Inflammation PDF

Prof Noha ElKady Professor pathology department Faculty of Medicine Objectives  Define inflammation  Differentiate between acute and chronic inflammation  Recognize the steps of extravasation of inflammatory cells  Recognize the process of chemotaxis and phagocytosis...

Prof Noha ElKady Professor pathology department Faculty of Medicine Objectives  Define inflammation  Differentiate between acute and chronic inflammation  Recognize the steps of extravasation of inflammatory cells  Recognize the process of chemotaxis and phagocytosis  Identify different examples of inflammation  Definition Local vascular and cellular response of living tissue against an injurious agent Aims of inflammation Fighting bacteria Localize infection Removal of damaged tissue Causes of inflammation Types of inflammation 1- Acute 2- Chronic  Cells in acute and chronic inflammation  Neutrophils: phagocytosis, pus cells  Lymphocytes: chronic  Plasma: chronic  Histiocytes: Chronic phagocytosis, monocytes  Eosinophils: allergy, parasitic  Mast cells: allergy (histamine, serotonine)  Giant cells: phagocytosis, histiocytes,  Acute & Chronic Inflammation Features Acute Chronic Onset Fast: minutes to hours Slow; days Cellular infiltrate Neutrophils mainly Monocytes/macrophages & Lymphocytes Tissue injury, fibrosis Usually mild and self Often severe and limited progressive Local & Systemic signs Prominent Less prominent Local signs of Inflammation The main events of inflammation 1- vascular response 2- inflammatory fluid exudate 3- inflammatory cellular exudate 1) Vascular Response  (1)Changes in Vascular Flow and Caliber  Vasodilatation (histamine)  Stasis (+ viscosity, swollen end.,open capillaries) 2) INCREASED PERMEABILITY and formation of fluid exudate  Histamine, Kinine  Endothelial “gaps”  Direct endothelial Injury 2)Inflammatory fluid exudate  Formation:  1-VD, +Permeability  2- + interstitial osmotic  3- -hydrostatic  Function:  Dilute toxin, chemical, poison  Bring antibodies  Supply nutrition for cells remove toxins  Supply fibrinogen ( localization, movement of inflammatory cells and fibroblasts  Composition of Exudate Appearance: Turbid Consistency: Viscous (like pus) Protein content: high 4-8 gm Specific gravity: high above 1018 Cell content: numerous neutrophilis On standing: clots 3) Cellular exudate EXTRAVASATION of neutrophils  MARGINATION (PMN’s go toward wall)  ROLLING (tumbling and EAPING)  (selectine-glycoprotein)  ADHESION (integrine-Ig)  TRANSMIGRATION (DIAPEDESIS)(PCAM)  Chemotaxis Definition: Is the directed movement of neutrophilis and macrophages in the area of inflammation towards the irritant depending on 1- exogenous bacteria product 2- endogenous mediators as complement, arachidonic acid metabolites and chemokines. Those lead to polimerization of actin and facilitation of movement LEUKOCYTE “ACTIVATION”  “triggered” by the offending stimuli for PMNs to: 1) Produce eicosanoids 2) Undergo DEGRANULATION 3) Secrete CYTOKINES  Phagocytosis Major benefit Definition: is the ingestion and destruction of bacteria, necrotic debris and foreign particles by the phagocytic inflammatory cells. Phagocytes Neutrophilis Macrophages 1- Recognition Opsonin(Ig, complement) 2- Engulfment 3- Killing and degradation (Oxidative and non-oxidative) Chemical MEDIATORS  Cellular  Plasma  HISTAMINE  COMPLEMENT  SEROTONIN  KININS  EICOSANOIDS  CLOTTING FACTORS  NITRIC OXIDE  Fibrinolytic  PLATELET ACTIVATING FACTOR (PAF)  Resolution Outcome of acute Regression & Healing inflammation Progression & spread Progression & Chronicity Summary of SEQUENCE OF EVENTS  VASODILATATION   INCREASED VASCULAR PERMEABILITY   LEAKAGE OF EXUDATE, stasis   Extravasation, MARGINATION, ROLLING, ADHESION, TRANSMIGRATION (DIAPEDESIS)   CHEMOTAXIS   PMN ACTIVATION   PHAGOCYTOSIS: Recognition,(Attachment), Engulfment, Killing (degradation or digestion)   TERMINATION 100% RESOLUTION, SCAR, or CHRONIC INFLAMMATION are the three possible outcomes  Types of acute inflammation acute inflammation Suppurative Non-Suppurative  Types of Acute Suppurative inflammation Suppurative inflammation Localised Diffuse Abscess Furuncle Carbuncle Cellulitis Characters and composition of pus  Non-coagulable creamy alkaline yellowish or yellow green fluid formed of:  1- fluid exudate without fibrin  2- pus cells, PNL, macropheges, RBCs  3- Liquified necrotic tissue  4- Bacteria and pigment  Abscess  Definition Localized suppurative acute inflammation  Cause Staph----Excess fibrin  Site: Skin, organs  Microscopically:  1-Central zone of necrotic tissue and dead neutrophils.b.  2-Peripheral zone of inflamed tissue.  