Burns Pathology

Quick Answer

Burn injury causes thermal damage to skin and underlying tissues through heat, chemicals, electricity, or radiation. The pathological response involves both local tissue injury (Jackson zones) and systemic inflammatory responses including burn shock, hypermetabolism, and immunosuppression (PMID: 32061313).

Key Pathological Concepts:

• Jackson Zones: Coagulation (central necrosis), Stasis (threatened but salvageable), Hyperemia (vasodilated, will heal)
• Burn Shock: Hypovolemic-distributive shock with massive capillary leak syndrome peaking at 8-12 hours post-injury
• Hypermetabolic Response: Catecholamine-driven state with metabolic rate 150-200% baseline, persisting 12-24 months
• Immunosuppression: SIRS followed by CARS leading to "immunoparalysis" and high sepsis risk

ICU Relevance:

• Fluid resuscitation guided by Parkland formula (4 mL/kg/%TBSA) but titrated to urine output
• Airway management critical with inhalation injury - prophylactic intubation often required
• Recognition of secondary organ dysfunction (ARDS, AKI, hepatic failure)

Exam Focus:

• Draw and label Jackson zones with clinical implications
• Explain capillary leak pathophysiology and time course
• Describe Parkland formula and resuscitation targets
• Outline hypermetabolic response and nutritional implications

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CICM First Part Exam Focus

What Examiners Expect

Written SAQ:

Common question stems:

• "Describe the pathophysiology of burn shock" (appears in ~30% of First Part exams)
• "Outline the local and systemic effects of thermal injury"
• "Explain the Jackson zones model of burn wound injury"
• "Describe the hypermetabolic response to major burns"
• "Outline the pathophysiology of inhalation injury"
• "Explain fluid resuscitation in major burns with reference to Parkland formula"

Expected depth:

• Detailed molecular mechanisms of capillary leak
• Quantitative values (Parkland formula, TBSA calculation methods)
• Clear diagrams of Jackson zones with clinical implications
• Integration of local and systemic pathophysiology
• Time course of physiological changes (ebb and flow phases)

Written MCQ:

Common topics tested:

• Jackson zones definition and clinical significance
• Burn depth classification (superficial, partial, full thickness)
• Capillary leak mechanisms and mediators
• TBSA calculation methods (Rule of 9s, Lund-Browder)
• Parkland formula and modifications
• Inhalation injury pathophysiology
• Hypermetabolic response characteristics

Difficulty level:

• Application of pathological principles to resuscitation decisions
• Calculation of fluid requirements
• Recognition of inhalation injury features

Oral Viva:

Expected discussion flow:

1. Define/Describe - Jackson zones, burn depth classification
2. Explain Mechanism - Capillary leak, inflammatory cascade, organ dysfunction
3. Quantify - TBSA methods, Parkland formula, metabolic rate increases
4. Apply to ICU - Resuscitation endpoints, airway decisions, nutritional support
5. Compare/Contrast - Superficial vs full thickness, thermal vs chemical
6. Integrate - Multiorgan effects and long-term consequences

Common viva scenarios:

• "Tell me about the pathophysiology of major burns"
• "Explain how you would assess burn depth and surface area"
• "Describe the systemic response to a 40% TBSA burn"
• "What are the features and management of inhalation injury?"

Pass vs Fail Performance

Pass Standard:

• Accurate description of Jackson zones with correct clinical implications
• Clear explanation of capillary leak mechanism with time course
• Correct application of Parkland formula with resuscitation endpoints
• Ability to explain hypermetabolic response with nutritional implications
• Draws clear diagrams of burn pathophysiology when asked
• Links pathology to clinical management decisions

Common Reasons for Failure:

• Confusing Jackson zones (particularly zone of stasis significance)
• Incorrect Parkland formula or calculation errors
• No understanding of capillary leak time course
• Inability to describe inhalation injury pathophysiology
• Cannot calculate TBSA using Rule of 9s
• Poor integration of local and systemic pathophysiology

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Key Points

Must-Know Facts

1. Jackson Zones (1953): Three concentric zones - Zone of Coagulation (central irreversible necrosis), Zone of Stasis (threatened tissue, potentially salvageable), Zone of Hyperemia (vasodilated, will recover). Zone of stasis can convert to coagulation with poor resuscitation, hypotension, or infection (PMID: 13059150)

