patho 9

Inflammation, Tissue Repair, and Wound Healing

Cardinal Signs of Acute Inflammation

Acute inflammation is a rapid, protective response to tissue injury or infection, characterized by distinct clinical signs.

• Rubor (Redness): Caused by increased blood flow to the affected area due to vasodilation.

• Tumor (Swelling): Results from accumulation of fluid (exudate) in tissues.

• Calor (Heat): Elevated temperature at the site due to increased blood flow and metabolic activity.

• Dolor (Pain): Stimulation of nerve endings by chemical mediators and pressure from swelling.

• Functio laesa (Loss of function): Impaired function due to pain and swelling.

Protective Responses and Bodily Repair

The body initiates several protective mechanisms in response to injury or infection to restore tissue integrity.

• Inflammatory reaction: Immediate response to injury or infection, involving immune cells and mediators.

• Immune response: Activation of specific and nonspecific defenses to eliminate pathogens.

• Tissue repair and wound healing: Processes that restore tissue structure and function after damage.

Causes of Inflammation

Inflammation can be triggered by various physical, chemical, and biological factors.

• Immune response to infectious microorganisms: Bacteria, viruses, fungi, and parasites can initiate inflammation.

• Trauma: Physical injury to tissues.

• Surgery: Tissue disruption during medical procedures.

• Caustic chemicals: Exposure to harmful substances.

• Extremes of heat and cold: Thermal injury.

• Ischemic damage: Reduced blood supply leading to tissue injury.

Granulomatous Inflammation

Granulomatous inflammation is a chronic inflammatory response characterized by the formation of granulomas.

• Associated with foreign bodies: Splinters, sutures, silica, asbestos.

• Associated with microorganisms: Mycobacterium tuberculosis (tuberculosis), Treponema pallidum (syphilis), sarcoidosis, deep fungal infections, brucellosis.

Vascular Changes in Inflammation

Inflammation involves dynamic changes in blood vessels to facilitate immune cell migration and mediator delivery.

• Immediate transient response: Occurs with minor injury; brief vasodilation and increased permeability.

• Immediate sustained response: Follows more serious injury; prolonged vascular changes and vessel damage.

• Delayed hemodynamic response: Increased capillary permeability 4–24 hours after injury, seen in sepsis and chronic inflammation.

Cellular Stage of Acute Inflammation

The cellular phase involves the recruitment and activation of white blood cells at the site of injury.

• Phagocytic leukocytes: Move into the area to remove injury-causing agents.

• Granulocytes: Neutrophils (first responders), eosinophils, basophils.

• Monocytes: Largest white blood cells; differentiate into macrophages in tissues.

Direction of Cellular Response

Leukocytes follow a coordinated sequence to reach and act at the site of inflammation.

• Margination: Leukocytes move toward the vessel wall.

• Adhesion: Attachment to endothelium via adhesion molecules (selectins, integrins, immunoglobulins).

• Transmigration: Squeezing through endothelial cells into tissues.

• Cytokines: Proteins for cell signaling and immune response.

• Aggregation and movement: Inflammatory cells aggregate and migrate into underlying tissue.

Inflammatory Mediators

Various chemical mediators regulate the intensity and duration of inflammation.

• Histamine: Causes vasodilation and increased vascular permeability.

• Cytokines: Signal and regulate immune responses; often over-released in sepsis.

• Arachidonic acid metabolites: Eicosanoids such as prostaglandins and leukotrienes (promote/inhibit inflammation, pain, clotting), omega-3 fatty acids (anti-inflammatory).

• Platelet-activating factor: Increases vascular permeability, vasodilation, and cytokine production.

• Plasma proteins: Synthesized in the liver, circulate in blood, initiate or amplify inflammation.

Types of Inflammatory Exudates

Exudates are fluids that accumulate at sites of inflammation, varying in composition and appearance.

Type	Description
Serous	Watery, low protein; plasma entering inflammatory site
Hemorrhagic	High red blood cell content; severe tissue injury and vessel damage
Membranous/Pseudomembranous	Necrotic cells in fibropurulent exudate on mucous membranes
Purulent/Suppurative	Pus; degraded white blood cells, proteins, tissue debris
Fibrinous	High fibrinogen; thick, sticky meshwork

Basic Patterns of Inflammation: Acute vs. Chronic

Inflammation can be classified based on duration and cellular composition.

• Acute inflammation: Short duration, nonspecific early response; neutrophil infiltration; exudate formation; removal of injurious agent and limitation of tissue damage.

• Chronic inflammation: Prolonged duration (days to years); associated with chronic diseases; infiltration by mononuclear cells (macrophages, lymphocytes); fibroblast proliferation; tissue damage and repair.

Systemic Manifestations of Inflammation

Inflammation can produce systemic effects beyond the local site of injury.

• Acute phase response: Systemic reaction with physiological and biochemical changes for host defense and tissue repair.

• Alterations in white blood cell count:

  • Leukocytosis: Increased WBC count, especially neutrophils; triggered by infection, injury, autoimmune disorders.

  • Leukopenia: Decreased WBC count; can occur in autoimmune diseases (e.g., SLE), bone marrow suppression.

• Fever: Elevated body temperature due to pyrogenic cytokines.

• Sepsis and septic shock: Severe, life-threatening systemic inflammation; symptoms include low blood pressure, tachycardia, mental confusion.

Healing by Primary or Secondary Intention

Wound healing aims to restore tissue continuity and function, with two main patterns.

• Primary intention: Healing of small, clean wounds with minimal tissue loss.

• Secondary intention: Healing of wounds with significant tissue loss or contamination; slower and involves more granulation tissue.

Factors Regulating the Healing Process

Wound healing is regulated by local and systemic factors, including chemical mediators and cell-matrix interactions.

• Chemical mediators and growth factors: Regulate cell proliferation, migration, and differentiation.

• Extracellular and cell matrix interactions: Provide structural support and signaling for tissue repair.

• Stages of wound healing:

  1. Homeostasis

  2. Inflammation (fight infection, clean debris)

  3. Proliferation (new tissue formation, granulation)

  4. Remodeling (scar strengthening)

Note: Underlying diseases (e.g., poorly controlled diabetes) can impair healing by reducing circulation, weakening immune responses, and increasing infection risk. High blood sugar damages blood vessels, reducing oxygen/nutrient delivery.

Causes of Impaired Wound Healing

Several factors can delay or prevent effective wound healing.

• Malnutrition: Lack of essential nutrients impairs cell function and repair.

• Impaired blood flow and oxygen delivery: Reduces tissue regeneration capacity.

• Impaired inflammatory and immune responses: Limits defense against infection and tissue repair.

• Infection: Prolongs inflammation and tissue damage.

• Wound separation: Physical disruption of healing tissue.

• Foreign bodies: Persistent irritants in the wound.

• Age effects: Older adults are more vulnerable to chronic wounds (pressure, diabetic, ischemic ulcers) and heal more slowly than younger individuals.