By Dr Mohammad Manzoor Mashwani

What is inflammation?CausesSigns Types Components Functions of inflammationOverview of inflammation Specific host defences Summary

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Inflame means to set a fireIt is a dynamic response of vascularized tissue to injury.Fundamentally a protective response.To rid the organism of both the initial cause of cell injury like microbes and toxins and the consequences of such injury e.g necrotic cells and tissues.The survival of organisms depends on their ability to get rid of damaged or necrotic tissues and foreign invaders, such as microbes. The host response that accomplishes these goals is called inflammation. *

Inflammation to a specific tissue is denoted by the suffix "ITIS", following the name of the tissue:Example: Appendicitis, cholecystitis, pulpitis and gingivitis.Pneumonia .

If no inflammation Infections go uncheckedWounds would never healInjured tissues might remain permanent sores.

In the practice of medicine the importance of inflammation is that it can sometimes be inappropriately triggered or poorly controlled, and is thus the cause of tissue injury in many disorders.

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Infections (viral,bacteral,parasitic)Trauma (blunt, penetrating)Physical & chemical agentsTissue necrosisForeign bodies (dirt, sutures)Immune reactions (hypersensitivity reactions)*

Four cardinal signs

Callor (heat)Rubor (Redness)Tumor (Swelling)Dolor (Pain)

May also observe:5. Loss of function*

Cardinal Signs of InflammationDolorCalorRuborTumorLoss of Functionfirst described by Celsus more than 2000 years ago.

Chronological patternAcute inflammationChronic inflammation

Morphological patternSerous inflammationSuppurative inflammationFibrinous inflammationUlcer

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Time view acute (days) subacute (weeks) chronic (months-years)

Connective tissue cellsConnective tissue matrixVessels Soluble proteins

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1. Destroy and remove pathogens.2. If destruction is not possible, to limit effects by confining the pathogen and its products.3. Repair and replace tissue damaged by pathogen and its products.*

Inflammation is a complex reaction of responses of blood vessels and leukocytes. Principal defenders are:Plasma proteinsLeukocytes & Tissue phagocytes derived from circulation. Being in blood they can home any site where they may be needed. As invaders such as microbes and necrotic cells are typically present in tissues, outside the circulation, it follows that the circulating cells and proteins have to be rapidly recruited to these extravascular sites. The inflammatory response coordinates to achieve this goal.

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Inflammatory response repair It destroys, dilutes, and walls off the injurious agent, series of events that try to heal the damaged tissue.Repair begins during inflammation but reaches completion usually after the injurious influence has been neutralized. In the process of repair the injured tissue is replaced through regeneration of native parenchymal cells, by filling of the defect with fibrous tissue (scarring) or, most commonly, by a combination of these two processes.*

Inflammation may be harmful in some situations. When inappropriately directed against self tissues or is not adequately controlled, it becomes the cause of injury and disease. Inflammatory reactions underlie common chronic diseases, such as rheumatoid arthritis, atherosclerosis, and lung fibrosis, as well as life-threatening hypersensitivity reactions to insect bites, drugs, and toxins.Anti-inflammatory drugs, control the harmful sequelae of inflammation yet not interfere with its beneficial effects.Inflammation may contribute to a variety of diseases that are not thought to be primarily due to abnormal host responses.

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Host Defenses

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IntroductionResistance: Ability to ward off (prevent) disease.Nonspecific Resistance: Defenses that protect against all pathogens.Specific Resistance: Protection against specific pathogens.

Susceptibility: Vulnerability or lack of resistance.*

Mechanical DefensesChemical DefensesCellular elements of blood

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I.Mechanical DefensesSkin and Mucous Membranes

A. Skin LayersEpidermis: Thin outer epithelial layer.Contains Langerhans cells, dead cells, and keratin.Dermis: Thick inner layer of connective tissue.

Infections are rare in intact skin. Exceptions.

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B. Mucous Membranes: Lining of gastrointestinal, genitourinary, andrespiratory tracts.

Epithelial layer secretes mucus which maintains moist surfaces.Although they inhibit microbial entry, they offer less protection than skin. Several microorganisms are capable of penetrating mucous membranes:Papilloma-virus Treponema pallidumEnteroinvasive E. coliEntamoeba histolytica

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Lacrimal apparatus: Continual washing and blinking prevents microbes from settling on the eye surface. Saliva: Washes microbes from teeth and mouth mucous membranes. Mucus: Thick secretion that traps many microbes.Nose Hair: Coated with mucus, filter dust, pollen, and microbes.Ciliary Escalator: Cilia on mucous membranes of lower respiratory tract move upwards towards throat at 1-3 cm/hour. Coughing and sneezing: Expel foreign objects. Urination: Cleanses urethra.

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II.Chemical Defenses:Sebum: Oily substance produced by sebaceous glands that forms a protective layer over skin. Contains unsaturated fatty acids which inhibit growth of certain pathogenic bacteria and fungi.pH: Low, skin pH usually between 3 and 5. Caused by lactic acid and fatty acids.Perspiration: Produced by sweat glands. Contains lysozyme and acids.Lysozyme: Enzyme that breaks down gram-positive cell walls. Found in nasal secretions, saliva, and tears.*

Gastric Juice: Mixture of hydrochloric acid, enzymes, and mucus. pH between 1.2 to 3 kills many microbes and destroys most toxins. Many enteric bacteria are protected by food particles. Helicobacter pylori neutralizes stomach acid and can grow in the stomach, causing gastritis and ulcers.

Transferrins: Iron-binding proteins in blood which inhibit bacterial growth by reducing available iron.

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Cell Type # Cells/mm3 Function

Erythrocytes (RBC) 4.8-5.4 million Transport O2 and CO2

Leukocytes (WBC 5000-11000 Various A. Granulocytes: 1. Neutrophils Phagocytosis 2. Basophils Produce histamine 3. Eosinophils Toxins against parasites some phagocytosisB. Monocytes/Macrophages PhagocytosisC. Lymphocytes Antibody production (B cells) Cell mediated immunity (T cells) Platelets 300,000 Blood clotting*

II. Second Line of Defense1. Phagocytosis: Derived from the Greek words Eat - cell. Phagocytosis is carried out by white blood cells: macrophages, neutrophils, and occasionally eosinophils.Neutrophils predominate early in infection.Wandering macrophages: Originate from monocytes that leave blood and enter infected tissue, and develop into phagocytic cells.Fixed Macrophages (Histiocytes): Located in liver, nervous system, lungs, lymph nodes, bone marrow, and several other tissues.*

Stages of Phagocytosis

1. Chemotaxis: Phagocytes are chemically attracted to site of infection.2. Adherence: Phagocyte plasma membrane attaches to surface of pathogen or foreign material. Adherence can be inhibited by capsules (S. pneumoniae) or M protein (S. pyogenes). Opsonization: Coating process with opsonins that facilitates attachment. Opsonins include antibodies and complement proteins.*

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Stages of Phagocytosis

3. Ingestion: Plasma membrane of phagocytes extends projections (pseudopods) which engulf the microbe. Microbe is enclosed in a sac called phagosome.4. Digestion: Inside the cell, phagosome fuses with lysosome to form a phagolysosome. Lysosomal enzymes kill most bacteria within minutes and include:Lysozyme: Destroys cell wall peptidoglycanLipases and ProteasesRNAses and DNAsesAfter digestion, residual body with undigestable material is discharged.*

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