1. Inflammation

2. “In-flame” – to set fire Inflammation is: “dynamic response of vascularised tissue to injury” It is a protective response intended to eliminate the initial cause of cell injury as well as the resultant necrotic cells Serves to bring defense & healing mechanisms to the site of injury

3. A Roman writer Cornelius Celsius (1st century) described the first 4 cardinal signs of inflammation and Virchow described the 5th one:
Calor
Heat
Rubor
Redness
Tumor
Swelling
Dolor
Pain
Functio laesa
Loss of function

4. Inflammation is divided into :
1- Acute inflammation Short duration: few minutes to a few days Vascular changes: exudates formation Main inflammatory cells: Neutrophils (Polymorhs ) and macrophages 2-Chronic inflammation Weeks to months or years Vascular proliferation Fibrosis – Scarring Fibroblasts, Lymphocytes and macrophages 3-Subacute inflammation It grades between the acute and chronic types

5. Acute inflammation It is the immediate and early response to injury
Delivers leukocytes to sites of injury to clear any invading agents
Acute inflammation includes two events:
1-Vascular events
2-Cellular events

6. 1-Vascular events: A- Changes in vascular caliber and flow:
Start very quickly after injury
The changes occur in the following order:
1- Transient vasoconstriction of arterioles:
- It is an inconstant finding
- Disappears within 3 to 5 seconds

7. 2- Vasodilation is the fundamental event:
First involves the arterioles and then the capillary beds in the area resulting in increase blood flow
This vascular expansion is the cause of the redness (erythema) and heat

8. 3- Slowing of the circulation:
Microvasculature becomes more permeable causing the escape of protein-rich fluid into the extravascular tissues
This concentrates red blood cells and in turn slowing the circulation.
These changes are reflected microscopically by dilated vessels packed with red blood cells,this process is called stasis
4- After stasis occurs, leukocytes (Neutrophils) migrate to the extracellular tissues

9. B- Change in vascular permeability
In the earliest phase of inflammation:
The arteriolar vasodilation and increased blood flow cause an increase in intravascular hydrostatic pressure and the movement of fluid from capillaries. This fluid is called “transudate”
Soon the transudate is overshadowed by increasing vascular permeability that allows the movement of protein-rich fluid and cells into the interstitial space. This fluid is called “exudate”

10. Differences between transudate and exudate
1-Over shadows transudation phase of Inflammation. 2-Results from vascular permeability. 3-Protein –rich (2-4 gm%) 4-High specific gravity. 5-Are present.
1-Found in early phase of inflammation. 2-Results from intravascular hydrostatic pressure. 3-Protein-poor (< 2 gm%) 4-Low specific gravity. 5-Neutrophils and fibrinogen are absent.

11. The loss of protein-rich fluid into the extracellular tissues reduces the intravascular osmotic pressure and increases the osmotic pressure of the interstitial fluid
The net result is outflow of water and ions into the extravascular tissues. This fluid accumulation is called oedema

12. 2- Adhesion & transmigration between endothelial cells
2-Cellular events
The events of extravasation of leukocytes from vascular lumen are divided into :
1- Margination & rolling
2- Adhesion & transmigration between endothelial cells
3- Emigration towards chemotactic stimulus
4-Phagocytosis and degranulation

13. 1- Margination & rolling
Leukocytes are pushed out of the central axial column (where they normally flow)
The process of leukocyte accumulation at periphery of vessels is called margination
Leukocytes transiently stick along the way, a process called rolling.

14. The loose & transient adhesions involved in rolling are mediated by the selectin family members
Selectins include:
E-selectin : Expressed in endothelium
L-selectin : Expressed on most leukocytes
P-selectin : Expressed in endothelium & platelets

15. 2- Adhesion and transmigration
Adhesion: Leukocytes firmly stick to endothelial surfaces
Adhesion is mediated by molecules of Ig superfamily on endothelial cells that bind to integrins expressed on leukocytes
Transmigration (Diapedesis): Leukocytes crawl between endothelial cells and through the basement membrane into extravascular space. This is mediated by a cell-cell adhesion molecule called platelet endothelial cell adhesion molecule 1 (PECAM-1)

17. Neutrophils are predominant in acute inflammation for the first 6-24hrs and then undergo apoptosis.
In extravascular tissue, neutrophils are replaced by monocytes as they live longer than neutrophils and they persist for long periods as tissue macrophages

