1. INFLAMMATION
DR: AFAF ElNASHAR

2. INFLAMMATION Definition :
Inflammation is a reaction of the living tissue to injury, it represents a protective response aimed at disposal of the initial cause of injury.
It is characterized by vascular changes resulting in formation of fluid and cellular exudates and cellular changes.

3. INJURIOUS AGENTS:
Infectious living irritants: bacteria, viruses, fungi, parasite,
Physical agents: heat, sun ray, hot, radiation.
Trauma
Chemical agents: acids, alkali, poisons, drugs.
Immunological process:

4. CLASSIFICATION OF INFLAMMATION
ACUTE → SUPPURATIVE
NON SUPPURATIVE
Acute inflammation is rapid, lasts for days to few weeks, and polymorphes are predominant.
SUBACUTE: lasts between weeks to A month,
CHRONIC → SPECIFIC
NON SPECIFIC
Chronic inflammation is slowly, takes weeks to months, plasma cells, lymphocytes and fibrosis are predominant.

5. ACUTE INFLAMMATION
Local changes occurs at the site of irritant tissue: →local tissue damage and release of chemical mediators → inflammatory response
It includes:
Vascular phase: → formation of inflammatory fluid exudate
Cellular phase:→ formation of inflammatory cellular exudate

6. 1- Local tissue damage where the central cells are dead (necrosis), surrounded by degenerated cells that liberate chemical mediators.
2- Local vascular changes:
Transient vasoconstriction.
Dilation of the blood vessels due to the direct effect of the chemical mediator (histamine) and local axon reflex→↑blood flow to the site of injury→ hyperemia

8. Slowing of the blood flow(stasis)
It is due to:
1- formation of fluid exudates → ↑ viscosity of the blood
2- effect of histamine (endothelial contraction)→ slowing of blood flow →↑ vascular permeability → ↑ viscosity of the blood
3- Dilation of the capillaries will distribute the blood in large number of B.vs.

10. INFLAMMATOY FLUID EXUDATE
Inflammatory fluid exudate is a high protein content serous fluid, rich in fibrinogen and plasma proteins, Specific gravity is more than 1018, turbid and clots on standing.
Formation of inflammatory fluid exudate: due to several factors : 1- ↑ vascular permeability due to
( endothelial contraction or damage).
2- ↑capillary hydrostatic pressure due to vasodilation and ↑ blood flow.
3- ↑ osmotic pressure of the interstitial tissue (due to tissue necrosis)

11. INFLAMMATORY FLUID EXUDATE
FUNCTION OF THE FLUID EXUDATE:
1- Dilute the toxins, chemical poison and enzymes at the site of inflammation so ↓ its effect
2-Brings AB, and chemical mediators from the blood to the site of injury
3-Supply nutrients for the inflammatory cells and drives the waste products away from the site of injury.
FATE OF INFLAMMATORY FLUID EXUDATE:
drained by lymphatic to the regional lymph node
If it carries microorganism, it reach the LN → lymphangitis and lymphadenitis.
It may reach blood → septicemia, bacteremia and toxemia

12. INFLAMMATORY CELLULAR EXUDATE
1- Margination (pavement) of the polymorphes on the endothelial lining as a result of hemostasis.
His process is achieved by adhesion molecules on both the polymorphes and the endothelial cells
2- Emigration of polymorphes between the endothelial cells through the inter-endothelial spaces leaving the blood vessels to the interstitial tissue followed by RBs and monocytes.
3- Chemotaxis: is the directed movement of the polymorphes towards the site of injury by the effect of chemotactic factors (bacterial products, complements, lymphokines, and polymorphes cell components.

