Week 2 lecture 2 Applied Pathophysiology: Healing and Tissue Repair

Applied Pathophysiology: A Conceptual Approach to the Mechanisms of Disease

• This lecture series covers applied pathophysiology, using a conceptual approach to understand disease mechanisms.
• The modules specifically cover inflammation and tissue repair, healing, and chronic inflammation.
• The course material is adapted from a 2022 textbook, Applied Pathophysiology: A Conceptual Approach (4th Edition) by Judi Nath, Carrie Braun, and Cindy Anderson.
• The lecture series is delivered by Dr. Romeo Batacan Jr. within the MPAT12001 Medical Pathophysiology Lecture Series.

Healing and Tissue Repair

• Inflammatory response initiates the healing process.
• Goals of tissue healing and repair: cover the wound, clear debris, restore structural integrity, and restore functional integrity.
• Healing involves three phases: inflammatory, proliferative, and remodeling.

Covering the Wound and Clearing Debris

• Hemostasis, vasoconstriction, and clot formation occur at injury.
• A protective scab (thrombus) forms from dried blood.
• This barrier prevents harmful substances from entering, and limits plasma loss.
• Neutrophils enter the injured area first, followed by macrophages.
• Macrophages digest and remove necrotic cells and debris.

Restoring Structural Integrity

• Tissue lysis by enzymes and construction by growth factors and matrix proteins balance tissue repair.
• Extracellular matrix (ECM), including the basement membrane and connective tissue layers, is crucial for structure.

Restoring Functional Integrity

• Healing aims to restore tissue function.
• Three processes achieve this goal: resolution (restoration of tissue), regeneration (replacing damaged tissue), and replacement (producing scar tissue).
• Tissue types, like labile (constantly regenerating), stable (regeneration capability), and permanent (no regeneration), affect healing.

Remodeling

• Remodeling begins 3 weeks after injury and can last for 6 months.
• Scar tissue continues to remodel, with collagen synthesis by fibroblasts and collagenase enzyme activity are key players.
• The scar's architecture reorients to increase tensile strength.

Conditions that Promote Wound Healing

• Adequate vascular and cellular inflammatory responses are crucial.
• Effective cellular regeneration, adequate dietary intake, and sufficient vitamins (A & C) are essential.
• Adequate blood flow promotes healing.

Cutaneous Wound Healing by Intention: Primary

• Small wounds with closely approximated edges heal by primary intention.
• Healing occurs quickly with minimal cell proliferation and neovascularization.
• Risk of infection is reduced, and scarring is minimal.

Cutaneous Wound Healing by Intention: Secondary

• Large, open wounds with substantial tissue loss heal by secondary intention.
• Extensive cell proliferation and granulation tissue develop.
• Collagen deposition occurs.
• Granulation tissue is progressively replaced by scar tissue.
• Risk of infection and scarring is higher.

Complications of Healing

• Impaired wound healing can occur at any stage.
• Primary factors include ineffective inflammatory responses, inadequate immune responses, inadequate nutritional status, and poor tissue perfusion.
• Potential complications include infection, ulceration, dehiscence, keloid development, and adhesions.

Complications of Healing: Infection

• Microorganism invasion hinders all aspects of wound healing.
• Initial defenses are compromised.
• Inflammatory processes are prolonged and hinder granuloma tissue formation.
• Collagen deposition is inhibited.

Complications of Healing: Ulceration

• Inadequate perfusion prevents proper healing.
• Crater-like lesions in skin or mucous membranes often develop.
• Persistent microorganism presence prevents healing.
• Conditions like pressure ulcers are resistant to treatment.

Complications of Healing: Dehiscence

• Deficient scar formation leads to wound splitting.
• Opens the possibility of infections.
• Possible causes include mechanical stress (coughing, movement) later in the recovery period and poor extracellular matrix development and inadequate collagen synthesis.

Complications of Healing: Keloids

• Excessive collagen production causes hypertrophic scars.
• Keloids are often cosmetic concerns.
• Removal might lead to recurrence.
• More common in people with dark skin tones and between 10-30 years old.

Complications of Healing: Adhesion

• Impaired collagen deposition leads to fibrous tissue connecting organs within the serous cavity.
• Common result of abdominal surgery.
• Leads to impaired organ movement, pain, and loss of function.

Chronic Inflammation

• Recurrent inflammation lasting several weeks or more.
• Acute inflammatory and immune responses fail.
• Granuloma and scarring often result.

Cells of Chronic Inflammation

• Monocytes/macrophages and lymphocytes are prominent.
• Monocytes mature into macrophages.
• Proteinases destroy elastin and tissue components.
• Ongoing tissue destruction occurs.
• Fibroblasts develop extensive scarring.
• Functional and structural deformities may result.

Granuloma Formation

• Chronic inflammation sometimes leads to granuloma formation.
• Granulomas are nodular inflammatory lesions containing macrophages, that encapsulate harmful substances.
• Inflammation often originates from difficult-to-control injuries, poorly digested foreign bodies (splinters, sutures, silica, asbestos), or specific microorganisms (tuberculosis, syphilis).

General Manifestations

• During inflammation, symptoms mirror those of acute inflammation (redness, heat, swelling, and pain).
• Scarring and granuloma formation can occur.
• Systemic symptoms like fever, anemia, malaise, weakness, fatigue, and anorexia may be present.
• During remission, symptoms typically disappear.

This quiz explores key concepts in applied pathophysiology, focusing on the mechanisms of disease related to healing and tissue repair. It covers the inflammatory response, phases of healing, and the strategies involved in wound management, adapted from a 2022 textbook. Test your understanding of these essential medical concepts.