2.4 Pathology Lecture.pptx

Inflammation and Wound Healing SCI1018-N PATHOLOGY Dr. Ahmad Khundakar Learning outcomes •At the end of the lecture you should be able to: • Understand causes and mechanisms behind inflammation • Identify types of inflammation • Examine the main processes underlying wound healing, including phases...

Inflammation and Wound Healing SCI1018-N PATHOLOGY Dr. Ahmad Khundakar Learning outcomes •At the end of the lecture you should be able to: • Understand causes and mechanisms behind inflammation • Identify types of inflammation • Examine the main processes underlying wound healing, including phases and factors delaying wound healing • Describe the causes and mechanisms behind fibrosis Inflammation • Inflammation response of vascularised tissues to infection and damaged tissue • Allocates cells and molecules of host defence to sites where they are needed to eliminate agents (e.g. microbes, toxins) • Protective response essential for survival Causes of Inflammation • Infection Different pathogens elicit variable inflammatory response (e.g. staphylococcus aureus usually acute inflammatory response, mycobacterium leprae (leprosy) typically persistent infection and chronic inflammation) • Tissue necrosis • Occurs regardless of cell death • E.g. ischaemic damage • Foreign bodies • Splinters, dirt, sutures • Immune reactions (hypersensitivity) • Autoimmune diseases (e.g. psoriasis, arthritis) • Fibrosis Arrows: contiguous cells, cell swelling, loss of detail, neutrophils and cell debris (Elmore et al, 2014) Clinical Signs of Inflammation? Clinical Signs of Inflammation? Clinical Signs of Inflammation? • Heat: Increased chemical activity and blood flow to skin surface • Redness: Caused by dilatation of arterioles/ increased blood flood • Swelling: Caused by accumulation of blood and damaged tissue cells • Pain: Injury of nerve fibres, pressure of haematoma, also due to chemical irritants • Loss of function: Increased pain/swelling Types of inflammation Acute Inflammation • Usually short duration (up to a few days) • Characterised by accumulation of neutrophils (acute inflammatory cell) • Sometimes leads to formation of pus (tissue fluid, dead neutrophils and microorganisms) Chronic Inflammation • Longer duration (> 1 week) • Accumulation of: • Specialised immune cells (e.g. B and T lymphocytes) • Plasma cells that secrete immunoglobulin and macrophages • Repair of damaged tissue after cause of inflammation removed • May produce new blood vessels (angiogenesis) and fibrosis Macrophage Can you identify the blood cells in the film? Chronic Inflammatory Diseases ⎼ Asthma • Chronic inflammatory disease of the airway leading to: • • • • Airway hyperresponsiveness Obstruction Mucus hyper-production Airway wall re-modelling • • Characterised by thickening and narrowing of the airway walls Transition from epithelial to mesenchymal tissue Chronic Inflammatory Diseases ⎼ Asthma • Chronic inflammatory disease of the airway leading to: • • • • Airway hyperresponsiveness Obstruction Mucus hyper-production Airway wall re-modelling • • Characterised by thickening and narrowing of the airway walls Transition from epithelial to mesenchymal tissue (EMT) Thinking back to last week’s lecture what kind of pathological adaptation is this? Chronic Inflammatory Diseases ⎼ Inflammatory Arthritis Chronic Inflammatory Diseases ⎼ Inflammatory Arthritis • Characterised by: • • • • • • • Pain Swelling Stiffness Diurnal pattern Erythema ‘Heat’ Systemically unwell • Anti-inflammatories helpful • Ibuprofen, naproxen Chronic Inflammatory Diseases ⎼ Rheumatoid Arthritis • • • • Chronic Inflammatory Deforming Polyarthritis: symmetrical in proximal interphalangeal (PIP)/metacarpophalangeal (MCP)/wrist/elbow/ shoulder/knee/ankle/foot • Disability • Rheumatoid factor +ve Rheumatoid Arthritis Testing • Physical testing of joints and limbs • Blood tests • Elevated erythrocyte sedimentation rate (ESR, or sed rate) • C-reactive protein (CRP) • Rheumatoid factor • Anti-cyclic citrullinated peptide (antiCCP) antibodies The graphs below are taken from a patient with elevated C-reactive protein (CRP) and erythrocyte sedimentation rate. Do you think this could be an indication of osteoarthritis? Outline your reasoning Wound Healing • Refers to a living organism's replacement of destroyed or damaged tissue by newly produced tissue • Wound - break in the skin or an organ caused by violence or surgical incision • Complex biological process consisting of four stages: • • • • Haemostasis Inflammation Proliferation Remodeling Haemostasis • Refers to the normal response of the vessel to injury by forming a clot to limit haemorrhage • Occurs when blood is present outside of the body or blood vessels • • innate response for the body to stop bleeding and loss of blood Without the ability to stimulate haemostasis the risk of haemorrhaging increases Haemostasis • Refers to the normal response of the vessel to injury by forming a clot to limit haemorrhage • Occurs when blood is present outside of the body or blood vessels • • innate response for the body to stop bleeding and loss of blood Without the ability to stimulate haemostasis the risk of haemorrhaging increases Three stages of haemostasis: 1, Vascular spasm (vasoconstriction) - produced by vascular smooth muscle cells controlled by the vascular epithelium. In initiated by sympathetic pain receptors. Haemostasis • Refers to the normal response of the vessel to injury by forming a clot to limit haemorrhage • Occurs when blood is present outside of the body or blood vessels • • innate response for the body to stop bleeding and loss of blood Without the ability to stimulate haemostasis the risk of haemorrhaging increases Three stages of haemostasis: 1, Vascular spasm (vasoconstriction) - produced by vascular smooth muscle cells controlled by the vascular epithelium. In initiated by sympathetic pain receptors. 