Pathophysiology Inflammation PDF

American University of Iraq – Baghdad College of Arts & Sciences Chapter 3 Inflammation, The Inflammatory Response, and Fever BIO 218 – Pathophysiology Spring 2024 Copyright © 2011 Wolters Kluwer...

American University of Iraq – Baghdad College of Arts & Sciences Chapter 3 Inflammation, The Inflammatory Response, and Fever BIO 218 – Pathophysiology Spring 2024 Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins Inflammation Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins  Inflammation Inflammation is a process by which your body's white blood cells and the things they make protect you from injury or infection from outside invaders, such as bacteria and viruses. Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins  Inflammation Inflammation is an automatic, complex immuno vascular response of vascularized tissues to cell injury that: 1. Neutralizes harmful agents 2. Removes dead tissue 3. Helps generate new tissue (healing) Characterized by elaboration of inflammatory mediators & fluid movement from blood vessels to tissues. Inflammatory conditions can by named after adding the suffix-itis Plays a key role in a number of diseases (e.g. bronchial to the affected organ or system (eg asthma, atherosclerosis, DM, ) carditis, bronchitis, appendicitis). It can be acute or chronic Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins TYPES OF INFLAMMATION Inflammation can be: 1. Acute 2. Chronic Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins  TYPES OF INFLAMMATION 1. ACUTE INFLAMMATION The five cardinal signs are: 1. Rubor (redness) 2. Tumor (swelling) 3. Calor (heat) 4. Dolor (pain) 5. Functio laesa (loss of function) Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins  TYPES OF INFLAMMATION 1. ACUTE INFLAMMATION Damaged cells release inflammatory mediators --stimulates inflammation. ECM components are also involved in the inflammatory response Cells (WBC) mobilized Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins  TYPES OF INFLAMMATION Damaged cells Acute inflammation: release Rapid response to injury Deliver mediators of host inflammatory defense leukocytes & plasma Acute mediators inflammation protein 3 main events: 1) Hemodynamic changes- 1. Local, early 2. Systemic (whole- changes in vascular responses body) responses physiology to increase blood flow. 2) Increase vascular permeability- microvascular changes to allow WBC and plasma vascular cellular white blood acute-phase proteins to get through stage stage cell response response 3) Migration of WBC to site of injury Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins  TYPES OF INFLAMMATION Acute Inflammation: Local Early Reponses 1. Vascular stage – Prostaglandins and leukotrienes affect blood vessels. – vasoconstriction follow quickly by vasodilation Transient – Arterioles and venules dilate. º Increasing blood flow to injured area º Redness and warmth result – Capillaries become more permeable. º Allowing exudate to escape into the tissues º Swelling and pain result Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins  TYPES OF INFLAMMATION Exudate is fluid that leaks out of blood vessels into nearby Serous: clear watery plasma Hemorrhagic exudate tissues. The fluid is made of cells, proteins, and solid materials. 1. Serous 2. Hemorrhagic 3. Fibrinous 4. Membranous Fibrous exudate Purulent: thick yellowl/brow 5. Purulent Acute inflammation may involve the production of exudates containing serous fluid (serous exudate), red blood cells (hemorrhagic exudate), fibrinogen (fibrinous exudate), or tissue debris and white blood cell breakdown products (purulent exudate). The outcome of acute inflammation generally results in one of three processes: 1. Resolution, 2. Progression to chronic inflammation, 3. Or Substantial scarring and fibrosis. Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins Patterns of vascular responses to inflammation A) Changes in Vascular Flow and Caliber: 1. After transient seconds from cell injury, there is vasoconstriction. 2. Then there is arteriolar vasodilatation, which result in increase local blood flow to capillary bed (this responsible for hotness & redness of area). 3. Movement of protein rich fluid into extravascular areas, this movement of fluid will leave the blood concentrated by RBCs (increase viscosity & slowing the circulation) & this called Stasis. 4. After stasis leukocytes (Neutrophils) change their normal flow in vessels, & begin to accumulate along the vascular endothelial surface (Margination). Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins  TYPES OF INFLAMMATION 1. Vascular stage 1.1. Immediate transient response (occurs with minor injury): The most common form of increased vascular permeability Limited to post-capillary venules Reversible process elicited by histamine, bradykinin, leukotrienes, and many other chemical mediators Endothelial cell contraction leads to intercellular gaps Rapid and short-lived reaction (minutes), hence immediate transient response 1.2. Immediate sustained response (occurs with serious injury): Endothelial cell necrosis & detachment caused by severe injury ( Burns, Infection, Toxin and Trauma ). Leak begins immediately after injury persists for several hours or days until vessels are thrombosed or repaired. It affects venules, capillaries and arterioles. Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins  TYPES OF INFLAMMATION 1. Vascular stage 1.3. Delayed hemodynamic response (occurs due to radiation injury): Sometime – direct injury to Endothelial Cells begins after a delay of 2-12 hr – lasts for several hours or days. It affects venules and capillaries. Mild – moderate thermal injury, radiation and bacteria toxins. Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins TYPES OF INFLAMMATION Damaged cells release inflammatory Acute mediators inflammation 1. Local, early 2. Systemic (whole- responses body) responses vascular cellular white blood acute-phase stage stage cell response response Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins  TYPES OF INFLAMMATION 2. Cellular stage 2. Cellular stage White blood cells enter the injured tissue: – Destroying infective organisms – Removing damaged cells – Releasing more inflammatory mediators to control further inflammation and healing 3. Leukocyte activation and Phagocytosis: Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins  TYPES OF INFLAMMATION 2. Cellular stage Adhesion: Leukocytes express adhesive proteins => Attach to the blood vessel lining Transmigration (Diapedesis): Leukocytes squeeze between the cells Chemotaxis: Leukocytes follow the inflammatory mediators to the injured area Phagocytosis: leukocytes engulf & breakdown the injurious agent Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins  Damaged cells Acute inflammation: release Rapid response to injury Deliver mediators of host inflammatory defense leukocytes & plasma Acute inflammation mediators protein 3 main events: 1) Hemodynamic changes- 1. Local, early 2. Systemic (whole- changes in vascular responses body) responses physiology to increase blood flow. 2) Increase vascular permeability- microvascular changes to allow WBC and plasma vascular cellular white blood acute-phase proteins to get through stage stage cell response response 3) Migration of WBC to site Leukocyte activation recruitment of injury and phagocytosis Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins TYPES OF INFLAMMATION 1. Cell derived inflammatory mediators at the injured area: Histamine and serotonin Platelet-activating factor (PAF) Cytokines – Colony-stimulating factors – Interleukins – Interferons – Tumor necrosis factor (TNF) Nitric oxide Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins  TYPES OF INFLAMMATION 2. Plasma-derived mediators (inflammatory mediators include proteins synthesized and released by the liver which travel in the plasma): 1. Kinins 2. Coagulation and fibrinolysis proteins 3. Complement system 4. C-reactive protein Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins  Other (plasma-derived) Inflammatory Mediators 2. Plasma-derived mediators (inflammatory mediators include proteins synthesized and released by the liver which travel in the plasma): 1. Kinins 2. Coagulation and fibrinolysis proteins 3. Complement system 4. C-reactive protein Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins  TYPES OF INFLAMMATION 2. Plasma-derived mediators (inflammatory mediators include proteins synthesized and released by the liver which travel in the plasma): 1. Kinins 2. Coagulation and fibrinolysis proteins 3. Complement system 4. C-reactive protein C-reactive protein (CRP), an acute phase protein belonging to pentraxin family of proteins, increases 1000-fold or more in concentration in blood during the occurrence of an injury, inflammation or tissue death. Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins  Damaged cells release inflammatory Acute inflammation mediators 1. Local, early 2. Systemic (whole- responses body) responses vascular cellular white blood acute-phase stage stage cell response response Leukocyte activation recruitment and phagocytosis Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins CLINICAL MANIFESTATIONS OF ACUTE INFLAMMATION: SYSTEMIC RESPONSES 1. Acute Phase Response 2. Change in WBC count (leukocytosis or leukopenia) Once the lymphocytes are activated, 3. Fever (pyrexia) they proliferate within the lymph node causing the lymph node to swell 4. Lymphadenitis Lymphadenitis Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins Clinical Manifestations of Acute Inflammation: Systemic Responses 1. Change in [proteins]plasma (e.g. SAA, CRP, Fibrinogen) 2. Skeletal muscle catabolism; -ve N-balance 3. ↑ ESR (erythrocyte sedimentation rate) 4. ↑ Number of leukocytes 5. Fever 6. ↑ Heart Rate 7. Anorexia 8. Somnolence 9. Malaise Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins Clinical Manifestations of Acute Inflammation: Systemic Responses 1. Acute Phase Response 1. Change in [proteins]plasma (e.g. SAA, CRP, Fibrinogen) 2. Skeletal muscle catabolism; -ve N-balance 3. ↑ ESR (erythrocyte sedimentation rate) 4. ↑ Number of leukocytes 5. Fever 6. ↑ Heart Rate 7. Anorexia 8. Somnolence 9. Malaise Elevation of body temp. due to upward displacement of the set point of the hypothalamic thermoregulatory center. Induced by cytokines (pyrogens TNFa, IL6 or ). and bacteria endotxins Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins Clinical Manifestations of Acute Inflammation: Systemic Responses 1. Acute Phase Response 1. Change in [proteins]plasma (e.g. SAA, CRP, Fibrinogen) 2. Skeletal muscle catabolism; -ve N-balance Physiological Significance of Fever 3. ↑ ESR (erythrocyte sedimentation rate) 4. ↑ Number of leukocytes  Enhancement of immune function: 5. Fever - increased motility and activity of WBCs - stimulation of interferon production Pyrogens refer to substances, often of biological - increased activity of T cells origin, that cause fever in living organisms  Inhibition of microbial growth - Fever sets up an environment that is not conducive to viral replication, while the fever also increase in sleepiness Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins CHRONIC INFLAMMATION Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins Chronic Inflammation Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins Chronic Inflammation  Fibrosis: the thickening and scarring of con nective tissue.  Angiogenesis: the development of new blood vessels. Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins  Chronic Inflammation Types of chronic inflammation 1. Chronic non-specific inflammation. Histologically, it is characterized by structureless and unorganized diffuse infiltration of tissues by inflammatory cells. 2. Chronic granulomatous Inflammation. A granuloma is an aggregation of macrophages (along with other cells) that forms in response to chronic inflammation. This occurs when the immune system attempts to isolate foreign substances that it is otherwise unable to eliminate. Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins Chronic Inflammation  Granulomatous lesions Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins Chronic Inflammation Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins Chronic Inflammation Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins Healing of tissue Copyright © 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins