Pathology Lecture 5 Acute Inflammation PDF

Faculty of Medicine Medical Education- Damietta University Level 1 Semester 1 Module PPM 104 Acute Inflammation  OBJECTIVES Understand the chain, progression and sequence of vascular and cellular events in the histologic evolution of acute inflammation Describe the role...

Faculty of Medicine Medical Education- Damietta University Level 1 Semester 1 Module PPM 104 Acute Inflammation  OBJECTIVES Understand the chain, progression and sequence of vascular and cellular events in the histologic evolution of acute inflammation Describe the roles of various chemical mediators of acute inflammation Define the possible outcomes of acute inflammation Visualize the morphologic patterns of acute inflammation Instructor information: Name : Dr Hazem Moh Abdullah Official e-mail.: [email protected] Mobile Number: 01146710982 Office hours: any time  Case scenario A clinical study is performed of patients with pharyngeal infections. The most typical clinical course averages 3 days from the time of onset until the patient sees the physician. Most of these patients experience fever and chills. On physical examination, the most common findings include swelling, erythema, and pharyngeal purulent exudate. Which of the following types of inflammation did these patients most likely have?  INFLAMMATION Definition: It is the vascular and cellular reaction of the living tissue against an injurious agent (irritant). The aim of inflammation: is to localize, destroy, eliminate the irritant and prepare the damaged area for repair. Nomenclature: Inflammation is usually designated by adding the suffix ‘itis’ to the affected organ e.g. tonsillitis, appendicitis.  Etiology of inflammation The irritant may be: Living: Bacteria, viruses, fungi & parasites. Non living: − Physical: excess heat, frost bite & irradiation. − Chemical: acids, alkalis, drugs and toxins. − Mechanical: trauma, mechanical friction and foreign bodies. − Immunological: antigen-antibody reaction. − Irritation by necrotic tissue.  TYPES OF INFLAMMATION Acute inflammation: with rapid onset, progressive course, short duration (hours to days), exudative in nature and followed by repair. Chronic inflammation: with gradual onset, progressive course, long duration (months to years), proliferative in nature and associated with repair. ACUTE INFLAMMATION  ACUTE INFLAMMATION PROTECTIVE RESPONSE NON-specific: The sequence of changes occurring in acute inflammation are NOT specific for the stimuli which cause them  ACUTE INFLAMMATION A. Local changes of acute inflammation: Local tissue necrosis surrounded by degeneration and release of chemical mediators. Local vascular changes: Changes in the vascular diameter Changes in the vascular wall Changes in blood flow Local exudative phenomena (formation of inflammatory exudate): Fluid exudate (inflammatory edema) Cellular exudate B. Systemic reaction to inflammation: e.g. fever, leukocytosis. ACUTE INFLAMMATION Neutrophil Polymorphonuclear Leukocyte, PMN, PML Many names, same cell The four “cardinal”, i.e., “classic” signs of inflammation REDNESS HEAT SWELLING PAIN. LOSS OF FUNCTION  VASCULAR AND CELLULAR CHANGES IN ACUTE INFLAMMATION Transient vasoconstriction Vasodilatation Increased vascular permeability Formation of fluid exudate (characters and differences between it and transudate) Emigration of leukocytes (neutrophils first them macrophages) Chemotaxis Phagocytosis (after opsonization) Bacterial destruction  Vascular Changes Changes in vascular flow and caliber Increased vascular permeability Vascular changes occur BEFORE any infiltration of inflammatory cells arrive. LEAKAGE OF PROTEINACEOUS FLUID (EXUDATE, NOT TRANSUDATE)  Acute inflammation &Vascular changes Initial (seconds-5 min) arteriolar vasoconstriction. Permanent arteriolar vasodilatation with increase in blood flow to the area causing redness & hotness Also, there’s increased vascular permeability (exudate & swelling) Schematic illustration of pathogenesis of increased vascular permeability in acute inflammation  Cellular Exudate Escape of inflammatory cells outside the blood vessels towards the irritant under the effect of chemotactic factors. N.B. transudate The transudate is a fluid that finds its way into the tissue spaces mainly due to increased intravascular hydrostatic pressure. Its characters are the reverse to that of exudates. Exudate Transudate Mainly due to increased cap. Permeability. Mainly due to increased intracapillary hydrostatic pressure. High protein content (4-8 gm%) Lower protein content (< 4 gm%) High specific gravity (> 1018). Low specific gravity (< 1018). Clot on standing due to its fibrin content. Doesn’t clot on standing. Contain inflammatory cells Doesn’t contain inflammatory cells. Steps of cellular exudate Margination and pavementation of leukocytes Emigration of leukocytes Chemotaxis Phagocytosis Sequence of changes in the exudation of leucocytes Margination and pavementation of leukocytes as a result of stasis, RBCs stick together to form rouleau  occupy the axial blood stream & leukocytes occupy the peripheral plasmatic zone (margination)  stick on the endothelial lining of the venules forming a layer (pavementation).This process is helped by chemical mediators which either increase expression of surface adhesion molecules or increase their synthesis that helps adhesion of leukocytes to the endothelium  Emigration of leukocytes leukocytes start to move by their amoeboid movement  leave the vessels through the dilated inter-endothelial spaces. Neutrophils predominate for 24 -48 hours & monocytes predominate after that as one of the monocyte chemotactic factors is derived from emigrating neutrophils PMN's that are marginated along the dilated venule wall (arrow) are squeezing through the basement membrane and spilling out into extravascular space. The acute inflammatory response shown here is marked by vasodilation with margination of neutrophils. Diapedesis of these neutrophils into the extravascular compartment is accompanied by exudation of fluid with edema. Here is an example of the fibrin mesh in fluid with PMN's that has formed in the area of acute inflammation. It is this fluid collection that produces the "tumor" or swelling aspect of acute inflammation.  