INFLAMMATION DR: AFAF ElNASHAR

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.

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:

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.

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

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

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.

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)

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

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.

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

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

Steps in neutrophil extravasation, 1

Steps of neutrophil extravasation, 2

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.

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

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

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:

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, ...

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

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

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)

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.

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

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.

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

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

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).

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.

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

Activation of Macrophages Activated CD4 Th1cell RESULT: RESULT:

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

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

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

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: