Inflammation and Tissue Repair Quiz

Inflammation, Tissue Repair & Wound Healing

• Inflammation is a physiological response to tissue injury, infection, or foreign bodies.
• It's mediated by inflammatory chemicals and aims to remove microorganisms, necrotic tissue, and initiate tissue repair.
• Cardinal signs of inflammation include redness, swelling, heat, pain, and loss of function.

Types of Immunity

• Innate Immunity:
  • Includes physical and chemical barriers like skin, mucosa, and substances like mucus, cilia, and skin secretions.
  • Has an inflammatory response—non-specific but important
  • Contains natural killer cells (a type of lymphocyte)
• Adaptive Immunity: A separate system

Acute Inflammation

• Vascular Phase:

  • Vasodilation at the site of injury increases blood flow, causing heat and redness.
  • Increased capillary permeability leads to fluid leakage into interstitial spaces, causing swelling and pain.
  • Proteins in the exudate pull in further fluid.

• Cellular Phase:

  • Activated platelets release inflammatory mediators.
  • Neutrophils migrate to the injury site, typically within 6-12 hours.
  • They engage in phagocytosis (ingest and destroy) pathogens.
  • Monocytes transform into macrophages
  • Macrophages secrete inflammatory mediators, continue phagocytosis, and have a longer lifespan than neutrophils.

Key Inflammatory Mediators

• Arachidonic Acid Metabolites (e.g., prostaglandins, leukotrienes): Synthesized by neutrophils and macrophages
  • Prostaglandins and leukotrienes can increase inflammation, making asthma worse.
• Bradykinin: Activated from plasma proteins, increases vascular permeability, induces smooth muscle contraction (bronchoconstriction), and increases pain sensitivity.
• Histamine: Released by mast cells, causes transient vasodilation and increased capillary permeability.
• Complement: Plasma proteins activated by antibodies or pathogen surfaces.
  • Opsonization: Coating pathogens to enhance phagocytosis.
  • Cell lysis: Destruction of cells.

Chemical Mediators (Cytokines)

• Cytokines are signaling molecules.
• IL-1 and TNF-α are released from activated macrophages.
• They stimulate neutrophils to adhere to endothelial cells and stimulate phagocytosis.
• They contribute to the acute phase response, which includes fever, release of neutrophils, hypotension, tachycardia, anorexia, malaise, and cortisol release.
• They stimulate increased inflammatory protein synthesis in the liver.

Chronic Inflammation

• Chronic inflammation arises from unresolved injuries, infections, or foreign bodies.
• Macrophages, lymphocytes, and fibroblasts become predominant.
• Fibroblasts increase scarring and deformity risk.

Examples of Chronic Inflammation

• Granuloma: Macrophages "wall off" foreign proteins (e.g., latent tuberculosis).
• Abscess: Fibroblasts wall off infection sites. Antibiotics usually don't penetrate abscesses; I&D (incision and drainage) is often necessary.

Inflammation & Disease

• Uncontrolled or inappropriate inflammation can damage tissues and contribute to various diseases, such as rheumatoid arthritis, sepsis, and inflammatory bowel disease.

White Blood Cell (WBC) Count Differential

• Normal WBC count: 5,000-11,000/mL³.
• Neutrophils: 40-70% of WBCs; primary responders to acute injury or infections; short lifespan
• Eosinophils: 1-6% of WBCs; involved in allergic reactions and infections involving intestinal parasites; release inflammatory chemicals
• Basophils: 0-2% of WBCs; release vasoactive substances (heparin, histamine) during inflammation
• Monocytes/Macrophages: 5% of WBCs; immature macrophages; circulate in blood; phagocytose pathogens and debris, involved in repairing injured tissue. Lymphocytes: Major immune cells involved in cell-mediated and antibody-mediated immunity.

Tissue Regeneration

• Tissue regeneration varies.
• Labile cells (e.g., mucosal linings, bone marrow) continuously divide and are quickly replaced.
• Stable cells (e.g., parenchymal cells in liver and kidney) stop dividing when no longer needed but can regenerate if necessary.
• Permanent cells (e.g., nerve cells, myocardial cells) cannot regenerate.

