Chronic Inflammation Quiz

Chronic Inflammation

• Definition: Inflammation of prolonged duration, where active inflammation, tissue injury, and healing occur simultaneously.
• Duration: Weeks to months or years.
• Features: Fibrosis (scarring), lymphocytes, and macrophages are key components.

Chronic Inflammation Characteristics

• Involves the persistence or recurrence of the injurious agent.
• Characterized by prolonged inflammation.
• Inflammatory cells damage tissue, while healing attempts occur.
• New vessel formation (angiogenesis) and fibrosis contribute to healing/repair.
• Mononuclear cells (macrophages, lymphocytes, and plasma cells) infiltrate the affected area.

Causes of Chronic Inflammation

• Unresolved acute inflammation: Examples include chronic abscesses.
• Repeated acute inflammation: Examples include chronic pancreatitis.
• Delayed hypersensitivity reaction: Examples of intracellular agents include brucellosis and viral infections, and examples of other agents include fungi and parasites.
• Repeated contact sensitivity: Examples include contact dermatitis.
• Foreign body reaction:
  • Endogenous material: Examples include fat and uric acid crystals in gout.
  • Exogenous material: Examples include suture material, asbestos, and silica.
• Autoimmune disease: Examples include Hashimoto's disease.
• Unknown reasons: Examples include inflammatory bowel disease and sarcoidosis.

Chronic Inflammatory Cells: Macrophages

• Origin: Derived from blood monocytes, migrating within the first 24 to 48 hours of acute inflammation.
• Transformation: Transform into large cells (macrophages) capable of phagocytosis.
• Activation: Can become activated, increasing cell size, lysosomal enzymes, and metabolic activity to kill ingested organisms.
• Effects in inflammation:
  • Phagocytosis.
  • Chemotaxis.
  • Tissue injury (due to ECM lysis and increasing injury).
  • Angiogenesis (increase in endothelial cells).
  • Fibrosis (increase in fibroblasts).
  • Multinucleated giant cells.
• Types: Different stimuli lead to the activation of two types of macrophages
  • Classically activated macrophages (M1): Microbicidal actions (phagocytosis, killing of bacteria and fungi), inflammation, and tissue repair. Driven by products and cytokines, especially IFN-γ.
  • Alternatively activated macrophages (M2): Tissue repair, fibrosis, and anti-inflammatory effects. Induced by IL-4 and IL-13, by TH2 cells (helper T cells) & other leukocytes.

Chronic Inflammatory Cells: Macrophages in Chronic Inflammation

• Secreted products after activation: Biologically active products, which can cause tissue injury and fibrosis. Including:
  • Proteases and plasminogen activator.
  • Complement components and coagulation factors.
  • Reactive oxygen species and NO.
  • Arachidonic acid metabolites.
  • Cytokines.
• Fibrosis: Growth factors influence the proliferation of smooth muscle cells and fibroblasts, leading to extracellular matrix production. Also, cytokines, angiogenesis factors, and collagenase contribute to this process.

Chronic Inflammatory Cells: Lymphocytes

• Stimulus: Mobilized in response to specific (infection) or non-specific stimuli (infarction, tissue trauma).
• T-lymphocytes: Have a reciprocal relationship with macrophages in chronic inflammation. Crucial for cellular immunity and macrophage interaction.
• B-lymphocytes: Responsible for antibody production; differentiate into plasma cells for this purpose.
• T-lymphocyte-macrophage interaction: Lymphocytes initially activated by macrophages presenting antigens on their cell surface. Activated lymphocytes produce mediators, including interferon-γ (IFN-γ) to activate macrophages. Activated macrophages release cytokines (IL-1 & TNF) to further activate lymphocytes. Resulting in an inflammatory focus where both persistent stimulation can occur until the triggering antigen is removed.

Chronic Inflammatory Cells: Eosinophils

• Found in inflammation due to parasitic infections or allergic reactions.
• Eotaxin is a chemokine for these cells.
• Major basic protein (MBP) is a toxic protein that damages tissue and parasites.

Chronic Inflammatory Cells: Mast cells

• Widely distributed in tissues, especially near blood vessels.
• IgE receptors, crucial in allergic reactions and anaphylactic shock.
• Primary source of histamine for mediating acute inflammation, and cytokines (e.g., TNF) in chronic inflammation.

Chronic Inflammation: Morphological Types

• **1. Non-specific:**General features of inflammation; examples include chronic cholecystitis and chronic pyelonephritis. Granulation tissue characterized by the formation of blood vessels, inflammatory cells, fibroblasts, and collagen. Aims to repair damaged tissue with fibrous tissue.
  • Morphology: Increased vasculature and increased numbers of lymphocytes / plasma cells are visible.
• 2. Granulomatous: A histological pattern involving granulomas; examples include leprosy, sarcoidosis, and syphilis.
• Granuloma types:
  • Infectious granulomas: Caseous necrosis (central area of necrosis); contains epithelioid macrophages.
  • Non-Infectious granulomas: No caseous necrosis; contains epithelioid macrophages.

Inflammation: The Other Defense Lines

• Lymphatics, lymph nodes, mononuclear phagocyte system: Secondary defense lines during inflammation. Lymphatic system drains edema fluid, leukocytes, debris, microorganisms into lymph nodes, causing lymphangitis and lymphadenitis.
• Bacteremia (infection spreading to blood): Can occur if microorganisms aren't contained within lymph nodes. Distant sites (heart valves, meninges, kidneys, joints) can be affected (e.g., endocarditis, meningitis, renal abscesses, septic arthritis).
• Phagocytic cells (liver, spleen, bone marrow): The next line of defense.

Systemic Effects of Inflammation

• Acute-phase response: Includes fever, malaise, anorexia, somnolence, wasting, hypotension; alterations in circulating leukocytes and hepatic synthesis of plasma proteins (e.g., fibrinogen).

• Cytokines (IL-1, IL-6, TNF): The most important mediators of acute-phase reaction. They're produced by leukocytes & other cells in response to infection, immune response, and toxic injury.

• Fever: TNF induces IL-1 production, which in turn stimulates IL-6 production. TNF and IL-1 act on the thermoregulatory center to induce fever via prostaglandin production.

• Changes in leukocyte count: Certain infections cause specific increases (e.g., bacteria: PMNs, parasites with allergy: eosinophils, viruses: lymphocytes).

Acute vs Chronic Inflammation

• Duration: Acute (days), Chronic (weeks/months).

• Onset: Acute (sudden), Chronic (gradual).

• Inflammatory cells: Acute (neutrophils, macrophages), Chronic (lymphocytes, macrophages, fibroblasts).

• Vascular changes: Acute (active vasodilation, increased permeability), Chronic (new vessel formation, granulation tissue).

• Cardinal signs: Acute (present), Chronic (lack of, or low-grade).

• Tissue necrosis, fibrosis: Acute (typically absent), Chronic (typically present).

• Systemic manifestations: Acute (fever), Chronic (low-grade fever, weight loss).

• Peripheral blood changes: Acute (neutrophil leukocytosis), Chronic (variable—increased plasma IG).