Inflammation: Physiology and Types

Inflammation

• Physiological Role: Inflammation is a vital immune response triggered by harmful stimuli like infection or tissue injury. It aids in survival during infection or injury and maintains tissue homeostasis.
• Cardinal Signs: Redness (rubor), Swelling (tumor), Heat (calor), Pain (dolor)
• Acute Inflammatory Response: Involves the delivery of blood components to the site of infection or injury.
• Stages of Acute Response:
  • Recognition of infection/injury
  • Release of soluble mediators
  • Vasodilation, increased blood flow
  • Vascular leakage, edema
  • Extravasation of fluid and leukocytes (primarily PMNs)
  • Phagocytosis, release of toxic compounds
  • Elimination of infection, tissue repair, resolution

Different Types of Inflammation

• Triggers: Infection, Tissue Injury, Tissue stress and Malfunction
• Physiological Purpose: Host defense against infection, Tissue repair response, Adaptation to stress and restoration of homeostatic state
• Pathological Consequences: Autoimmunity, inflammatory tissue damage and sepsis, Fibrosis, metaplasia, Tumor growth, Diseases of homeostasis, Autoinflammatory diseases

Inflammation Sensors

• Pattern Recognition Receptors (PRRs):
  • Toll-like Receptors (TLRs)
  • Nod-like Receptors (NLRs)
  • Rig-like Receptors (RLRs)
  • C-type Lectin Receptors

Inflammation Mediators

• Influence: Vasculature functionality and leukocyte recruitment.

Inflammation Mediators (1)

• Vasoactive Amines: Histamine and serotonin produced by mast cells and platelets degranulation.
• TNF-α, IL-1b, IL-6: Stimulate hepatocytes to synthesize and secrete acute phase proteins

Sepsis- Septic Shock

• Sepsis: Organ dysfunction due to a dysregulated host response to infection.
• Septic Shock: Subset of sepsis with a drop in blood pressure unresponsive to vasopressors or fluid replacement, associated with poor outcomes.
• Causative Agent: Bacterial septicemia (Gram+/-)
• Mechanism: Systemic activation of TLRs on monocytes, massive release of inflammatory mediators, activation of coagulation and complement cascades, leading to uncontrolled systemic inflammation
• Consequences: Shock from loss of blood pressure, widespread coagulation (DIC), immunosuppression, immunoparalysis, multi-organ failure, death

Regulation of Inflammation

• Control Points: Inducers, Sensors, Mediators, Target tissues
• Major Anti-inflammatory Mediators: IL-10, TGF-β, glucocorticoids

Regulation of Inflammation (2)

• HPA axis: Hypothalamic-pituitary-adrenal axis controls production of corticosteroids, potent anti-inflammatory hormones.

Outcomes of Inflammation

• Chronic Inflammation: Granuloma, Tertiary lymphoid organs, Scarring, Fibrosis, Loss of function
• Acute Inflammation: Elimination of infection, Tissue repair, Resolution (Homeostasis)

Resolution of Inflammation

• Mechanisms: Switching from proinflammatory prostaglandins to anti-inflammatory lipoxins, transition from neutrophil to monocyte recruitment.

Phases of Acute Inflammation:

• Not specified in the text.

Possible Outcomes of Acute Inflammation

• Complete Resolution: Tissues capable of regeneration, minimal tissue damage
• Abscess Formation: Occurs with some bacterial or fungal infections.
• Scarring (Fibrosis): In tissues unable to regenerate, Excessive fibrin deposition organized into fibrous tissue.
• Progression to Chronic Inflammation:

Granulomatous Inflammation

• Characteristics: A distinctive pattern of chronic inflammatory reaction dominated by activated macrophages with an epithelial-like appearance.
• Microscopic Aggregation: Macrophages transformed into epithelioid cells surrounded by mononuclear leukocytes.
• Typical of: Mycobacterial infections (TB, leprosy), fungal infections.
• Syncytial Giant Cells: Polykaryons within granulomas

Chronic “Low Grade” Inflammation

• Trigger: Not well defined, does not seem to involve infection or tissue damage.
• Inflammation: Low grade, smoldering.

Summary

• Inflammation: Vital immune response against harmful stimuli.
• Acute Inflammatory Response: Involves coordinated delivery of blood components to the site of infection or injury.
• Inflammatory Mediators: Production varies by time point and cell type.
• Mediator Influence: Altering vasculature functionality and leukocyte recruitment.
• Leukocyte Adhesion Cascade: Distinct steps for adhesion.
• Acute Phase Response: Innate body defense mechanism.
• Sepsis: Uncontrolled systemic inflammation due to massive release of TNFa and IL-1b.
• Chronic Inflammation: Distinct from acute inflammation, occurs when infection isn't cleared or tissue isn't repaired.

This quiz explores the physiological role of inflammation in immune responses, covering its cardinal signs and stages of acute response. It also discusses different types of inflammation and their triggers. Test your knowledge on how inflammation aids in survival and tissue repair.