2. Burn Depth Classification: Superficial (epidermal only, erythema, heals 7-10 days), Superficial partial-thickness (papillary dermis, blistering, heals 10-14 days), Deep partial-thickness (reticular dermis, mottled, heals 3-8 weeks with scarring), Full-thickness (entire dermis, leathery/waxy, requires grafting) (PMID: 30843555)

3. Total Body Surface Area (TBSA): Rule of 9s (adult): Head 9%, each arm 9%, anterior trunk 18%, posterior trunk 18%, each leg 18%, perineum 1%. Lund-Browder chart more accurate, especially in children where head is proportionally larger. Palm = 1% TBSA for scattered burns (PMID: 29288000)

4. Burn Shock Pathophysiology: Hypovolemic-distributive shock caused by massive capillary leak. Inflammatory mediators (histamine, bradykinin, prostaglandins, leukotrienes, TNF-α, IL-1β, IL-6) increase microvascular permeability. Peak leak at 8-12 hours, maximal edema at 18-24 hours, capillary integrity restored by 24-48 hours (PMID: 24979134)

5. Capillary Leak Mechanisms: Endothelial glycocalyx degradation, VE-cadherin internalisation, increased transcytosis. Loss of protein reflection coefficient leads to plasma protein extravasation. Starling forces overwhelmed by permeability changes. Oedema occurs both locally and systemically in major burns (>20% TBSA) (PMID: 31387720)

6. Parkland Formula: Crystalloid 4 mL × body weight (kg) × %TBSA burned. Half given in first 8 hours from time of burn, remainder over next 16 hours. Titrate to urine output 0.5-1 mL/kg/hr adults, 1-1.5 mL/kg/hr children. Formula is starting point only (PMID: 32061313)

7. Hypermetabolic Response: Catecholamine-mediated increase in metabolic rate to 150-200% baseline. Ebb phase (first 24-48 hours): hypometabolic. Flow phase (days to months): hypermetabolic with protein catabolism, lipolysis, gluconeogenesis, insulin resistance. Can persist 12-24 months post-injury (PMID: 19793552)

8. Protein Catabolism: Skeletal muscle breakdown at 200-250 g protein/day in major burns. Negative nitrogen balance despite aggressive feeding. Loss of 10% lean body mass significantly increases mortality. Protein requirements 1.5-2.0 g/kg/day (PMID: 25183331)

9. Immunosuppression: Biphasic immune response - SIRS followed by CARS (Compensatory Anti-inflammatory Response Syndrome). Neutrophil dysfunction (impaired chemotaxis, respiratory burst), T-cell anergy (Th1→Th2 shift), monocyte HLA-DR downregulation ("immunoparalysis"). High infection and sepsis risk (PMID: 27150165)

10. Inhalation Injury: Three components: (1) Thermal injury to upper airway (above glottis), (2) Chemical injury from smoke particles to lower airways, (3) Systemic toxicity (CO, cyanide). Increases mortality 2-3 fold. May have delayed presentation - airway edema peaks 12-24 hours (PMID: 30210330)

Essential Equations

Parkland Formula:

Fluid (mL) = 4 × Weight (kg) × %TBSA burned

• Half given in first 8 hours from time of burn
• Remainder over next 16 hours
• Titrate to urine output 0.5-1 mL/kg/hr

Rule of 9s (Adults):

Head = 9%
Each arm = 9%
Anterior trunk = 18%
Posterior trunk = 18%
Each leg = 18%
Perineum = 1%

Modified Brooke Formula:

Fluid (mL) = 2 × Weight (kg) × %TBSA burned

• Used by some centres (less fluid than Parkland)

Carboxyhaemoglobin Half-life:

Room air: 320-360 minutes
100% O2: 60-90 minutes
Hyperbaric O2 (3 ATA): 20-30 minutes

Energy Requirements (Major Burns):

Curreri Formula: 25 kcal/kg + 40 kcal/%TBSA/day
Toronto Formula: REE × 1.2 (activity factor)
Indirect calorimetry preferred if available

Normal Values Table

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Definition and Epidemiology

Definition

Burn injury is tissue damage caused by heat, chemicals, electricity, radiation, or friction. The severity depends on:

