Inflammation

General pathology is a very important subject that you need to understand

very well before proceeding to systemic pathology. So you should
understand basic mechanisms of inflammation, injury + the main aspects
of inflammation. After that it will be very easy for you to understand the
.subsequent courses (cardiovascular module, respiratory module ….. etc)

I think you have ready study the mechanisms of cell injury and today will
.start discussing the inflammation

As you know any organism to survive need to eliminate the invaders from
their body or from their tissues. And these invaders are made from
infectious agents (microbes or dead tissues or …..). So the main process
(mechanism) that these organisms beat harmful agents is what we called
INFLAMATION. The inflammation is a dynamic process of chemical or
physiological or cellular interactions that occur in response to stimuli that
cause cell injury in the vascularized tissue. So you should know types of
.cell injury, the causes of cell injury

.Inflammation has beneficial and harmful effects on the body or cells

Inflammation results in accumulation of leucocytes (white blood cells)

.and fluids in the extra vascular spaces or tissues

What is the effect of the inflammation? It is the elimination of the cause

of cell injury (microbes, viruses, infectious agents)

And after that this inflammation process will eliminate such agent (By
diluting or neutralizing) and this will lead to necrotic cells (or dead
tissues), also the process itself is taking care of this to eliminate such
necrotic or dead or abnormal tissues or cells. After that it paves the way
for proper repair (subsequent events of inflammation), we need to repair
the tissue because inflammation of dead cells will lead to some kind
damage, after this damage to the cells (blood vessels) we need to repair

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and this process will set the seam for subsequent repairing and other
.regeneration effect

How do we call different kinds of inflammation of different body, (prefix

pr suffix) (prefix which come before the word. or suffix after the word)

For inflammation process we use the suffix –it is after the tissue name

For example :-If we have inflammatory process in the appendix we call

.this inflammatory Appendicitis

.For the Dermis (of the skin) we call it Dermatitis

.For the Gallbladder we call it Cholecystitis

For the Meninges (the membranes around brain and spinal cord) we call it
.Meningitis

?So what are the possible causes of inflammation

usually any cause that make cell injury will trigger an inflammatory (
)response

.Microbial infections: bacteria, viruses, fungi, parasites -1

Immunologic: hypersensitivity (contact with some substances that -2

cause irritation like allergy) autoimmune reactions (in which the immune
.system attack the body antigens)

.Physical agents: trauma, heat, cold, ionizing radiation -3

.Chemical agents: acids, alkali, bacterial toxins, metals -4

Foreign materials: sutures (surgical sutures in the operation. We -5

.usually see that the body attacks the sutures material), dirt

Tissue necrosis: ischemic necrosis. Tissue necrosis, will lead to -6

inflammatory process because the necrotic tissue (dead cell) must be
removed from the body

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So who are the players in this process (the participants)? So there are
different players from different categories which all together come to play
:this kind of inflammatory process

-:All of them will be discussed in details later on

White blood cells and platelets (Neutrophils, monocytes, -1

.lymphocytes, eosinophils, basophils)

Plasma proteins: Coagulation, fibrinolytic system, kinin system, -2

.complements system

Endothelial cells and smooth muscles of vessels (The components of -3

.blood vessels)

So we need to get some sort of endothelial damage and endothelial cell {

contraction to allow the increase of permeability of blood component to
}get out of blood vessel

Extracellular matrix and stromal cells (stroma means the matrix or -4

supporting tissue of an organ, as distinguished from its parenchyma or
functional element.) :Mast cells, fibroblasts (a modified macrophages) ,
macrophages & lymphocytes - Structural fibrous proteins, adhesive
.glycoproteins, proteoglycans, basement membrane

You know the extra cellular matrix interaction is one of the most
important things in pathogenesis of either inflammation (or any other
reaction process) because the extra cellular matrix is directly controlling
process or body on the growth of inflammation (interaction or different
.process)

So I will summarize the component of inflammation, you will see here

Blood vessels

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Smooth muscles

Basement membrane

In the normal situation there is just a little space between the cells and it
allows only minimum escape some fluids (or proteins) outside to the
extracellular matrix, and in these blood vessels we have different
components, we have the plasma, plasma proteins and different kinds of
white blood cells including (monocyte, neutrophiles, eosinophiles and
basophiles, lymphocytes) also we have red blood cells and platelets in
addition to this we have clotting factors (Kininogens and complement
components)

And out of this we have the connective tissue cells (fibroblast and
macrophages and mast cells),Fibroblast is term of modified macrophages
and it has the heredity to differentiate into fibrous tissue to rebuild
.damaged tissue and that is why we call it fibroblast

