INFLAMMATION

Objectives -

1. Recognize and describe lesions of inflammation

2. Outline the pathogenesis of inflammatory processes
3. Relate the various mediators to the vascular and
cellular events in the inflammatory process
4. Be able to give a morphologic diagnosis

TABLE OF CONTENTS
(Inflammation)

Introduction to Inflammation…………………………………………... 2
Acute Inflammation ……………………………………………………. 7
Chronic inflammation……………………………...…………………… 12
Morphologic diagnosis of exudative inflammation……………………. 17
Cellular components of inflammation…………….……………………. 27
Immune-mediated inflammation………………….…………………… 36
Healing and repair………………………………….…………………… 43

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 Introduction to Inflammation
This lesson corresponds to the web lesson of the same name. 

SUMMARY OF IMPORTANT CONCEPTS FOR THIS LESSON

DEFINITION AND CARDINAL FEATURES

Definition:
- Inflammation is the response of living tissue to injury. It involves a well-organized
cascade of fluid and cellular changes within living tissue.
Cardinal features:
 Rubor (redness); Tumor (swelling); Calor (heat); Dolor (pain); Functio laesa (loss
of function)
CAUSES
 Etiologic agents – viruses, bacteria, fungi, parasites
 Hypersensitivity – body reacts against itself, there are four types of reactions
 Physical and chemical agents - trauma, sunburn, acid
 Necrosis - anoxia, trauma
EFFECTS
What’s good about inflammation? Drugs, antibodies, mediators can get in; fibrin and
then fibrosis can wall it off
What’s bad about inflammation? Cytokines can make you sick, tissue can get destroyed,
swelling won’t quit

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 Introduction to Inflammation

What is inflammation?
Inflammation is the response of living tissue to injury. It
involves a well-organized cascade of fluidic and cellular
changes. It is recognizable grossly and histologically and
has both beneficial and detrimental effects locally and
systemically.

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 transport and deposit fluid
and cells in the extravascular space.

Some general characteristics of inflammation are as follows:

1. The inflammatory process is redundant and complex. This makes it a challenging

subject to study. You will see that many mediators of inflammation have the same
functions and many mediators have multiple functions. Also, the same mediator may
have different effects on different tissues.
2. The process is continuous over a period of time. Peracute, acute, subacute, and
chronic are terms used to describe different stages of inflammation.
3. Inflammation is caused by a stimulus and removal of the stimulus should result in
abatement of inflammation. If it doesn’t get fixed in the acute period, it becomes
chronic.
4. Blood is the primary delivery system for inflammatory components.
5. Inflammation is on a continuum with the healing process.

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 RUBOR, TUMOR, CALOR et DOLOR

The four principal effects of inflammation (rubor, tumor,

calor et dolor) were described nearly 2,000 years ago by the
Roman Aulus Cornelius Celsus, more commonly known as
Celsus. (He wasn’t actually a practitioner of medicine.
Rather, he wrote an encyclopedia that had many volumes
about all kinds of subjects. Only the volume concerning
medicine survived.)

Redness (rubor)
An acutely inflamed tissue appears red, due to dilatation of small blood vessels within the
damaged area (hyperemia).
Swelling (tumor)
Swelling results from edema, the accumulation of fluid in the extravascular space as part
of the inflammatory fluid exudate, and to a much lesser extent, from the physical mass of
the inflammatory cells migrating into the area.
Heat (calor)
Increase in temperature is readily detected in the skin. It is due to increased blood flow
(hyperemia) through the region, resulting in vascular dilation and the delivery of warm
blood to 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,
especially bradykinin and some of the prostaglandins.
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 described in Celsus’ written work. Movement of an
inflamed area is inhibited by pain, either consciously or by reflexes, while severe
swelling may physically immobilize the affected area.

Causes of Inflammation

Microbial infections
One of the most common causes of inflammation is microbial infection. Microbes
include viruses, bacteria, protozoa, fungi and various parasites. Viruses lead to death of
individual cells by intracellular multiplication, and either cause the cell to stop
functioning and die, or cause explosion of the cell (cytolytic), in which case it also dies.
Bacteria release specific toxins – either exotoxins or endotoxins. What’s the difference?
Exotoxins are produced specifically for export (like anthrax toxins or tetanus toxins)
whereas endotoxins are just part of the cell walls of Gram negative bacteria and they do
terrible things to the body too but they aren’t as specific in their actions as the exotoxins.
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Hypersensitivity reactions
A hypersensitivity reaction occurs when an altered state of immunologic responsiveness
causes an inappropriate or excessive immune reaction that damages the tissues. The types
of reaction will be discussed in more detail later (In the lesson on Immune Mediated
Inflammation).
Physical agents, irritant and corrosive chemicals
Tissue damage leading to inflammation may occur through physical trauma, ultraviolet or
other ionizing radiation, burns or excessive cooling ('frostbite'). Corrosive chemicals
(acids, alkalis, oxidizing agents) provoke inflammation through direct tissue damage.
These chemical irritants cause tissue damage that leads directly to inflammation.
Tissue necrosis
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, malaise, and leukocytosis. The local effects are usually clearly
beneficial, for example the destruction of invading microorganisms, but at other times they
appear to serve no obvious function, or may even be harmful.

Beneficial effects of inflammation Harmful effects of inflammation

Dilution of toxins Persistent cytokine release
Entry of antibodies Destruction of normal tissues
Fibrin formation Swelling
Delivery of nutrients and oxygen Inappropriate inflammatory response
Stimulation of immune response

Systemic Effects of Inflammation

Both acute and chronic inflammation, even if well localized, can have effects on the whole body.
The main ones are:

Leukocytosis
Leukocytosis is a common feature of inflammatory reactions. Leukocytosis means that
there is an abnormally high number of circulating white blood cells. A general rule is that
increased neutrophils indicate a bacterial infection whereas increased lymphocytes are
most likely to occur in viral infections. This is one reason why we often do a CBC when
an animal is sick – gives us more clues.
Fever
Fever is a common systemic response to inflammation. Fever is most often associated
with inflammation that has an infectious cause, although there are some non-infectious

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 febrile diseases. Fever is coordinated by the hypothalamus and involves a wide range of
factors. Here are some of the contributors to fever:

What is the function of fever? The elevation of body temperature is thought to improve
the efficiency of leukocyte killing and may also impair the replication of many invading
organisms.

