Inflammation I - PPT - Tagged (1) PDF

Inflammation 1 and 2 Acute & Chronic Happy Deepawali Halloween Dr. Neelam Maheshwari Associate Professor-Bond University & Clinical Microbiologist- GCUH  Principles of my teaching AIM: To make you good, safe and humble doctors OBJECTIVES: Fun filled i...

Inflammation 1 and 2 Acute & Chronic Happy Deepawali Halloween Dr. Neelam Maheshwari Associate Professor-Bond University & Clinical Microbiologist- GCUH  Principles of my teaching AIM: To make you good, safe and humble doctors OBJECTIVES: Fun filled infusion of “ Father of medicine “ for its clinical application 1. Addressed as Dr Maheshwari 2. Familiarise with students F2F/Interaction/QA/Discussion/Chats/Spotlight 3. Case based, experiential learning. 4. Learning outcomes & Take-home messages 5. Tabled summary of important concepts 6. Important for learning 7. Extra slides at end for bedtime reading and will not be tested in exams 8. Quiz/Formative exams 9. Please ask questions and politely interrupt for clarification 10. Respect, professional attire and teamwork  Learning objectives Year LO- Y1SS05 Biochemical and cellular processes (replication, membrane transport, interaction with extracellular environment) that define cells as the fundamental unit of life Semester LO SS4 Explain what is meant by inflammation in terms of the cells involved and how this relates to the symptoms of red, hot, swollen, painful, restricted movement Session LO 1. To familiarise with the terminologies and concepts of inflammation Definition, cardinal signs and significance 2. To understand the process, sequence of events and components of inflammation 3. To differentiate between two main types and morphological patterns of inflammation 4. To acquaint with outcomes of inflammation  DEFINITION Latin origin: ‘inflammare’ Definition: A primary (first line) defence of innate immune system in response to tissue injury inorder to eliminate the cause of injury and set the platform for tissue repair Components: Stimulus, Vessels, Cells, Mediators Process: complex 1. Recognition of stimulus 2. Vascular events 3. Cellular events 4. Resolution and repair In clinical world put suffix : ‘itis’ : example : Cellulitis, Arthritis, Appendicitis  COMPONENTS of inflammation Four (4) Major Components of inflammation 1. STIMULUS 2. VESSELS Veins Arteries Lymphatics 3. CELLS White blood cells Platelets Tissue cells 4. MEDIATORS Plasma proteins, Complements Cytokines, Chemicals Cell surface proteins Stimuli proteins (microbes) Component prominence varies for acute and chronic inflammation  Inflammation Process: STEPS (SEQUENCE) 1. Presence of Stimulus 2. Vascular changes: I. Vasodilatation II. Increased vascular permeability: Leakage of vascular fluid, cells and plasma proteins 3. Cellular events -Leukocytes and Mediators I. Recruitment of leukocytes i. Margination ii. Migration iii. Chemotaxis (Migration towards chemokines) II. Recognition of the stimuli by leukocytes iv. Attachment :of leukocytes by receptors to stimuli v. Activation : of leukocytes for removal of stimuli III. Removal of the stimuli vi. Phagocytosis: by leukocytes vii. Killing/Degradation of stimuli 4. Resolution viii. Regeneration or Repair of local tissue Later in Sem2 : Wound healing and repair  Sequence : Presence of stimulus, Vasodilation, Recruitment, Recognition, Removal, Resolution. OR  Sequence : Presence of stimulus, Vasodilation, Margination, Chemotaxis, Attachment, Activation, Phagocytosis, Degradation, Repair.  Each step is Regulated/Controlled  Step-1: Stimulus To initiate inflammation A. Types of stimuli =Aetiology/Cause B. Sources of stimuli ( VINDICATE) Exogenous Vascular: Ischemia/hypoxia – Physical Infections/Inflammation – Chemical Neoplasm/Nutritional – Environmental Drugs/Degeneration – Biological Iatrogenic/Idiopathic Endogenous – Immune reaction Congenital/Connective tissue disorder Autoimmunity/Allergy Trauma(Physical /Chemical/Thermal)/Toxins Environmental/Endocrinal  Exogenous stimuli Physical : Fall-Trauma Biological: Infection- Anthrax bacilli Chemical : Acid burns Environmental: Frost bite  Endogenous stimuli 1. Immune mediated reaction  Step 2. Vascular changes Aim: Is to bring cells and chemical mediators to the site of injury 2 Vascular changes 1. Vasodilatation Injury causes transient vasoconstriction, then histamine and nitric oxide act on smooth muscles causing opening of arterioles and capillaries within 4-6 hrs of injury causing vasodilatation. Dilated vessels can hold more blood=vessel engorgement =HYPERAEMIA REDNESS=RUBOR and SWELLING (TUMOR) 2. Increased vascular Permeability Endothelial cell contraction and histamine/kinin cause transcytosis of neutrophils and leakage of fluid and plasma proteins through gaps between endothelial cells into the extracellular tissue = SWELLING= TUMOR Clinically called ODEMA 2. Leakage of plasma 3. Leukocyte emigration and proteins = oedema  Vascular changes-contd. 3. Lymphatic changes Lymphatic vessels dilate and proliferate (LYMPHANGITIS) to drain leaked extravascular fluid/cells/stimulus/cell debris to the lymph nodes for removal =Lymph node inflammation (LYMPHADENITIS) Lymphangitis is seen as red streaks on the skin due to dilatation of the lymphatic vessels from the site of injury towards the draining lymph nodes= Swollen regional lymph nodes Very typical with Intravenous drug abusers ( IVDU) 3(I)Recruitment: Margination & migration Diapedesis Neutrophils predominate acute inflammation Lymphocytes predominate with chronic/viral inflammation Eosinophils predominate with allergic reactions/parasites First 6-24 h Neutrophils come which are replaced by monocytes/macrophages in 24-48 hr Why Neutrophils migrate first, even with chronic inflammation?  3(I)iii: Chemotaxis Definition: Directional movement of leucocytes towards the site of injury along a chemical gradient created by chemokines CHEMOKINES: Chemicals that mediate kinesis are produced by: Bacteria: Bacterial peptides ( Act as Stimuli) Blood; Complement-C5 Cell: Cytokines: IL-1, TNF Cells: Arachidonic acid metabolites present on cell membrane, e.g.: phospholipid of leukocytes, mast cells, endothelial and platelets. 3(II) Recognition: Attachment and Activation of leukocytes to stimulus How leucocytes recognise stimuli like microbes or dead cells in tissues Sensors on leucocytes for microbes, chemicals and dead cells 3(III) Removal: Phagocytosis & Killing ROS Oxidative burst/Respiratory burst  5 CARDINAL SIGNS of Inflammation Cardinal signs (symptoms) Pathophysiological mechanism Comments Latin (General) Vasodilation, Increased vascularity ( hyperaemia), Celsus tetrad 1. Rubor (Redness) Increased blood flow 2. Tumor (Swelling) Vasodilation, leakage of cells, plasma and proteins 3. Calor (Heat) Vasodilation, Increased vascularity & flow, Chemical mediators 4. Dolor (Pain) Stretching of pain receptors and nerve by inflammatory exudate, Chemical mediator-kinin, Vasodilation, Increased vascularity 5. Functio laesa Pain, Swelling, Disruption of tissue structure, Loss of Virchow (Loss of function) tissue due to injury or repair by fibrosis added 5th  TYPES of inflammation: 2 main Features Acute Chronic Onset Quick: Within mins-hours-days Slow: over weeks or months Duration Short: Days to < 2 weeks Duration: > 6 weeks to years Stimulus Short and eliminated quickly Lingering for longer time Predominant cells Neutrophils Lymphocyte Macrophages Process Stimuli + Vascular events + Cellular Stimuli + Vascular events+ Cellular events+ Tissue events + Resolution destruction + Resolution (Fibrosis) Tissue injury (Mainly) swelling and vasodilation, Self-limiting Tissue destruction & fibrosis, Progressive 5 Cardinal signs First 4 Prominent Loss of function prominent Examples Trauma: Fall/Stab/Cut/Gunshot Infections: Tuberculosis Infections: Abscess/Pneumonia Autoimmune: Rheumatoid arthritis, SLE Vascular: Myocardial Infarction Chemicals: Silicosis/Gout Pathology: Microscopic  Acute inflammation-Cellulitis Clinical Examples APPROPIATE EXPOSUE COMPARE AND FIRST EXAMINE WHICH SIDE ?  Chronic Inflammation – Tuberculosis (TB) Chest X ray: TB cavity lung Lung TB= Gross: Caseous Inflammation/Cavity  OUTCOMES of Inflammation Depends on stimulus type/intensity/duration, site of injury, tissue affected and the hosts ability to mount a response. 1 3 4 2  SIGNIFICANCE of inflammation TREAT- Beneficial effects=Friend Neutralises/disposes of the injurious stimulus and cell debris Limits the damage extent Sets the stage for tissue repair Alerts the adaptive Immune TRICK- Harmful effects=Foe system Tissue damage -Functio laesa Spread ---chronicity/death Excessive repair (e.g., Keloid) Precursor for cancers: IBD---Ca colon Maddie's birthday Treat: 2020 Eggless Spongy Orange poopy cake with half side having elements of inflammation 1. Stimuli- Maddie's birthday 2. Vascular events : dilatation and leaky ness – red color with milk 3. Cell components- white and brown choc chips(phagocytes) and walnuts as macrophages 4. Plasma proteins and complements : Orange rinds, zest and white sugar 5. Chemokines and cytokines : fresh Orange juice, vanilla and yoghurt 6. Healing and repair: Fibrosis - coconut shreds