Inflammation 312

Inflammation

Ellen Steidl, MS, RN, CCRN, CHSE

N312 Pathophysiology I

University of North Dakota

Learning Objectives

• Describe the physiological mechanisms of the vascular and cellular phases of inflammation. The physiological mechanisms include the activation of vascular responses and cellular responses that are crucial for tissue repair and protection.

• Explain the key functions of the first and second lines of defense. The first line of defense includes natural barriers such as the skin and mucous membranes, while the second line encompasses the inflammatory response aimed at protecting the body from injury and infection.

• Discuss the concept of inflammation, including purpose and effects on the body. Inflammation serves to protect tissues, facilitate healing, and oppose pathogens; it has both local and systemic effects on tissues and organ systems.

• Describe the role of the plasma protein systems of the inflammatory response, including the complement system, coagulation system, and kinin system. These systems activate in response to inflammation to mediate processes such as clotting, pathogen clearance, and pain response.

• Identify the cells involved in inflammation. Key cells include neutrophils, macrophages, monocytes, mast cells, eosinophils, and basophils.

• Describe the cardinal signs of acute localized inflammation. These signs include redness (erythema), heat, swelling (edema), pain, and loss of function.

• Describe the following signs of acute systemic inflammation. Acute systemic inflammation may manifest as fever, increased white blood cell (WBC) count, and malaise.

• Describe the physiological mechanisms of chronic inflammation. Chronic inflammation can arise from prolonged immune response leading to persistent tissue damage and repair processes.

• Compare and contrast acute and chronic inflammation. Acute inflammation is rapid and serves protective functions, while chronic inflammation is prolonged and can lead to tissue destruction.

• Explain the etiology, disease process, manifestations, diagnosis, and treatment of Kawasaki Disease. Kawasaki Disease is characterized by acute inflammation and requires timely treatment to prevent cardiovascular complications.

Required Reading

• Norris, T. L. (2020). Porth’s Essentials of Pathophysiology (5th ed.). Wolters Kluwer.

  • Chapter 9: 192-203

  • Chapter 27: 713-715

Human Defense Mechanisms

• Natural Barriers:

  • Composed of physical, mechanical, and biochemical barriers present at birth to protect the body from pathogens.

  • 1st Line of Defense: Natural barriers provide a first approach to prevent entry of pathogens.

• Inflammatory Response:

  • Activated as a protective measure to prevent infection, promote healing, and respond to injury.

  • 2nd Line of Defense: Involves a rapid, nonspecific response to a wide variety of tissue damages.

1st Line of Defense

Physical, Mechanical, and Biochemical Barriers

• Physical & Mechanical Barriers:

  • Include tightly bound epithelial cells, skin, mucous membranes in the GI, GU, and respiratory tracts that prohibit the passage of microorganisms.

  • Normal mechanisms include the sloughing of dead skin cells, urination, vomiting, and respiratory cleansing (e.g., coughing, sneezing) that remove pathogens.

• Biochemical Barriers:

  • Secretions include mucous, sweat, saliva, tears, earwax, and substances from sebaceous glands that inhibit pathogen growth.

Normal Microbiome

• Contributes to innate protection by:

  • Competing for nutrients, blocking pathogen adhesion, and producing inhibitory chemicals and toxic proteins.

• Disruption by broad-spectrum antibiotics can shift the normal microbiome balance, leading to increased vulnerability to infections by opportunistic pathogens such as C. difficile (gut) and Pseudomonas (skin).

2nd Line of Defense

Acute Inflammation

• Inflammation: Local and/or systemic response activated due to a break in the epithelial barrier.

  • Aims to protect the body from infection and initiates tissue repair.

  • Characterized by inflammatory mediators and movement of fluids, generally represented by the suffix “-itis” in pathological terms.

• Benefits of Inflammation:

  • Prevents infection, promotes interaction with the adaptive immune system, and prepares tissues for healing.

Phases of Acute Inflammation

Phase 1: Vascular Phase

• Characterization: Changes in small blood vessels at the injury site leading to edema.

  • Initiates with temporary vasoconstriction followed by vasodilation mediated by Nitric Oxide and Histamine, causing heat and redness.

• Increased vascular permeability allows for protein-rich fluid (exudate) to enter the extravascular space resulting in swelling and pain.

• Fluid movement results in blood stasis and clot formation which localizes microbial spread.

Phase 2: Cellular Phase

Part I: Leukocyte Margination, Adhesion, and Transmigration

• Process Detail:

  • Includes the delivery of leukocytes (mainly neutrophils) to the site of injury through margination, adhesion, and transmigration facilitated by slowing blood flow.

  • Neutrophils exit circulation to the tissue via chemotaxis, a process driven by signaling, recognizing, and invading pathogens.

