Inflammation Overview and Pathophysiology

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Questions and Answers

What is the primary function of the inflammatory response?

To remove foreign invaders and necrotic tissue (correct)

To suppress the immune system

To increase tissue necrosis

To enhance chronic diseases

Which type of white blood cell is primarily involved in acute inflammation?

Monocytes

Eosinophils

Lymphocytes

Neutrophils (correct)

Which feature is NOT characteristic of acute inflammation?

Fast onset

Severe and progressive tissue injury (correct)

Neutrophil infiltration

Prominent local and systemic signs

What step in the inflammatory response involves the removal of the injurious agent?

Removal of the agent Signup and view all the answers

What mediators are primarily responsible for increased vascular permeability during inflammation?

Histamine and kinins Signup and view all the answers

What is one of the signs of acute inflammation?

Redness Signup and view all the answers

Which characteristic distinguishes chronic inflammation from acute inflammation?

Presence of fibroblasts Signup and view all the answers

Which of the following processes occurs during acute inflammation?

Vasodilation Signup and view all the answers

What is the primary function of complement proteins in inflammation?

Mediate leukocyte chemotaxis and opsonization. Signup and view all the answers

What triggers the activation of the coagulation proteins during inflammation?

Activation of factor XII. Signup and view all the answers

What characterizes the initial leukocyte response in acute inflammation?

Adhesion to the endothelium. Signup and view all the answers

Which of the following is NOT a beneficial effect of acute inflammation?

Formation of scar tissue. Signup and view all the answers

Which of the following outcomes occurs as a result of acute inflammation?

Complete resolution to histologic normality. Signup and view all the answers

What primarily characterizes chronic inflammation?

Mononuclear cell infiltration. Signup and view all the answers

Which factor contributes to the development of fibrosis during chronic inflammation?

Prolonged exposure to toxic agents. Signup and view all the answers

What is the primary effect of vasoactive amines such as histamine and serotonin?

Induce vasodilation and increased vascular permeability Signup and view all the answers

What is a common cause of chronic inflammation?

Autoimmune disorders. Signup and view all the answers

Which cells predominately infiltrate sites of inflammation during the early stages?

Neutrophils Signup and view all the answers

What mediates the firm attachment of leukocytes to the endothelium during recruitment?

Integrins Signup and view all the answers

What is the main role of reactive oxygen species (ROS) generated in activated leukocytes?

To kill microbes and induce tissue injury Signup and view all the answers

Which cytokines are key mediators in acute inflammation?

TNF, IL-1, IL-6, and chemokines Signup and view all the answers

What process describes the movement of leukocytes through the interendothelial spaces?

Transmigration Signup and view all the answers

Which of the following is NOT a consequence of leukocyte effector mechanisms?

Inflammation contributing to tissue repair Signup and view all the answers

Which components are antagonized by lipoxins in the inflammatory response?

Arachidonic acid metabolites Signup and view all the answers

Which of the following is a characteristic of chronic inflammation?

Persistent inflammation and tissue injury Signup and view all the answers

What is primarily responsible for the amplification and prolongation of the inflammatory response in chronic inflammation?

Bidirectional interactions between macrophages and lymphocytes Signup and view all the answers

Which of the following cytokines is secreted by T lymphocytes to activate macrophages?

IFN-γ Signup and view all the answers

What type of inflammation is characterized by the aggregation of activated macrophages with an epithelioid appearance?

Granulomatous inflammation Signup and view all the answers

Which of the following conditions can lead to granulomatous inflammation?

Tuberculosis infection Signup and view all the answers

Which systemic effect of inflammation is directly stimulated by cytokines acting on liver cells?

Production of acute-phase proteins Signup and view all the answers

What does the cell cycle regulate regarding cell proliferation?

The entry of quiescent cells into division Signup and view all the answers

How are tissues classified based on their proliferative capacity?

Into labile, stable, and permanent tissues Signup and view all the answers

What are the characteristics of embryonic stem (ES) cells?

They are pluripotent. Signup and view all the answers

What is the primary role of collagen in the extracellular matrix (ECM)?