13. How are leukocytes induced to adhere?
Redistribution of the receptors
Cytokine induction of the receptors
Increased avidity of

14. INFLAMMATORY CELLULAR EXUDATE
TYPES OF CELLS IN ACUTE INFLAMMATION
Polymorph nuclear leucocytes (neutrophils)
Macrophages
Activation of phagocytic cells: by the effect of chemical mediators released at the site of injury → 1- ↑ receptors on the surface of the cells (adhesion receptors).
2- activation of contractile actin and myosin → ↑ mobility of the cells.
3-activation of oxidative burst → release of reactive oxygen species

15. Steps in neutrophil extravasation, 1

16. Steps of neutrophil extravasation, 2

18. 4- Phagocytosis: it is the process of recognition and engulfing of the bacterial parts by polymorphes
It occurred by coating the bacteria by opsonin (immunoglobuline and complements factors).
Phagocytic cells recognized the opsonized bacteria and engulf it by the pseudopodia and formation of phagosome that fused with lysosomal granules leads to release of the proteolytic enzymes ( powerful bacetricidal effect)( formation of reactive oxygen species as oxygen peroxide and superoxide) that degradate the bacterial particles.

20. Neutrophil: lysosomal granules
Smaller, dump into phagocytic vacuoles within cell but also easily release contents extracellularly
Larger, dump granule contents primarily into phagocytic vacuoles within cell

21. CHEMICAL MEDIATORS cell Cell-derived chemical mediators
Mast cells, basophiles, platelets
histamine
vasoactive amines
Argentaffin cells, platelets
serotonine
prostaglandin
Arachedonic acid metabolites
neutrophiles
leukotreins
Activated lymphocytes
Lymphokines ( interferon) IL-2
cytokines
monocytes
Monokines (TNF), IL-1
Neutrophiles, macrophages
Lysosomal enzymes
platelets
Platelet-activating factor
Kinin, complements, clotting system, fibrinolytic system
Plasma factors
Bacterial products

22. 2 Major cytokines of inflammation
Cytokine effects may be:
1) On the same cell that produces them:
2) On cells in nearby vicinity:
3) systemic:

24. Systemic symptoms fever (irritation of thermoregulatory centre)
TNF, IL-1
IL-6 – high RBCs sedimentation rate (via fibrinogen)
leukocytosis - increased WBCs number
bacteria – neutrophils
parasites – eosinophils
viruses - lymphocytosis
leukopenia - decreased WBCs number
viral infections, salmonella infections, rickettsioses
immunologic reactions – “acute phase reactants“
C-reactive protein, complement, fibrinogen, ...

25. Outcomes of acute inflammation
1. resolution - restoration to normal, in limited injury
chemical substances neutralization
normalization of vascular permeability
apoptosis of inflammatory cells
increased lymphatic drainage
2. healing by granulation tissue / fibrous scar
tissue destruction
fibrinous inflammation  adhesions, fibrosis
purulent inflammation  abscess formation (pus, pyogenic membrane, resorption - pseudoxanthoma cells - weeks to months)
3. progression into chronic inflammation

26. TYPES OF ACUTE INFLAMMATION
Non suppurative
Suppurative
Catarrhale
Localized
Membranous
Diffuse
Serous
Serofibrinous
Fibrinous
Hemorrhagic
Necrotizing
Allergic

28. Acute suppurative inflammation
Definition: sever acute inflammation characterized by pus formation, caused by staph aureus, strept hemolyticus, gonococci and pneumococci.
Staph infection.....tissue necrosis.....dead neutrophiles (pus cells)...release of proteolytic enzymes .....liquefactive necrosis..... Pus formation
composition of pus: (pus cells, liquefied necrotic tissue, bacteria, inflammatory cells and exudate)

29. Types of suppurative inflammation
Localized: abscess, carbuncle, furuncle
Diffuse: cellulitis, appendicitis, peritonitis.
Abscess:A localized suppurative inflammation caused by staph result in a small cavity filled with pus. The common site is the subcutaneous tissue but it can occurred in any site. It is composed of central necrotic tissue surrounded by inflammatory cells healing by evacuation and granulation tissue.