We have the Matrix which contains the extracellular cells. And this
matrix consists of a lot of fibers like elastic fibers, collagen fibers or
proteoglycans. Anf the interactions between these cells and this matrix is
.very important to inflammatory process

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Is all inflammation is same (same type or same kind), the answer to this is
No.Of course we have different kinds of inflammation, the main two
:types are

Acute Inflammation and Chronic Inflammation

So from the names Acute means (something that resolve rapid or quickly)
and Chronic means (it takes longer time to be prepared) So what is the
?main difference here

:Acute Inflammation

Duration: very short here (minutes to days)

.It is characterized by the Predominance of neutrophils (the first arrivals)

We have more exudation (Fluid & plasma protein) into the connective
.tissue,so it exudates because it has higher protein content

:Chronic Inflammation

.Duration: days to years

It is characterized by the Predominance of lymphocytes and

.macrophages

Tissue destruction by the products of inflammatory cells

Vascular proliferation and fibrosis (new blood vessels production) low

exuadation

.We are going to explain the two types in more details

Acute Inflammation

.Definition: Early response of vascularized tissue to injury

:The Aim of Acute Inflammation

Recruitment of neutrophils (white blood cells) in the first three days -1

initially, and monocytes (after 3 days) to clear the cause of injury and
.remove necrotic cells

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Deliver plasma proteins: antibodies, complement systems, others -2
(which can help in counter acting and remove the infectious agents we
.have)

The Two Components of Acute Inflammation :

We have two main components: the vascular changes & the cellular
events

:The Vascular Changes -1

:We have three main mechanisms

A- Vasodilatation (To deliver more blood and inflammatory cells to

the site of infection to make more destruction of infectious agents)

B- Increased vascular permeability (which means we need to get

proteins and components outside the blood to reach the site if
inflammation or infection)

C- Stasis (Stasis means slowing down in the stream, it is

immunological to have more leakage of the plasma and it's component.
When a lot of plasma proteins go out the concentration of rbc's will
increase so the blood will become more viscous and it will slow down.
.This will lead to margination of leukocytes because it's larger than rbc's

:The Cellular Events -2

.A- Emigration of cells from microvessels to outside

.B- Accumulation of these cells at sites of injury

So the process is orchestrated by release of chemical mediators such two

events (vascular and cellular) and the way that vascular changes happen
or initiated and then the migration of cells are fully controlled and in a
very good harmony by what we called chemical mediators and cytokines
(are released by different kind of cells, the component of inflammation:
Endothelial cells or Lymphocyte or the Monocyte …… etc to organize
such process)

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This is example of Acute Inflammation process of the blood and you see
.the predominance of neutrophils, so this is example of pneumonia

?So what are the Local Manifestations of Acute Inflammation

Normally the hydrostatic pressure and the plasma colloid pressure will
control the blood flow in and out of the vessel, the plasma colloid
pressure is produced by the content of blood of proteins

The hydrostatic pressure is produced by the pressure of the fluid through

the lumen to outside. So we have like counter acting each other keeping
the balance between the fluid extra migration and fluid coming inside the
.cells in a control pulse (we call this Homeostasis)

:In the figure above

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We normally have a net pressure to outside at the arteriolar side (the net
forces are to outside). We need the blood to get out for nutrition and to
……eliminate the other substances or to get oxygen etc

The pressure in the region in between the arteriole and the venule ( in the
.capillaries) is less different,it is equivalent

The pressure in the venule side is usually (the net pressure) to inside and
this is mainly to remove the fluid and the cells from outside back to the
.venule

:In the figure below

You can see here, increase in the blood flow due to vasodilatation,
e
n
d
o
t
h
e
l
i
a
l
c
o
n
t
r
action, escape of the fluid and the molecules to the outside which we call
it exudation (if it contains high protein content) and of course lead to the
.inflame process

There are five classic signs of acute inflammation

Heat: It -1
occurs because of the increase in the blood flow and this will
.increase the temperature at the site of the increase blood flow

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.Redness: It occurs because of the Vasodilatation -2

Swelling:It occurs if there is more escape of fluid and proteins -3

to the connective tissue you will have edema and this will lead to
.swelling

Pain:Of course such swelling, hotness and redness will -4

.compress the local areas and will lead to pains

.Loss of Function:Serious pains will lead to loss function -5

?Now what are the specific forms of vascular changes that we have

Arteriolar dilatation follows transient vasoconstriction (the first initial -1

step of the vascular changes)

Increased vascular permeability and stasis: Arteriolar vasodilatation -2

will lead to increase in the Hydrostatic pressure and lead to more fluid
outside to the connective tissue and it will lead to what we call it
.transudate

Later stages: the blood vessels become leakier and this will
result in → loss (leakage) of proteins and more cells and this will lead to
.what call it exudate

Margination of leukocytes: the WBC is the larger than the RBC -3

components so the RBC will flow through the centre of stream of the
.blood and the WBC will go around it near the periphery of the vessel

:Fluid Movement in Microcirculation in Normal Tissue

:In the Figure below

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In the normal state the net flow is out (in arteriole side) & the net flow is
.in (in venule side) & there is no net flow of at the capillaries region

Fluid Movement in Microcirculation in Inflamed Tissue

:In this Figure below

You can see here 1)that the net flow in the arteriole regoin is out and is
.longer than usual because of the vasodilatation and increasing blood flow

The capillary also has more Hydrostatic pressure because the )2

vasodilatation so there will be an out net flow in the capillary region
.unlike the normal state which doesn’t have

the venule will become dilated also. So the net flow will be out of the )3
.venule unlike the normal net flow which is in

-:Al that is due to

increase hydrostatic pressure due to vasodilation-1

decrease plasma colloid pressure due to leakega of plasma protein . so -2

.the net flow will be out in all the micro vessels

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?How does inflammation lead to leakiness of endothelial cells

:Endothelial cell contraction -1

This will limiting the intracellular spaces between the endothelium, and
.this will allow the fluid to escape outside

.It is Reversible -

Immediate transient response with short life usually last for (15-30 -
.minutes)

Induced by: histamine, bradykinin, leukotrienes, neuropeptide substance -

.P

.Mostly in postcapillary venules -

:Endothelial cell retraction -2

.It is also Reversible -

.It is more prolong Starts 4-6 hours after injury and stays for 24 hours -

.Induced by: IL-1, TNF, and IFN-g -

:Direct endothelial injury -3

Severe injury. Detachment of endothelial cells in order to increase -

exudation

.We call it Immediate Sustained Response -

All microvessels can be affected {which means arterioles, venules -

and capillaries can be affected}

:Delayed Prolonged Response -4

.Begins after delay (2-12 hours), lasts for hours or days -

Caused by thermal injury, UV radiation, and bacterial toxins. And -

.affect only the venules and capillaries

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:Leukocyte-Dependent Endothelial Injury -5

Which is mediated by one of the activated Leukocyte which -

produce many toxin that will damage endothelium (cytokines)

Increased Intracytosis (Transcytosis) of proteins through -6

:Vesiculovacuolar Pathway

This is mainly stimulated by VEGF (Vascular Epithelial Growth -

Factor); this means we will have more transport of protein and plasma
through the vesicular pathways which are present within the cells
.(endothelial cells)

:Leakage from newly formed blood vessels -7

In any inflammatory process usually in later stages, we can get what we -

call angiogenesis; and this is probably one of the earlier stages of
regeneration; creating more new blood vessels to bring more blood for
such generation and repairing. These newly formed blood vessels still
.leaky until they mature enough to form intracellular junctions

Doctor: Your husband needs a silent environment so that he can rest. Here
.are some sleeping pills

?Wife:‫كتب‬ ‫اللي‬will
When .‫مني‬I give
‫هاي مو‬
it to‫النغاشة‬
him
.‫التفريغ هو اللي حطها‬
Doctor: Those are for you! : Wink

:This is an example of Edema

You can see the vesicle and this is because of accumulation of fluid
.outside the microvessles

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:Edema in Inflammation has two types

:TRANSUDATE -1
Mechanism: hydrostatic pressure imbalance across vascular -
endothelium (escape of more fluids)
Fluid of low protein content (ultra filtrate of blood plasma) -
.Specific gravity <1.012 -

:Exudate -2
Mechanism: alteration in normal permeability of small blood -
.vessels in area of injury
Fluid of high protein content (>.3g/dl) & increased -
.cellular debris
.Specific gravity >1.020 -
someone ask the dr about the specific gravity and he answered that *
.it just a number of measurement for a test

:Cellular Events

Margination, rolling and adhesion. (we will go in details) -1

.Transmigration between endothelial cells -2

.Migration in the interstitium toward the site of stimulus -3

Phagocytosis and degranulation. Killing the infectious agent -4

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 .Release of leukocyte products -5

:This an example of Neutrophil Margination

As you see thee rbc's in the

center of the vessel and the
.leukocytes are around it

Done by: Waleed Al-Nasser

Corrected by : correction team (fa3el 5eer)

…Forgive me for any mistake & sorry for the late

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 Thanks to my all friends: Al-qaisi & Anagreh & Younes &
Khtaeeb and to heroes team : Shlool & Quaz'a & Tamimi &
………… Qudsi

.………… "Special thanks for "Al-Hasan

When the Mirror of Life Gets Misty with the Fog of Reality, Just try wiping it with
....your Faith and You Will See the Clear Reflection of your Dreams Once Again

WWM

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