Endotoxemia
Sepsis is the term used for disease due to toxic bacterial products circulating in the blood.
Endotoxemia specifically refers to circulating gram-negative bacterial toxic products
(LPS). There are some cell wall products released from gram-positive bacteria that can
have a similar toxic effect.

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 Acute Inflammation
 This lesson corresponds to the web lesson of the same name. 

SUMMARY OF IMPORTANT CONCEPTS FOR THIS LESSON

Inflammation has VASCULAR and CELLULAR events:

1. VASCULAR EVENTS
Vasodilation
And then increased Vascular permeability

2. CELLULAR EVENTS
Cells move out of the vessels into the area of inflammation using chemotaxis
Inflammatory cells become activated and then can phagocytose offending materials

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 ACUTE INFLAMMATION

In the early stages of inflammation, the affected tissue becomes reddened, due to increased blood
flow, and swollen, due to edema fluid. These changes are the result of vascular response to
inflammation. The vascular events of the acute inflammatory response involve three main
processes:

1. changes in vessel caliber and, consequently, blood flow (hemodynamics)

2. increased vascular permeability and
3. formation of the fluid exudate

1. Changes in Vessel Caliber

The microcirculation consists of the network of small capillaries lying between arterioles, which
have a thick muscular wall, and thin-walled venules. Capillaries have no smooth muscle in their
walls to control their caliber, and are so narrow that red blood cells must pass through them in
single file. The smooth muscle of arteriolar walls forms pre-capillary sphincters that regulate
blood flow through the capillary bed. Flow through the capillaries is intermittent, and some form
preferential channels for flow while others are usually shut down. In other words, there is not
blood flowing through all capillaries all the time. They take turns. When inflammation happens,
none of them gets to take their scheduled tea break. They are all open.

Experimental evidence indicates that blood flow to the injured area may increase up to ten-fold
as vessels dilate. What causes this to happen? MEDIATORS - including nitric oxide, histamine
and prostaglandins (PGI2) and LTB4.

2. Increased vascular permeability

In acute inflammation, the capillary hydrostatic pressure increases, and there is also escape of
plasma proteins into the extravascular space due to increased vascular permeability (endothelial
contraction allowing proteins to escape between cells). Consequently, much more fluid leaves
the vessels than is returned to them. The net escape of protein-rich fluid is called exudation;
hence, the fluid is called an exudate.
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What causes the increase in vascular permeability in acute inflammation?

There are two mechanisms –

 Chemical mediators of acute inflammation may cause retraction of endothelial cells,
leaving intercellular gaps (chemical mediated vascular leakage).
 Toxins and physical agents may cause necrosis of vascular endothelium, leading to
abnormal leakage (injury induced vascular leakage).

3. Formation of the Cellular Exudate

How do white blood cells get out of the circulation and into the area where they are needed?

Cells are called out to the area of inflammation in a process called CHEMOTAXIS.

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 Chemotaxis of leukocytes

The movement of leukocytes from the vessel lumen in a directional fashion to the site of tissue
damage is called chemotaxis. All granulocytes and monocytes respond to chemotactic factors
and move along a concentration gradient (from an area of lesser concentration of the factor to an
area of greater concentration of the factor).

Important neutrophil chemotactic factors

Bacteria are strongly chemotactic for neutrophils

C5a, C3a
Fibrin, fibrinopeptides
Leukotriene B4 (LTB4)
IL-8 (a chemokine, from macrophages)

Important eosinophil chemotactic factors

Histamine
IL-5 (also known as eotaxin, a chemokine, from mast cells)

Important monocyte chemotactic factors

Complement factors
Fibrinopeptides

Okay, now the WBCs are where they were meant to be.
What’s next? Now they attack the offender.

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 Microbicidal Activity of Leukocytes
Leukocytes play a very important role in microbial killing. In any inflammatory response,
leukocyte activation is a prerequisite to their full participation in the process. Leukocytes
become activated during inflammation.

Leukocytes and phagocytosis

The process whereby cells ingest solid particles
is termed phagocytosis. The first step in
phagocytosis is adhesion of the particle to be
phagocytosed to the cell surface. The phagocyte
ingests the attached particle by sending out
pseudopodia around it. These meet and fuse so
that the particle lies in a phagocytic vacuole
(also called a phagosome) bounded by cell
membrane. Lysosomes, membrane-bound
packets containing the toxic compounds, then
fuse with phagosomes to form phagolysosomes.
It is within these that intracellular killing of
microorganisms occurs.

Intracellular killing of micro-organisms by leukocytes

Neutrophils and macrophages are specialized cells, containing noxious antimicrobial agents.
Neutrophils produce hydrogen peroxide (bactericidal by itself) which reacts with
myeloperoxidase in the cytoplasmic granules to create oxygen radicals which are wickedly
damaging. Antibacterial cationic proteins, lysozyme, and defensins all affect bacterial
permeability so the bacteria leak to death.

 Release of lysosomal products from the cell damages local tissues and can kill
microorganisms outside of the cell. Enzymes such as elastase and collagenase will chew
through tissue. Some of the compounds are pyrogens, producing fever by acting on the
hypothalamus. Acid hydrolases degrade tissue matrixes.
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 Chronic Inflammation
This lesson corresponds to the web lesson of the same name. 

SUMMARY OF IMPORTANT CONCEPTS FOR THIS LESSON

Definition:
Host response to an inciting stimulus that goes on for weeks or months

Characteristics:
Not usually red or hot (unlike acute inflammation)
Do not “ooze”
Productive or proliferative
Often present in infections with higher order organisms (mycobacteria, fungi, metazoan
parasites) and in many autoimmune diseases

Histologic appearance:
Primarily mononuclear cells involved
Fibroblasts and new blood vessels, together called “granulation tissue”

Granulomatous inflammation
Is always chronic
Is composed predominantly of macrophages
May have multinucleate giant cells – macrophages fuse

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 Chronic Inflammation

Chronic inflammation, like its acute cousin, is a host response to an inciting stimulus. There are,
however, some distinct differences. First and foremost is the time factor. Chronic inflammation
is considered to be inflammation of prolonged duration - weeks to months. Second, rather than
being just exudative, chronic inflammation usually is productive or proliferative. Chronic
inflammation is rarely gooey. Cells in the chronic inflammatory process tend to produce
substances that add new tissue, such as collagen and new blood vessels. Many of these changes
also represent the repair process and there is a blurry continuum between chronic inflammation
and the whole repair process. In general, chronic inflammation is characterized by inflammation,
tissue destruction, and attempts at repair all happening at once.