2, Platelet plug formation Platelets adhere to damaged endothelium to form a platelet plug (primary haemostasis) Haemostasis • Refers to the normal response of the vessel to injury by forming a clot to limit haemorrhage • Occurs when blood is present outside of the body or blood vessels • • innate response for the body to stop bleeding and loss of blood Without the ability to stimulate haemostasis the risk of haemorrhaging increases Three stages of haemostasis: 1, Vascular spasm (vasoconstriction) - produced by vascular smooth muscle cells controlled by the vascular epithelium. In initiated by sympathetic pain receptors. 2, Platelet plug formation - Platelets adhere to damaged endothelium to form a platelet plug (primary haemostasis). 3, Clot formation - clotting factors activated in a sequence of events known as 'coagulation cascade’ - leads to the formation of fibrin ‘mesh’ from inactive fibrinogen plasma protein (holds platelet plug in place) Haemostasis • Refers to the normal response of the vessel to injury by forming a clot to limit haemorrhage • Occurs when blood is present outside of the body or blood vessels • • innate response for the body to stop bleeding and loss of blood Without the ability to stimulate haemostasis the risk of haemorrhaging increases Inflammation • ‘Clean-up- phase • Damaged and dead cells are cleared out, along with bacteria and other pathogens or debris • Phagocytosis - white blood cells engulfs destroys debris and pathogens • Platelet-derived growth factors released into the wound • cause migration and division of platelets Proliferation • Angiogenesis, collagen deposition, granulation tissue formation, epithelialisation and wound contraction • Fibroblasts grow and form a new, extracellular matrix by excreting collagen and fibronectin • Epithelial cells proliferate and move to top of wound bed Driskell lab, Washington State University Remodelling (maturation) • Collagen is realigned along tension lines • Cells no longer needed are removed by apoptosis The histology picture is taken from the left ventricle of patient with a history of heart disease. Which of the following statements do you think is true? He had a myocardial infarction (heart attack) yesterday He had a myocardial infarction 5 days ago He had a myocardial infarction 2 months ago He hasn’t had a heart attack! Acute versus Chronic Wounds Factors Delaying Wound Healing General factors: Local factors: • Type, size, location of wound • Apposition, lack of movement • Infection: suppuration, gangrene, tetanus (secondary haemorrhage) • Blood supply: arterial, venous • Foreign material: debris, glass, sutures, necrotic tissue • Radiation damage • Age • General state of health chronic diseases (e.g. diabetes, rheumatoid arthritis) • • • • Drugs (e.g. steroids) General cardiovascular status General dietary deficiencies (e.g. protein) Specific dietary deficiencies • • vitamin C sulphur-containing amino acids Chronic Wounds Linked to Infections Chronic Wounds Diabetic • Hyperglcaemia can lead to poor blood circulation needed for wound healing • Incomplete wound healing, increases the risk of: • • • • Fungal infections Bacterial infections Gangrene Poor remodelling Complications in Wound Repair • Insufficient fibrosis: • • • Wound dehiscence Hernia Ulceration • Excessive fibrosis: • • • Cosmetic scarring Hypertrophic scars Keloid • Excessive contraction: • • Limitation of joint movement (contractures) Obstruction of tubes & channels (strictures) Wound dehiscence Fibrosis • Formation of excess fibrous connective tissue in an organ or tissue in a reparative or reactive process • Replacement of normal ‘parenchymal’ tissue • Occurs after severe or persistent tissue injury • • Repair cannot be accomplished by parenchymal regeneration alone Leads to formation of a permanent fibrotic scar Fibrosis • Forms granulation tissue • ‘pink, soft, granular’ gross appearance • Composed of fibroblasts and thin-walled capillaries, in loose extracellular matrix • Gradually accumulates connective tissue matrix (collagen) resulting in dense fibrosis Fibrosis – Cystic Fibrosis • Cystic fibrosis disease of exocrine gland function involving multiple organ systems • Mainly results in chronic respiratory infections (e.g. staphylococcus aureus, haemophilus influenzae) and pancreatic enzyme insufficiency • Causes clogging of the airways due to mucus build-up, decreased mucociliary clearance, and resulting inflammation (e.g. neutrophil recruitment) Currently, no effective medicine is available to cure CF. But doctors can prescribe medicines that help slow the progression of the disease. Which of these types of medicine can do this? A. Bronchodilators B. Antibiotics C. Decongestants D. Mucolytics E. All of the above Learning outcomes •You should now be able to: • Understand causes and mechanisms behind inflammation • Identify types of inflammation • Examine the main processes underlying wound healing, including phases and factors delaying wound healing • Describe the causes and mechanisms behind fibrosis Quiz Time! Go to socrative.com Room name: Thank you