Inflammation PDF

INFLAMMATION Inflammation  Definition: Inflammation is a response of vascularised living tissues to injury. Inflammation is a protective response. The ultimate goal of inflammation is to get rid of the injurious agent  Classification: Inflammation is classified into : acute and chronic. Acu...

INFLAMMATION Inflammation  Definition: Inflammation is a response of vascularised living tissues to injury. Inflammation is a protective response. The ultimate goal of inflammation is to get rid of the injurious agent  Classification: Inflammation is classified into : acute and chronic. Acute inflammation is rapid in onset and of short duration (a few minutes to hours). Chronic inflammation follows acute inflammation, or may be insidious in onset. It lasts for a longer duration.  Signs of inflammation 1. Rubor – redness 2. Calor – heat 3. Dolor –pain 4. Tumor –swelling 5. Functio laesa – loss of function ACUTE INFLAMMATION Triggers of acute inflammation: 1. Infections (bacterial, viral and parasitic) and microbial toxins. 2. Trauma 3. Physical and chemical agents 4. Foreign bodies 5. Immune reactions 6. Tissue necrosis Changes in inflammation Inflammation is a complex process that includes  1. Vascular changes  2. Cellular changes Vascular changes: This can be studied under two subheadings:  1. Changes in vascular flow and caliber.  2. Increased vascular permeability Changes in inflammation Changes in vascular flow and caliber: The initial response of arterioles to an injurious stimulus is vasoconstriction. This lasts for a few seconds. This is followed by vasodilatation, with increase in the blood flow.  The increase in blood flow causes: redness (hyperemia), mild swelling and increase in temperature. Vascular changes (Contd)  This forces fluid through the vessel wall into the tissues. This fluid is called the transudate.  This is followed by increased permeability of vessel wall permitting the movement of protein rich fluid as well as cells into the interstitium. This fluid is called an exudate. Vascular changes (Contd) Increased vascular permeability: This is brought about by 3 mechanisms: i. Contraction of endothelial cells resulting in increased inter-endothelial spaces ii. Endothelial injury resulting in endothelial cell necrosis and detachment iii. Transcytosis – increased transport of fluids and proteins through the endothelial cells. Cellular changes  Rouleaux formation: special arrangement of RBCs, caused by the slow blood flow in the dilated capillaries & venules.  Margination The movement of WBCs towards the periphery closer to the endothelium of the vessels.  Pavementing. Attachement of WBCs to the endothelium by adhesion molecules.  Diapedesis The attached leukocytes then insert pseudopods between the endothelial cells.. They finally reach the extravascular space.  Chemotaxis The leukocytes then migrate in the extracellular space towards a chemotactic stimulus. Cellular changes Chemotaxis The emigration of the extravasated leukocytes towards the site of injury is called chemotaxis. This movement is oriented along a chemical gradient. The substances towards which the leukocytes move are called chemoattractants. Chemoattractants are of 2 types: 1. Exogenous Eg.: bacterial products 2. Endogenous Eg.: complement proteins (C5a), leukotrienes and cytokines. Phagocytosis Phagocytosis is described in 3 steps 1. Recognition and attachment: major opsonins are IgG antibodies, the C3b 2. Engulfment: the leukocytes produces pseudopods around the particle to be engulfed 3. Killing and degradation  Cells in inflammation  The nature of leucocyte infiltrate varies with the duration.  During the first 6 – 24 hours, neutrophils predominate. They are short-lived & disappear after 24 – 48 hours.  Within this time, neutrophils are replaced by monocytes. They survive longer and proliferate in the tissues. Therefore, monocytes predominate in chronic inflammation Killing and degradation Oxygen independent mechanisms which are responsible for microbial killing include, Bactericidal permeability increasing protein(BPI) Lysozyme Lactoferrin Defensins Major Basic Protein (MBP) Chemical mediators  Plasma-derived: ◦ Complement, kinins, coagulation factors ◦ Many in “pro-form” requiring activation (enzymatic cleavage)  Cell-derived: ◦ Preformed, sequestered and released (mast cell histamine) ◦ Synthesized as needed (prostaglandin) Outcomes of acute inflammation Acute inflammation has 1 of 4 outcomes: 1. Abscess formation (Necrotic tissue surrounded by inflammatory cell and exudative fluid) 2. Progression to chronic inflammation 3. Resolution: tissue goes back to normal 4. Repair: healing by scarring or fibrosis 19  Chronic Inflammation Inflammation of: 1. Prolonged duration (weeks or months) 2. Accompanied by tissue destruction 3. And repair by fibrosis [healing and repair] proceeding simultaneously. Causes of Chronic Inflammation 1. As a progression from acute inflammation 2. Persistent Infection : ex: Treponema pallidum 3. Prolonged exposure to the toxic agents 4. Autoimmunity HISTOLOGIC FEATURES Cells of chronic inflammation: mononuclear cells 1. Lymphocytes 2. Macrophages 3. Plasma cells MORPHOLOGIC FEATURES 1. Tissue destruction: induced by the persistent offending agent or by the inflammatory cells. 