Providing mechanical support. Signup and view all the answers

What occurs in fibrinous inflammation?

A meshwork of threads forms. Signup and view all the answers

What is a potential outcome of damaged extracellular matrix (ECM)?

Repair through scar formation. Signup and view all the answers

Which type of inflammation is characterized by the presence of pus?

Suppurative (Purulent) Inflammation Signup and view all the answers

What defines ulceration in tissue injury?

Erosion of an epithelial surface due to necrosis. Signup and view all the answers

Which of the following describes the function of proteoglycans in the ECM?

They serve as a reservoir for growth factors. Signup and view all the answers

Induced pluripotent stem (iPS) cells are derived from which type of cells?

Mature adult cells. Signup and view all the answers

Study Notes

Inflammation

Inflammation is the host response to foreign invaders and necrotic tissue, it can cause tissue damage
It's a protective response, aimed at removing the initial cause of cell injury, necrotic cells
It can have harmful effects like anaphylactic shock, rheumatoid arthritis, and atherosclerosis

Main Components of Inflammation

Vascular reaction
Cellular response
Both are activated by mediators derived from plasma proteins and various cells.

Steps of Inflammatory Response

Recognition of the injurious agent
Recruitment of leukocytes
Removal of the agent
Regulation (control) of the response
Resolution (repair)

Features of Acute & Chronic Inflammation

Acute Inflammation
- Onset: Fast (minutes or hours)
- Cellular Infiltrate: Mainly neutrophils
- Tissue Injury: Usually mild and self-limited
- Local and Systemic Signs: Prominent
Chronic Inflammation
- Onset: Slow (days)
- Cellular Infiltrate: Monocytes/macrophages and lymphocytes
- Tissue Injury: Often severe and progressive
- Local and Systemic Signs: Less prominent, may be subtle

Acute Inflammation

Short duration (few minutes - few days)
3 Key Characteristics:
- Increased blood flow (hyperæmia)
- Leakage of plasma proteins (exudation)
- Emigration of leukocytes (neutrophilic)
Outcome can be:
- Elimination of the noxious stimulus and repair of the damaged tissue
- Persistent injury resulting in chronic inflammation
Signs of acute inflammation:
- Heat (calor)
- Redness (rubor)
- Swelling (tumour)
- Pain (dolor)
- Loss of function (functio læsa)

Reaction of Acute Inflammation

Vasodilation is induced by chemical mediators like histamine
Increased vascular permeability is induced by histamine, kinins, and other mediators
This increased permeability allows plasma proteins and leukocytes to enter the site of infection or tissue damage, resulting in edema

Leukocyte Recruitment to Sites of Inflammation

Leukocytes are recruited from the blood into the extravascular tissue
Leukocyte recruitment is a multistep process:
- Loose attachment to endothelium (mediated by selectins)
- Firm attachment to endothelium (mediated by integrins)
- Migration through interendothelial spaces

Leukocyte Effector Mechanisms

Leukocytes eliminate microbes and dead cells by phagocytosis
Destruction is caused by free radicals and lysosomal enzymes
Enzymes and ROS may be released into the extracellular environment

Major Cell-Derived Mediators of Inflammation

Vasoactive Amines: Histamine and serotonin, causing vasodilation and increased vascular permeability
Arachidonic Acid Metabolites: Prostaglandins and leukotrienes involved in vascular reactions, leukocyte chemotaxis, and other reactions of inflammation
Cytokines: Proteins produced by many cell types, mediating multiple effects like leukocyte recruitment
ROS: Roles include microbial killing and tissue injury
NO: Effects are vasodilation and microbial killing
Lysosomal Enzymes: Roles include microbial killing and tissue injury

Plasma Protein–Derived Mediators of Inflammation

Complement Proteins: Activation leads to the generation of multiple breakdown products responsible for leukocyte chemotaxis, opsonization, and cell killing
Coagulation Proteins: Activated factor XII triggers the clotting, kinin, and complement cascades
Kinins: Mediate vascular reaction and pain

Sequence of Events in Acute Inflammation

Increased blood flow leads to erythema and warmth
Increased vascular permeability results in an exudate of protein-rich extravascular fluid (tissue edema)
Leukocytes, initially neutrophils, adhere to the endothelium and migrate to the site of injury
Phagocytosis, killing, and degradation of the offending agent follow

Benificial Effects of Acute Inflammation

Dilution of toxins
Exudation of protective antibodies
Fibrin formation delays bacterial spread
Exudation of plasma mediators
Exudation of nutrient materials
Promotion of immunity

Outcomes of Acute Inflammation

Complete resolution to normality
Fibrosis: Occurs in tissues that don't regenerate, after substantial tissue destruction, or with extensive fibrinous exudates
Abscess formation in pyogenic infection
Progression to chronic inflammation

Chronic Inflammation

Longer duration (days or years)
Characteristics:
- Infiltration by mononuclear cells (monocytes, lymphocytes, and macrophages)
- Tissue destruction
- Tissue repair (vascular proliferation and fibrosis)

Causes of Chronic Inflammation

Persistent infections
Prolonged exposure to toxic agents
Autoimmune disorders

Features of Chronic Inflammation

Prolonged host response to persistent stimulus
Characterized by persistent inflammation, tissue injury, attempted repair, and immune response
Cellular infiltrate consisting of activated macrophages, lymphocytes, and plasma cells, often with prominent fibrosis

Cells Involved in Chronic Inflammation

Macrophages derived from monocytes, increasing in size with more active metabolism
Lymphocytes, plasma cells, eosinophils
Macrophages secrete:
- Acid and neutral proteases
- Complement components
- Oxygen-free radicals and nitric oxide
- Cytokines (IL-1, TNF)

Granulomatous Inflammation

Aggregation of activated macrophages as (epithelioid) appearance
Causes:
- Bacterial infection (e.g., tuberculosis, leprosy, syphilis)
- Parasitic (e.g., Bilharziasis)
- Fungal (e.g., Histoplasmosis)
- Inorganic metals (e.g., Silica, berylliosis)
- Foreign body
- Unknown (e.g., Sarcoidosis)

Systemic Effects of Inflammation

Fever: Cytokines stimulate production of prostaglandins in the hypothalamus
Production of acute-phase proteins: C-reactive protein is stimulated by cytokines acting on liver cells
Leukocytosis: Cytokines stimulate production of leukocytes from precursors in the bone marrow
In severe infections, septic shock: Fall in blood pressure, disseminated intravascular coagulation, metabolic abnormalities; induced by high levels of TNF

Cell Proliferation, The Cell Cycle, and Stem Cells

Regeneration of tissues is driven by proliferation of uninjured cells and replacement from stem cells
Cell proliferation occurs when quiescent cells enter the cell cycle
The cell cycle is tightly regulated by stimulators and inhibitors
Tissues are divided into labile, stable, and permanent, according to the proliferative capacity of their cells
Continuously dividing tissues (labile tissues) contain mature cells that are capable of dividing and stem cells
Stem cells from embryos (ES cells) are pluripotent
Adult tissues contain adult stem cells capable of generating multiple cell lineages
Induced pluripotent stem cells (iPS cells) are derived by introducing genes into mature cells, acquiring many characteristics of stem cells

Extracellular Matrix and Tissue Repair

The ECM provides mechanical support to tissues and acts as a substrate for cell growth.
It regulates cell proliferation and differentiation
An intact ECM is required for tissue regeneration, damage to the ECM results in scar formation

Morphologic Patterns of Acute & Chronic Inflammation

Serous Inflammation: Effusions of watery, protein-poor fluid
Fibrinous Inflammation: Occurs in severe injuries, appearing as a meshwork of threads or as an amorphous coagulum
Suppurative (Purulent) Inflammation: Manifested by the presence of a large amount of purulent exudates (pus)
Ulceration: Erosion of an epithelial surface by necrosis with associated subepithelial inflammation

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Description

This quiz explores the complex process of inflammation, including its protective role, harmful effects, and the key components involved in the inflammatory response. Test your knowledge on acute versus chronic inflammation and the steps involved in resolving tissue injury.