3- granulation tissue---fibrosis  Clinical red, hot, swollen, Pus  Fate: Heal, complications  PUS = PURULENT ABSCESS = POCKET OF PUS PURULENT, FIBRINOPURULENT Boil-Furuncle  Small abscess related to hair follicle or sebaceous gland Carbuncle multiple communicating abscess Risk: Diabetics Site: back of neck Diffuse suppurative Inflammation  Causative organism:streptococcus haemolyticus producing  Enzyme 1-fibrinolysin, hyalouronidase and 2-spreading factor  Examples:  Cellulitis  Appendicitis  Peritonitis  Abscess Cellulitis Def Localized suppurative Diffuse suppurative examination examination Causative organism Staph Strept Mechanism Excess fibrin fibrinolysin, hyalouronidase andspreading factor Site Any tissue Loose tissue Pus Thick yellow Thin sangonous Spread Less More common Types of Acute Non-Suppurative inflammation necrotizing Haemohrragic serous Non- Allergic Suppurative Fbrinous Membranous serofibrinous Catarrhal Types of Acute Non-Suppurative inflammation Catarrhal inflammation: Rhinitis, excess mucous Serous inflammation: Pleuritis, Excess watery fluid exudate Pseudoembranous: Diphteria, Fibrin patches Chronic inflammation CAUSES of CHRONIC INFLAMMATION 1) PERSISTENCE of Infection 2) PROLONGED EXPOSURE to insult Types Non-specific: follow acute Specific: granuloma GRANULOMAS  Def: Chronic specific inflammation with nodular collection of epitheliod cells , lymphocytes and giant cells  Etiology Infective Bacteria: TB, Leprosy, Syphilis Parasitic: Bilh, Leishmania Fungi: Madura foot Non-infective Selecosis, FB Unknown Chrons, Sarcoidosis Components of Granuloma  4 COMPONENTS  HISTIOS, epitheliod cells (main component)  “GIANT” CELLS Langhan’s FB  LYMPHS  FIBROBLASTS  Classification (types)of GRANULOMAS 1. Granuloma with caseation: TB 2. Granuloma without caseation: Sarcoidosis, Chron’s, BILH, Selicosis 3. Suppurative granuloma: Cat scrach disease,Lymphgranuloma 4. Foreign body granuloma: thread, silicon implant  Langhans giant cell Foreign body giant cell - Definition of cell injury - Causes of cell injury -Types of cell injury:  Cell injury Definition: A sequence of events ( biochemical & morphologic) upon exposure of the cell to injurious agent injurious agents Morphologic Biochemical changes Changes Causes of cell injury  Effects of cell injury Injurious agents Severity & duration of Cell Effect of injurious vulnerability cell injury agent Adaptation Injury  Effects of cell injury Injurious agents Minor More severe Injury injury Adaptation Injury In ability to adapt Hyperplasia Hypertrophy Metaplasia Effects of cell injury  Types of cell injury Cell death Cellular swelling t Fatty change  Types of cell injury Reversible cell injury Irreversible cell injury (Degeneration) (Cell Death) Severity of injurious Mild injury Severe injury agent Duration of injurious Short duration. Long duration. agent Includes a) Cellular swelling a) Necrosis (cloudy swelling and b) Apoptosis hydropic swelling). b) Fatty change  Reversible cell injury Accumulation t Reversible cell injury Reversible cell injury Characterized by accumulation of Small amount water in the cells Causing cellular swelling  Reversible cell injury Organs affected & microscopic picture : 1- Size: cell swelling Liver 2- Cytoplasm: fine granules Kidney Heart  Reversible cell injury Liver No significant Clinical Picture: Kidney change Proteinuria Heart Dilatation  Reversible cell injury Fate:  Reversible cell injury large Injurious agents Persistence of Injurious agents  Reversible cell injury Organs affected & microscopic picture : 1- Size: cell swelling 2- Cytoplasm: Lage clear vacuoles Liver Skin Kidney Viral hepatitis Viral Infection Renal tubule Allergic, Burns epithelium  Reversible cell injury Definition: Reversible cell injury characterized by pathological accumulation of excess fat in parenchymatous cells. Sites: most commonly affect liver. It also affect heart, kidney & muscles Injurious agents  Reversible cell injury Causes: Excess fat in diet Viral hepatitis Reversible cell injury the cytoplasm of Signet ring shape A- Degeneration means: a. Irreversible cell injury c- Abnormal cell injury b. Reversible cell injury d- Necrosis of the cells B-Liver cells with fat accumulation showed: a. Signet ring appearance c- Moth eaten appearance b. Spindle nuclei d-Inclusion bodies Definition: - Types of irreversible cell injury - Pathologic basis of apoptosis - Pathologic basis of necrosis - Types of necrosis  Types of cell injury Cell death Cellular swelling t Fatty change Irreversible cell injury  Irreversible cell injury Red blood cells Irreversible cell injury Decreases size of tissues  Irreversible cell injury Microscopic picture:  Irreversible cell injury Definition: Death of large groups of cells or tissues within the living body. It occurs either directly or follows reversible injury  Irreversible cell injury Causes:  Irreversible cell injury Microscopic picture: Nuclear changes Cytoplasmic changes  Irreversible cell injury Types:  Irreversible cell injury Types: 1-Coagulative necrosis - The most common type - Caused by ischemia (cutting of arterial blood supply). - Affect all organs except brain. - Preserving the outlines of the cells and tissue architecture  Irreversible cell injury Types: 2-Liquefactive necrosis - Occurs in the brain - Caused by ischemia (cutting of arterial blood supply). - The affected tissues become structureless due to rapid liquefaction by enzymes released from necrotic cells and neutrophils  Irreversible cell injury Types: 3-Caseous necrosis - Induced by cell mediated immunity - Most common example is tuberculosis (T.B) - The affected tissues become yellowish cheesy like - Combination of coagulative and liquefactive necrosis  Irreversible cell injury Types: 4-Fat necrosis A- Enzymatic: - Occur in acute pancreatitis - -Escape of lipase enzyme which cause digestion of peritoneal fat B-Traumatic: - Occur in breast due to trauma - -The fat cells rupture and self digestion occur - -Clinically: Hard breast mass misdiagnosed as cancer  Irreversible cell injury Fate: Lymphatics Engulfed by macrophages Drained by lymphatics Irreversible cell injury 1. Which of the followings is characteristic for apoptosis: a. Always pathologic c- Could be physiologic or pathologic. b. Death of large group of cells. d- The affected cells are enlarged. 2- Which of the following types of cell injury is surrounded by inflammation: a. Cloudy swelling c- Fatty change b. Apoptosis d-Necrosis Prof. Noha El-Kady Professor of Pathology ‫ جامعة المنوفية‬- ‫كلية الطب‬ LEARNING OBJECTIVES  Recognize types of Repair  List factors controlling repair  Mention mechanisms controlling repair  Stem cells and their types  Examples of repair  Healing by connective tissue  Wound healing by Primary and secondary intension  Repair The replacement of damaged tissue by new healthy one. Types of repair  Regeneration Replacement of damaged cells by new cells of the same kind.  Healing by connective tissue Replacement of damaged cells by connective tissue (fibrosis or gliosis).  Classification of body cells according to power of regeneration Continuously dividing cells Permanent cells (Labile cells) Quiescent (Stable cells) ` Labile cells Intestinal epithelium Haematopoietic Surface epithelium Ducts draining exocrine organs Epithelium of uterus, and fallopian tubes; urinary tract Regeneration Stable cells Mesenchymal cells Dermis Parynchematous cells Endothelial Liver, kidney, and pancreas. fibroblasts, smooth muscle cells; Partial regeneration plus scar Liver is special Permanent cells CNS Muscle cells Nerve cells Skeletal, cardiac Scar Stem cells  These are cells capable for :  1-Self-renewal capacity  2-Asymmetric replication: this means that after each cell division, some progeny enter a differentiation pathway, while others remain undifferentiated, retaining their self-renewal capacity.  