Wound Healing Process

• Phase I (Hemostasis): Stop blood loss.
• Phase II (Inflammatory): Clean debris. Neutrophils and macrophages arrive at the injury site to phagocytose bacteria and debris.
• Phase III (Proliferative): Build new tissue. Fibroblasts synthesize collagen and induce angiogenesis to form new blood vessels.
• Phase IV (Remodeling): Strengthen the new tissue. Collagen reorganizes to strengthen the scar through scar remodeling for 2 years.

Wound Healing Types

• Primary intention: Wound edges are approximated; heals via surface epithelialization.
• Secondary intention: Wound edges are not approximated, and healing is bottom-up by granulation tissue.

Things Needed for Effective Wound Healing

• Removal of necrotic tissue.
• Control of infection.
• Adequate nutrition.
• Adequate oxygen delivery: this can impact a healing wound if oxygen cannot reach it from the blood supply.
• Maintain a moist wound environment.

Causes of Impaired Wound Healing

• Malnutrition (protein, carbohydrate, vitamins—A, C, and zinc).
• Vascular disease (decreased oxygen release, microvascular disease, impaired leukocyte function).
• Diabetes.
• Hypoxia.
• Smoking.
• Medications (corticosteroids, chemo).

Types of Wounds

• Surgical wounds
• Traumatic wounds (Lacerations, abrasions, contusions, punctures)
• Pressure ulcers
• Burns
• Arterial ulcers
• Venous stasis ulcers

Wound Dehiscence/Evisceration

• Dehiscence: Separation of a surgical wound.
• Evisceration: Protrusion of organs through an open surgical wound.

Pressure Ulcers

• Skin breakdown caused by un-relieved pressure over bony prominences.
• Caused by poor nutrition, incontinence, and moisture.
• Factors reducing tissue resistance include: duration of pressure, friction, shear, aging, diabetes, moisture, and vascular disease.
• Risk factors for ulcers include: paralysis/immobility, orthopedic surgery, confusion/sedation, impaired sensation, heart failure, arterial disease, COPD, diabetes, malignancy, and elderly patient status.

Pressure Ulcer Assessment

• Staging (I–IV)
• Size (length, width, depth)
• Wound bed (granulation, slough, eschar, necrotic tissue)
• Drainage
• Peri-wound skin
• Undermining
• Tunneling

Pressure Ulcer Treatment

• Maintain moist wound bed and avoid maceration.
• Remove non-viable tissue.
• Treat infection.
• Avoid cytotoxic solutions.
• Relieve pressure and improve nutrition.

Debridement

• Removal of necrotic tissue (e.g., heel eschar with mechanical, autolytic, or enzymatic methods)
• Necessary for sepsis or advancing cellulitis. Generally, avoid debriding heel eschars, however, other instances of the wound being infected may require debridement.

Arterial Ulcers

• Etiology: atherosclerosis, tissue hypoxia, trauma.
• Location: distal extremities.
• Appearance: necrotic, minimal drainage.
• Prevention/Assessment/Treatment: improve perfusion, protect from injury, assess wound circulation, ankle-brachial index, keep wound clean, hyperbaric therapy, revascularization.

Venous Stasis Ulcers

• Etiology: chronic venous insufficiency, edema.
• Location: medial malleolus, tibial.
• Appearance: jagged, weeping.
• Prevention/Assessment/Treatment: control edema, protect from injury, assess wound circulation, ankle-brachial index, keep wound clean (debride as needed), hyperbaric therapy, compression.

Critical Thinking/Review Questions

• Why do corticosteroids impair wound healing?
• What factor is most important to heal an arterial ulcer? A venous stasis ulcer?
• Which chemical mediator is involved in generating a febrile response to an infection?
• Which white blood cell is the primary responder to bacterial infection?
• Which tissue type is best able to be regenerated?
• Which wound type heals by secondary intention?
• Which condition is likely to cause chronic inflammation?
• What stage is this pressure ulcer?