Chronic Inflammation

What do we mean by chronic inflammatory response?

One of the factors is the time factor but its not a factor that depends on the
definition of chronic inflammation

How do we get chronic inflammations?

Possibly an acute inflammation may proceed to become a chronic
inflammation and this is in a case where the injurious agent is persistent
Or sometimes, the injurious agent is very difficult to get rid of, so the
inflammation would be of chronic nature from the start
With chemicals like arsenic and certain antibodies can proceed to becoming a
chronic inflammation

Persistent infections: like syphilis, viruses, fungi

So an exposure to certain toxins whether they’re form outside or from the
body itself like the lipids in the body since when they accumulate they
become harmful and the body tries to get rid of them

Antibody of our body directed against our tissues and these antibodies will
elicit chronic inflammatory reaction and it will be the cause of chronic
inflammation from the start

How do we know this is a chronic and not acute?

In acute inflammation there are 2 responses, a Vascular response and a
Cellular response
However, in Chronic inflammations there are 4 main features by which the
body responds to the injury

1. An evidence/presence of an Immune system: could be presence of

lymphocytes(T or B), B lymphocytes proceed to become Plasma cells so
finding these aswell, and also a presence of antibodies and also
macrophages

2. This immune response may ask the cell to destroy this antigen that the
neutrophils aren’t able to getting rid of it, therefore, you’ll find an
evidence of phagocytosis this is usually by the macrophages through
the antibodies which stimulate the compliment system which stimulate
the compliment response which release the c3b , … ,,, and opsonizing
agent this is an immune phagocytosis seen through the presence of
macrophages and immunoglobulins

Or there would be a non-immune phagocytosis

3. Necrosis: there should be an evidence of necrosis which is the cell death

and usually this necrosis affects scattered cells. So usually there is
evidence of cell death

4. Repair: you must find in the tissue that is affected an evidence of

repair the tissue will start to repair itself inspite of the presence of
destruction and the repair of the tissue will be usually by forming new
vessels and laying down the fibroblasts -fibroblastic proliferation and
collagen deposition(fibrosis) this is why an area may looked scarred
and this area that looks different is called a fibroblastic cell..??

The Histological Features of Chronic inflammation

You’ll find a presence of macrophages, lymphocytes and plasma cells confirms
the presence of an immune response and phagocytosis
Youll also find tissue destruction that is caused by the release of cytokines form
the inflammatory cells monocytes,plasma cells

You’ll also find evidence of replacement of damaged tissue and this by finding
fibroblast and new vessel formation angiogenesis

Macrophages: they’re got from circulatory monocytes released from the stem
cells of the bone marrow and when there is an injurious agent they come to
the site in the interstitial space and the macrophages will try to go to this site
and this usually after the failure of the neutrophils by adhering to the
endothelium and then by migration. When it reaches the site, it is stimulated
to kill. This stimulation is by either of 2 mechanisms
Either by the, non-immune mechanism or the Immune mechanism

What are the non-immune mechanism that activate the macrophage

They’ll be either the endotoxins released by the bacteria and they’ll stimulate
the macrophages
Or by certain mediators or fibrino

There’s a change where the macrophage changes into an activated

macrophage

The other way of change is by a release of enterpheron gamma which is

released by the lymphocytes and this is responsible for the activation of the
macrophage

What does the active macrophage do?

It responds by causing two reactions
Tissue engulfment but also through this there’s a release of toxins that
leak and cause destruction of nearby tissue to nearby by the
macrophages
That’s why you find tissue destruction
At the same time it’ll release certain substances from their granules
which stimulates the tissue repair
Platelet like growth factor, transforming growth factor, fibroblast growth
factor these are the substances released that stimulate angiogenesis and
collagen formation

Lymphocytes: you’ll also find them in the chronic inflammation

Eosinophils: you can also find them persisting in chronic inflammation

because there are no cells that can respond to an allergy or the parasites
other than eosinophils because they have a content that is able to
destroy the parasitic cells and mediated an antibody mediated response
so they release from their granules and substance which is toxic to
parasites

