of phagocytosis (Chédiak-Higashi syndrome)
An autosomal recessive condition characterized by neutropenia
(decreased numbers of neutrophils), defective degranulation, and
delayed microbial killing
C. Defect of bactericidal activity (Chronic granulomatous disease)
Patients susceptible to recurrent bacterial infection. Chronic
granulomatous disease results from inherited defects in the
genes encoding several components of NADPH oxidase, which
generates superoxide.
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Thermal injury, diabetes, malignancy,
sepsis, immunodeficiencies
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Hemodialysis, diabetes mellitus
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Chemotaxis
Adhesion
Leukemia, anemia, sepsis, diabetes,
neonates, malnutrition
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Phagocytosis and microbicidal activity
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Patterns of Acute Inflammation
Outcomes of Acute Inflammation
Patterns of chronic Inflammation
Defect in leukocyte function
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Complement deficiency
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Systemic manifestation
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Complement deficiency
hereditary deficiency of
C3 results in an
increased susceptibility
to infection with
pyogenic bacteria.
Deficiencies of the late
components of the
classical complement
pathway (C5-C8) result
in recurrent infections by
Neisseria
Inherited deficiencies of C1q, C2, and C4
increase the risk of immune complexmediated disease (e.g., SLE)
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hereditary deficiency of complement components,
especially C3 (critical for both the classical and
alternative pathways), results in an increased
susceptibility to infection with pyogenic bacteria.
Inherited deficiencies of C1q, C2, and C4 do not
make individuals susceptible to infections, but they
do increase the risk of immune complex-mediated
disease (e.g., SLE), possibly by impairing the
clearance of apoptotic cells or of antigen-antibody
complexes from the circulation.
Deficiencies of the late components of the classical
complement 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 C1
inhibitor allows C1 activation, with the
generation of down-stream vasoactive
complement mediators
The result is hereditary angioedema,
characterized by recurrent episodes of
localized edema affecting the skin and/or
mucous membranes.
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Patterns of Acute Inflammation
Outcomes of Acute Inflammation
Patterns of chronic Inflammation
Defect in leukocyte function
Complement deficiency
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Systemic manifestation
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Acute phase
reaction/response
- IL-1 and TNF
- Fever
- Malaise
- Anorexia
Bone marrow
- leukocytosis
- IL-1 + TNF
Lymphoid organs
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Liver
-IL-6, IL-1, TNF
-Acute phase
proteins
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C-reactive protein
Lipopolysaccharide
binding protein
Serum amyloid A
a-2 macroglobulin
Haptoglobin
Ceruloplasmin
fibrinogen
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Fever is produced in response to Pyrogens
What are pyrogens?
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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 convert
AA into prostaglandins.
Fever
•In the hypothalamus, the
prostaglandins, especially PGE2,
stimulate the production of
neurotransmitters such as cyclic
AMP, which function to reset the
temperature set-point at a higher
level.
•NSAIDs, including aspirin , reduce
fever by inhibiting cyclooxygenase
and thus blocking prostaglandin
synthesis.
•fever may induce heat shock
proteins that enhance lymphocyte
responses to microbial antigens.
Increased erythrocyte sedimentation rate
•The rise in fibrinogen causes erythrocytes to form stacks (rouleaux) that
sediment more rapidly at unit gravity than do individual erythrocytes. This is the
basis for measuring the erythrocyte sedimentation rate (ESR) as a simple test
for the systemic inflammatory response,
Increased erythrocyte sedimentation rate during inflammation
(ESR)
TNF
IL-1
IL-6
Hepatic synthesis of some plasma proteins
most notably fibrinogen
Rapid agglutination of erythrocytes
Inflammation
Systemic Manifestations
Leukocytosis:
WBC count climbs to 15,000 or 20,000 cells/μl
most bacterial infection
Lymphocytosis:
Infectious mononucleosis, mumps,
German measles
Eosinophilia: bronchial asthma,
hay fever, parasitic infestations
Leukopenia: typhoid fever,
infection with rickettsiae/protozoa
An experiment introduces bacteria into a
perfused tissue preparation. Leukocytes
then leave the vasculature and migrate
to the site of bacterial inoculation. The
movement of these leukocytes is most
likely 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
with fever for the past month. On physical
examination, she has a temperature of 37.5°C,
and on auscultation of the chest, crackles are
heard in all lung fields. A chest radiograph
shows many small, ill-defined nodular opacities
in all lung fields. A transbronchial biopsy
specimen shows interstitial infiltrates with
lymphocytes, plasma cells, and epithelioid
macrophages. Which of the following infectious
agents is the most likely cause of this
appearance?
(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
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Neutrophils
Cardinal signs of
inflammation
Lymphatics
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Active hyperemia
Edema, occ.fibrin thrombi
Role to remove exudate
Can lead to inflammation.
Lymphangitis
Lymphadenitis