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Inflammation is your body's first line of defense against harm. It's like a fire alarm that goes off when there's trouble, causing redness, swelling, heat, and pain. These signs help your immune system rally its troops to fight off invaders and start healing.
But inflammation isn't always helpful. If it sticks around too long, it can cause damage. Chronic inflammation is linked to diseases like arthritis and heart problems. Understanding how inflammation works helps us see why it's both a friend and foe to our health.
Inflammation and Fever
Signs and causes of inflammation
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- Redness (rubor)
- Caused by vasodilation and increased blood flow to the affected area
- Swelling (tumor)
- Caused by increased vascular permeability and fluid accumulation in the tissue (edema)
- Heat (calor)
- Caused by increased blood flow and metabolic activity in the inflamed area
- Pain (dolor)
- Caused by the release of pain mediators (prostaglandins, bradykinin) and pressure on nerve endings due to swelling
- Loss of function (functio laesa)
- Caused by pain, swelling, and tissue damage impairing normal function of the affected area
- Causes of inflammation include:
- Infectious agents (bacteria, viruses, fungi, parasites)
- Physical factors (trauma, burns, frostbite)
- Chemical agents (toxins, irritants, acids)
- Immunological reactions (hypersensitivity, autoimmunity)
- Fever
- Defined as a regulated increase in core body temperature above the normal range (typically >37.5°C or 99.5°F)
- Caused by pyrogens (fever-inducing substances)
- Exogenous pyrogens: microbial products (lipopolysaccharide from Gram-negative bacteria)
- Endogenous pyrogens: cytokines (interleukin-1, interleukin-6, tumor necrosis factor-α)
- Pyrogens act on the hypothalamus, the thermoregulatory center of the brain, to raise the set point for body temperature
Benefits vs risks of inflammation
- Benefits of inflammation
- Containment of the injurious agent or process by creating a physical barrier (fibrin clot, granulation tissue)
- Removal of damaged tissue and debris by phagocytic cells (neutrophils, macrophages)
- Initiation of the healing process
- Recruitment of immune cells (neutrophils, macrophages) to the site of injury
- Release of growth factors (PDGF, FGF) and cytokines (TGF-β) to promote tissue repair
- Potential risks of inflammation
- Excessive or prolonged inflammation can cause tissue damage
- Release of reactive oxygen species (ROS) and proteolytic enzymes (elastase, collagenase) by immune cells
- Collateral damage to healthy tissue surrounding the inflamed area
- Systemic effects of inflammation
- Sepsis: life-threatening organ dysfunction caused by a dysregulated host response to infection
- Systemic inflammatory response syndrome (SIRS): a generalized inflammatory response that can occur in the absence of infection (trauma, pancreatitis)
- Chronic inflammation can contribute to the development of various diseases
- Atherosclerosis: chronic inflammation of blood vessels leading to plaque formation
- Rheumatoid arthritis: autoimmune disorder causing chronic inflammation of joints
- Inflammatory bowel disease (Crohn's disease, ulcerative colitis)
- Neurodegenerative disorders (Alzheimer's disease, Parkinson's disease)
- Excessive or prolonged inflammation can cause tissue damage
Acute vs chronic inflammation
- Acute inflammation
- Rapid onset and short duration (usually a few days)
- Characterized by the classic signs of inflammation (redness, swelling, heat, pain, and loss of function)
- Mediated by neutrophils and macrophages recruited to the site of injury
- Typically resolves once the injurious agent is removed or neutralized and tissue repair is completed
- Involves the acute phase response, a systemic reaction to inflammation including fever and changes in plasma protein composition
- Chronic inflammation
- Prolonged duration (weeks, months, or even years)
- Lower intensity compared to acute inflammation but persistent
- Characterized by the presence of lymphocytes, plasma cells, and macrophages in the affected tissue
- Persistence of the inflammatory stimulus or failure of the resolution process leading to ongoing inflammation
- Can lead to tissue destruction, fibrosis, and loss of function over time
- Potential long-term effects of chronic inflammation
- Tissue remodeling and fibrosis
- Excessive deposition of extracellular matrix components (collagen, fibronectin)
- Can lead to organ dysfunction (cirrhosis of the liver, pulmonary fibrosis)
