Download L02 Pathophysiology/inflammation : Done by : Marwa Al

L02
Pathophysiology/inflammation :
Done by : Marwa Al-gharabat
Acute inflammation :
Definition: It is a rapid host response that serves to deliver leukocytes and
plasma proteins, such as antibodies, to sites of infection or tissue injury.
*“Acute” is general description ,immediate response not delayed “short
duration “
Acute inflammation has 3 major components:
(1) alterations in vascular caliber that lead to an increase in blood flow
→vasodilation to increase blood flow →increase number of leukocytes that
migrate to the site of injury
(2) structural changes in the microvasculature that permit plasma proteins
and leukocytes to leave the circulation, (in general it’s cause edema )
Inflammation is not in the blood is in the tissue ,if the inflammation was in
the blood this condition is called “ septic” which cause septic shock .
*If you remember ,there is two response for inflammation : vascular and
cellular response, vascular response →vasodilation ,changes in
microvascular net of blood vessels adjacent to the site of inflammation ,so
that the gaps between the endothelial cell become wider which would
permit proteins and leukocytes to leave the circulation to the adjacent
tissue, BUT if this thing happen in each vessel this will be a disaster ,why ?
The circulation will not be effected any more and that’s lead to sever
hypotension →systemic hypotension ,and we called the condition in this
case : shock !! what ever the reasone was ;septic shock or hypotensive
shock .” this is life-threatening “. To avoid this ,the structural changes is
limited to the site of inflammation .
(3) emigration of the leukocytes from the microcirculation, their
accumulation in the focus of injury, and their activation to eliminate the
offending agent. (neutrophilic infiltration )
-If we are talking about leukocyte in general ,there is a process called
phagocytosis , phagocytosis is basically removal of offending agent in the
site of inflammation by specific type of cell , the most effective phagocytic
cells are macrophages then we have neutrophils and in order to that
sometime we called neutrophils “microphages”
(( NOTE: we called macrophages in blood →monocyte , when they leave the
blood → macrophages )).
*we must be able to distinguish between the component and
manifestation .
*Manifestation →signs and symptoms:(different in chronic ):
1-rubor (redness)→due to vasodiltion and blood flow
2-swelling →due to widening in intercellular gaps between the
endothelial cell
3- calor →due to increase in blood flow
4-pain →the severity of the pain does not necessary correlate with the
inflammation , if the pain ↑ that’s not mean that inflammation will ↑
* NOTE : there are inflammatory mediator that activate nociceptore on
sensory neuron and it will initiate a pain signals and that occur in many
way like releasing chemicals or inflammatory mediator such
prostaglandins ,substance B .. etc .
5-loss of function → for example inflammation of joint or internal organs
,in joint “osteoarthritis “→cause rigidity in joint and due to pain the
patient try not to use the affected joint , this is part of host mechanism
to prevent damage ,the purpose of pain is like :
(leave that site alone  )in order to optimize healing and we called that
“ adaptive inflammation “→ pain associated with inflammation for
specific progress which is to optimize tissue healing then the pain stop
and every thing goes back to normal .
In acute inflammation, this type of inflammation is associated with
complete healing compared to chronic inflammation , BUT not always !
sometime acute inflammation change to chronic type if the injury was
sever or if there was deficiency in some component (proteins,
inflammatory mediator ..) and that prevent optimum healing .
Causative stimuli :
1-infection → typically pain more associated with bacterial and viral
infection , example :fungitis ; ‫ التهاب الحلق‬can be viral or bacterial
depending on the age , viral is more common in children and bacterial in
age of (5-15) years .
2-trauma (blunt and penetrating ) :
Blunt → ‫مثال الضرب باستخدام العصا و من دون ان تخترق الجلد و االنسجه‬
Penetrating → ‫مثال باستخدام سكين او مسمار او اي شيئ يخترق الجلد و االنسجه‬
3-physical (burns ,frostbite ,irradiation ) and chemical agent
Burns → depending on it’s degree for example if we have third degree of
burns the pain will be typically absent , why ? because the sensory end
had been damaged “ no feeling “
4-tissue necrosis , very potent trigger of inflammation “ very painfull
unless they have neuropathic “ .
