Inflammation Flashcards
What is stress?
a state manifested by a specific syndrome of the body developed in response to any stimuli that made an intense systemic demand on it
What parts of the nervous system play a role in the stress response?
Neuronal pathways, RAS, cerebral cortex, limbic system, thalamus, hypothalamus, pituitary gland
What are the residual effects that may occur following a stress response?
-Headaches, nausea, insomnia, and emotional disturbances
-Prolonged or frequent stress responses can lead to: Ulcers, CV and kidney disease, long term mental health issues, reproductive issues, irregular menstruation, under/overactive stress response
What does Corticotropin-Releasing Factor (CRF) do?
-Secreted by the hypothalamus
-Induces secretion of Adrenocorticotropic Hormone (ACTH) from the anterior pituitary gland
What does Adrenocorticotropic Hormone (ACTH) do?
-Secreted by the anterior pituitary gland
-Stimulates the secretion of cortisol (glucocorticoid hormone) from the adrenal glands
What does cortisol do?
-Secreted by the adrenal glands
-Maintains blood glucose levels, enhances effects of CV catecholamines, inhibits less essential activities (hematopoiesis, immune responses, etc
What does Angiotensin II do?
-Stimulates release of norepinephrine, enhances CRF formation and release, causes vasoconstriction
-Key part of the Renin-Angiotensin-Aldosterone system
What does Antidiuretic Hormone (ADH) aka vasopressin do?
-Secreted by the posterior pituitary gland
-Increased water retention by the kidneys, vasoconstriction
-Many other hormones are involved in smaller roles, and many are not fully understood
What is suppressed during stress response?
The bodies stress response also suppresses its immune response
What are red blood cells (aka erythrocytes)?
-Most abundant formed element
-Primary function is transport of O2 and CO2 via hemoglobin
What is hemoglobin
-Globin protein and 4 heme rings
-Each heme ring contains iron ion (Fe2+) that binds to one O2 molecule - each hemoglobin molecule binds with 4 O2
What is erythropoiesis?
The production of RBCs in the red bone marrow
What are white blood cells (aka leukocytes)?
-Granular or agranular, based on having cytoplasmic granules
-Short lifespan (even shorter during inflammation /infection)
What are neutrophils?
phagocytes (most abundant WBC)
What are eosinophils?
combats histamine in allergic reactions
What are basophils?
intensifies inflammatory response in allergic reactions
What are lymphocytes?
immune response (B cells, T cells)
What are monocytes?
phagocytes (become macrophages when the migrate)
What is leukocytosis?
increased circulating WBCs (normal during infection, inflammation, stress, etc)
What is leukopenia?
decreased circulating WBCs (not normal)
What are platelets?
-Membrane enclosed fragments of larger cells
-Lifespan of 5-9 days
-Contain and release chemicals to promote blood clotting
-Aggregate (stick together) to form a platelet plug
What is hemostasis?
sequence of events to stop bleeding
What is inflammation?
-The reaction of vascularized tissues to an injury
-Involves a wide variety of physiologic and pathologic responses intended to eliminate the initial cause of cell injury, removal of damaged tissue, and generation of new tissue
What is added to a word for inflammatory conditions?
The suffix -itis is typically added
What are the signs and symptoms of inflammation?
(PRISH)
Pain - release of certain chemicals
Redness - increased blood flow to affected area
Immobility - loss of function
Swelling - accumulation of fluids
Heat - increased blood flow to affected area
What is acute inflammation?
-The early protective response of local tissues and their blood vessels to injury
-Relatively short duration (minutes to days)
-Critical to the restoration of homeostasis
-Occurs before adaptive immunity is established and is aimed at removing the injurious agent and limiting the extent at tissue damage
What can acute inflammation be triggered by?
Infections, immune reactions, blunt and penetrating trauma, physical or chemical agents, tissue necrosis
What are the 2 components of acute inflammation?
Vascular stage (increased blood flow) and cellular stage (migration of leukocytes)
What cells and tissues are involved in this process?
Endothelial, WBCs, connective tissue cells (mast cells, fibroblasts, macrophages, lymphocytes), extracellular matrix (ECM)
What is the ECM?
fibrous proteins (collagen and elastin), adhesive glycoproteins, proteoglycans
What are endothelial cells?
Single-cell inner lining of blood vessels
What do endothelial cells do in acute inflammation?
-produce antiplatelet and antithrombotic agents that maintain vessel patency and vasodilators and constrictors that regulate blood flow
-function as a selectively permeable barrier to inflammatory stimuli
-regulates leukocyte extravasation
-movement of leukocytes out of circulation toward damaged tissue
-synthesizes and releases inflammatory mediators
What do platelets do in acute inflammation?
-Once activated, they release inflammatory mediators to aid in the process
-Over 300 proteins are released
-Causing increased vascular permeability and altered endothelial adhesion
What do neutrophils do in acute inflammation?