- Increased risk of developing certain cancers
- Chronic inflammation can create a microenvironment that promotes tumor growth and metastasis
- Examples: colorectal cancer in inflammatory bowel disease, hepatocellular carcinoma in chronic hepatitis
- Exacerbation of age-related diseases
- Inflammaging: a low-grade, chronic inflammatory state associated with aging
- Contributes to the development and progression of age-related diseases (osteoarthritis, sarcopenia, Alzheimer's disease)
- Tissue remodeling and fibrosis
Inflammatory mediators and processes
- Histamine: released by mast cells and basophils, causing vasodilation and increased vascular permeability
- Complement system: a group of plasma proteins that enhance the immune response and promote inflammation
- Leukocyte adhesion cascade: the process by which white blood cells adhere to and migrate through blood vessel walls to reach the site of inflammation
- Resolution of inflammation: the active process of returning inflamed tissue to its normal state, involving specialized pro-resolving mediators
Key Terms to Review (83)
Activated macrophages: Activated macrophages are immune cells that have been stimulated by cytokines to enhance their phagocytic, antimicrobial, and antigen-presenting capabilities. These cells play a critical role in the body's defense mechanisms against pathogens and in inflammatory responses.
Acute inflammation: Acute inflammation is the immediate and early response of the body to harmful stimuli like pathogens, damaged cells, or irritants. It aims to eliminate the initial cause of cell injury, clear out necrotic cells and tissues, and establish a repair process.
Acute rheumatic fever: Acute rheumatic fever is an inflammatory disease that can develop as a complication of untreated or poorly treated Streptococcus pyogenes throat infections. It primarily affects the heart, joints, skin, and brain.
Antisepsis: Antisepsis is the practice of using chemical agents to eliminate or inhibit pathogenic microorganisms on living tissues, particularly skin and mucous membranes. It is a crucial procedure in preventing infections during medical procedures.
Antihistamine: An antihistamine is a type of medication that blocks histamine receptors to alleviate symptoms of allergic reactions. They are commonly used to treat conditions such as hay fever, urticaria, and other hypersensitivities.
Bradykinin: Bradykinin is a peptide that causes blood vessels to dilate (enlarge), leading to increased permeability and allowing immune cells to access affected tissues. It plays a crucial role in inflammation and pain signaling.
Chronic inflammation: Chronic inflammation is a prolonged inflammatory response that can last for months or years, often due to persistent infection, autoimmune response, or prolonged exposure to harmful agents. It involves the continuous presence of immune cells and can lead to tissue damage and disease.
Complement system: The complement system is a group of proteins that enhance the ability of antibodies and phagocytic cells to clear pathogens from an organism. It forms part of the innate immune response and also helps bridge innate and adaptive immunity.
Crisis phase: The crisis phase is the period during which the body's innate immune response reaches its peak in combating an infection, characterized by intense inflammation and fever. It marks a critical point where either recovery or severe disease progression can occur.
Cytokines: Cytokines are small proteins released by cells, especially those of the immune system, that have a specific effect on interactions and communications between cells. They play crucial roles in regulating immune responses and inflammation.
Edema: Edema is the abnormal accumulation of fluid in interstitial tissues, leading to swelling. It can be caused by various factors, including infections that affect the circulatory and lymphatic systems.
Elastase: Elastase is a proteolytic enzyme that breaks down elastin, a key component of connective tissue. It is produced by certain bacteria and fungi as a virulence factor to facilitate tissue invasion.
Elephantiasis: Elephantiasis is a parasitic infection characterized by extreme swelling of the limbs and other body parts. It is most commonly caused by the filarial worms Wuchereria bancrofti, Brugia malayi, and Brugia timori.
Erythema: Erythema is the medical term for redness of the skin or mucous membranes caused by increased blood flow in superficial capillaries. It often presents as a primary response to infection, inflammation, or irritation.
Fever: Fever is an elevated body temperature that occurs as part of the body's immune response to infection or inflammation. It acts as a defense mechanism to inhibit the growth of pathogens and enhance immune function.
Granuloma: A granuloma is an organized collection of immune cells formed in response to chronic inflammation, often due to persistent pathogens or foreign substances. It serves to isolate the offending agent but can also contribute to tissue damage.
Hereditary angioedema: Hereditary angioedema (HAE) is a genetic disorder characterized by recurrent episodes of severe swelling in various parts of the body, including the skin, gastrointestinal tract, and airways. It results from a deficiency or dysfunction of C1 inhibitor, a protein involved in regulating the complement system.
Hypothalamus: The hypothalamus is a small region of the brain that plays a crucial role in maintaining homeostasis by regulating various autonomic processes, including body temperature and fever response.
Inflammation: Inflammation is the body's immediate response to injury or infection, characterized by redness, heat, swelling, and pain. It aims to eliminate the initial cause of cell injury, clear out damaged cells and tissues, and establish repair.
Lipopolysaccharide (LPS): Lipopolysaccharide (LPS) is a large molecule found in the outer membrane of Gram-negative bacteria. It plays a crucial role in bacterial pathogenicity and triggers strong immune responses in hosts.
Lymphatic filariasis: Lymphatic filariasis is a parasitic disease caused by microscopic, thread-like worms that infect the lymphatic system, leading to severe inflammation and chronic swelling. It is transmitted to humans through the bites of infected mosquitoes.
Neutrophils: Neutrophils are a type of white blood cell that play a crucial role in the innate immune response. They are the first responders to microbial infection and are highly active in phagocytosis.
Opsonins: Opsonins are molecules that enhance phagocytosis by marking antigens for an immune response. They bind to the surface of pathogens, making them more recognizable to phagocytic cells.
PAMPs: Pathogen-associated molecular patterns (PAMPs) are molecular structures found on pathogens that are recognized by the innate immune system. These patterns trigger an immune response aimed at eliminating the pathogen.
Plasma cells: Plasma cells are differentiated B lymphocytes that produce and secrete large quantities of antibodies. They play a critical role in the humoral immune response by targeting specific antigens.
Pyrogens: Pyrogens are substances that cause an increase in body temperature by triggering the hypothalamus to elevate the body's set point. They can be exogenous, originating from outside the body such as bacteria, or endogenous, produced within the body like cytokines.
Pus: Pus is a thick fluid composed of white blood cells, dead tissue, and bacteria, typically resulting from an infection. It is a sign of the body's immune response to fight off pathogens.
Rheumatoid arthritis: Rheumatoid arthritis is a chronic autoimmune disorder characterized by inflammation of the joints, leading to pain and deformity. It occurs when the immune system mistakenly attacks the body's own tissues.
Scarlet fever: Scarlet fever is an infectious disease caused by the bacterium Streptococcus pyogenes, characterized by a red rash and high fever. It primarily affects children and can have serious complications if untreated.
Toxic shock syndrome: Toxic shock syndrome (TSS) is a rare, life-threatening condition caused by bacterial toxins, primarily from Staphylococcus aureus and Streptococcus pyogenes. It leads to sudden high fever, rash, and multi-organ failure.
Tubercle: A tubercle is a small, rounded nodule formed by the aggregation of immune cells, primarily macrophages, around a pathogen. It is commonly associated with the body's response to Mycobacterium tuberculosis.
Tuberculosis: Tuberculosis (TB) is a contagious bacterial infection caused by Mycobacterium tuberculosis. It primarily affects the lungs but can spread to other organs.
Vasodilation: Vasodilation is the widening of blood vessels resulting from relaxation of the muscular walls of the vessels. It increases blood flow to tissues and helps in thermoregulation and immune response.
Vasoconstriction: Vasoconstriction is the narrowing of blood vessels due to the contraction of muscular walls, primarily in arteries and arterioles. This process reduces blood flow and increases blood pressure.