There’s another cell I didn’t catch

Granulomatous Inflammation

We have two patterns of chronic inflammation

Either Immune mediated or non-immune mediated

What is the hallmark feature of chronic inflammatory response? It is the

presence of the chronic granuloma
What does that mean? It is a focal area of granulomatous inflammation
an area of activated macrophages surrounded by lymphocytes with
tissue destruction and area of healing it is called a granuloma—in simple
granuloma it is an activated macrophages because an activated
macrophages means it acts on tissue destruction, has an immune
response and tissue repair

When a macrophages is activated changes its shape and enlarges its

cytoplasm and full of toxins and the nucleus will be pulled apart and
ready to form a pseudopods to engulf and this is almost similar to the
epithelial cell that’s why we refer to macrophages as an epitheloid cell
When these macrophages become large they form a cascade of them
joining to each other causing the formation of a giant cells
These giant cells may be found and may not be found but a
granulomatous inflammation is a distinctive feature of chronic
inflammation and has to be there always

Foreign body Granuloma:

There is a gauze that is left by the doctor inside which is foreign body
that the body will react against it by forming a granulomotus and it will
still persist that’s why the only thing they do is that they localize this
gauze and as this needs a very big macrophages, the macrophages will
then form a granuloma and they also adhere together forming a giant
cell

Sometimes the granuloma maybe due to the immune response:

The immune response is insoluble, the T cells which mediate the
reaction are insoluble. So it will elicit a granuloma formations Syphillis,
TB, Leprosy

Distinctive pattern of chronic inflammation:

How to know that the body is responding by an acute response rather
than by a chronic inflammatory response from the same injurious agent
action?

1. The type of cells in acute is mainly neutrophils

While in chronic its lymphocytes, macrophages, plasma cells

2. Duration

3. Evidence of Fibrosis in chronic inflammation

4. Evidence of Angiogenesis in chronic inflammation

5. Evidence of vascular response in acute, presence of vasodilation and

increase in permeability showing the cardinal signs which are ABSENT
in chronic inflammation

6. Presence of necrosis which will be found in chronic inflammation

7. Possible presence of giant cells in chronic inflammation

Acute inflammation would have systemic features that are related to

the cytokines which lead to an increase in the temperature of the
body or due to hormonal release or metabolic release

But the systemic features in chronic inflammation ??

These systemic features of the chronic inflammation sometimes is

caused by the persistence of the granuloma causing a granulomoutos
reaction itself
Like what would happen in syphilis
The granuoloma is causing a destruction of nearby tissue and these
features may erode vessels, may cause pressure and if this happens
in the trachea it can compress it
This could happen In Edema but the thing with edema is that the
lyphatics can get rid of it however granuloma cannot be

The fever in acute inflammation is a high grade fever which affects

the thermoregulatory centre
But in chronic inflammation there is a low grade fever but it persists
for a long time

The mediators which elecits response like loss of apetit and nausea
where in chronic inflammations
It can cause a loss of weight since it increase metabolic activity
So loss of weight is more prominent in chronic inflammation

In chronic inflammation there is evidence of presence of high

immunoglobulin levels, but in acute there is a response by protein
like the c reactive protein or prealbumin which are released by the
liver

So the body responds by different ways

There is a response between acute and chronic inflammation which

are mentioned in some books and this called Subacute inflammation
which has features of both acute and chronic inflammatory response

Sometimes patients may have a chronic inflammation and ontop of it

there is an acute inflammation
Eg Chronic inflammation in Stomach and then a new acute
inflammation comes
Acute ontop of Chronic inflammatory response/process

Summary of mediators for the acute

Mediators for vasodilation
Prostgalandins prostacyclin I
Nitric Oxide
Histamine

Mediators for increased vascular permeability

Histamine, serotonin

Mediators for chemotaxis

C5a Leakotriene B4
Chemokines
IL-1, TNF
Bacterial products

Fever ( systemic feature of inflammation )

IL-1  directly stimulate the center
Tumour necrosis factor  continuous release of this factor causes
loss of weight
Prostaglandin

Pain
-mostly by Bradykinins
- prostaglandins- especially E

Tissue damage
- Neutrophil and macrophage lysosomal enzymes
- Oxygen metabolites
- Nitric Oxides
Question: the macrophages are activated by either Lymphocytes through
enterpheron gamma to do its function OR in an non-immune response it is
activated by endotoxins released by bacteria which will activate the
macrophages, sometimes it is by chemical mediators the same chemical
mediators can activate the macrophages