-Primary phagocyte that arrives to the inflammatory site early
-Granules contain enzymes and antibiotic material that are used to destroy engulfed microbes or dead tissue
-Neutrophil count in the blood increases substantially during the inflammatory process
-After being released from the bone marrow they only have a lifespan of 10 hours - during inflammation, more are constantly being created and released (sometimes before they are fully mature)
What do monocytes and macrophages do in inflammation?
-Arrive at the inflammation site shortly after neutrophils and live longer
-Produce potent vasoactive inflammatory mediators to help promote the regeneration of tissues
-Play a key role in chronic inflammation
What do eosinophils, basophils, and mast cells do for inflammation?
-Produce lipid mediators and cytokines that induce inflammation
-Particularly important in immediate hypersensitivity reactions and allergic disorders
What do eosinophils do?
- Contain a protein toxic to parasitic worms that cannot be phagocytized
-Control the release of specific chemical mediators in allergic reactions
What do basophils do?
-Granules of basophils contain histamine and other inflammatory mediators
-Bind to the antibody immunoglobulin E (IgE) - similar to mast cells
-Triggers the release of histamine and other vasoactive agents
What do mast cells do?
-Similar derivation to basophils but lodge in tissues instead of remaining in circulation
-Activation causes release of histamine and cytokines as well as the synthesis of prostaglandins
-Also triggers other inflammatory cells
What occurs in the vascular phase of inflammation?
-Tissue damage causes an immediate and brief vasoconstriction in microcirculation (venules, capillaries and arterioles)
-Vasodilation follows causing blood, and with it, inflammatory mediators, to rush to the site of injury (redness and warmth)
-Inflammatory mediators trigger an increase in the permeability of the vascular membrane (endothelial cells) causing fluid to leak into the extravascular space, this slows the blood flow in the micro vessels
-Changes in osmotic pressure pull more fluid into the tissues leading to swelling, pain and decreased function
What is the cellular phase?
-Marked by movement of phagocytic leukocytes into the area of infection
-Leukocytes in the blood take time to arrive so mast cells and macrophages propositioned in the tissues initiate the rapid response
What occurs in the celluar phase?
-Mast cells and tissue macrophages start working while intravascular leukocytes make their way to the infection/tissue damage
-Leukocytes accumulate along the vessel wall (margination) and release cytokines
-Cytokines trigger the endothelial cells to adhere to the leukocytes and allow passage through
(transmigration)
-Leukocytes find their way to the infection via chemotaxis
-Microbes/damaged tissue are destroyed via phagocytosis
What produces the signs and symptoms of inflammation?
by chemical mediators
What are plasma derived mediators?
Coagulation factors and complement proteins. Must be activated
What are cell derived mediators?
Histamines, cytokines, etc. Located in granules and must be secreted or newly synthesized
What is histamine?
-Stored in many different tissue cells as preformed histamine
-Mostly in connective tissue adjacent to blood vessels (mast cells)
-One of the first mediators to be released in acute inflammation
-Causes dilation of arterioles and increased permeability of venules
-Binds to H1 receptors in endothelial cells
-Antihistamine drugs are H1 receptor antagonists
What is Platelet-Activating Factor (PAF)?
Induces platelet aggregation, activates neutrophils, eosinophil chemoattractant
What are Arachidonic Acid Metabolites?
-Release of arachidonic acid leads to production of other important inflammatory mediators
-Prostaglandins, thromboxane, leukotrines (LTs)
-ASA - inhibits synthesis of thromboxane and prostaglandins
What do leukotrines do?
increased microvessel permeability
What do prostaglandins do?
inhibits inflammatory cell function. Vasodilation.
What does thromboxane A2 do?
vasoconstriction. Promotes platelet function.
What do cytokines do?
-Many different inflammatory and immune functions
-Result in: fever, hypotension, increased HR
What do chemokines do?
-A type of cytokine
-Recruit and direct the migration of immune and inflammatory cells
What does NO do?
Smooth muscle relaxation, platelet antagonist, leukocyte recruiter
What do oxygen free radicals do?
-Free radical - atom/ion with an unpaired valance electron - highly chemically reactive
-May be released by other inflammatory cells and mediators
-Can increase inflammatory process and create further tissue damage
What are exudates?
mass of cells and fluid that has leaked out of blood vessels or organs
What is serous exudate?
watery, low in protein. Plasma entering inflammation site
What is hemorrhagic exudate?
damaged blood vessels, or capillary leakage of RBCs
What is fibrinous exudate?
++fibrinogen. Thick and sticky
What is membranous exudate?
develop on mucous membranes. Contain necrotic cells
What is purulent exudate?
pus. Composed of degraded WBCs, protein, tissue debris
What is an abcess?
localized area of inflammation containing purulent exudate surrounded by a neutrophil layer
What is an ulceration?
site of inflammation where an epithelial surface has become necrotic and eroded. Subepithelial inflammation active.
What is chronic inflammation?
