Inflammation 3

MORPHOLOGIC PATTERNS OF ACUTE

INFLAMMATION
• Serous
• Fibrinous
• Suppurative
• Ulcerative
• Morphology of acute inflammation depends
on:
1. The severity of the inflammatory response
2. its specific cause
3. particular tissue involved

The importance of recognizing these

morphologic patterns is that they are often
associated with different eliciting stimuli and
clinical situations.
• Serous inflammation
• is characterized by watery, relatively protein-
poor fluid that,
• derived from:
1. the serum
2. the secretions of mesothelial cells lining the
peritoneal, pleural, and pericardial cavities.
• Eg. The skin blister resulting from a burn or
viral infection.
• Fluid in a serous cavity is called an effusion.
• Fibrinous inflammation
• It is a consequence of severe injuries with a
vascular permeability that allows fibrinogen to
pass the endothelial barrier.
• A fibrinous exudate is characteristic of
inflammation in the lining of body cavities,
such as the meninges, pericardium, and
pleura.
• Histologically, the accumulated extravascular
fibrin appears as an eosinophilic meshwork of
threads or as an amorphous coagulum
• Fate:
• Resolution: exudates is degraded by fibrinolysis,
and the debris are removed by macrophages,
resulting in restoration of the normal tissue
structure.
• Organization: is the ingrowth of fibroblasts and
blood vessels leading to scarring
• For example, organization of a fibrinous
pericardial exudate forms dense fibrous scar
tissue that bridges or obliterates the pericardial
space and restricts myocardial function.
• Suppurative (purulent) inflammation
• is manifested by the presence of large
amounts of purulent exudate (pus) consisting
of neutrophils, necrotic cells, and edema fluid.
• Causes :
•
• Staphylococci infection.
• Abscesses are focal collections of pus that may be
caused by:
• seeding of pyogenic organisms into a tissue or
• by secondary infections of necrotic foci.
• Abscesses typically have a central, largely necrotic
region rimmed by a layer of preserved
neutrophils), with a surrounding zone of dilated
vessels and fibroblastic proliferation indicative of
early repair.
• As time passes the is replaced by connective
tissue (fibrosis).
• An ulcer is a local defect of the surface of an
organ or tissue that is produced by necrosis of
cells and sloughing of inflammatory necrotic
tissue.
• Ulceration can occur only when tissue necrosis
and resultant inflammation exist on or near a
surface.
• Eg. Mucosal ulcers and skin ulcers
 CHRONIC INFLAMMATION
• Chronic inflammation is inflammation of
prolonged duration (weeks to months to
years) in which active inflammation, tissue
injury, and healing proceed simultaneously.
 Acute inflammation is Chronic inflammation is
characterized by characterized by
* vascular changes
* edema
* predominantly * mononuclear cells Infiltration
neutrophilic infiltrate (macrophages, lymphocytes,
and plasma cells)
* Tissue destruction: largely
induced by the products of the
inflammatory cells
* Angiogenesis: new vessel
proliferation
* fibrosis
 Injury

Acute inflammation Chronic inflammation

When the acute response e.g., viral infections

cannot be resolved:
Resolution 1.persistence of the
injurious agent
(TB)
2.interference with
the normal process
of healing (DU)

Chronic inflammation
 Chronic inflammation arises in the
following settings:

1. Persistent infections
2. Immune-mediated inflammatory diseases
(hypersensitivity diseases).
3. Prolonged exposure to potentially toxic
agents.
Persistent infections by microbes that are
difficult to eradicate:
• These include mycobacteria, Treponema
pallidum (causative organism of syphilis), and
certain viruses and fungi, all of which tend to
establish persistent infections and elicit a T
lymphocyte-mediated immune response
called delayed-type hypersensitivity
Immune-mediated inflammatory diseases
(hypersensitivity diseases):
• Diseases that are caused by excessive and
inappropriate activation of the immune
system
1. autoimmune diseases: immune reactions
against self antigens (rheumatoid arthritis
and inflammatory bowel disease)
2. allergic diseases: Immune responses against
common environmental substances
(bronchial asthma)
Prolonged exposure to potentially toxic agents:

1. exogenous materials such as inhaled

particulate silica (silicosis)
2. endogenous agents such as plasma lipid
components, which may contribute to
atherosclerosis
 Chronic Inflammatory Cells and
Mediators
Macrophage
• Is the dominant cell of chronic inflammation
• derived from circulating blood monocytes
• are normally diffusely scattered in most
connective tissues
• in organs:
1. liver (Kupffer cells),
2. spleen and lymph nodes (sinus histiocytes),
3. central nervous system (microglial cells)
4. lungs (alveolar macrophages).
• These cells comprise the (mononuclear
phagocyte system) also known by the older
name of (reticulo-endothelial system).
• Macrophages act:
1. as filters for particulate matter, microbes,
and senescent cells
2. as sentinels to alert the(T and B
lymphocytes) to injurious stimuli.
Macrophages are activated by:
• bacterial endotoxin
• cytokines (IFN-γ by T lymphocytes)
• various mediators produced during acute
inflammation
• ECM proteins such as fibronectin
They produce:
• Enzymes: proteases and plasminogen
activator
• ROS
• Cytokines such as IL-1 and TNF
• growth factors (influence the proliferation of
smooth muscle cells and fibroblasts and the
production of ECM)
Lymphocytes, Plasma Cells, Eosinophils, and Mast
Cells
• Lymphocytes and macrophages interact in a
bidirectional way
• Macrophages present antigens to T cells and
produce IL-12 that stimulate T-cell responses
• Activated T lymphocytes produce IFN-γ, which is
a powerful activator of macrophages, promoting
more antigen presentation and cytokine
secretion.
• The result is a cycle of cellular reactions that
sustain chronic inflammation.
• Plasma cells develop from activated B
lymphocytes and produce antibodies directed
against:
1. antigens in the inflammatory site
2. altered tissue components.
Eosinophils
• are found in inflammation due to:
1. parasitic infections
2. allergies.
• They produce major basic protein which is
toxic to parasites (also causes epithelial cell
necrosis).
Mast cells
• are sentinel cells in connective tissues, and
they can participate in both acute and chronic
inflammatory responses.
• mast cells are "armed" with IgE antibody.
• are central players in allergic reactions,
including anaphylactic shock.
• Produce histamines and AA metabolites that
elicit the early vascular changes of acute
inflammation
 Granulomatous inflammation
• Granulomatous inflammation is a distinctive
pattern of chronic inflammation characterized
by aggregates of activated macrophages that
assume an epithelioid appearance.
• Morphology
• Granuloma is an aggregate of activated
epithelioid macrophages surrounded by a
collar of lymphocytes
• Older granulomas may have a rim of
fibroblasts and connective tissue.
• multinucleated giant cells 40 to 50 μm in
diameter may be found in granulomas.
• epithelioid cells in granulomas have pink,
granular cytoplasm with indistinct cell
boundaries.
• Giant cells consist of a large mass of
cytoplasm and many nuclei, and they derive
from the fusion of 20 or more macrophages.
• Necrosis?
• In granulomas associated with tubercle
bacillus infection, a combination of hypoxia
and free-radical injury leads to a central zone
of necrosis.
• Grossly, this has a granular, cheesy
appearance and is therefore called caseous
necrosis.
• Microscopically, this necrotic material appears
as amorphous, structureless, granular debris,
with complete loss of cellular details.
• Healing of granulomas is accompanied by
fibrosis that may be quite extensive.
SYSTEMIC EFFECTS OF INFLAMMATION
• systemic inflammatory response
syndrome(acute-phase reaction)
• The cytokines TNF, IL-1, and IL-6(produced by
leukocytes and other cell types) are the most
important mediators of the acute-phase
reaction.
• The acute-phase response consists of several
clinical and pathologic changes.
• Fever, characterized by an elevation of body
temperature, usually by 1° to 4°C, especially
when inflammation is caused by infection.
• Fever is caused by pyrogens that act by
stimulating prostaglandin (PG) synthesis in the
vascular and perivascular cells of the
hypothalamus.
• exogenous pyrogens: Bacterial products, such
as lipopolysaccharide (LPS)
• endogenous pyrogens cytokines such as IL-1
and TNF
• pyrogens increase the levels of
cyclooxygenases that convert AA into
prostaglandins.
• In the hypothalamus the PGs stimulate the
production of neurotransmitters, which
function to reset the temperature set point at
a higher level.
• NSAIDs, including aspirin , reduce fever by
inhibiting cyclooxygenase and thus blocking
PG synthesis.
• Elevated plasma levels of acute-phase
proteins,
• are C-reactive protein (CRP), fibrinogen, and
serum amyloid A (SAA) protein.
• mostly synthesized in the liver
• CRP and SAA, bind to microbial cell walls, and
they act as opsonins and fix complement, thus
promoting the elimination of the microbes.
• Fibrinogen binds to erythrocytes and causes
them 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,
• Elevated serum levels of CRP are now used as
a marker for increased risk of myocardial
infarction or stroke in patients with
atherosclerotic vascular disease.
• Leukocytosis is a common feature of
inflammatory reactions, especially those
induced by bacterial infection.
• The leukocyte count usually rises to 15,000 or
20,000 cells/μL, but sometimes it may reach
extraordinarily high levels, as high as 40,000
to 100,000 cells/μL.
• These extreme elevations are referred to as
leukemoid reactions because they are similar
to the white cell counts obtained in leukemia.
• Most bacterial infections induce an increase
in the blood neutrophil count, called
neutrophilia.
• Viral infections, such as infectious
mononucleosis, mumps, and German measles,
are associated with increased numbers of
lymphocytes (lymphocytosis).
• Bronchial asthma, hay fever, and parasite
infestations all involve an increase in the
absolute number of eosinophils, creating an
eosinophilia.
• Certain infections (typhoid fever and
infections caused by some viruses, rickettsiae,
and certain protozoa) are paradoxically
associated with a decreased number of
circulating white cells (leukopenia), likely
because of cytokine-induced sequestration of
lymphocytes in lymph nodes.
• Other manifestations of the acute-phase
response include increased heart rate and
blood pressure; decreased sweating, rigors
(shivering), chills, anorexia, somnolence, and
malaise.
• Chronic inflammation is associated with a
wasting syndrome called cachexia, which is
mainly the result of TNF-mediated appetite
suppression and mobilization of fat stores.
• In severe bacterial infections (sepsis), high
levels of TNF cause disseminated intravascular
coagulation (DIC), hypoglycemia, and
hypotensive shock. This clinical triad is
described as septic shock.