Fever: Fever is an elevation of the body's temperature above the normal range, typically as a result of the immune system's response to an infection or other illness. It is a common symptom that indicates the body is fighting off a pathogen or responding to inflammation.
Complement System: The complement system is a complex network of proteins that work together as part of the immune system's chemical defenses. It is a crucial component of the body's innate and adaptive immune responses, playing a vital role in inflammation, pathogen elimination, and the clearance of immune complexes.
Acute Phase Response: The acute phase response is a rapid, systemic, and nonspecific reaction of the body to various forms of inflammation, infection, tissue damage, or other stressors. It is a coordinated series of physiological and biochemical changes that occur to help the body combat the underlying cause of the disturbance and restore homeostasis.
Neutrophils: Neutrophils are a type of white blood cell that play a crucial role in the body's innate immune response. They are the most abundant type of white blood cells and are the first responders to sites of infection or inflammation, acting as the body's primary defense against bacterial and fungal pathogens.
Lymphocytes: Lymphocytes are a type of white blood cell that play a crucial role in the body's immune response. They are responsible for recognizing and responding to foreign invaders, such as bacteria, viruses, and other pathogens, as well as abnormal cells within the body.
Macrophages: Macrophages are a type of large white blood cell that play a crucial role in the immune system's cellular defenses, inflammation and fever response, antigen presentation, and defense against bacterial infections. They are derived from monocytes and act as the first line of defense against pathogens and damaged cells.
Histamine: Histamine is a biogenic amine that plays a crucial role in various physiological and pathological processes within the human body. It is primarily involved in the regulation of immune responses, inflammation, and hypersensitivity reactions.
Vasodilation: Vasodilation is the widening or dilation of blood vessels, particularly the arteries and arterioles, which leads to an increase in blood flow. This physiological process is crucial in various bodily functions, including cellular defenses, inflammation, and hypersensitivity reactions.
Inflammation: Inflammation is a complex biological response of the body's immune system to various stimuli, such as pathogens, damaged cells, or irritants. It is a protective mechanism that helps the body eliminate harmful agents and initiate the healing process.
Cytokines: Cytokines are a diverse group of small proteins secreted by various cells, primarily immune cells, that act as signaling molecules to coordinate and regulate immune responses, inflammation, and other physiological processes. They play a crucial role in cellular defenses, pathogen recognition, inflammation, adaptive immunity, and various immune-related disorders and conditions.
Rubor: Rubor, or redness, is one of the five classic signs of inflammation, along with dolor (pain), calor (heat), tumor (swelling), and functio laesa (loss of function). It is a visible manifestation of the body's immune response to injury, infection, or irritation, and is characterized by a localized reddening of the affected area.
Interleukin-6: Interleukin-6 (IL-6) is a multifunctional cytokine that plays a central role in the body's inflammatory response and fever regulation. It is produced by a variety of cells, including T cells, B cells, monocytes, and endothelial cells, and acts as a signaling molecule to coordinate the immune system's reaction to infection, injury, or other stressors.
Rheumatoid Arthritis: Rheumatoid arthritis is an autoimmune disorder characterized by chronic inflammation of the joints, leading to pain, stiffness, and progressive joint damage. It is a systemic condition that can affect various organs and tissues throughout the body.
Chronic Inflammation: Chronic inflammation is a prolonged and persistent inflammatory response in the body, characterized by the continuous activation of the immune system and the presence of inflammatory cells and mediators. It is a key feature of many chronic diseases and can lead to tissue damage and dysfunction over time.
Prostaglandins: Prostaglandins are a group of lipid-based compounds that act as signaling molecules in the body, playing crucial roles in inflammation, fever, and other physiological processes. They are derived from arachidonic acid and are produced by various cells throughout the body.
Dolor: Dolor is the medical term used to describe the subjective experience of physical pain or discomfort. It is a fundamental component of the inflammatory response and a key indicator of various pathological conditions.
TGF-β: TGF-β, or Transforming Growth Factor-beta, is a multifunctional cytokine that plays a crucial role in various physiological and pathological processes, including inflammation, immune regulation, and autoimmune disorders.
Tumor: A tumor is an abnormal growth of cells that can be either benign (non-cancerous) or malignant (cancerous). Tumors are a key aspect of the inflammatory response and can be associated with fever, as they can trigger an immune reaction in the body.
Edema: Edema is the abnormal accumulation of fluid in the body's tissues, often resulting in swelling. It is a common symptom associated with various medical conditions and can occur in different parts of the body.
Bradykinin: Bradykinin is a potent vasodilator and pro-inflammatory peptide that is released during the inflammatory response. It plays a crucial role in the regulation of blood pressure, vascular permeability, and the initiation of pain and fever.
Tumor Necrosis Factor-α: Tumor necrosis factor-α (TNF-α) is a pro-inflammatory cytokine produced primarily by activated macrophages and other immune cells. It plays a central role in the inflammatory response and the regulation of immune cells, making it a key mediator of both inflammation and fever.
Elastase: Elastase is a proteolytic enzyme that breaks down the structural protein elastin, which is a key component of the extracellular matrix in various tissues. It plays a crucial role in the context of pathogen recognition, phagocytosis, and the inflammatory response.
Pyrogens: Pyrogens are substances that can induce fever by stimulating the release of inflammatory mediators, such as cytokines, in the body. They are an important factor in the context of inflammation and fever, as they can trigger the body's immune response and lead to the development of these physiological conditions.
Atherosclerosis: Atherosclerosis is a chronic inflammatory condition characterized by the buildup of plaque, composed of cholesterol, fatty substances, cellular waste products, calcium, and other materials, within the inner lining of the arteries. This gradual accumulation of plaque can restrict blood flow and increase the risk of heart attack, stroke, and other cardiovascular events.
Systemic Inflammatory Response Syndrome: Systemic Inflammatory Response Syndrome (SIRS) is a clinical condition characterized by a widespread inflammatory response to a variety of severe clinical insults, including infection, trauma, burns, and other critical illnesses. It is a dysregulated immune response that can lead to organ dysfunction and, if uncontrolled, progress to life-threatening sepsis.
Functio Laesa: Functio laesa, or impaired function, refers to the disruption or impairment of normal physiological function in the body as a result of disease, injury, or other pathological processes. It is a key concept in the understanding of inflammation and fever, as these conditions can lead to various functional impairments within the affected tissues and systems.
Phagocytic Cells: Phagocytic cells are a type of immune cell that play a crucial role in the body's defense against pathogens and foreign substances. These cells are capable of engulfing and digesting harmful microorganisms, cellular debris, and other unwanted materials, thereby protecting the host from infection and disease.
Calor: Calor is the Latin word for 'heat' and refers to the sensation of warmth or elevated temperature associated with various physiological processes, particularly in the context of inflammation and fever.
Interleukin-1: Interleukin-1 (IL-1) is a pro-inflammatory cytokine produced by various cells, including macrophages, dendritic cells, and endothelial cells. It plays a crucial role in the body's inflammatory response and the regulation of immune functions.
Hypothalamus: The hypothalamus is a small, but critical, region of the brain that plays a vital role in regulating various physiological processes, including inflammation and fever. As a key component of the neuroendocrine system, the hypothalamus serves as a bridge between the nervous system and the endocrine system, allowing it to coordinate the body's response to both internal and external stimuli.
Fibrosis: Fibrosis is the formation of excess fibrous connective tissue in an organ or tissue, often as a result of injury, inflammation, or disease. It is a pathological process that can impair the normal function of the affected organ or tissue.
FGF: FGF, or Fibroblast Growth Factor, is a family of proteins that play a crucial role in regulating various cellular processes, including cell growth, differentiation, and survival. FGFs are involved in a wide range of physiological and pathological processes, particularly in the context of inflammation and fever.
Sepsis: Sepsis is a life-threatening condition that arises when the body's response to an infection spirals out of control, triggering widespread inflammation that can lead to organ dysfunction and even death. It is a critical medical emergency that requires prompt recognition and treatment to prevent severe complications.
