1. Professor of Pathology Faculty of Medicine Ain Shams University
Dr. Riham Abu-Zeid
Professor of Pathology
Faculty of Medicine
Ain Shams University

2. Inflammation 1

4. Inflammation Definition:
It is a protective response of living tissues to eliminate
cause of cell injury by
diluting
destroying
or neutralizing
harmful agents e.g. micro- organisms and
toxins.
necrotic cells and tissues resulting from that injury.

5. Intended Learning Outcomes (ILOs):
Define inflammation and recognize its clinical manifestations & systemic effects.
Explain vascular & cellular events in acute inflammation and describe its morphology.
Describe the cellular events in chronic inflammation.
Compare acute inflammation with chronic inflammation.
Define granulomatous inflammation and list its causes.
Apply the rules of acute and chronic infl. to predict the features of infl. in the different organs of the body.
Define toxemia, bacteremia, septicemia and pyemia. Recognize types, possible clinical manifestations and pathological features.

7. Types of inflammation:
Acute inflammation
Chronic inflammation
onset
duration
Rapid
Short (few minutes up to few days)
IF severe →fulminant acute inflammation
Gradual
Longer duration (days to years)
N.B
Chronic active inflammation
Chronic active :chronic with acute exacerbation
Subacute a stae bet acute amd chronic
N.B
Subacute inflammation

8. Causes of acute inflammation

9. What is the aim of acute inflammation ?
Leucocytes & plasma proteins
injury

10. How does acute inflammation deliver leucocytes and Plasma prts ?

11. 1-Acute inflammation
Acute inflammatory response can be divided into two components:
I.Vascular changes.
II.Cellular events. 

12. I-Vascular changes Changes in vascular caliber & blood flow
1- Immediate Transient V.C of arterioles
2-Persistent progressive V.D >>>??
B-Increased vascular permeability
VC for seconds in severe >>5 mins
VD leads to readness
permeability= remove the barriers on side of street so that cars can reach site of destruction and let the soldiers reach
VD and permeabilty … edema

13. 2-Persistent progressive vasodilatation
mainly in arterioles within half an hour of injury
↑ blood flow & ↑local intravascular hydrostatic pr. with movement of fluid ( plasma containing little protein) .
Erythema & Warmth
transudate

14. How does Increased vascular permeability occur?

15. B-Increased vascular permeability
Mechanisms of increased vascular permeability
1-Endothelial cell contraction
Mediated by histamine, bradykinin, leukotrienes
2-Endothelial cell retraction
Mediated by cytokines as TNF & interleukin-1 (IL-1).
3-Endothelial injury

16. B-Increased vascular permeability
Mechanisms of increased vascular permeability
1.Endothelial cell contraction
2.Endothelial cell retraction
3.Endothelial injury
Mediated by
histamine, bradykinin, leukotrienes
cytokines as
TNF & interleukin-1 (IL-1).
Direct (burns)
Activated Leucocytes
Most common cause of increased permeability
Leads to intercellular gaps
Change in cytoskeleton of endoth cells
Cell necrosis> leakage
1& 2Reversible

17. B-Increased vascular permeability
>movement of protein-rich fluid & cells into the interstitium (EXUDATE)
Edema d.t outflow of water & ions into extravascular tissues.
Stasis d.t ↑blood viscosity
Margination of leucocytes (principally neutrophils) along the vascular endothelial surface
The loss of protein-rich fluid into the perivascular space results in:
1. Reduction in the intravascular osmotic pressure and increase in the osmotic pressure of the interstitial fluid. The net result is outflow of water and ions into the extravascular tissues.
Fluid accumulation in extravascular spaces (edema) is responsible for swelling at the local site of acute inflammation.
2. The red blood cells become more concentrated, thereby increasing blood viscosity and leads to slowing of circulation (stasis).
As stasis develops, leucocytes (principally neutrophils) accumulate along the vascular endothelial surface, a process called margination.

18. transudate What is cause of edema in inflammation ? exudate
Early dt inc vasodilatation >inc .hydrostatic pressure
Late dt inc. Vasc. permeability
transudate
exudate

19. Remember Early steps in inflammation ?

20. II- Cellular events (A.Leucocyte recruitment B.Leuc. activation)
1) Margination and rolling
2) Firm adhesion
3)Transmigration
4)Chemotaxis

21. II- Cellular events A.Leucocyte recruitment B.Leuc. activation

22. 1)Margination and Rolling (Selectin)
Stasis
leucocytes accumulate at the periphery of vessels
SELECTIN (receptors expressed on leucocytes & endothelium)
Margination
SELECTIN
Rolling & transient
adhesion
 As a result of stasis, leucocytes are pushed out of the central axial column and become accumulated at the periphery of vessels. This is called margination, (Fig.3.4).
 Subsequently, leucocytes tumble on the endothelial surface, transiently sticking along the way, a process called rolling.
The weak and transient adhesions involved in rolling are mediated by the selectin family (receptors expressed on leucocytes and endothelium).

