Inflammation I 2024.PDF

Acute inflammation and outcomes ◼ ◼ ◼ ◼ ◼ Introduction Acute Inflammation Processes and mechanisms Morphology Outcomes Learning outcomes ◼ ◼ ◼ ◼ To understand the concept of acute Inflammation To explain the processes and key factors involved To describe its morphological features To show knowledge...

Acute inflammation and outcomes ◼ ◼ ◼ ◼ ◼ Introduction Acute Inflammation Processes and mechanisms Morphology Outcomes Learning outcomes ◼ ◼ ◼ ◼ To understand the concept of acute Inflammation To explain the processes and key factors involved To describe its morphological features To show knowledge on its outcomes Acute inflammation and outcomes ◼ ◼ ◼ ◼ ◼ Introduction Acute Inflammation Processes and mechanisms Morphology Outcomes Inflammation ◼ Latin, Inflamatio, to set on fire ◼ Biological reaction to noxious stimulus such as microbes, burns and trauma ◼ Fundamentally protective process but may potentially be harmful leading to tissue injury ◼ Can be divided into: ❑ ❑ Acute Inflammation Chronic Inflammation Acute inflammation and outcomes ◼ ◼ ◼ ◼ ◼ Introduction Acute Inflammation Processes and mechanisms Morphology Outcomes Acute inflammation ◼ Firstly described by Celsus, a Roman writer in 1st century AD, with the 4 cardinal clinical signs: ❑ ❑ ❑ ❑ ◼ Rubor (Redness) Tumor (Swelling) Calor (Heat) Dolor (Pain) Virchow later added the 5th sign ❑ Functio Laesa (Loss of function) Acute inflammation Acute inflammation Rapid host response to deliver leucocytes and plasma proteins such as antibodies to the sites of infection or tissue injury ◼ To protect the body from further injury in response to ❑ ❑ ❑ ❑ ❑ Infection Trauma (blunt or penetrating) Burns/frostbite (thermal and chemical) Allergic reactions Tissue necrosis Occurs immediately and lasts hours – days ◼ Consists of vascular and cellular reactions ◼ Acute inflammation and outcomes ◼ ◼ ◼ ◼ ◼ Introduction Acute Inflammation Processes and mechanisms Morphology Outcomes Three major components of acute inflammation ◼ Vascular dilation to increase blood flow ◼ Structure changes in the microvasculature to allow plasma proteins and leukocytes to leave the circulation ◼ Emigration of the leukocytes from the microvasculature, their accumulation in the injury site and their activation to eliminate the offending agent Vascular reaction ◼ Vessel dilation and increased blood flow ◼ Leakage of plasma fluid and protein ◼ Leukocyte emigration and accumulation in the site of injury Normal Inflamed Vessel dilation ◼ ◼ ◼ ◼ One of the earliest signs of acute inflammation - quick To increase blood flow Results in heat and redness (hyperaemia) Induced by the actions of several mediators on VSM ❑ ❑ ❑ Histamine Bradykinin NO Mediators of vascular reactions Name Source Function Histamine Mast cells, basophiles, platelets Arteriole dilatation, Increase of venous permeability Bradykinin Kinin System Vasodilatation, Increase vascular permeability, Pain Nitric Oxide Endothelial cells Vasodilatation Increased vascular permeability (leakage) ◼ ◼ ◼ A hall mark of acute inflammation Allow plasma fluid and protein to escape from the circulation into extracellular tissue The cause of oedema Mechanisms ❑ ❑ ❑ Endothelial cell contraction to increase intercellular spaces Endothelial cell injury and detachment Increased transport of fluid and protein through the endothelial cells Leukocyte recruitment Movement of leukocytes from vessel lumen to interstitial tissue is called extravasation 1. Leukocyte adhesion to endothelium Endothelial adhesion molecules: P-selectin E-selectin CD34 ICAM-1 VCAM-1 2. Leukocyte migration through endothelium 3. Chemotaxis of leukocytes A process that leukocytes emigrate toward the site of injury driven by substances called chemoattractants Cellular components ◼ Leukocytes – some act as phagocytes; others release enzymatic granules ◼ Migration of these leukocytes is a critical step of inflammation ◼ Initially phagocytic cells – neutrophils followed by monocytes ◼ Produce inflammatory mediators that maintain the inflammatory response Cellular reaction Chemotaxis A process that leukocytes are attracted by chemotactic agents to the site of injury once outside of the blood vessel Chemoattractants: ◼ Exogenous: ❑ ◼ bacterial products Endogenous: ❑ ❑ ❑ complement components cytokines products of lipoxygenase pathway (leukotriene B4) Leucocyte recognition Through leukocyte receptors ◼ ◼ ◼ ◼ Receptor for microbial products: Toll-like receptor (TLRs) G protein-coupled receptors: Recognise short bacterial peptide containing N-formylmethionyl residues Receptors for opsonins: Example of opsonins: antibodies, complements, lectins Receptor for cytokines: IFN Phagocytosis Removal of the offending agents 1. Recognition and attachment 2. Engulfment ▪ Engulfed particle fuses with lysosome to form phagolysosome ▪ Degranulation 3. Killing ▪ ROS (oxidative burst generated by NADPH oxidase) ▪ Other lysosomal enzymes Acute inflammatory cytokines Cytokines TNF-α: IL-1 IL-6 Principal sources macrophages, mast cells, T lymphocytes macrophages, endothelial cells, epithelial cells macrophages, other cells chemokines macrophages, endothelial cells,T lymphocytes, mast cells, other cells Acute inflammation and outcomes ◼ ◼ ◼ ◼ ◼ Introduction Acute Inflammation Processes and mechanisms Morphology Outcomes Morphological patterns ◼ Fibrinous Characterised by fibrinous exudate which can lead to scar formation and limitation of function ◼ Purulent Pus filled fluid consisting of neutrophils and dead cells Typically caused by staphylococcal infections Morphological patterns ◼ Serous Copious effusion of nonviscous serous fluid. Typical example is skin blister ◼ Ulcerative Necrotic loss of tissue from the surface, exposing lower layers leading to formation of an ulcer Purulent inflammation Bronchopneumonia Multiple bacterial abscesses Abscess contains neutrophils and cellular debris and is surrounded by congested blood vessels Acute inflammation and outcomes ◼ ◼ ◼ ◼ ◼ Introduction Acute Inflammation Processes and mechanisms Morphology Outcomes Outcomes of acute inflammation ◼ Complete resolution ❑ ❑ ◼ Injury is limited or short lived Little tissue damage Healing by connective tissue replacement (fibrosis) ❑ ❑ ◼ Substantial tissue damage Fibroblasts grow into the area of damage Progression to chronic inflammation In class MCQ Acute inflammation is a rapid host reaction in response to which of the following situations? a)Infection b)Trauma c)Burns d)Allergy e)All of the above