30. Complications of abscess:
spread (lymphatic to regional LN, blood spread.... Bacteremia, pyemia,
inadequate drainage... chronic abscess
Complicated healing..keloid, fistula, sinus, ulcer.

31. Furuncle: a small abscess related to hair follicels
Furuncle: a small abscess related to hair follicels. Common at the face and the neck.
Carbuncle: a localized suppuration in the subcutenous tissue that form multiple communicating foci in the subcutaneous tissue that opened in through several openings. The sites are the back, scalp. It is due to the dense fibrous tissue septa extended from the deep fascia to the dermis.

32. Cellulitis: acute diffuse suppurative inflammation
It is due to fibrinolysine and hyaluronidase......leads to failure to localization of the suppuration

33. Non suppurative inflammation
Catarrhal inflammation: acute inflammation of the mucus membranes.....excess mucus production
Rhinitis, bronchitis.
Hemorrhagic inflammation: produce fluid exudate rich in RBCs
(due to vascular damage) small box.
Necrotizing inflammation: produce excess necrotic tissue
Allergic inflammation

34. Serofibrinous: acute inflammation characterized by production of excess fluid exudate rich in fibrinogen ( serous membranes , pleura, pericardium, peritoneum)
Fibrinous inflammation: produced exudate rich in fibrinogen (pneumonia).
Serofibrinous: acute inflammation characterized by production of excess fluid exudate rich in fibrinogen ( serous membranes , pleura, pericardium, peritoneum)
Fibrinous inflammation: produced exudate rich in fibrinogen (pneumonia).
Serous inflammation: acute inflammation with production of excess serous fluid (burn, viral infection)
Serofibrinous: acute inflammation characterized by production of excess fluid exudate rich in fibrinogen ( serous membranes , pleura, pericardium, peritoneum)
Fibrinous inflammation: produced exudate rich in fibrinogen (pneumonia).

35. Membranous inflammation:
acute inflammation characterized by a membrane formation (diphtheria and bacillary dysentry.The organism settled on the mucosa produce exotoxins....mucosal necrosis (pseudo membrane formation).....diffuse of the exotoxin to the blood....sever toxemia.

36. Chronic Inflammation
Definition: inflammation of prolonged duration (weeks-months-years) in which active inflammation, tissue destruction, and tissue repair are simultaneously present.
Clinical settings of chronic inflammation:
Persistent infections (eg, M. tuberculosis)
Prolonged exposure to toxins (silicosis)
Autoimmunity (rheumatoid arthritis)
Neoplasia

37. Activation of Macrophages
Activated CD4 Th1cell
RESULT:
RESULT:

38. Histopathology of chronic inflammation
Mononuclear cell infiltration (3 cell types):
Tissue destruction with replacement of damaged tissue by well-vascularized young fibrous tissue
Biopsy temporal artery, H&E

39. chronic
Acute
Longe duration
mild
Short
sever
Duration and severity
Started as chronic or
followed acute
Started as acute
start
Mild ( forigen body)
Sever (microorganism)
Organism or irritant
Lymphocytes, plasma cells, macrophages
polymorphes
Inflammatory cells
Little
progressive
Prominant
Inflammatory exudate
Tissue necrosis
fibrosis
Granulation tissue
healing

40. Granulomatous inflammation
1. Bacteria
TBC
leprosy
syphilis (3rd stage - gumma)
2. Parasites + Fungi
3. Inorganic metals or dust
silicosis
berylliosis
4. Foreign body
suture (Schloffer “tumor“), breast prosthesis, vascular graft
5. Unknown
– sarcoidosis, Wegener´s granulomatosis, Crohn disease

41. Morphologic type of granuloma 2
Immune granulomas: :incited by poorly soluble particles which induce cell-mediated immune response involving activated macrophages processing and presenting Ag to T-lymphocytes
: formed by fusion of activated macrophages; showing peripheral wreath-like arrangement of multiple nuclei
+ central necrosis: