Inflamation

drh. M. Arfan Lesmana, M.Sc.

Fakultas Kedokteran Hewan, Universitas Brawijaya
Email: [email protected]
Remember our old friends, rubor, tumor, calor et dolor? Plus
functio laesa too.
Introduction
• Inflammation is the response of living tissue to injury.
• Some form of an inflammatory response is seen in virtually all living
organisms, but the higher life forms have the unique ability to use the
blood vascular system to deposit fluid and cells in the extravascular
space.
• The acute inflammatory response has 3 main functions.
• The affected area is flooded by a mixture of blood and tissue
components collectively called the acute inflammatory exudate. The
exudate carries proteins, fluid and cells from local blood vessels into
the damaged area to mediate local defenses.
• If a causative agent (e.g. bacteria, foreign body) is present in the
damaged area, it can be destroyed and eliminated by components of
the exudate.
• The damaged tissue is broken down and partially liquefied, and the
debris removed from the site of damage and the healing process
begins.
• The inflammatory response is continuous with the process of repair.
Acute inflammation is short, lasting only a few hours to days. Longer
inflammatory responses are referred to as chronic inflammation.
• The hallmark of chronic inflammation is the presence of
predominantly macrophages in the exudates and perhaps also the
formation of fibrous connective tissue. This fibrous connective tissue
formation results in organization or scar formation.
• There is an intermediate stage of inflammation that has not begun to
organize yet, but is past the acute stage. This form of inflammation is
known as subacute inflammation.
Causes of Inflammation
• One of the most common causes of inflammation is microbial
infection. These microbes include viruses, bacteria, protozoa, fungi
and various parasites. Viruses lead to death of individual cells by
intracellular multiplication. Bacteria release synthesized exotoxins or
cell wall components (endotoxin) that specifically initiate
inflammation
Hypersensitivity reactions
• A hypersensitivity reaction occurs when an altered state of
immunological responsiveness causes an inappropriate or excessive
immune reaction which damages the tissues. The types of reaction
will be discussed in more detail later.
Physical agents
• Tissue damage leading to inflammation may occur through physical
trauma, ultraviolet or other ionizing radiation, burns or excessive
cooling ('frostbite')
Irritant and corrosive chemicals
• Corrosive chemicals (acids, alkalis, oxidizing agents) provoke
inflammation through direct tissue damage. These chemical irritants
cause tissue damage that leads directly to inflammation

Renal infarct. Necrotic tissue will be surrounded by neutrophils.

Death of tissues from lack of oxygen or nutrients resulting from

inadequate blood flow (infarction) is a potent inflammatory
stimulus. The edge of a recent infarct often shows an acute
inflammatory response.
Effects of Inflammation
• The effects of inflammation can be both local and systemic. The
systemic effects of acute inflammation include fever, leukocytosis
and vascular changes. These will be discussed in more detail later in
this unit. The local effects are usually clearly beneficial, for example
the destruction of invading microorganism, but at other times they
appear to serve no obvious function, or may even be harmful.
Beneficial effects
• Both the fluid and cellular exudates may have useful effects.
Beneficial effects of the fluid exudate are as follows:
Entry of antibodies. Increased vascular permeability allows
antibodies to enter the extravascular space, where they may
lead either to lysis of microorganisms, through the participation
of complement, or to phagocytosis by opsonization. Antibodies
are also important in neutralization of toxins.

Fibrin formation. Fibrin formation

from exuded fibrinogen may
mechanically impede the movement
of micro-organisms, trapping them
and so facilitating phagocytosis.
Stimulation of immune response. The drainage of this fluid
exudate into the lymphatics allows particulate and soluble
antigens to reach the local lymph nodes where they may
stimulate the immune response.
Harmful effects
• As we all know however, the inflammatory response has significant
harmful effects. Most of these are caused by release of lysosomal
enzymes by inflammatory cells. Some of these harmful effects
include:
• Destruction of normal tissues. Enzymes such as collagenases,
elastases and other proteases may degrade normal tissues, resulting
in their destruction. For example in type III hypersensitivity reactions
and in some types of glomerulonephritis small vessels are damaged.
• Swelling. The swelling of acutely inflamed tissues may be harmful. At
right is a dog with a swollen face due to an anaphylactic reaction. If
that swelling occurs in the larynx, VERY BAD. Inflammatory swelling is
especially serious when it occurs in an enclosed space such as the
cranial cavity. Thus, acute meningitis or an intra-cerebral abscess may
raise intracranial pressure to the point where blood cannot move
easily in the brain, there is depression of cardiac and respiratory
centers and OOPS, death
Inappropriate inflammatory response. Sometimes, acute
inflammatory responses appear inappropriate, such as those which
occur in type I hypersensitivity reactions where the provoking
environmental antigen (e.g. pollen) otherwise poses no threat to the
individual.
Clinical Aspects of Acute Inflammation
• The four principal effects of inflammation were described nearly
2,000 years ago by Celsus:
• Redness (rubor). An acutely inflamed tissue appears red, for example
skin affected by sunburn, or the eye in acute conjunctivitis. This is due
to dilatation of small blood vessels within the damaged area.
Remember hyperemia?

Hyperemic scrotum of a bull that has a skin infection (see

the crustiness at the bottom).
• Heat (calor). Increase in temperature is readily detected in the skin. It
is due to increased blood flow (hyperemia) through the region,
resulting from vascular dilatation and the delivery of warm blood to
the area. Systemic fever, which results from some of the chemical
mediators of inflammation, also contributes to the local temperature
• Swelling (tumor). Swelling results from edema, the accumulation of
fluid in the extravascular space as part of the inflammatory exudate,
and to a much lesser extent, from the physical mass of the
inflammatory cells migrating into the area.
• Pain (dolor). Pain results partly from the stretching and distortion of
tissues due to inflammatory edema and, in part from some of the
chemical mediators of acute inflammation, including bradykinin, the
prostaglandins and serotonin.
• Loss of function (functio laesa). Loss of function, a well-known
consequence of inflammation, was added by Virchow (1821-1902) to
the list of features drawn up by Celsus. Movement of an inflamed
area is consciously and reflexively inhibited by pain, while severe
swelling may physically immobilize the affected area.
Clinical indicators of inflammation
Clinical indications of an inflammatory process usually include one or
all of the following:
• General malaise
• Fever
• Pain, often localized to the inflamed area
• Leukocytes
Cellular changes
• An increased leukocyte count with an increase in neutrophil count in
the peripheral blood is a typical response to acute inflammation. The
leukocytes respond to chemoattractants originating from the site of
injury. In inflammation, neutrophils are released from the bone
marrow into the blood in larger numbers than are normally present.
Therefore, when a blood sample is taken, increased numbers are
seen. Often in viral infections, there will be an increase in
lymphocytes. Sometimes, increased numbers of monocytes can be
present in severe or more chronic inflammation.
This is a photomicrograph of a blood smear showing normal
neutrophils. These cells are also called polymorphonuclear
leukocytes because of the multiple lobulations in the nucleus.

In severe cases of inflammation, there may be increased

numbers of immature (band) neutrophils. These cells are
named for the band like appearance of the nucleus.

In neutrophils, lobulation increases with maturity. These young

cells are released from the bone marrow before they are
completely "ripe", so their their nuclei are not yet fully
lobulated
Non-cellular changes
• Inflammation is mediated in large part by soluble substances
(mediators) found in plasma. Specific acute phase proteins, like
fibrinogen, may be measured in blood to monitor inflammatory
processes.
Macroscopic appearance of inflammation
• The morphologic appearance of inflammation is modified according
to the tissue involved and the type of agent provoking the
inflammation. Several descriptive terms are used for the appearances.
We'll practice labeling lesions many times over the course of the next
three weeks and in all subsequent pathology course
Serous inflammation
• In serous inflammation, there is abundant protein-rich fluid exudate
with a relatively low cellular content. Examples include inflammation
of the serous cavities, such as peritonitis, and inflammation of a
synovial joint, acute synovitis. Vascular dilatation may be apparent to
the naked eye, the serous surfaces appearing injected, i.e. having
dilated, blood-laden vessels on the surface, (like the appearance of
the conjunctiva in 'blood-shot' eyes).

Serous exudate in the thoracic cavity.

A "runny nose" is serous exudation.
Catarrhal inflammation
• When mucus hypersecretion accompanies acute inflammation of a
mucous membrane, the appearance is described as catarrhal. This
type of inflammation is usually seen in the acute stage of
inflammation in organs that have abundant goblet (mucus producing)
cells, such as the respiratory tract and the colon. As the disease
progresses, other inflammatory components may be seen such as
neutrophils (mucopurulent).

Catarrhal enteritis. Note mucous flowing out of the intestinal

lumen. Cat.
A "snotty nose" is catarrhal inflammation. It is a little bit more
severe than the serous inflammation.
Fibrinous inflammation
• When the inflammatory exudate contains abundant fibrinogen, this
polymerizes into a thick fibrin coating. This is often seen in acute
pericarditis and gives the parietal and visceral pericardium a 'bread
and butter' appearance. When you think "bread and butter", think
about dropping the bread butter side down on the floor and picking it
up again - this is what fibrin can look like.

Fibrin on the surface of the spleen. Fibrinous peritonitis; or

fibrinous perisplenitis
Hemorrhagic inflammation
• Hemorrhagic inflammation indicates severe vascular injury. As a result
blood predominates in the exudate

Here is a little kangaroo (roo actually) that had a hemorrhagic

pneumonia due to infection with Toxoplasma. There are
numerous areas of local necrosis caused by Toxoplasma, and
resulting damage to vessels, so it is hemorrhagic inflammation
Suppurative (purulent) inflammation
• The terms 'suppurative' and 'purulent' denote the production of pus,
which consists of dying and degenerate neutrophils. When you see
pus, think bacteria

The underside of the brain of this dog has green exudate that
contains neutrophils. The diagnosis for this would be purulent
meningitis.
• The pus may become walled-off by granulation tissue or fibrous tissue
to produce an abscess (a localized collection of pus in a tissue).

In this pig's brain, a collection of purulent material surrounded

by a fibrous connective tissue capsule is located between the
cerebrum and the cerebellum. This is a brain abscess.

If a hollow viscus fills with pus, this is called empyema, for

example, empyema of the gall bladder or of empyema the
guttural pouch. When pus fills the thorax, we can call it thoracic
empyema.
Necrotizing inflammation
• The products of inflammation (proteolytic enzymes and other
nastiness) and vascular occlusion by thrombosis may result in
widespread necrosis of the affected organ. The term necrotizing can
be used to describe this kind of inflammation. As with other types of
inflammation, necrotizing can occur in conjunction with an influx of
neutrophils (necropurulent) or hemorrhage (necrohemorrhagic). The
combination of necrosis and bacterial putrefaction is called gangrene

Dark brown areas represent areas of pulmonary necrosis due

to bacterial pneumonia – this is a gangrenous pneumonia. The
usual cause is aspiration, something that should have stayed in
the GI tract got inhaled into the lung
Morphologic Diagnosis of Inflammation
Serous exudate
• This is a very mild form of inflammation and may indicate a minor injury, or
it may be the start of something more serious. (In general, SEROUS is NOT
SERIOUS!). Serous fluid is what accumulates inside a blister. Also, it is the
clear yellow material that comes out of a minor skin wound.
• The most common places to find serous exudate is on the skin surface
("hot spot" in flea allergy dermatitis) or in a body cavity, or in your nose!
• In general serous exudates results when inflammatory mediators create
endothelial gaps large enough for fluid and some protein to leak out. More
severe capillary damage would result in either fibrin or red blood cells
being mixed within the fluid. By definition there are few leukocytes in this
exudate.
This horse had abdominal surgery and died two days
later of another cause.
Because of the manipulation of the intestines at
surgery, there was an outpouring of serous fluid into
the abdomen, resulting in a "serous peritonitis."
This is from a postmortem on a cat. There is excess yellow fluid
in the abdomen - this is a serous peritonitis. This cat had feline
infectious peritonitis.
In this case, knowing the disease, it can be safely stated that
this mild serous peritonitis was a harbinger of worse things to
come.
Fibrinous exudate
• In serous exudation, just very small molecules of protein get out of
the blood stream and into the tissue. With fibrinous exudation, the
vascular insult is more severe, and larger holes develop, allowing
fibrinogen to get out into the tissue as well. When fibrinogen reaches
tissue, it turns into fibrin. Fibrinous exudation is always an indication
of an more severe insult.
• Don't confuse the adjective fibrinous (means fibrin in the exudate)
with fibrous (is not a modifier of an exudate and means composed of
fibrous connective tissue).
• In the earliest stages, fibrin just appears as a light meshwork, which
may have a granular appearance grossly.

The lung is from a sheep in the early stages of infection

with Pasteurella multocida, the pleura is responding with
an outpouring of fibrin, which forms strands on the surface
of the lung.
These strands can be peeled off readily, in contrast to a
chronic process where the fibrin becomes organized by
fibrous connective tissue and becomes tough and is
considerably more adherent.
This is from a cat with feline infectious peritonitis.
Note the granular appearance to the serosa of the intestinal loops - this is due to bits of fibrin.
Also, there is a layer of fibrin over the liver. In some places, there is a distinctly strandlike appearance.
 Fibrin is eosinophilic and strandlike microscopically.
Often there are neutrophils associated with it because it
is a powerful chemoattractant for these cells. When
This poor tortoise had an acute stomatitis. Dissection of
neutrophils become prominent, we get some pus mixed
the oral cavity reveals a layering of fibrin over various
in with the fibrin, and the inflammation is referred to as
parts of the oral cavity.
fibrinopurulent.
 Diphtheritic membrane! This term implies that the
When necrosis is extensive, the fibrin can be pretty thick.
tissue underneath the fibrin is necrotic resulting in
Often it is adherent to the mucosal surface, as in the tightly adhered fibrin.
intestine of this pig infected with Salmonella
Here is another example, from a tortoise with a
gastrointestinal tract infection.
Sometimes there is so much fibrin all at once that it forms
a cast inside the lumen.
The tissues on the left consist of intestine and gall bladder
from a cow with salmonellosis. Each cavity has a big
tubular cast of fibrin (fibrinous cast).
• In many cases, the fibrin gets resorbed without causing any problems.
However, fibrin is a good stimulus for fibrosis to begin. So, if the fibrin
stays around for too long, especially on serosal surfaces, fibroblasts
migrate in and start to make collagen.
• If the fibrin exists between two serosal surfaces, such as between gut
and gut or between pleura and pleura, then the fibrosis can result in
permanent adhesions which impair motility.
• It is very important that you distinguish between fibrinous and
fibrous. They are very different processes and it is too bad that the
words sound so similar.
• Often fibrinous inflammation (which is always ACUTE) will LEAD to
fibrous but it does not always necessarily follow. When fibrosis does
occur that is an indication that the process is CHRONIC.