5-foreign body , the difference between this cause and the second cause
that in the second one even we remove the cause of injury the
inflammation take place in order to healing ,but in this one if we don’t
remove the foreign body there is gonna be continuous inflammation
6-immune reaction (hypersensitivity reaction ), we have 5 type of
hypersensitivity reaction ,
Anaphylactic reaction → this is type one
Type one hypersensitivity →absolute contra indication use of drug, most
common type of drug hypersensitivity is : penicillin , sulfa drug .
** in the coming lecture we are going to talk about another type of cell
death “ apoptosis” ,
apoptosis →is a programmed cell death ,occur in many steps and it’s
doesn’t trigger inflammation
necrosis → involuntary cell death cause by injury , and in this type of cell
death there is a leakage for intracellular component to the surrounding
tissue and this will trigger inflammation
** EDEMA :
As a reminder the fluid can be exudate or transudate , the one that
associated with inflammation is exudate
Exudates + leukocytes → pus ‫القيح‬
Changes in Vascular Flow and Caliber:
-Vasodilation is one of the earliest manifestations of acute
inflammation.
-Increased permeability of the microvasculature, with the outpouring of
protein-rich fluid into the extravascular tissues.
Note : rich in protein → exudates
What is purpose of structural changes in blood vessels adjacent to the
site of inflammation ?
1.to allowed protein and leukocyte to leave blood vessels to adjacent
tissue
2.to have stasis ,reduction of blood flow , to ease leakage of proteins and
leukocyte to the adjacent tissue , and it’s serve as recognition site , the
stasis act as alarm system “ to tell leukocyte that you getting close to the
injury site “
The exact location were the leukocyte leave the circulation is controlled
by binding to specific receptor → in that site of binding leakage occur .
-Migration of leukocytes through the vascular wall into the site of injury
** increase vascular permeability , how ??
contraction of epithelial cell → ↑ in inter endothelial spaces → widening
in inter cellular gaps between endothelial cell
**endothelial injury → endothelial cell necrosis and detachment , for
example : damage in in blood vessels →↑ in permeability → formation
of gaps → ↑ leakage of protein and fluid .
** Increased transport of fluids and proteins, called transcytosis,
through the endothelial cell ,
Transcytosis : transmission of fluid and protein from blood to tissue
******** ********** *********
CHEMOTAXIS :
Recruitment of leukocyte “neutrophils “ to the site of inflammation , by
releasing of inflammatory mediators in the blood .
NOW : how the leukocyte know that this is the site of inflammation ??
-depending on :1. Reseptor (exact site )
2. concentration of chemicals that cause chemotaxis
Look at figure in slide 23 .
There is a receptors on the surface of endothelial cell and on the surface
of neutrophils .
Binding to a specific endothelial receptor will determinethe site of
migration of leukocyte into the adjacent tissue .
** CHEMOTSXIS STEPS :
1- When the leukocyte get close to the site of inflammation , the stasis
occur , and the concentration of chemotaxis ↑ → rolling occur
There is a specific receptor ( P-selectin , E-selectin and ICAM ) on the
surface of endothelial cells , and integrin on the neutrophils.
ICAM → family of receptor that are involved in so many process and
certain pathogens use this receptor e.x : in common cold .
2- Integrin activation by chemokines . ( kines is a general term for active
substances secreted or present in the cell , chemokines is a cytokine
involved in chemotaxis )
3- P-selectin and E-selectin slow dowen the movement of leukocyte
(doesn’t stop the movement )
4- Binding with ICAM ( full stop of leukocyte movement )
5- The stopping is the site of leakage . (final phase ) through the gaps
*******************************************************
the activation of the receptor depend on the site of activation .the
receptor is important to determine a pin point for leaving the
circulation to the adjacent tissue NOTE : EXTRAVASATION MEAN
LEAVING THE BLOOD VESSELS IN GENERAL ,IMPORTANT IN
CHEMOTHERAPY
GOOD LUCK 