Beneficial & Harmful Effects of Acute Inflammation PDF

Beneficial & harmful effects, sequelae & systemic effects of acute inflammation Prof Dr Thidar Aung Learning Objectives Students will be able to 1. Explain the sequelae of acute inflammation. 2. Explain the beneficial, harmful and systemic effects of acute inflammation. Manipal University College Ma...

Beneficial & harmful effects, sequelae & systemic effects of acute inflammation Prof Dr Thidar Aung Learning Objectives Students will be able to 1. Explain the sequelae of acute inflammation. 2. Explain the beneficial, harmful and systemic effects of acute inflammation. Manipal University College Malaysia (MUCM) 2 Sequelae of acute inflammation 1. 2. 3. 4. Resolution Abscess formation Progression to chronic inflammation Healing by fibrosis Manipal University College Malaysia 4 1. Resolution of Acute Inflammation The battle between the injurious agent and the host may end with restoration of the site of acute inflammation to normal. Complete resolution is the usual outcome when:a. the injury is limited or short-lived. b. there has been little tissue destruction. c. the damaged parenchymal cells can regenerate. Manipal University College Malaysia 5 Resolution of Acute Inflammation Must actively terminate inflammation to prevent bystander destruction of tissues Mechanisms of resolution: Short half-life of neutrophils and inflammatory mediators Neutrophils undergo apoptosis – macrophages ingest Macrophages will change character and promote repair (anti-inflammatory - M2) Release inhibitory cytokines (IL-10 and TGF-b) Limit inflammation Growth factors - Promote repair (FGF) Act on fibroblasts Lipid mediators – switch to production of anti-inflammatory lipoxins, resolvins, and protectins Manipal University College Malaysia 6 2. Abscess formation Acute inflammation fail to resolve e.g acute bacterial pneumonia  extensive tissue destruction  formation of a cavity the inflammation continues to smolder leads to abscess formation (e.g.a chronic lung abscess) Manipal University College Malaysia 7 3. Progression to chronic inflammation Acute to chronic transition occurs when the inflammatory response persists, due to: - the perseverance of the injurious agent or - some interference with the normal process of healing. Manipal University College Malaysia 8 4. Healing by fibrosis This occurs : a. after extensive tissue destruction. b. when the inflammatory injury involves tissues that are incapable of regeneration. c. when there is abundant fibrin exudation. Manipal University College Malaysia 9 Consequences of impaired inflammation I. Defective inflammation ↑ susceptibility to infection Delay in wound healing Tissue damage II. Excess Inflammation Allergies Important in Cancer Atherosclerosis IHD (ischemic heart disease) Alzheimer’s disease Fibrosis as a sequel of chronic infections, metabolic conditions Manipal University College Malaysia 10 Beneficial Effects of Inflammation 1. Dilution of Toxins by the edema fluid. 2. Entry of antibodies due to increased vascular permeability into extravascular space 3. Transport of drugs e.g. antibiotics to the site where bacteria are multiplying 4. Fibrin meshwork formation that forms a scaffold for inflammatory cell migration & also limits the spread of infections. Fibrinogen  Fibrin (delays bacterial spread) Destruction of microbial agent 5. Delivery of nutrients and oxygen 6. Stimulation of immune response Manipal University College Malaysia 11 Harmful effects 1. Swelling & edema that can be detrimental for e.g., acute epiglottitis that 2. 3. 4. 5. may be life threatening. Rise in tissue pressure that contributes to tissue necrosis. Digestion of adjacent viable tissue. Sever damaging allergic reaction. Generalized increase in vascular permeability can cause shock as seen in anaphylactic reactions. Manipal University College Malaysia 12 Systemic effects of inflammation Inflammation cytokine induced systemic reactions acute-phase response. The cytokines TNF, IL-1, and IL-6 are important mediators of the acute-phase reaction; other cytokines, notably interferons, also contribute. Infections→ reactions to cytokines ↓ Acute phase response or the systemic inflammatory response syndrome (SIRS) Manipal University College Malaysia 13 Systemic effects of inflammation Fever : in response to pyrogens →∆PG synthesis in Hypothalamus →∆cAMP →reset the temperature set point Increase in acute phase proteins: C reactive protein (CRP), fibrinogen, and serum amyloid protein (SAA) Leukocytosis Other manifestation of acute phase response: →↑ pulse and BP, ↓sweat, shivering, chills, anorexia, somnolence, malaise, due to the effects of cytokines on CNS Septic shock : triad of DIC (disseminated intravascular coagulation), hypoglycaemia, cardiovascular failure Manipal University College Malaysia 15 Leukocytosis Common feature of inflammatory reactions Bacterial infection - Usually 15,000 or 20,000 cells/μl, - 40,000 to 100,000 cells/μl (Leukemoid reactions) Accelerated release of cells from the bone marrow (shift to the left) Most bacterial infections induce Neutrophilia Viral infections-Lymphocytosis Typhoid fever , Rickettsiae-Leukopenia bronchial asthma, hay fever, and parasitic infestations- Eosinophilia Manipal University College Malaysia 16 Sepsis Sepsis :- severe bacterial infection Large amounts of LPS & TNF Multiple small thrombi by expressing Tissue Factor (TF) on Endothelial cells (EC) Also, by inhibiting TFPI (TF pathway inhibitor) Septic shock – Triad 1. Liver failure – no Gluconeogenesis (Hypoglycemia) 2. Loss of perfusion pressure & heart failure – hemodynamic shock 3. Disseminated Intravascular Coagulation (DIC) – Multiple Thrombi in circulation & Fibrin split products Multi Organ Failure Mainly Lung (ARDS), Liver also Kidney & Bowel Manipal University College Malaysia 17