-Self-perpetuating and may last weeks to years
-Often caused by recurrent progressive acute inflammation, failed acute response or chronic
disease process
-Macrophages and lymphocytes are more commonly abundant in chronic inflammation (neutrophil heavy in acute inflammation)
-We also see a proliferation of fibroblasts instead of exudates
-Higher chance of scarring and deformity than acute inflammation
What are the causes of chronic inflammation?
typically low-grade, persistent infections or irritants that are unable to penetrate deeply or spread rapidly
What is nonspecific chronic inflammation?
-Diffuse accumulation of macrophages and
lymphocytes
-Ongoing chemotaxis leads to their continued infiltration, and their long lifespan contributes to the build up
-Leads to fibroblast proliferation and scar tissue (parenchymal or stromal tissue)
As inflammatory mediators are released into the blood stream, what systemic manifestations
can occur?
-Acute Phase Responses
-White Blood Cell Response
-Lymphadenitis
What are acute phase responses?
-Changes in plasma protein levels - inflammatory cells and mediators
-Weakness/fatigue - skeletal muscle catabolism for amino acids and energy
-Fever - cytokines affect hypothalamus thermoregulatory center
-Anorexia, somnolence, malaise
What is a white blood cell response?
-Leukocytosis is a very common sign of inflammation – especially when caused by a bacterial infection
-Depending on the type of inflammatory stimulus, there will be an increase or decrease in different types of leukocytes
What is lymphadenitis?
Enlargement of one or more lymph nodes
What is systemic inflammatory response syndrome (SIRS)?
-In severe bacterial infections (sepsis), the large quantities of microorganisms result in an uncontrolled inflammatory response
-Production and release of large amounts of inflammatory cytokines
What do the cytokines in SIRS cause?
Generalized vasodilation, increased vascular permeability, intravascular fluid loss, myocardial depression, shock
What does Acetylsalicylic Acid (ASA, Aspirin) do?
-Inhibits platelet synthesis of thromboxane A2 - a potent vasoconstrictor and inducer of platelet aggregation
-Inhibits prostaglandin synthesis (reduced fever, pain, swelling)
What does Ibuprofen (Advil) and Acetaminophen (Tylenol) do?
Inhibits prostaglandin synthesis (reduced fever, pain, swelling)
What is tissue regeneration?
Injured cells are replaced with cells of the same type, leaving no trace of injury
What is tissue replacement?
injured cells are replaced with connective tissue, leaving. Permanent scar.
What is parenchymal tissue?
functional tissue/cells - (Hepatocytes, myocytes)
What is stromal tissue?
structural and supporting tissue/cells - (Connective tissue, blood vessels, extracellular matrix (ECM))
According to their ability to undergo tissue regeneration, body cells are divided into what 3 types?
Labile Cells, Stable Cells, Permanent Cells
What are labile cells?
-cells that continue to divide and replicate throughout life
-surface epithelial cells (skin, oral cavity, GI/GU and reproductive tracts)
What are stable cells?
-cells that stop dividing when growth (of the organism) ceases
-Capable of undergoing regeneration when necessary -Parenchymal cells of the liver and kidney, smooth muscle, vascular endothelium)
What are permanent cells?
-cannot undergo mitotic cell division (replaced with scar tissue)
-nerve cells, skeletal/cardiac muscle cells
What is granulation tissue?
Glistening red, moist connective tissue that contained newly formed capillaries, proliferating fibroblasts and residual inflammatory cells
What is scar tissue?
Fibroblasts work to build onto granulation tissue with a network of collagen fibers, elastic tissue inactive fibroblasts, and other ECM components.
What is the extra cellular matrix (ECM)?
network of proteins and other molecules that surround, support and give structure to cells and tissues (fills the spaces between cells of connective tissue)
What are growth factors?
-hormone-like molecules that interact with specific cell receptors to control and direct tissue repair
-control the proliferation, differentiation and metabolism of cells involved in wound healing
What is wound closure by primary intention?
primarily for smaller injuries and typically results in no
scar tissue
What is wound closure by secondary intention?
For larger wounds. Slower process and typically results in larger amounts of scar tissue. Smaller wounds that become infected may end up healing by secondary intention
What occurs in the inflammatory phase of wound healing?
-Hemostasis
-Neutrophils (phagocytes) arrive first
-Macrophages after 24hrs
-Growth factor
What occurs in the proliferative phase of wound healing?
-Fibroblasts
-Synthesizes and secretes collagen and growth factor
-Induces angiogenesis and endothelial cell proliferation
-Epithelialization – wound edges proliferate inwards
What occurs in the remodeling phase of wound healing?
-3 weeks after injury up to 6+ months
-Scar tissue is remodeled to improve its tensile strength and shrink
-Performed by fibroblasts synthesizing collagen
-Decrease in vascularity
What factors effect wound healing?
-Malnutrition, impaired blood flow, hypoxia,
impaired inflammatory and immune response,
infection, wound separation, foreign bodies,
age
-Some disorders including: diabetes mellitus, peripheral artery disease, venous insufficiency, nutritional disorders