2. Attempts at healing by connective tissue replacement of damaged tissue, accomplished by angiogenesis and fibrosis Tissue Macrophages A. Kupffer cells – LIVER B. Alveolar macrophages – LUNG C. Sinus Histiocytes – CONNECTIVE TISSUE D. Fixed and free macrophages – SPLEEN &LYMPH NODES E. Microglial cells – NERVOUS SYSTEM F. Osteoclasts – BONE G. Langerhans' cells – SKIN H. Dendritic cells – LYMPHOID TISSUE Chronic Cervicitis: note Chronic cholecystitis - Gall lymphocytes forming bladder with thickened wall due to Lymphoid follicles fibrosis  Possible Outcomes of Chronic Inflammation 1- Scarring  Fibrosis of the area of injury visible clinically.  Fibrosis is mediated by various growth factors secreted by macrophages. 2-Granulomatous Inflammation  Granulomatous inflammation: is a histologically distinctive form of chronic inflammation  Feature: GRANULOMA ◦ Granulomas are aggregates of macrophages, (epithelioid cells,) in response to chronic inflammation ,usually with a surrounding zone of lymphocytes and fibrosis. To eliminate infectious organisms or foreign bodies.It may have a central area of caseation ( example : tuberculosis ).  Fibrous peritoneal adhesions following peritonitis 25 Fibrosis around the A typical tuberculous Granuloma Granuloma : Langhans giant cells WOUND HEALING  WOUND HEALING  Healing of skin wounds provides a classical example of combination of regeneration and repair.  Wound healing can be accomplished in one of the following two ways: 1- Healing by first intention (primary union) 2- Healing by second intention (secondary union). 28 HEALING BY PRIMARY INTENTION  When the injury involves only the epithelial layer, the principal mechanism of repair is epithelial regeneration.  Example: healing of sterile surgical wounds.  The wound has the following characteristics:  clean and uninfected;  surgically incised;  without much loss of cells and tissues  edges of wound are approximated by surgical sutures. The sequence of events in primary union : 1. Initial haemorrhage. Immediately after injury 2. Acute inflammatory response. This occurs within 24 hours 3. Epithelial changes. The basal cells of epidermis from both the cut margins start proliferating and migrating towards incisional space 4. Organisation. By 3rd day, fibroblasts also invade the wound area. 5. Suture tracks. When sutures are removed around 7th day, much of epithelialised suture track is avulsed and the remaining epithelial tissue in the track is absorbed. However, sometimes the suture track gets infected HEALING BY SECONDARY INTENTION  When cell or tissue loss is more extensive, such as in large wounds, abscesses, ulceration, and ischemic necrosis (infarction) in parenchymal organs, the repair process involves a combination of regeneration and scarring.  Example: healing of large wounds and all infected wounds.  The wound have the following characteristics:  Open with a large tissue defect  Infected  Having extensive loss of cells and tissues  The wound is not approximated by surgical sutures but is left open The sequence of events in secondary union : 1. Initial haemorrhage. 2. Inflammatory phase. 3. Epithelial changes. 4. Granulation tissue. 5. formed by proliferation of fibroblasts and neovascularisation 6. Wound contraction.  Contraction of wound is an important feature of secondary healing, not seen in primary healing. Due to the action of myofibroblasts present in granulation tissue, the wound contracts to one-third to one fourth of its original size. 6. Presence of infection. Bacterial contamination of an open wound delays the process of healing due to release of bacterial toxins that provoke necrosis, suppuration and thrombosis. Surgical removal of dead and necrosed tissue, debridement, helps in preventing the bacterial infection of open wounds.  HEALING BY SECOND INTENTION HEALING OF SKIN ULCERS Factors Affecting Wound Healing  Local factors: 1. Site of wound: skin wounds heal better than wounds occurring in the internal organs. 2. Mechanical factors: wounds at joint heal slowly if the area is not kept immobile. 3. Size of wound: small wounds heal faster than the large wounds. 4. Sterile wounds heal faster than the infected wounds. Factors Affecting Wound Healing  Systemic factors: 1. Diabetes mellitus: delays wound healing secondary to diabetic microangiopathy. 2. Malnutrition and vitamin C deficiency: delays wound healing. 3. Inadequate blood supply 4. Glucocorticoids: anti – inflammatory and inhibit collagen synthesis. Complications of Wound Healing: 1. Infection of wound due to entry of bacteria delays the healing. 2. Implantation (epidermal) cyst formation may occur due to persistence of epithelial cells in the wound after healing. 3..Pigmentation. Healed wounds may at times have rust-like colour due to staining with haemosiderin. 4. Wound Dehiscence: due to deficient scar This is especially seen in diabetics and patients on corticosteroid treatment. 5. Keloid formation & hypertrophic scars: due to excessive scar formation resulting from excessive scarring and defective remodeling. 6. Formation of contractures: result from large scars.Contractures over the joint results in immobility. THANK YOU