Grossly, chronic inflammation does not have as much rubor (redness) or calor (heat) as in the
acute reaction. Also, exudates aren’t so grossly apparent as they are in acute inflammation.
Because of the fibroplasia and neovascularization, areas affected by chronic inflammation tend
to be slightly swollen and firm. If fibrosis is extensive the lesions can be large and disfiguring.
Fibrosis (granulation tissue) is the best indicator that the inflammatory response is chronic.

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Chronic inflammation tends to occur under the following conditions:

Infections by organisms which are resistant to killing and clearing by the body tend to cause
chronic inflammation. Such persistent organisms include some of the higher bacteria
(including mycobacteria), fungi, and quite a few metazoan parasites.
Repeated bouts of acute inflammation can result in a chronic reaction.
Prolonged exposure to toxins can cause chronic inflammation.
Chronic inflammation is a common component in many of the autoimmune diseases. Because
the reaction is against a host epitope, which is always present, the inflammation is by
definition chronic and persistent.

Because chronic inflammation doesn’t ooze, rather its exudates tends to be kind of solid and
white or grayish and it looks the same no matter what the cell types, the only way to add an
exudative moniker is to see the histology. Here are the cell types:

1. The simplest type of chronic inflammation has mostly lymphocytes with lesser numbers of
macrophages. This will occur mostly in viral infections where the virus survives longer than
the acute phase. This is called “lymphohistiocytic”.
2. Chronic active inflammation is the same but in this one there are still some neutrophils
present, so there are acute things going on inside of the chronicity. This happens in many
bacterial infections that are not due to very pus-producing bacteria.
3. Next is granulomatous - here the cell types are almost all macrophages. Good examples
here are fungal infections or mycobacteria.
4. Some people use a term pyogranulomatous - which means granulomatous but within the
macrophages are pockets of neutrophils. The most common disease causing this is FIP.
5. Granulomas occur when the inciting cause stimulates macrophages but the agents are
distributed discretely within an organ. Think TB. Think Blastomyces. Think foreign body.

But with all of these types, there is evidence of fibroblasts moving in and some new blood
vessels.

If plasma cells are present in the inflammation, you know two

things. First, it is a chronic problem because it takes a good 2-4
weeks to generate plasma cells. Second, there must be some
persistent antigen in there, because plasma cells indicate the
body needs plenty of antibody at the site.

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Granulomatous inflammation

There is one specific subset of chronic inflammation that deserves special attention, and that is
granulomatous inflammation. Histologically, it is very characteristic and is described below.

Granulomatous inflammation is any inflammatory response consisting predominantly of

macrophages

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Macrophages often differentiate into cells called epithelioid macrophages and these cells are
found within granulomatous infiltrates. Their cytoplasm is abundant and finely granular, with
indistinct cell boundaries, so that they resemble epithelial cells more than macrophages (hence
the name - epitheliOID). Ultrastructurally, these cells contain abundant rough endoplasmic
reticulum and a prominent Golgi apparatus but are poor at phagocytosis. Consequently, their
role is believed to be biosynthesis and protein secretion.

A granuloma is a focally discrete chronic inflammatory reaction comprised

predominantly of epithelioid macrophages that are organized or aggregated in closely
packed collections. There is often a central core of caseous debris at the center of the
granuloma surrounded by macrophages that in turn are encircled by a ring of
lymphocytes and organizing fibroblasts.

Other cell types unique to granulomatous inflammation include the multinucleate giant cells,
sometimes called Langhans cells. These are cells formed by the fusion of macrophages and they
can look pretty spectacular under the microscope. But they are poorly phagocytic. Seeing giant
cells means – hey, our regular old standard issue macrophages couldn’t take care of this problem,
so we had to band together. Very often it is a big old problem, too large to phagocytose, like a
foreign body, or a fungus.

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 Morphologic diagnosis in inflammation
This lesson corresponds to the web lesson of the same name. 
SUMMARY OF IMPORTANT CONCEPTS FOR THIS LESSON

MORPHOLOGIC DIAGNOSIS

COMPONENTS OF A MORPHOLOGIC DIAGNOSIS FOR INFLAMMATION:

1. Severity
Mild, moderate, severe

2. Time course
Peracute, acute, subacute, chronic

3. Distribution of lesion
Focal?
Multifocal?
Locally extensive?
Diffuse?

4. Type of Exudate
Difference between exudates and transudate
Serous
Fibrinous
Catarrhal
Purulent
Abscess
Hemorrhagic
Mixed

5. Inflammatory name associated with the organ - usually it is just -itis, but there are
exceptions.

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 Morphologic diagnosis in inflammation

A morphologic diagnosis is the way we describe and communicate about lesions. A

morphologic diagnosis consists of a series of terms that serve to paint a picture with words. The
important categories of words to include in your morphologic diagnosis include –

KNOW THIS TABLE:

S SEVERITY How bad is it? Mild or moderate or marked/severe?

T TIME COURSE Is it peracute, acute, subacute or chronic?

D DISTRIBUTION Is it focal, multifocal or diffuse?

E What is the character of the inflammatory material –

EXUDATE serous, catarrhal, purulent, fibrinous, granulomatous,
fibrosing?
T TISSUE Where the heck is it? (plus –itis)

So, every inflammatory lesion could consist of FIVE WORDS.

1. Severity
The terms we usually use to describe severity are subjective – mild, moderate, severe. Some
people use “marked” instead of “severe.” Is the problem causing serious compromise (marked)?
Or is it just a little thing that is an annoyance (mild)? You’ll get used to figuring out which word
to use here.

2. Time course designation for inflammation

Peracute happens so fast you hardly even know it has happened. A good example would be a
serious myocardial problem where the animal dies before there is even any evidence, clinically,
grossly, or histologically, that the heart was damaged. Acute inflammation is short-lived, lasting
only a few hours to a few days. If it persists for an extended period, like more than two weeks
or so, then it is referred to as chronic inflammation. The hallmark of chronic inflammation is the
formation of fibrous connective tissue (starts as granulation tissue) in the area of inflammation.
An abundance of macrophages also may be a feature. This fibrous connective tissue formation
results in organization or scarring.

You may have noticed there is a little bit of a time gap between acute and chronic - the term
subacute can be used here.

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  Peracute – minutes or hours
 Acute – a few hours to a few days
 Subacute – the nebulous period between acute and
chronic
 Chronic – weeks to months
*Note: Peracute and subacute are not used as often as
the other two.

Peracute  Acute  Subacute  Chronic

3. Extent of Lesion

This may be the easiest part of the morphologic diagnosis. If just one small part of the organ is
affected, it is FOCAL. If there are several small parts affected, it is MULTIFOCAL. If the
whole organ is affected, it is DIFFUSE. But what if it is diffuse, but just in one part of the
organ? Then it is FOCALLY (or LOCALLY) EXTENSIVE.

4. Types of Exudates

 Serous exudate

Serous inflammation is characterized by the outpouring of a translucent, thin fluid that may
accumulate on a mucosal surface, skin, or in the peritoneal, pleural, and pericardial cavities.
Serous inflammation is a common manifestation of the acute inflammatory reaction and usually
indicates the insult is mild. What does it look like? Think of a mild skin wound - the clear to
yellowish fluid that oozes out is serous exudate. Other examples would include the fluid that

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accumulates in a blister or a runny nose in hay fever. Serous exudates are usually the result of a
mild, often transient irritant.

What is the significance of a serous exudate? It may just be the early phase of a more intense
exudate and a warning of a more serious problem to follow.

Serous exudate on an ulcerated sarcoptic mange site. Serous fluid accumulating within the pericardial
Just oozing clear fluid – this is serous exudate. sac. Hydropericardium is really serous exudate.

What is the outcome of a serous exudate? If it doesn’t progress to something worse, the fluid is
reabsorbed as the inflammation resolves.

 Fibrinous exudate

Fibrinous exudation occurs in more severe conditions that allow the escape of larger fibrinogen
molecules from the vascular system. As the vascular damage becomes more marked, instead of
just serous fluid seeping out, fibrinogen gets out as well. When fibrinogen reaches the tissue it is
converted to fibrin, which is the chief component of this type of inflammation.

What is the gross appearance of fibrinous exudation? Fibrinous inflammation occurs chiefly on
mucous and serous membranes. Prime locations include the entire respiratory and digestive
tracts, pleura, peritoneum, and pericardium.

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Fibrin in the opened thorax of a horse. Very Fibrin on the mucosal surface of the intestines in a
YELLOW (typically very yellow in horses) and cow with salmonellosis. String-like.
STRINGY.

In the earliest phases, the surface with a fibrinous exudate has a slightly roughened appearance,
and will be slightly dull and granular. Think buttered bread, dropped butter side down on the
floor. Pick it up – fibrin deposition looks like this. As the deposition of fibrin increases, there
will be yellowish strands present. These can be peeled off. If the insults are repeated, these
yellowish strands can accumulate into a carpet of fibrin. This thick layering of fibrin that can be
peeled away is termed a pseudomembrane. If there is extensive necrosis of underlying areas so
that the fibrin is tightly adhered to the tissue and is harder to peel away, it is called a diphtheritic
membrane. This term diphtheritic membrane came from human diphtheria, caused by
Corynebacterium diphtheriae. If there is so much fibrin that it gushes out and forms a large
accumulation mimicking the shape of the tubular organ, then it is termed a fibrin cast. This
happens in very severe intestinal infections, such as parvovirus in dogs or salmonellosis in cattle.

What is the outcome of fibrinous inflammation? If it is not too severe, it may resolve without
any sequelae. If it is extensive, fibroblasts may migrate in and begin organizing the exudate
through the generation of fibrous connective tissue. Sometimes this can be harmful. For
instance, with fibrinous inflammation in the peritoneal cavity, two fibrin-covered serosal
surfaces of gut may stick to each other. If fibroblasts come in and make permanent connections,
then two loops of intestine are stuck to each other forever. This will impede gut motility! Other
places this can be bad is in the pericardium or pleura. Fibrous adhesions will impede function as
heart or lungs need to be able to slip around freely inside those spaces and not be anchored by
fibrous adhesions. As this connective tissue formation process begins, we refer to it as
“organizing.” Once it is fully organized, it is “fibrous tissue.” Please remember that fibrosis or
fibrous tissue is NOT a type of inflammation, it is growth of new cells and laying down of
collagen leading to repair. The two terms FIBROUS and FIBRINOUS are just way too similar
SOUNDING. It is unfortunate because the processes they represent are HUGELY DIFFERENT.

Fibrin = acute. Fibrous = chronic. BIG DIFFERENCE

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 Catarrhal exudate

Catarrhal exudate is a term that is not used very often. It represents excessive mucus production
and so can only be used for inflammation in organs where mucus is already being produced. It is
most often associated with the mucosal surfaces of the intestinal, reproductive, and respiratory
tracts. It is seen in mild or persistent infections of these areas. Sometimes the word “mucous”
used synonymously with catarrhal.

What does catarrhal

exudate look like
grossly? Catarrhal
inflammation
appears as a thin
gray-yellow blanket
of excess mucus.
Think snot.

So far, we have covered non-cellular exudates. Now we’ll move into those exudates that contain
cells as a primary component.

 Purulent exudate

Purulent exudate is PUS. Pus is an accumulation of dead neutrophils. Neutrophils have

enzymes that help to liquefy the surrounding tissue, and so the result is a homogenous mass of
creamy pus. Think humus. Think vanilla pudding. Another term for purulent inflammation is
suppurative. The two can be used interchangeably. Pyo- is the prefix for anything with pus -
pyothorax, pyometra. Pyogenic bacteria are, by definition, bacteria that promote the body’s
production of pus. They are strongly chemotactic for neutrophils which accumulate and turn
into….pus.

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Abscess in a vertebral body. Pus can look sort of dry like Or, it can be very fluid, as in this pyometra.
this.

What does purulent exudate look like grossly? The consistency may vary somewhat, depending
on the host species, the inciting agent, and duration. If pus is present for a while and the inciting
agent is removed, the pus becomes dry, or “inspissated”. Also, the color may vary due to the
inciting agent. Almost all cases of pus formation are due to bacteria. If the purulent
inflammation is well circumscribed and surrounded by a fibrous wall or capsule, it is called an
abscess (see box below).

What is the significance of purulent inflammation? This is a prompt and violent reaction against
irritants and pathogens. The neutrophils are moving in to neutralize the offending agent. In 99%
of cases, bacteria will be in there, or HAD been in there.

What are the outcomes? One consequence is that localized purulent inflammation can break
loose and spread to other areas. This may result in septicemia if infection spreads to the blood
stream. If it does not spread, the resorption of pus is not without ill effects, including fever and
general signs of illness. If purulent inflammation is close to a body surface, it often discharges to
the outside, which is much better. Sometimes it does this through the formation of a fistulous
tract.

