Chapter 5 – Inflammation and Healing

Body Defenses

• Three hierarchical defensive lines act against pathogens or injury.
  • First line (nonspecific):
  • Mechanical/physical barriers: unbroken skin, intact mucous membranes.
  • Protective fluids: tears, saliva, mucus, gastric acid/juices.
  • Second line (nonspecific):
  • Phagocytosis by neutrophils & macrophages.
  • Inflammatory response (vascular + cellular events).
  • Interferon production (antiviral signaling).
  • Third line (specific):
  • Adaptive immunity:
    • Humoral: production of antigen-specific antibodies.
    • Cell-mediated: cytotoxic T-cell responses.
• Interaction path: when nonspecific barriers are breached → phagocytosis/inflammation activated → if still overcome, specific immune responses initiated.

Normal Capillary Exchange

• Not every capillary in a bed is open simultaneously; openings match metabolic demand & waste removal needs.
• Arterial end: movement of fluid, electrolytes, O₂, nutrients is driven outward by net hydrostatic pressure.
• Venous end: inward movement of fluid, CO₂, metabolic wastes facilitated by osmotic (oncotic) pressure due to plasma proteins (largely albumin) retained in blood.

Inflammatory Response vs. Normal Exchange

• Sequence after injury:
  1. Vasodilation → ↑ blood flow (hyperemia).
  2. ↑ Capillary permeability → plasma proteins + water exit → exudate forms in interstitial fluid.
  3. Chemotaxis draws leukocytes to site.
  4. Phagocytosis by neutrophils first, then macrophages.
• Key chemicals released: bradykinin (from injured cells), histamine (from mast cells/basophils), prostaglandins (PGs), etc.

Physiology & Significance of Inflammation

• Universal, protective, nonspecific defense; disorders described with suffix –itis.
• Provides early warning (redness, pain, swelling, etc.) that may reveal otherwise hidden pathology.
• Not synonymous with infection; infection is one cause among many.

Causes of Inflammation

• Direct trauma (cut, sprain).
• Caustic chemicals (acid, drain cleaner).
• Ischemia / infarction.
• Allergic reactions.
• Temperature extremes (burns, frostbite).
• Foreign bodies (splinters, glass).
• Microbial infection.

Step-by-Step Cascade

1. Injured cells release bradykinin.
2. Bradykinin activates pain receptors.
3. Mast cells & basophils release histamine.
4. Bradykinin + histamine → capillary vasodilation & permeability ↑.
5. Possible bacterial entry.
6. Neutrophils & monocytes migrate (chemotaxis).
7. Neutrophils phagocytize invaders; monocytes transform into macrophages for sustained phagocytosis.

Acute Inflammation – Vascular & Cellular Events

• Always same basic process; timing/intensity vary with etiology.
• Chemical mediator actions:
  • Vasodilation (↓ resistance, ↑ flow).
  • Hyperemia (warmth, redness).
  • ↑ Capillary permeability (swelling).
  • Chemotaxis (cell recruitment).

Key Chemical Mediators (Table 5-1)

• Histamine: immediate vasodilation, ↑ permeability.
• Chemotactic factors: attract neutrophils.
• Platelet-activating factor (PAF): activates neutrophils, platelet aggregation.
• Cytokines (ILs, lymphokines): ↑ plasma proteins & ESR, fever, chemotaxis, leukocytosis.
• Leukotrienes: later vasodilation, ↑ permeability, chemotaxis.
• Prostaglandins: vasodilation, pain, fever, potentiate histamine.
• Kinins (e.g., bradykinin): vasodilation, pain, chemotaxis.
• Complement: vasodilation, ↑ permeability, chemotaxis, ↑ histamine release.

Local Effects (5 Cardinal Signs)

• Redness & warmth: due to hyperemia.
• Swelling (edema): protein & fluid shift into interstitium.
• Pain: pressure on nerves + chemical mediators (bradykinin, PGs).
• Loss of function: nutrient deficit + edema hindering mobility.

Exudate Types

• Serous: watery, few proteins/WBCs.
• Fibrinous: thick, sticky, high fibrin & cell content.
• Purulent: thick, yellow-green, abundant leukocytes, microbes, debris; forms abscess (localized pocket).
• Hemorrhagic: blood-tinged when vessels damaged.

Systemic Effects

• Mild fever (pyrexia) via pyrogens.
• Malaise, fatigue, headache, anorexia.

Course of Fever

1. Pyrogens released → hypothalamic set-point resets higher.
2. Body conserves/produces heat: chills, shivering, pallor, ↑ basal metabolic rate & HR, curling up.
3. Plateau at new high T (feel warm).
4. If pyrogens removed (tx) → set-point normalizes.
5. Heat loss: vasodilation, sweating, lethargy, body extension.
6. Return to baseline.

Laboratory Changes (Table 5-3)

• Leukocytosis: ↑ WBC (esp. neutrophils).
• Differential shift: pattern suggests bacterial vs. viral.
• ↑ Plasma proteins (fibrinogen, prothrombin).
• C-reactive protein (CRP): appears 24{-}48\,\text{h} post-acute inflammation/necrosis.
• ↑ ESR: elevated proteins ↑ RBC settling rate.
• Cell enzymes/isoenzymes: released from necrotic cells; may localize damage.

Diagnostic Tests

• Leukocyte count, ESR, differential, plasma proteins, specific isoenzymes to identify necrosis source.

Potential Complications

• Infection: edematous tissue + nutrient-rich exudate facilitate microbial growth; some microbes resist phagocytosis.
• Skeletal muscle spasm: protective reaction to pain/inflammation.

Chronic Inflammation

• Follows acute episode when cause persists.
• ↓ Swelling/exudate but ↑ lymphocytes, macrophages, fibroblasts.
• Ongoing tissue destruction + fibrous scar deposition.
• Granuloma may form around foreign material (e.g., splinter).
• Deep ulcers possible due to prolonged necrosis & poor regeneration → risk of perforation & scarring.

Treatment Strategies

Pharmacologic

• Glucocorticoid benefits: ↓ capillary permeability, potentiates epi/norepi, ↓ leukocytes & mast cells, suppresses immune response.
• Glucocorticoid adverse: lymphoid atrophy, reduced hemopoiesis, protein catabolism, delayed healing/growth, Na⁺/H₂O retention, ↑ gluconeogenesis.

Non-Drug Modalities

• RICE: Rest, Ice, Compression, Elevation.
• Elevation, mild-moderate exercise, physiotherapy, occupational therapy.
• Adequate nutrition & hydration.
• Anti-inflammatory herbs/spices: turmeric, black pepper, ginger, rosemary, cloves, cayenne, basil, peppermint, cinnamon, sage, coriander, etc. (contain phytochemicals analogous to drug mediators).

Healing & Tissue Repair

Types

• Resolution: minimal damage; cells recover.
• Regeneration: damaged tissue replaced by identical functional cells (mitotic tissues).
• Replacement: functional tissue replaced by fibrous scar → loss of function.

First Intention (Clean Incised Wound)

1. Clot & scab form, neutrophils arrive (inflammation).
2. Granulation tissue + epithelial regeneration bridge gap; macrophages clean debris; capillaries invade.
3. Minor narrow scar remains.

Second Intention (Large Gap / Infected Wound)

1. Similar initial inflammation.
2. Larger granulation tissue, abundant collagen deposition.
3. Extensive scar contracts → larger, puckered scar.

Scar Formation & Complications

• Loss of function: absence of specialized structures (hair follicles, nerves, receptors).
• Contractures/obstructions: nonelastic tissue restricts movement or organ lumen.
• Adhesions: fibrous bands linking normally separate surfaces.
• Hypertrophic/Keloid: excess collagen → raised rigid scars.
• Ulceration: impaired blood supply at scar edge causes breakdown.

Burns

Etiologies

• Thermal (flame, hot liquids), chemical, radiation, electrical, light, friction.

Depth Classification

• Superficial partial-thickness (1st-degree): epidermis + superficial dermis; redness, minimal/no blisters.
• Deep partial-thickness (2nd-degree): epidermis + part dermis; blistering.
• Full-thickness (3rd & 4th-degree): destruction of all skin layers ± subcutaneous tissue, muscle, bone.

Local & Systemic Consequences

• Dehydration & edema, shock, respiratory issues, severe pain, infection, hypermetabolism during healing.

Rule of Nines – Adult BSA Estimate

• Total head: 9\% (anterior 4.5\% + posterior 4.5\%).
• Each arm: 9\% (anterior 4.5\% + posterior 4.5\%) → two arms 18\%.
• Trunk: 36\% (anterior 18\% + posterior 18\%).
• Each leg: 18\% (anterior 9\% + posterior 9\%) → two legs 36\%.
• Perineum/genitals: 1\%.
• Sum = 100\% TBSA (total body surface area).

Healing of Burns

• Hypermetabolism persists; caloric & protein needs surge.
• Immediate clean wound covering reduces infection risk.
• Long healing period; scar tissue forms even with grafting.
• Physiotherapy & occupational therapy essential to maintain mobility/function.
• Surgical release of restrictive scars may be needed.

Pediatric Considerations

• Growth can be stunted during acute recovery due to high metabolic demand.
• ↑ Inflammatory mediators may compromise renal function.
• Repeated grafts or surgeries required to accommodate growth & limit contractures.