Nothing Special   »   [go: up one dir, main page]
Scribd Logo
Upload

Welcome to Scribd!

  • 2 views

    Chronic Inflammation

    Uploaded by

    Muhammad Faheem
    Chronic inflammation is a prolonged response lasting weeks or months where inflammation, tissue injury, and repair occur simultaneously. It can be caused by persistent infections, hypersensitivity reactions, prolonged toxic exposures, or other diseases. Morphologically, it features infiltration of mononuclear cells and attempts at healing amid ongoing tissue destruction. Macrophages and lymphocytes play dominant roles through secretion of cytokines and chemokines that activate other cells and recruit additional immune cells. Granulomatous inflammation forms structures to wall off persistent antigens. Systemic effects include fever through prostaglandin stimulation and acute phase responses mediated by cytokines like TNF, IL-1, IL-6 that induce liver synthesis of proteins such as C-reactive protein and serum amyloid A.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd

    Chronic Inflammation

    Uploaded by

    Muhammad Faheem
    2 views17 pages
    Chronic inflammation is a prolonged response lasting weeks or months where inflammation, tissue injury, and repair occur simultaneously. It can be caused by persistent infections, hypersensitivity reactions, prolonged toxic exposures, or other diseases. Morphologically, it features infiltration of mononuclear cells and attempts at healing amid ongoing tissue destruction. Macrophages and lymphocytes play dominant roles through secretion of cytokines and chemokines that activate other cells and recruit additional immune cells. Granulomatous inflammation forms structures to wall off persistent antigens. Systemic effects include fever through prostaglandin stimulation and acute phase responses mediated by cytokines like TNF, IL-1, IL-6 that induce liver synthesis of proteins such as C-reactive protein and serum amyloid A.

    Original Description:

    Copyright

    © © All Rights Reserved

    Available Formats

    PDF, TXT or read online from Scribd

    Did you find this document useful?

    Is this content inappropriate?

    Chronic inflammation is a prolonged response lasting weeks or months where inflammation, tissue injury, and repair occur simultaneously. It can be caused by persistent infections, hypersensitivity reactions, prolonged toxic exposures, or other diseases. Morphologically, it features infiltration of mononuclear cells and attempts at healing amid ongoing tissue destruction. Macrophages and lymphocytes play dominant roles through secretion of cytokines and chemokines that activate other cells and recruit additional immune cells. Granulomatous inflammation forms structures to wall off persistent antigens. Systemic effects include fever through prostaglandin stimulation and acute phase responses mediated by cytokines like TNF, IL-1, IL-6 that induce liver synthesis of proteins such as C-reactive protein and serum amyloid A.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    2 views17 pages

    Chronic Inflammation

    Uploaded by

    Muhammad Faheem
    Chronic inflammation is a prolonged response lasting weeks or months where inflammation, tissue injury, and repair occur simultaneously. It can be caused by persistent infections, hypersensitivity reactions, prolonged toxic exposures, or other diseases. Morphologically, it features infiltration of mononuclear cells and attempts at healing amid ongoing tissue destruction. Macrophages and lymphocytes play dominant roles through secretion of cytokines and chemokines that activate other cells and recruit additional immune cells. Granulomatous inflammation forms structures to wall off persistent antigens. Systemic effects include fever through prostaglandin stimulation and acute phase responses mediated by cytokines like TNF, IL-1, IL-6 that induce liver synthesis of proteins such as C-reactive protein and serum amyloid A.

    Copyright:

    © All Rights Reserved
    Download as PDF, TXT or read online from Scribd
    Download as pdf or txt
    of 17

    Pathology

    Response of Body to Injury & Infection

    Pharm D 3rd Prof


    Bahauddin Zakariya University Multan

    Waseem Ashraf
    Topic
    Chronic Inflammation

    Recommended Books:
    • Robbins and Cotran PATHOLOGIC BASIS OF DISEASE 1st South Asia Edition
    Chronic Inflammation
    Chronic inflammation is a response of prolonged duration (weeks or months) in which
    inflammation, tissue injury and attempts to repair coexist, in varying combinations.
    Causes of Chronic Inflammation
    Persistent infection
    • Difficult to eradicate infections (mycobacteria, fungal, viral, parasitic)
    • Delayed type hypersensitivity
    • Granulomatous inflammation
    Hypersensitivity diseases
    • Autoimmunity diseases (arthritis)
    • Allergic diseases (asthma)
    Prolonged exposure to potentially toxic agents, either exogenous or endogenous
    • Silica or small particles (exogenous)
    • Atherosclerosis
    Some other diseases or metabolic disorders e.g., Alzheimer disease / Type 2 Diabetes
    Morphologic Features
    Infiltration with mononuclear cells (Macrophages, lymphocytes and plasma cells)
    Tissue destructions
    Attempts at healing
    Cells and Mediators of Chronic Inflammation
    Macrophages
    • Dominant role in chronic inflammation
    • Release of cytokines & growth factors
    • Activating other cells (T lymphocyte)
    Circulating Monocytes
    Monocytes
    (half-life 1 day)
    Tissue Macrophages
    (half-life several months to years)
    Liver – Kupffer cells
    Spleen & Lymph nodes – Sinus histiocytes
    Central Nervous System – Microglial cells
    Lungs – Alveolar macrophages