3-Multilineage potential ( pluripotent or multipotent)  4-Long- term viability. MARROW STROMAL CELL STEM CELLS (TOTIPOTENTIAL*) EMBRYONIC ADULT 1-MARROW (HEMOCYTOBLAST) (hematopoetic stem cells) 2-NON-MARROW (RESERVE) Applications of stem cells in medicine 1-Treatment of diabetes, Alzahimar 2-Replace damaged tissues like brain, muscle and liver , bone & cartilage 3- Re-grow human teeth & hair. Factors affecting repair Mechanisms controlling Repair Growth factors EGF, FGF, PDGF, TGF alpha and beta Removal of chemical factors inhibitig mitosis (Chalones) Removal of Contact inhibition Cell matrix intearaction Regeneration Skin  Epidermis regeneration of basal cell  Dermis Granulation tissue scar Repair of liver after damage Normal liver Mild damage Massive gmage Intact framework destroyed framework regeneration Liver cirrhosis Liver cirrhosis Repair of bone Steps of Healing of bone fracture Haematoma Inflammation Granulation tissue (soft callus) Provisional callus (woven bone) Hard osseous callus (lamellar bone) Remodeling Bone marrow regeneration Remodelling Performed by osteoblasts and osteoclasts Directed by muscle and weight-bearing stresses Causes of imperfect bone healing Local factors: General factors  Inadequate  Old age immobilization  Nutritional deficiency  Gucocorticoides  Pathological fracture  Diabetes mellitus.  Soft tissue interposition  Ischemia  infection Healing of nervous system Nervous system Central peripheral Gliosis regenerate  Replacement of damaged tissue by granulation tissue which matures into fibrous (scar) tissue. Steps of the repair by scar:  Proliferation stage Angiogenesis (New capillaries) Arise from capilaries at edges of damaged area. 1-Sart solid endothelial buds----hollowed, filled with blood 2- Hemopoitic stem cells (HScs) Newly formed capillaries has no Basement Membrane. They bring nutrition to proliferating fibroblasts. Fibrogenesis  1-fibroblast migration 2- proliferation 3- secretion of collagen) arise from resting fibrocytes at edges of damaged area….migration……. proliferation ,secretion of collagen Granulation tissue  Consists of 2 components  Capillaries and fibroblasts.  G/P Moist, red, granular, velvety , - Fragile bleeds easily, Not sensitive, Resistant to infection  M/P  -Capillaries , Fibroblasts + - Inflammatory cells Maturation of Granulation tissue (Scaring) -Fibroblasts ---collagen fibers & ground substances -Fibroblasts contract (myofibroblasts) ----smaller lesion -Fibroblasts ----fibrocytes -Remodelling -Finally ----avascular strong fibrous tissue ( scar ) Remodeling  Rearrangement of collagen fibers parallel to the surface to get the maximal strength of tissue.  (arranged to give a full tensile strength)  Granultion tissue Mature Scar Grossly Moist red granular firm grayish white Microscopic -Myriads of newly -Few or no formed thin walled capillaries capillaries -Active plump -Resting fibrocytes fibroblasts -Dense collagen -Scanty collagen type type I III Healing of wounds Primary and secondary intention (union) Steps of Healing by Primary union (intention)  Small Bl clot, debris  Epithelialization  Granulation tissue  10-14 days Scap separation  Scar  Months- Ys ( Remodelling )  NB.Occurs in Clean surgical non-gapping wounds Comparison between healing of wounds by primary and secondary union Primary Secondary Time Rapid Slow type of Wound Clean surgical non-gapping Infected gapping crush Tissue loss Less, minimal Much Inflammation Mild Severe Epithelialization Occurs first before GT After granulation tissue Granulation tissue Less Much Scar Small, thin regular Large, thick irrigular Contraction rapid slow Complications Rare Common Steps of Healing by secondary intention (union)  Large Bl.clot, necrotic debris + Pus  Granulation tissue  Epithelialization  Scar  Months- Ys ( Remodelling )  NB.Occurs in Infected gapping crush wounds Primary Secondary Complications of wound healing  Chronic ulcer  Sinus  Fistula Defective  Keloid Excess  Contracture  Implantation , inclusion (epidermoid) cyst. Complications of wound healing Excessive Defective healing healing Hypertrophic Ulcer contracture scar Sinus Implantation Keloid cyst Fistula Excessive healing Hypertrophic scar: when the scar is elevated above the level of surrounding normal skin. Keloid: when the scar extends beyond the edges of wound. Keloid Mass projecting above the surface and formed of excess collagen Ulcer Defect in surface epithelial covering Sinus Blind end tract that opens on a surface Fistula Double opening tract that communicates between two surfaces  contracture Limited movement with deformity due to healing by fibrosis on a joint area Implantation cyst Sub-epidermal cyst filled with keratin