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 An abscess represents a subset of purulent
inflammation. An abscess is defined as a
discrete accumulation of pus surrounded by a
fibrous capsule. They are usually formed in
response to a focal bacterial infection. The
neutrophils are unable to fully overcome the
infection and if they accumulate in large
enough numbers, the body responds by walling
off the focus of infection with a circumferential
band of collagen. Although the inciting cause
is now effectively separated from spreading to
other parts of the body, the fibrous wall also
prevents delivery of antibiotics to the site.

Oops – hard to treat!

Guinea pig abscess (left) and

cleaning out a tomcat abscess
(right) - these things can hold a
LOT of pus!!!

 Hemorrhagic exudate

Hemorrhagic exudates are characterized by large numbers of erythrocytes. The holes in the
blood vessels are large enough that everything comes out so that the appearance of the exudate is
very much like blood. Hemorrhagic exudates are usually mixed with serum, fibrin, and
leukocytes. Distinguishing hemorrhagic exudates from simple hemorrhage can be problematic.

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What is the significance of hemorrhagic inflammation? This type of inflammation is usually
caused by highly virulent microorganisms or by acute poisoning by certain chemicals. It arises
quickly and is often fatal. There is massive damage to endothelium.

What is the outcome of hemorrhagic inflammation? Often very serious.

 Mixed exudates

Mixed exudates are more common than simple ones because the inflammatory process
frequently persists long enough to evoke the exudation of more than one type of exudate. Lots of
word combinations - fibrinohemorrhagic, mucopurulent, etc.

Opened pericardial sac of a cow with hardware Blackleg in a calf. Here the exudate would be
disease. You would call this exudate characterized as “necrohemorrhagic.”
“fibrinopurulent.”

 Granulomatous “exudate”

These represent exudates where the majority of cells are macrophages. However, these exudates
don’t usually “ooze”. They are not usually WET.

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Designation of organ or location
The location of inflammation is designated in the morphologic diagnosis by using a prefix that
refers to the organ and the "itis" suffix. For example: inflammation of the skin = derma + titis;
inflammation of the bone marrow = osteomyel + itis. Before moving to the next topic, review the
more extensive list of prefixes in the table below. Practice adding “itis” to the end of each prefix
to name an inflammatory process in the designated organ or tissue.

COMMONLY USED ANATOMIC PREFIXES FOR INFLAMMATION (-itis)

Arter ............................................... artery Nephr.............................................kidney

Arthr ................................................. joint Odont............................................... tooth
Balan ......................................glans penis Omphalo ................................... umbilicus
Blephar .......................................... eye lid Oophor ........................................... ovary
Bronch ......................................... bronchi Ophthalm............................................ eye
Burs ................................................. bursa Orch.............................................. testicle
Cellul ............................ connective tissue Oste .................................................. bone
Cheil .................................................... lip Osteomyel .......................... bone marrow
Cholecyst.............................. gall bladder Ot.........................................................ear
Col ...................................................colon Pericard ................................ pericardium
Conjunctiv ............................. conjunctiva Splen ............................................. spleen
Dermat............................................... skin Trache .......................................... trachea
Encephal.......................................... brain Periost .................................... periosteum
Endocard .............................endocardium
Enter ........................................... intestine
Esophag ................................... esophagus
Funicul ............................. spermatic cord
Gastr ........................................... stomach
Gingiv .............................................. gum
Gloss .............................................tongue
Hepat ................................................ liver
Kerat.............................................. cornea
Lamin ............................................... hoof
Laryng ........................................... larynx
Lymphaden ......................... lymph nodes
Mening ..................................... meninges
Metr ................................................ uterus
Myel ....................................... spinal cord
Myocard .............................. myocardium
Myos ............................................ muscle
26
 Cellular Components of Inflammation
This lesson corresponds to the web lesson of the same name. 
SUMMARY OF IMPORTANT CONCEPTS FOR THIS LESSON

GRANULOCYTES
Neutrophils
 Usually most abundant cell in the blood
 Important in acute inflammation (first cell to arrive)
 nucleus is multilobed (starts out with only two lobes, kind of like a horseshoe, or
“band”)
 very phagocytic
 Neutrophil-specific, or secondary granules, contain lysozyme, collagenase
 Short-lived once in tissue, from 6-72 hours
 End stage cell, don’t divide
Eosinophils
 Have big pink or red granules, with Major Basic Protein, which will help to kill
parasites
 Live 8-12 days
 End stage cell, don’t divide
Basophils and mast cells
 Different origin of each of these cells but similar function
 Not very many anywhere, in blood or in tissue
 When you see them, it usually means allergy
 They are strongly chemotactic for eosinophils so the two cell types may occur
together
 Can continue to divide, even when in tissue
 Can be powerful vasodilators (‘cause they got lots o’ histamine)
MONONUCLEAR CELLS
Lymphocytes
 Small round cells with large non-lobed nucleus
 Come in B cell and T cell varieties
Mononuclear phagocytes
 Big cells, lots of cytoplasm, big indented nucleus
 Monocytes in blood become macrophages when they go to the tissue
 Can live for as long as one month in tissue
 Heavy duty phagocytes

           

27
 Cellular Components of Inflammation
This lesson corresponds to the web lesson of the same name. 
In order to understand types of inflammation, it is essential to grasp the different categories of
inflammatory cells, to be able to recognize them morphologically, and to understand the different
situations in which they occur.

Granulocytes
Granulocytes consist of neutrophils, eosinophils, basophils, and heterophils in some species.

 Neutrophils
Neutrophilic leukocytes are also known as polymorphs, “polys”, and polymorphonuclear cells.
In some species, notably guinea pigs, birds and rabbits, the term heterophil is used to describe
the functional counterpart. These cells are key cells involved in the earliest events associated
with inflammation.

Neutrophils are formed in the bone marrow from granulocytic stem cells, the myeloblasts. What
causes their release from the bone marrow when needed in inflammation? The nucleus of a very
immature neutrophil is slightly indented; after that, it assumes a “band” shape. As the neutrophil
28
continues to mature, the nucleus becomes hyper-indented to take on a multilobed configuration
with multiple constrictions (therefore called PolyMorphoNuclear cells, or PMNs). Even with the
vast numbers of neutrophils in the body, there are severe infections in which tissue demand
exceeds the vascular supply. The body responds by releasing neutrophils from the storage pool
in the bone marrow to increase the number in the circulation. This increase is called a
neutrophilic leukocytosis. If the tissue demand for neutrophils persists or increases, many of the
immature forms, or “bands,” will be released as well. This is referred to as a “left shift.”

Neutrophils leave the blood in response to tissue

damage. They migrate rapidly to areas where they
are needed. Bacteria have factors that are very
chemotactic for neutrophils.

29
Neutrophils have a short half-life. Depending on the severity of the lesion, they survive hours to
a couple of days at a site of inflammation. They last less than a day in blood.

Once at the site, neutrophils’ main functions are to phagocytose small particles and kill microbes.
There are three phases to phagocytosis. First, the particles must attach to the cell surface. Then
the particle must be ingested. Third, the particle has to be digested within the cell. Attachment
is greatly enhanced if the particle is coated, or opsonized, by specific IgG antibodies or non-
specific C3b fragments from plasma.

Ingestion occurs after the particle has attached to the cell. Pseudopodia extend to surround and
engulf the material, creating a phagosome, and internalizing the particle.

Digestion occurs when the lysosomes

move toward the phagosome and
eventually fuse, emptying their
enzymes into the pocket, and
inactivating the particle.

Neutrophils are the most common cell

in purulent exudate. In fact, that’s
what pus is - an accumulation of dead
neutrophils. Most bacteria produce
very strong chemotactic factors that
attract neutrophils. Consequently,
any accumulation of pus should make
you think that bacteria are present.

How can you recognize neutrophils in tissue microscopically? The multilobed nucleus makes
this cell an easy one to recognize.

As neutrophils die in large numbers within inflamed tissues, their contents are released into the
extracellular fluids. Their enzymes cause local tissue digestion with liquefaction which mixes
with the pus and makes it all more liquid.

30
  Eosinophils

Eosinophilic granulocytes are so called because of the presence of big red-pink cytoplasmic
granules. Eosin is the pink stain and because the granules pick up so much of the stain, the cells
are “eosin-loving” or eosinophils. The eosinophilic granules vary in size in the different species,
being large and prominent in the horse, and quite small and almost inconspicuous in the cat. The
granules contain Major Basic Protein, which is toxic to parasites.

Eosinophils are similar to neutrophils in their maturation and release sequences, but there are not
very many of them in the blood. Like neutrophils, eosinophils are also end cells that do not
replicate after release. Extravascularly, they are slightly more long-lived than neutrophils, on the
order of 8-12 days. Eosinophils are commonly found in mucous membranes.

What do they look like in tissue? Hooray, eosinophils are the easiest cell to recognize, especially
in horses, where the granules are especially big and bright.

Eosinophils are most often associated with 4 main types of reactions:

 surrounding fungi and metazoan parasites in tissues
 hypersensitivity reactions, including allergy and anaphylaxis
 certain tumors, especially mast cell tumors (why? Because mast cells attract eosinophils!)
 in the brain of pigs and cattle poisoned by excess salt, or prolonged water deprivation
(Why? No clue - nobody knows!)

Some of the strongest chemotactic factors for eosinophils include histamine and IL-5 (also
known as eotaxin), both of which come from mast cells.

Eosinophils are very effective at killing metazoan parasites. They attach via antibody and then
release their Major Basic Protein which causes parasites to disintegrate.
31
  Basophils and Mast Cells
Both basophils and mast cells possess distinct spherical basophilic to metachromatic cytoplasmic
granules.

Basophils are the third type of granulocytic

leukocyte. Produced in the bone marrow, they
occur in the circulation in very low numbers.
They emigrate into extravascular tissues at sites
of inflammation. They have a multilobed
nucleus.

Mast cells are widely distributed in connective tissue and

mucosal tissues throughout the body. They are
particularly abundant in skin, gastrointestinal mucosa, and
respiratory tract, all the host-environment interfaces.
Nucleus is round to oval and contains a prominent
nucleolus.

These cells are not phagocytic and are only sluggishly motile. Their main function is the
degranulation of their cytoplasmic contents when stimulated. This degranulation releases a
number of preformed proinflammatory products, including histamine, serotonin, eotaxin (IL-5),
and heparin.

The degranulation of these cells

usually is dependent on prior
fixation of antibody (IgE) to the cell
surface at Fc receptors and
subsequent binding of antigen to
these antibodies. This is the primary
mechanism of degranulation in
allergic responses. However, there
are other mechanisms of mast cell
degranulation including binding of
C5a and C3a.

The end result is increased vascular permeability, vasodilation, anticoagulation, tissue

destruction, and attraction of eosinophils. Basophils and mast cells are not end stage cells and
both are capable of continued division at the site of inflammation.

32
Mononuclear cells

 Lymphocytes
There are many types of lymphocytes but all appear similar morphologically. They are small
round cells with a round, hyperchromatic nucleus and scant, light blue staining cytoplasm. Under
the microscope, T and B cells look the same.

When B cells start to produce antibodies, they turn into…..

Plasma cells have a unique

appearance. They have more
cytoplasm than a lymphocyte and
this is often basophilic, with a pale
area or “halo” just next to the
nucleus. This “halo” represents the
Golgi apparatus. The nucleus is
usually eccentrically placed and the
chromatin often is clumped at the
periphery, creating a “clock-face”.
Takes a little imagination to see the
clock, in my opinion.

Seeing numerous plasma cells in an organ or a lymph node is an indication of chronic

antigenic stimulation.

33
  Mononuclear phagocytes
The term macrophage means “big eater.” Macrophage is the term we use to describe a
monocyte that has emigrated from the blood to the tissue. In addition, macrophages are routinely
found in a number of organs, as fixed cells within the vasculature, sampling all the material that
floats by. Some of these fixed macrophage cells include: Kupffer cells in the liver, pulmonary
intravascular macrophages (PIMs) in the lung, sinusoidal lining cells in the spleen, and microglia
in the CNS.

Macrophages do not divide at the site of inflammation. Compared to neutrophils, they are more
long-lived, surviving at an inflammatory site for as long as a month. They are also slower to
arrive at the site of inflammation, usually taking about 48 hours to get there.

They appear as large cells with bean shaped or oval nuclei with fine, diffusely scattered
chromatin. The cytoplasm stains a pale pinkish-blue and may contain vacuoles or particulate
debris.

The functions of macrophages are phagocytosis and destruction of foreign material and
presentation of antigen to lymphocytes.

In addition to their phagocytic function, activated macrophages produce and secrete a wide
variety of biologically active substances. Some of these include: cytokines, toxic oxygen
metabolites, proteases, nitric oxide, growth factors that promote fibrosis, and angiogenesis
factors. As such these cells are central figures in subacute and chronic inflammation.

34
When the inciting cause remains for a long
time, often macrophages will fuse, creating an
unusual cell, the multinucleated giant cell.

“Let’s join forces to fight the enemy.”

35
 IMMUNE MEDIATED INFLAMMATION
This lesson corresponds to the web lesson of the same name. 
SUMMARY OF IMPORTANT CONCEPTS FOR THIS LESSON

There are 4 main types of immune-mediated disease, or hypersensitivity:

Type I – IMMEDIATE
 “allergic” or “anaphylactic” type
 Dependent on production of IgE (some individuals make more than they should)
 On re-exposure, IgE binds mast cells and basophils, releasing vasoactive amines and
other mediators
 Result is local inflammation, edema
 Examples of local Type I: hay fever, urticaria
 Systemic Type I: anaphylaxis

Type II – CYTOTOXIC
 Production of IgG or IgM, they attach to target cells
 Then, one of three things happens, any of which kills the cell:
1. Complement attaches, punching a hole in the cell or facilitating phagocytosis
2. Killer cells attach to the antibody and kill the cell (ADCC)
3. Antibody kills the cell by binding to a key molecule
 Examples: immune-mediated anemia, myasthenia gravis

Type III – IMMUNE COMPLEX

 Requires persistent antigenemia, to which host makes lots of antibody
 Many antigen-antibody complexes floating around
 Some IgE gets produced, increased vascular permeability
 Antigen-antibody complexes get lodged in the vessel wall, glomerulus
 Complement is activated, pulls neutrophils in, they chew up vessel wall
 Example: membranous glomerulonephritis

TYPE IV - DELAYED
 Is mediated by CELLS rather than antibodies
 Occurs 24-48 hours after antigen is presented
 Most cells in the reaction are mononuclear
 Example: tuberculin reaction

           

36
 IMMUNE MEDIATED INFLAMMATION
Introduction

Immune mediated inflammation is simply inflammation that is caused by the immune

response. All immune responses are directed by lymphocytes. Therefore, lymphocytes and their
products drive immune mediated inflammation.

The immune response is not supposed to damage body tissues. Those immune-mediated
reactions that DO damage normal tissues are called Hypersensitivity Reactions. There are four
basic types. In reality, many reactions are combinations of two or more types with one type
predominating.

Type I - Anaphylactic or allergic hypersensitivity

These reactions include allergic reactions,

anaphylaxis, and atopy. Type I reactions can
be localized allergy or generalized
anaphylaxis. The reaction is mediated by
production of IgE by plasma cells in
response to certain antigens. IgE binds to
mast cell and basophil Fc receptors. These
cells are now specifically sensitized to a
given antigen, and upon re-exposure to the
antigen, IgE binds the antigen causing
immediate degranulation and synthesis of
inflammatory mediators by mast cell.

Examples of Type I hypersensitivity:

hay fever, urticaria, atopy, anaphylaxis

Histamine, heparin and serotonin are preformed in mast cell granules. Therefore, they are
released immediately upon degranulation causing vasodilation and increased vascular
permeability. Increased permeability of vessels means EDEMA.

37
First exposure to antigen causes plasma cells to produce IgE that binds to Fc receptors on mast
cells and basophils. You have to see it once in order to be RE-exposed, which is the time when
the hypersensitivity reaction kicks in.

There are also some mediators released that cause smooth muscle contraction (bronchospasm - in
asthma).

Why do some individuals develop allergies and others don’t?

It’s simple. Those who are allergy-prone make more IgE that what is useful. Normal individuals
synthesize only small amounts of IgE when exposed to the antigens and higher amounts of IgG
and IgM.

Anaphylaxis
Systemic anaphylaxis occurs when antigen is systemically distributed in a highly sensitized
individual. It is a generalized reaction mediated by mast cell and basophil granule release.
Principal mediators include histamine and cytokines. The reaction is characterized by smooth
muscle contraction in lungs and intestines, vasodilation, increased vascular permeability,

38
hypotension, vasomotor collapse, and pooling of blood in shock organs. Basically, death.
Domestic animals are less susceptible to anaphylactic shock compared to humans.

Special cases of type I reactions in veterinary medicine:

- Milk allergy in Jersey cattle - Due to missed milking, milk proteins (alpha casein) get into
circulation and act as antigens causing an allergic reaction. There is urticaria and sometimes
life threatening anaphylaxis.
- Allergies to vaccines and drugs are not uncommon.
- Chronic obstructive pulmonary disease (COPD, also known as heaves) happens in horses
that inhale fungal allergens from dusty hay.
- Warble fly larvae in cattle - Hypoderma bovis pupae develop under skin after larvae migrate
from heel to back. If pupae rupture an anaphylactic response can occur.
- Fly bite allergy - Horses may also develop type I allergies to Culicoides and Simulium fly
bites.

Type II - Cytotoxic Hypersensitivity

* Complement is activated and forms
MAC (membrane attack complex)
resulting in lysis of the target cell, or
antibody and complement opsonize
target cell so that neutrophils or
macrophages phagocytose target
cells and destroy them.
* ADCC (antibody-dependent cell
mediated cytotoxicity) - neutrophils,
macrophages, or lymphocytes (null
cells) bind to antibody and destroy
the target cell without phagocytosis,
through secretion of cytotoxic
compounds.
* Antibody binds to and inactivates or
down regulates a biologically active
molecule. An example is antibody
produced against acetylcholine
receptors in myasthenia gravis
resulting in subsequent muscular
weakness.

These reactions are also called cytotoxic or cytolytic because host cells are killed or undergo
lysis after reacting with antibody. This Type II, or Cytotoxic, Hypersensitivity depends on the
abnormal production of IgG or IgM directed against tissue antigens or a normal reaction to
foreign antigens expressed on host cells, as shown in the diagram above.
An examples of Type II hypersensitivity is neonatal isoerythrolysis in horses.
39
Type III - Immune-complex hypersensitivity
The third type of immunologic injury is also called immune-complex mediated hypersensitivity.
At the center of the pathogenesis is an antigen that won’t go away or can’t be neutralized, so
there are too many antigen-antibody complexes in the circulation. Immune complex disease is
seen in persistent infectious diseases. There are too many antigen-antibody complexes, they
settle out in blood vessels. Complement attacks them, causing increased permeability and
inflammation of the vessel wall.

Rules of engagement for Type III:

1. Exposure to antigen causes plasma cells to produce IgG or IgM.
2. In conditions of persistent antigenemia and slight antigen excess, soluble antigen- antibody
complexes form.
3. Deposition can be generalized (i.e. acute serum sickness) or localized (i.e.,
glomerulonephritis, Arthus reaction).
4. Examples include hypersensitivity pneumonia and immune complex glomerulonephritis.
Organs with fenestrated endothelium are particularly susceptible. Examples include the
glomerulus, synovium, and uvea.

Examples of Type III hypersensitivity:

rheumatoid arthritis, membranous glomerulonephritis

40
 When there are too many
ag-ab complexes circulating,
some get “stuck” in the
glomerulus. This disrupts
the membrane structure of
the glomerulus and makes it
leaky. Normally proteins
don’t pass through the
glomerulus into the urine
but when the membrane is
all disrupted, they can. So,
animals with membranous
glomerulonephritis often are
losing much protein into the
urine.

Type IV - Cell-mediated (or Delayed) Hypersensitivity

Also known as cell-mediated hypersensitivity (remember the other three are due to antibodies),
this form is a common response to many intracellular pathogens and to large or complex
infectious agents.

Type IV cell-mediated hypersensitivity is initiated by T lymphocytes specifically sensitized to

locally deposited antigen. The two effector mechanisms are: (1) delayed type and (2) direct
cytotoxicity.

41
Example - positive tuberculin skin test (DTH, type IV).

42
 Healing and Repair
This lesson corresponds to the web lesson of the same name. 
SUMMARY OF IMPORTANT CONCEPTS FOR THIS LESSON

Repair by regeneration
This is when an organ can make new cells, like the liver!

Repair by replacement
This is when an organ can’t make new cells and the repair is through fibrous tissue (scar),
like the heart.

Wound healing (all soft tissues):

Granulation tissue:
Composed of fibroblasts making collagen and endothelial cells making capillaries
Eventually becomes mature collagen (scar)(

Special considerations in repair:

Bone has a system all its own.
Nervous tissue cannot regenerate
Heart myofiber regeneration is not possible. You only get a scar.

           

43
 Healing and Repair
Inflammation and repair can be viewed as two parts of a single vital function, the physiologic
response to tissue injury, the objective of which is restoration of normal structure and function.
Up until now we have focused on the inflammation portion but it is good to remember that repair
starts pretty soon after inflammation does and then continues during and beyond the
inflammatory phase.

Perfect restoration of function is dependent upon the regeneration of lost cells by similar cells
(repair by regeneration), and the orderly arrangement of these new cells in relation to
preexisting cells so that tissue functions are restored.

If the original cells cannot be replaced by their own kind then they are replaced by other cell
types (repair by replacement), usually by fibrous connective tissue. If necrosis is extensive,
even tissues that are capable of regeneration are replaced by fibrous connective tissue.

There are three cell types based on ability to regenerate:

permanent cells ( almost never divide) -
nerve cell bodies, cardiac myocytes, cells of the lens
stable cells (will divide if stimulated) -
fibroblasts, osteoblasts, parenchyma of liver, kidney, pancreas and
endocrine glands, smooth muscle, vascular endothelium
labile cells (multiply through life) -
epithelial cells of surfaces or linings of ducts and hollow visci,
lymphoid and hematopoietic cells

44
Granulation tissue (= vascular fibrous connective tissue)

The term “granulation tissue” is derived from its pink soft granular appearance on the surface of
wounds. Granulation tissue is recognized histologically by the presence of newly formed fibrous
tissue and numerous small blood vessels. The fibrous connective tissue eventually may come to
have the maturity of the loose fibrillar connective tissue of normal histology, but in the formative
stages the fibroblasts are plump and only a few collagen fibrils have been produced.

Contraction occurs as a result of the action of myofibroblasts. These cells have features
intermediate between those of fibroblasts and smooth muscle cells. They appear in the wound
area 2 or 3 days after injury. Their origin is not entirely clear, but they probably derive either
from perivascular cells or from other mesenchymal cells. Contraction may reduce the original
defect by as much as 70% and greatly facilitate healing.

Fibroplasia begins early after injury, with existing fibroblasts adjacent to the wound being the
source of new fibroblasts. The immature fibroblasts are characterized by their plumpness,
basophilia, rich complement of rough endoplasmic reticulum, and prominent nucleoli, all
evidence of active synthesis. They are active in synthesizing glycosaminoglycans and collagen
fibers.

The new capillaries most commonly run in a

perpendicular direction to the outer surface of the
wound since their function is to carry supplies to
the free surface, while fibroblasts tend to grow in
from the side of the defect to bridge the gap. This
often produces a histological picture of capillaries
running at right angles to the direction of the
fibroblasts. The formation of new capillaries is
termed angiogenesis or neovascularization.

45
 It is important to distinguish the term granulation from granulomatous
inflammation. Although they sound similar, they are really quite different. As
different as fibrinous is from fibrous (know that distinction too).

Remember, granulation tissue is part of the repair process and consists of inflamed, proliferating
fibrous tissue and granulomatous refers to inflammatory infiltrates characterized by
macrophages.

And sometimes granulation tissue doesn’t know when to quit growing and start turning into the
permanent scar it is supposed to form. Think “exuberant granulation tissue” in horses, also
known as “proud flesh.” A healing process that goes too far and too long.

All this healing takes energy and if an animal is in a compromised state, the repair will take a
whole lot longer.

46
Repair of bone

Repair of bone is a specialized category of healing and repair and deserves individual
attention. Immediately following fracture of bone, blood flows out of the broken vessels
into the gap between the broken ends of bone and displaced or disrupted periosteum, and
into the surrounding soft tissue. A big callus forms with fibrovascular tissue. The
osteoprogenitor cells eventually invade into this callus and slowly new bone is formed
and then remodeled.

Repair of Nervous Tissue

Repair in the central nervous system (CNS) is very limited because mature neurons do
not divide. When damage occurs in the CNS, neurons and their processes are lost forever;
they cannot be regenerated. Take care of your neurons! In the peripheral nervous system
(PNS), injury to the nerves may be followed by regeneration if the nerve cell body
remains alive.

Repair of the Myocardium

Myocardial cells do not have any regenerative capacity. When they die, as in a heart
attack, they are gone forever and repair can only take place by fibrosis. This replacement
by fibrosis decreases myocardial contractility.

47