    Macrophage
    Major Pathways of
    Macrophages Activation

    1. Classical Macrophage Activation


    a) Phagocytosis
    b) Secretion of inflammatory mediators
    c) Antigen presentation to lymphocytes
    d) Lymphocyte activation

    2. Alternative Macrophage Activation


    a) Angiogenesis
    b) Tissue growth & repair
    Lymphocytes
    T & B lymphocytes gets activated by microbes and environmental antigens
    Adaptive immunity
    Main cells seen in tissue with chronic inflammation
    Sever and persistent response
    Granulomatous inflammation
    Predominant in autoimmunity and hypersensitivity reactions
    CD4+ T-cells secrete cytokines inducing inflammation and influencing its nature
    Three subsets of CD4+ T-cells

    TH1 INF-γ, activates macrophages in classic pathway

    IL-4, IL-5 & IL-13; recruits eosinophiles and activates


    TH2
    macrophages alternative pathway

    TH17 IL-17 , induce chemokines secretion and recruits PMNs


    Activated B-lymphocytes and Antibody Production
    Specific antibodies against foreign antigen or self antigen
    Role in inflammation is not clear

    Tertiary Lymphoid Organs


    Accumulated lymphocytes, antigen presenting cells and plasma cells
    Rheumatoid Arthritis – synovium
    Hashimoto thyroiditis – thyroid
    Gastric ulcer – H-pylori infected gastric mucosa
    Eosinophils

    IgE and parasitic infections


    Recruitment by adhesion molecules and specific
    chemokines (eotaxin) derived from leukocytes and
    epithelial cells
    Granules contain major basic proteins / highly
    cationic toxic to parasites
    May cause tissue damage
    Eosinophilic inflammation
    Neutrophils in Chronic
    Mast Cells
    Inflammation
    Abundant in soft tissues Can stay longer after acute inflammation
    Active in both acute and chronic inflammation (persistent microbes
    Mast cells and basophils express FCεRI binds or continuous activation by cytokines)
    with FC portion of IgE leading to degranulation Chronic osteomyelitis (neutrophils exudate for
    releasing Histamine and Prostaglandins (food months)
    allergy, venom, drug allergy) Lung damage by smoking & irritants
    In chronic inflammation release a variety of Acute on chronic (or acute on top of chronic
    cytokines inflammation)
    Granulomatous Inflammation
    Granulomatous inflammation is a form of chronic inflammation characterized by collections of
    activated macrophages, often with T-lymphocytes, and sometimes associated with central necrosis.

    Activated macrophages – abundant cytoplasm, resemble epithelial cells (epitheloid cells)


    may fuse, forming multinucleate giant cells

    Granuloma formation to contain an offending agent


    Strong activation of T lymphocytes leading to macrophage activation causing injury to normal tissues

    Immune Granulomas Foreign body Granulomas


    Persistent T-cell mediated immune response because Inert foreign bodies, in absence of T cells mediated response
    of persistent microbe or self antigen Inert substances such as talc, sutures or other larger fibers
    Macrophages activate T-cell to produce cytokines (IL-2) Not phagocytosed by macrophages, non-immunogenic
    which activates other T-cells perpetuating response Often surrounded by epithelioid cells or giant cells.
    and IFN-γ which activates the macrophages IFN-γ which activates the macrophages
    Granulomatous Inflammation May have necrotic or non-necrotic center

    Necrotizing Granuloma Non-necrotizing Granuloma


    Examples of diseases with
    Granulomatous Inflammation
    Systemic Effects of Inflammation
    Cytokine induced systemic reactions – acute phase response

    Stimuli Acute Phase Proteins


    • Bacteria – LPS etc. • Mostly synthesized in Liver
    • Viruses – double stranded RNA, viral proteins etc. • Plasma concentration raises by 100 folds in
    Inflammatory mediators acute response
    • TNF, IL-1 and IL-6 • C-reactive protein (CRP) Opsonization
    Complement system
    • Type 1 interferons • Serum Amyloid A (SAA) activation
    Fever • Fibrinogen Rouleaux formation (ESR)
    • Acute phase response to infection
    • Hepcidin Reduced availability of Iron (Anemia)
    • Exogenous pyrogens (LPS etc. from Bacteria)
    • Endogenous pyrogens (TNF, IL-1) • Elevated CRP – risk of CV diseases such as
    • Prostaglandins (specially PGE2) stimulating
    myocardial infarction
    the production of neurotransmitters that reset
    the temperature at higher level (1°C to 4°C). • Elevated SAA – risk of secondary amyloidosis
    • NSAIDs can reduce fever by inhibiting PGs
    Systemic Effects of Inflammation
    Cytokine induced systemic reactions – acute phase response

    Leukocytosis Other Manifestations


    • Increased leukocyte count 15,000 to 20,000 Increased heart rate, blood pressure, decreased
    cells/mL sweating, rigors, chills, anorexia, somnolence,
    • Or in some cases 40,000 to 100,000 cells/mL malaise etc.
    • Neutrophilia Sepsis
    • Eosinophilia • High level of cytokines (cytokine storm)
    • Increased vascular coagulation
    • Lymphocytosis • Hypotensive shock
    • Leukopenia (decreased wbc count) typhoid fever, • Metabolic disturbances (insulin resist. &
    viral, protozoal infection etc. hypoglycemia)
    • Septic shock
    • In non-infectious situation Systemic
    Inflammatory Response Syndrome (SIRS)

    You might also like