This is a fibrinous peritonitis from a horse. Had the animal

lived, this amount of fibrin would have made a great
framework for fibrosis to follow, resulting in a knot of intestines
with impaired mobility.
And holy mackerel, here is another horse, this one died
of pleuritis. Look at all these yellow strands of fibrin,
connecting the lung to the ribs.

When this amount of fibrin is on the pleural surface,

invariably, fibrous adhesions form between the visceral
and parietal pleura. The result is impaired ability to
expand the lungs and respiratory compromise.
Heart from a cat. Here the pericardial sac has been opened to
reveal a dense layer of fibrin all over the epicardium. The other really bad place for adhesions is on the lung.
• Catarrhal exudate
Catarrhal exudate consists of excess mucus. So, it is only
seen in tissues that already produce mucus. We already
talked about a runny nose as being serous exudate. Well,
add some mucus to that and it becomes catarrhal rhinitis,
as in this dog with canine distemper.
• Here are some other examples:
The mucosa of this bovine intestine is covered with
excess mucus. There may also be some fibrin mixed in
here too. Let's call it fibrinocatarrhal enteritis.
The animal was affected by mucosal disease, which is
caused by infection with bovine viral diarrhea virus.
Purulent exudate
Purulent = suppurative = pus
The essential elements in purulent exudates are neutrophils. Purulent
inflammation almost always signifies the presence of bacteria.

This is an opened mammary gland from a cow (teat is at

the left). What is the creamy tan material? Yes, it is pus
The gland is packed with neutrophils. Here is another picture of purulent inflammation. This is
from a dog with purulent prostatitis.
The gland lumens and interglandular spaces are filled with
neutrophils. Grossly, purulent exudate was oozing from
the cut surface.
• Purulent inflammation can have a variety of consistencies.

In this example of purulent sinusitis in a cow, the pus has

become thickened and dried. Often, this form of pus is
referred to as "inspissated" or "caseous".
Purulent exudate is often associated with fibrinous
exudate. In the examples above of a riproaring
pericarditis, both types of exudates are obviously present
and we would call this fibrionopurulent pericarditis.
On the left is the brain of a one-month-old lamb. There is
a diffuse purulent meningitis. The arrows are pointing to
the purulent exudate found within the sulci.
• If the purulent inflammation is well-localized by fibrous tissue, it is
referred to as an abscess. Here are some examples:

This foal didn't have much of a chance, with two brain

abscesses caused by Streptococcus equi.
The fibrous wall is very thin because the CNS has little
capacity to form connective tissue. Had this been in
another location, for example the liver, the fibrous capsule
would have been more prominent.
These multiple abscesses in a sheep spleen were caused
by Corynebacterium pseudotuberculosis, the agent of
caseous lymphadenitis.
This is a common cause of "wasting ewe syndrome." Not
surprising. So many neutrophils around and nonstop
production of inflammatory mediators.
This is a liver from a guinea pig that was doing
poorly for some time prior to death. Yersinia
pseudotuberculosis was cultured from the
abscesses.

As you have noticed purulent exudate can have

different colors. The color can be affected by a
number of variables. If blood is in the mix it may
be pink. If the bacteria has pigment they can
change the color. Necrotic tissue can add color
and the neutrophils can give the exudate a white
or green appearance.
Hemorrhagic inflammation is serious business. Some of
the most pathogenic agents cause hemorrhagic
inflammation. The holes in the blood vessels are big
enough to let even the erythrocytes out. Prognosis may be
guarded.

This is the lung of a lamb infected with Mannheimia

hemolytica. The lung is turgid and filled with fibrin and
inflammatory cells.
But in addition, it is diffusely reddened, indicating that
there has been considerable hemorrhage as well. A good
morphologic diagnosis for this lesion would be severe
acute diffuse hemorrhagic pneumonia.