Chemotaxis PMNs going to the site of “injury” after transmigration It is the directed movement of inflammatory cells on fibrin network towards the irritant guided by chemical substances (chemotactic agents) e.g. C3a & C5a, bacterial products  LEUKOCYTE ACTIVATION “triggered” by the offending stimuli for PMNs to: 1. Produce eicosanoids (arachidonic acid derivatives, 20 carbon chains) Prostaglandin (and thromboxane's) Leukotrienes Lipoxins 2. Undergo DEGRANULATION 3. Secrete CYTOKINES These three events are the results of leukocytes (i.e., neutrophils) being “activated”  Phagocytosis It is the process of recognition, engulfment and destruction of bacteria or foreign materials by the phagocytic inflammatory cells (Neutrophils & Macrophage).  Steps of phagocytosis 1. Recognition and attachment: this is helped by: Opsonin's (antibodies & some complement). Surface phagocytosis by trapping the bacteria between the phagocytic cell and tissue surface.  Steps of phagocytosis 2. Engulfment: The phagocytic cells engulf the irritant by their amoeboid movement (send pseudo-podia that surround it completely to form a cytoplasmic vacuole (phagosome). Lysosomes then fuse with the phagosome to form phagolysosome. 3. Destruction: of the engulfed material by proteolytic enzymes and oxygen dependent mechanisms (e.g. H2O2, OH). Stages in phagocytosis of a foreign particle  PHAGOCYTOSIS RECOGNITION ENGULFMENT KILLING (DEGRADATION/DIGEST ION)  GENENAL FEATURES OF CHEMICAL MEDIATORS Chemical mediators are chemical substances that control the inflammatory response (responsible for initiation and promotion of the vascular and cellular phenomena). Cellular mediators originated and secreted either from granules in the cells (e.g. histamine) or synthesized de novo (e.g prostaglandins). Plasma-derived mediators (e.g. complement) are found in plasma in precursor forms & must be activated by series of proteolytic changes. Most of the mediators quickly decay after release. Almost all mediators perform their action by binding to specific receptors on target cells.  FUNCTIONS OF CHEMICAL MEDIATORS Vasodilatation of arterioles, venules & capillaries: mainly by histamine prostaglandin & bradykinin. Increase capillary permeability: mainly by histamine, bradykinin, C3a, C5a & oxygen metabolites. Chemotaxis: (mainly by C3a, C5a & TNF). Phagocytosis: by C3b (opsonization). Fever & Leukocytosis: (by IL-1 & TNF). Pain (by bradykinin & Prostaglandin). Systemic effects of acute inflammation (1) Fever: Occurs especially with infections associated with spread of the organisms into the blood spread. Cause: pyrogens (i.e. fever producing substances): Exogenous: released from bacteria and fungi. Endogenous: from leucocytes (= cytokines) -Fever is produced principally by cytokines especially (interleukin 1 (IL-1) and tumor necrosis factor (TNF). (2) Leucocytosis: Common with bacterial infection.  Termination of Acute Inflammation The inflammatory response is a host defense mechanism but may cause tissue injury by the activated leukocytes & should be terminated to minimize tissue damage. The activated leukocytes produce: Adhesion molecules O2 free radicals Degranulation Intra-cellular contractile fibers Increase intra-cellular Ca+ The mechanisms that could terminate acute inflammation Short half-lives of chemical mediators by degrading enzymes. Short half-lives of neutrophils that die by apoptosis within few hours after leaving blood. Production of anti-inflammatory cytokines e.g. transforming growth factor-β (TGF-β) and IL-10, from macrophages and other cells. Neural impulse (cholinergic discharge) inhibit production of TNF in macrophages.  Fate of acute inflammation Resolution: Complete restoration of tissues to normal after acute inflammation. (resolution or regeneration) Healing by fibrosis after tissue destruction: In tissues that can not regenerate. There is abundant fibrin exudate. Progression to chronic inflammation. Progress to suppuration with abscess formation Spread of infection Lymphatics: lymphangitis and lymphadenitis Blood: Bacteremia, septicemia, toxemia and pyemia Summary and wrap up  Discussion & Feedback 2-5 minutes  MCQ 1. Which of the following is not a feature of acute inflammation: A. Persistent vasoconstriction. B. Vasodilatation. C. increased vascular permeability. D. Vascular stasis. E. Emigration of leucocytes. 2. Which of the following factors participates in the formation of inflammatory fluid exudate: A. Increased intravascular osmotic pressure B. Increased vascular permeability C. Decreased osmotic pressure of the interstitial tissue D. Increase hydrostatic pressure.  MCQ Chemotaxis is defined as? A. Generation of chemical mediators B. Toxic effect of chemical substances C. Chemical reaction at site of inflammation D. Attraction of leukocytes towards certain chemical products Signs of acute inflammation include all except? A. Anemia B. Redness C. Hotness D. Pain  References Robbin’s pathologic basis of disease