18. 3- Emigration: Chemotaxis and activation
Chemotaxis: The directional movement of leukocytes toward sites of injury under the guidance of specific chemicals (chemotactics)
Many exogenous and endogenous substances act as chemotactic for leukocytes including:
- soluble bacterial products
- components of the complement system (C5a)
- products of the lipoxygenase pathway of arachidonic acid metabolism
- cytokines

19. 4- Phagocytosis and degranulation
Phagocytosis consists of three steps:
1- Recognition and attachment of the particle to the leukocyte
2- Engulfment and phagocytic vacuoles formation
3- Killing and degradation of the ingested material

20. 1- Recognition and attachment
This process is facilitated by serum proteins called Opsonins.
Opsonins bind to specific receptors on microbial surface and that in turn enhance binding with opsonins receptors on leukocytes.
Opsonins include:
- IgG (Fc portion)
- C3b fragment of complement

21. 3- Killing and degradation
2- Engulfment
Binding of opsonized particles to leukocyte surface triggers engulfment.
In engulfment, pseudopods are extended around the binding microbe forming a phagocytic vacuole .
3- Killing and degradation
Microbial killing is achieved by the action of reactive oxygen species .

22. Morphologic patterns of inflammation
1- Serous inflammation
Characterised by serous exudates (watery)
Examples : some viral infections (vesicles of herpes simplex) and burn forming skin blister.

23. 2- Fibrinous inflammation:
Follows severe injuries with greater vascular permeability.
High-protein exudates rich with fibrin.
e .g. Fibrinous pericarditis and pnenmonia.

24. 3- Suppurative (purulent) inflammation:
Large amount of purulent exudate (pus) consisting of: neutrophils, necrotic cells, and edema
Caused by pyogenic bacteria
Types of suppurative inflammation:
1- Focal: Abscess, Furuncle (Boil), Carbuncle
2- Diffuse: Cellulitis, Suppurative appendicitis…others

25. Dilated vessels & fibroblasts
Abscess
It is the focal collection of pus.
Central necrotic area
Neutrophils
Dilated vessels & fibroblasts

26. Carbuncle Furuncle (Boil)
It is small abscess related to hair follicle, sebaceous or sweat gland
Carbuncle
Mainly common in diabetic patients.
is an abscess formed of multiple suppurative foci in the skin and soft connective tissue and discharging pus through several openings

27. Cellulitis Is the diffuse type of suppurative inflammation of
connective or soft tissue .

28. 4- Haemorrhagic inflammation:
More blood vessel destruction leading to escaping of RBCs to interstitial spaces.
Common in pneumonia.
5- Catarrhal inflammation:
Occurs when mucous membranes are inflamed.
Common in upper respiratory tract viral infections, as a common cold

29. 6- Membranous and pseudomembranous inflammation:
The formed membrane consists of fibrin, dead epithelial cells and neutrophils
Caused by bacteria that grow on the surface of mucous membranes and produce exotoxins as in diphtheria and bacillary dysentery

30. 7- Ulceration:
Ulcer is a local (discontinuity) defect in an epithelial surface caused by the shedding of dead epithelial cells.
Common in epithelial surfaces: skin, gastric epithelium, colonic mucosa…others

31. sinus
Sinus
it is an abnormal passage leading from a suppurating cavity to the body surface.
Fistula
it is an abnormal tract connecting two cavities or between the hollow viscera and the surface.
Fistula
Hollow organ

32. Some important chemical mediators
Histamine and serotonine
Function
1) Arteriolar dilation
2) Increased vascular permeability
Soon after its release, histamine is inactivated by histaminase

33. Hageman factor (Factor XII)
Activation of:
Clotting system
Kinin system:
- Fibrinolytic system
- Complement system

34. Kinin system activation
Bradykinin function:
- Increase vascular permeability
- Arteriolar dilation
- Bronchial smooth muscle contraction
- Causes pain

35. Clotting system activation

36. Fibrinolytic system activation

37. Important functions of generated complement components:
1- Vascular effects:
C3a and C5a (also called anaphylatoxins) increase vascular permeability and induce histamine release resulting in vasodilation

38. 2- Leukocyte activation, adhesion and chemotaxis:
C5a activates leukocytes and increases the affinity of their adhesion to endothelium
C5a acts as a potent chemotactic for neutrophils,
3- Phagocytosis:
C3b and C3bi act as opsonins and induce phagocytosis

39. Outcomes of acute inflammation
1- Resolution, occurs when the injury is limited
2- Scarring or fibrosis, occurs when the injury is massive or when inflammation occurs in tissues that do not regenerate
3- Progression to chronic inflammation

40. Dr/Mona kamal
Thank you