Inflammatory Bowel Disease: Inflammatory bowel disease (IBD) is a group of chronic, inflammatory conditions that affect the gastrointestinal tract, primarily the small and large intestines. IBD is characterized by an abnormal immune response that leads to persistent inflammation and damage to the digestive system.
Acute Inflammation: Acute inflammation is the body's immediate and short-term response to harmful stimuli, such as pathogens, damaged cells, or irritants. It is a protective mechanism that aims to remove the initial cause of cell injury, clear out necrotic cells and tissues damaged from the original insult, and initiate the healing process.
PDGF: PDGF, or Platelet-Derived Growth Factor, is a potent mitogen and chemoattractant that stimulates the growth, proliferation, and migration of various cell types, particularly fibroblasts, smooth muscle cells, and cells of mesenchymal origin. It plays a crucial role in the inflammatory response and wound healing processes.
Crohn's Disease: Crohn's disease is a type of inflammatory bowel disease (IBD) that causes chronic inflammation and irritation in the digestive tract. It can affect any part of the gastrointestinal system, from the mouth to the anus, but it most commonly occurs in the end of the small intestine (the ileum) and the beginning of the colon.
Ulcerative Colitis: Ulcerative colitis is a chronic inflammatory bowel disease that causes inflammation and ulcers in the lining of the large intestine (colon) and rectum. It is characterized by periods of flare-ups and remission, and can significantly impact a person's quality of life if not properly managed.
Inflammaging: Inflammaging is the chronic, low-grade inflammation that occurs with aging, characterized by the persistent activation of the immune system and the increased production of inflammatory mediators. This process contributes to the development and progression of various age-related diseases.
Sarcopenia: Sarcopenia is the age-related loss of skeletal muscle mass and strength, leading to decreased physical function and mobility. It is a key factor in the development of frailty and is closely linked to the processes of inflammation and fever.
Leukocyte Adhesion Cascade: The leukocyte adhesion cascade is a multi-step process that facilitates the recruitment and migration of white blood cells (leukocytes) from the bloodstream to sites of inflammation or infection. This cascade is a crucial component of the body's immune response and inflammation.
Cirrhosis: Cirrhosis is a chronic liver disease characterized by the replacement of normal liver tissue with non-functioning scar tissue. This condition can lead to a variety of complications and is often associated with inflammation and viral infections of the gastrointestinal tract.
Pulmonary Fibrosis: Pulmonary fibrosis is a chronic, progressive lung disease characterized by the formation of scar tissue within the lungs. This scarring impairs the lungs' ability to function properly, leading to breathing difficulties and reduced oxygen supply to the body.
Resolution of Inflammation: Resolution of inflammation is the process by which the body actively terminates and restores homeostasis after an inflammatory response. It involves the coordination of various cellular and molecular mechanisms to return the affected tissue to its normal state and function.
Osteoarthritis: Osteoarthritis is a degenerative joint disease characterized by the breakdown and eventual loss of the cartilage that cushions the ends of the bones where they meet to form a joint. This leads to the bones rubbing together, causing pain, swelling, and loss of motion in the affected joint.
Plasma Cells: Plasma cells are terminally differentiated B lymphocytes that are responsible for the production and secretion of antibodies, playing a crucial role in the humoral immune response. These specialized cells arise from activated B cells and are central to the adaptive immune system's ability to provide long-lasting protection against pathogens.
Lipopolysaccharide: Lipopolysaccharide (LPS) is a complex molecule found in the outer membrane of Gram-negative bacteria. It is a key component of the bacterial cell wall and plays a crucial role in various aspects of microbiology, immunology, and pathogenesis.
Reactive Oxygen Species: Reactive oxygen species (ROS) are highly reactive molecules containing oxygen, including superoxide, hydrogen peroxide, and hydroxyl radicals. They are generated as byproducts of normal cellular metabolism and play important roles in microbial growth and the inflammatory response.
Collagenase: Collagenase is an enzyme that breaks down the protein collagen, which is a major structural component of connective tissues in the body. This enzyme plays a crucial role in the catabolism of lipids and proteins, as well as in the inflammatory response during injury or infection.