Part II: Leukocyte Activation and Phagocytosis

• Opsonization: Involves coating pathogens with C3b and antibodies which helps in their recognition and engulfment by neutrophils.

• Phagocytosis: The process of ingestion and destruction of microorganisms and cellular debris facilitated by leukocytes through actions such as adherence, chemotaxis, and diapedesis.

Mediators of Inflammation

Cell-Derived Mediators

• Endothelial Cells: Form a selective barrier, produce antithrombotic agents, and are integral in inflammation.

• Platelets (Thrombocytes): Fragmented components that, when activated, contribute to hemostasis and release inflammatory mediators that affect endothelial and vascular functions.

• Neutrophils: Predominantly involved in early responses, removing debris and pathogens through phagocytosis; consist of short-lived components of pus.

• Monocytes & Macrophages: Monocytes transform into macrophages to become active phagocytes during inflammation and are important in tissue repair.

• Eosinophils: Important in defense against parasitic infections and in allergic reactions, modulating vascular response.

• Basophils: Involved in acquiring immunity by releasing histamine and mediating allergic responses, especially through IgE receptor mechanisms.

• Mast Cells: Central to inflammatory processes, releasing potent mediators, and can be activated through various stimuli leading to degranulation and synthesis of defense factors.

Plasma-Derived Mediators

Overview

• The systems include the Complement System, Clotting System, and Kinin System. These proteins circulate in inactive forms until activated and participate in inflammatory response through cascades of sequential reactions.

Complement System

• Functions include direct pathogen destruction, enhancement of inflammatory responses, and leukocyte chemotaxis.

• Utilizes multiple pathways for activation leading to vasodilation and increased permeability.

Clotting System

• Involves formation of a fibrin mesh to block pathogen spread, assist immune cell trapping, stop bleeding, and provide structure for healing.

Kinin System

• Primarily involves Bradykinin, which mediates vasodilation, increased permeability, smooth muscle contraction, and pain response.

Manifestations of Inflammation

Local Signs

• The five cardinal signs include:

  • Redness (Erythema)

  • Heat

  • Swelling (Edema)

  • Pain

  • Loss of function.

• Additional signs include the formation of exudates, abscesses, and ulcerations.

Systemic Signs

• When local inflammation becomes systemic, a notable acute-phase response emerges characterized by:

  • Changes in plasma protein concentrations, catabolism of skeletal muscle due to cytokine release, and alterations in thermoregulation leading to fever.

  • Systemic symptoms such as malaise, anorexia, and lymphadenitis may occur based on circulating inflammatory mediators.

Chronic Inflammation

• Defined as inflammation lasting more than two weeks, which may arise following an unsuccessful acute response or from persistent irritants.

• Associated with significant tissue destruction, scarring, and granuloma formation, it predominantly features monocytes, macrophages, and lymphocytes in the inflammatory process.

• Chronic inflammation exhausts the immune system, contributing to cognitive dysfunction and chronic disease development.

Comparison: Acute vs. Chronic Inflammation

Lifespan Considerations

Pediatric Considerations

• Neonates possess immature immune and inflammatory responses, making them susceptible to infections due to inefficient neutrophil function and deficient plasma protein systems.

Aging Considerations

• Elderly individuals face delayed inflammation correlated with chronic illnesses such as diabetes, diminished immune response, higher infection rates, and impaired TLR function.

Kawasaki Disease

Description

• Also known as Mucocutaneous Lymph Node Syndrome, it is an acute febrile inflammatory disease primarily affecting children, potentially leading to severe cardiac complications.

Etiology and Key Risk Factors

• Primarily affects children under five; higher incidence in males and certain ethnicities.

• Factors: delayed treatment, young age, prolonged fever, and specific lab markers such as elevated WBC counts.

Pathophysiology

• Often follows infections; characterized by vasculitis affecting arterial walls that may lead to stenosis or thrombus formation.

• Progresses through acute, subacute, and convalescent phases.

Phases of Kawasaki Disease

Acute Phase

• Onset with high fever, conjunctivitis, rash, and specific oral manifestations (e.g., strawberry tongue).

Subacute Phase

• Duration until signs resolve; risk for coronary aneurysms peaks during this phase.

Convalescent Phase

• Gradual resolution of clinical signs, with potential lingering inflammatory changes to cardiac tissues.

Cardiac Involvement

• Up to 25% may experience coronary artery dilation and myocardial ischemia or failure.

Diagnosis

• Based on fever persisting longer than five days and four principal features; supported by imaging as necessary.

Treatment

• Primary interventions include IV immunoglobulin and aspirin, supported by corticosteroids for severe cases and routine cardiac monitoring for complications.

Questions?

• Engage in clarifying ambiguities for a comprehensive understanding of inflammation and its systemic implications.