23. 2) Firm adhesion (Integrins )
Normally Integrins are expressed on leucocyte and don’t bind to their ligands
Cells at site of inflammation
cytokines(chemokines)
Activate endothelial cells to increase expression of ligands (ICAM-1 & VCAM-1) to integrins
Activate loosely adherent leucocytes
integrins
 This adhesion is mediated by integrins expressed on leucocyte cell surfaces interacting with their ligands on endothelial cells.
 Integrins are normally expressed on leucocyte membranes and do not adhere to their appropriate ligands until the leucocytes are activated by chemokines secreted by many cells at the sites of inflammation. (displayed on endothelial cell surface)
 At the same time, other cytokines, notably TNF and IL-1 (also secreted at sites of infection and injury), activate endothelial cells to increase their expression of ligands for integrins. These ligands include:
 ICAM-1 (intercellular adhesion molecule 1) and
 VCAM-1 (vascular cell adhesion molecule 1). E L
Leuc
Int
Firm adhesion

24. Chemokines 3)Transmigration (DIAPEDESIS)
Leucocytic  migration by squeezing between cells at intercellular junctions diapedesis mainly in the venules.
PECAM-1 (platelet endothelial cell adhesion molecule 1)
mediated by
Chemokines produced in extravascular tissues,
PECAM-1 expressed on leucocytes & endothelial cells
Chemokines

25. COLLAGENASES degrade vascular basement membranes
Migration in interstitial tissues toward a chemotactic stimulus
After passing through the endothelium, leucocytes cross vascular basement membranes by focally degrading them by secreted collagenases
COLLAGENASES degrade vascular basement membranes .

26. What are the steps of leucocytic recruitment?
a.Margination & rolling
b.Firm adhesion
c.Diapedesis
chemokines
a.L- selectin
b.Integrins
Stimulus activates inflamm cells either secrete preformed mediators or form new mediators at same time stimulationof the liver produce medaitors e both are differently activated according to enzymes produce other factors and mediators some have local effects eg chemoataxis or opsonization other have systemic effects as fever etc BM
& VCAM-1
d.Chemotaxis

27. Neutrophils predominate in first 6-24 hrs
Type of recruited cell depends on
Nature of stimulus
Age of inflammation
Neutrophils predominate in first 6-24 hrs
Replaced by Monocytes in hrs

28. 4)Chemotaxis directed movement of leukocytes toward
sites of infection /injury
Chemotactic agents
Exogenous
Endogenous
IL-8
Cytokines
C5a
C3a
Complement
Leukoreine B4
Arachidonic acid metabolites
Cytokines, (IL-8).
Components of the complement system, (particularly C5a and C3a).
Products of arachidonic acid metabolism, (leukotriene B4).
Soluble bacterial
products

29. Chemotactic molecules bind to specific cell surface receptors.
How does the leucocyte
recognize the chemotactic agents
Chemotactic molecules bind to specific cell surface receptors.

30. B-Leucocyte Activation By
Microbes
Products of necrotic tissue
Mediators

31. What are the functions of Leukocytes after their Activation??????????????
Phagocytosis
Destroy phagocytosed microbes and remove dead tissues.
Amplify the inflammatory reaction
Phagocytosis of particles, an early step in the elimination of harmful substances.
Production of substances that destroy phagocytosed microbes and remove dead tissues (lysosomal enzymes and reactive oxygen and nitrogen species).
Production of mediators that amplify the inflammatory reaction, including arachidonic acid metabolites and cytokines.

32. Phagocytosis a.Recognition & attachment b.Engulfment
Neutrophils & macrophages ingest bacteria & foreign particles.
a.Recognition & attachment
Opsonins
IgG ,C3b
b.Engulfment
c.Killing and Degradation
These opsonins are either present in the blood ready to coat microbes or are produced in response to the microbes.
Engulfment:
In engulfment, pseudopods are extended around the object, eventually forming a phagocytic vacuole.
The membrane of the vacuole then fuses with the membrane of a lysosomal granule, resulting in discharge of the granule's contents into the phagolysosome.

33. b-Engulfment a-Recognition &attachment c-Killing and Degradation
The complement system is a part of the immunesystem that helps or complements the ability of antibodies and phagocytic cells to clear pathogens from an organism.
c-Killing and Degradation

34. Lysosomal enzymes of neutrophils
c.Degradation
ROS
NOS
Degradation
Ros and lyosomes r most imp
Lysosomal enzymes of neutrophils

35. Inflammatory exudate Pathogenesis Composition
Increased vascular permeability
Arteriolar V.D
Increased osmotic pressure in interstitial fluid
Composition
Plasma or serum rich in fibrinogen
Neutrophils
Macrophages (tissue &blood)
Increased osmotic pressure in interstitial fluid d.t splitting of large protein molecules into smaller ones

36. Functions? Dilutes bacterial toxins
Brings antibodies to area of inflammation Agglutinins →fix bacteria Opsonins →coat bacteria to help phagocytosis Bacteriolysins→ destroy bacteria
Bacteriolysins
Contains fibrinogens changes to insoluble fibrin
network on which leucocyes moves in direction of organisms
localizes infection
localizes infection by surrounding the inflamed area
Contains leucocytes
kill the organisms

38. Role of Mediators in Different Reactions of Inflammation
Vasodilatation
↑ vascular permeability
Histamine,
prostaglandins,
nitric oxide
Histamine and serotonin, Leukotrienes C4, D4, E4
Bradykinin
Leucocyte recruitment Activation (CHEMOTAXIS)
Fever
IL-1, TNF,
prostaglandins
C3a, C5a,
Bacterial products,
Leukotriene B4, IL-1
Most mediators induce their effects by binding to specific receptors on target cells.
The actions of most mediators are tightly regulated; once activated and released from the cell, mediators quickly decay, inactivated by enzymes, eliminated or inhibited.
Tissue damage
Pain
Lysosomal enzymes
ROS
NOS
Prostaglandins
bradykinin