• Temperature and duration of exposure
• Depth of tissue injury
• Total body surface area (TBSA) affected
• Location (face, hands, feet, perineum, joints are critical areas)
• Associated injuries (especially inhalation injury)

Major burn is typically defined as:

• 20% TBSA in adults (>15% in children or elderly)

• 10% full-thickness burn

• Burns of face, hands, feet, genitalia, perineum, major joints
• Inhalation injury
• Electrical or chemical burns
• Burns with significant comorbidities

Epidemiology

Global Burden (PMID: 32792490):

• ~11 million burn injuries annually requiring medical attention worldwide
• ~180,000 deaths annually from burns
• Higher incidence in low- and middle-income countries
• Leading cause of disability-adjusted life years (DALYs) in many regions

Australian Context (PMID: 30638591):

• ~3,000 burn unit admissions annually
• Major burns (~20% TBSA): ~500 cases/year
• Mortality for major burns: 15-25% (improved from historical 50%)
• Common causes: flame (45%), scalds (35%), contact (10%), electrical (5%), chemical (5%)

Risk Factors:

• Age extremes (children <5 years, elderly >65 years)
• Male sex (higher occupational and risk-taking behaviour exposure)
• Socioeconomic disadvantage
• Aboriginal and Torres Strait Islander populations (higher incidence, more severe burns, remote access issues)
• Psychiatric illness (self-harm, impaired safety awareness)
• Alcohol and drug intoxication

Indigenous Health Considerations:

• 3-5 times higher burn incidence in Aboriginal and Torres Strait Islander populations
• Often more severe burns at presentation
• Remote location delays access to specialised care
• Cultural considerations for wound care and family involvement
• Higher complication rates due to comorbidities (diabetes, renal disease)
• Importance of Aboriginal Health Workers and cultural liaison
• Connection to Country important during prolonged hospitalisation

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Local Burn Wound Pathophysiology

Jackson Zones Model

In 1953, Douglas Jackson described the classic model of burn wound pathophysiology based on the severity of tissue damage and potential for recovery (PMID: 13059150).

Zone of Coagulation

Location: Central area, directly beneath heat source

Pathophysiology:

• Immediate coagulative necrosis from protein denaturation
• Temperatures >60°C cause irreversible cellular damage within seconds
• Complete loss of tissue architecture
• No blood flow (avascular)
• Cell membrane disruption
• Mitochondrial destruction
• DNA denaturation

Clinical Features:

• White, waxy, or charred appearance
• Insensate (nerve endings destroyed)
• No capillary refill
• Leathery texture in full-thickness burns

Outcome: Irreversible damage, requires surgical debridement and grafting

Zone of Stasis

Location: Surrounds the zone of coagulation

Pathophysiology (PMID: 10815217):

• Reduced but not absent perfusion
• Initially viable cells under ischaemic stress
• Microvascular injury with:
  • Vasoconstriction (thromboxane A2, endothelin-1)
  • Platelet aggregation and microthrombi
  • Fibrin deposition
  • Endothelial swelling
  • Increased interstitial oedema
• ROS generation from reperfusion
• Apoptosis pathway activation

Clinical Significance:

• Potentially salvageable with optimal management
• Highly vulnerable to "secondary insults":
  • Hypotension (inadequate resuscitation)
  • Hypovolaemia
  • Infection
  • Hypothermia
  • Tissue oedema (compartment syndrome)
  • Vasoconstricting drugs

Burn Wound Conversion:

• Without adequate perfusion, zone of stasis converts to zone of coagulation
• Deepens the burn injury (partial-thickness → full-thickness)
• Prevention is the goal of aggressive fluid resuscitation
• Occurs primarily in first 48-72 hours

Zone of Hyperemia

Location: Outermost layer

Pathophysiology:

• Vasodilation from inflammatory mediators (histamine, prostaglandins, nitric oxide)
• Increased blood flow
• Tissue is viable
• Minimal cellular injury

Clinical Features:

• Erythematous appearance
• Blanches with pressure
• Sensate (painful)
• Good capillary refill

Outcome: Recovers spontaneously within 7-10 days unless complicated by severe infection or sepsis

Molecular Mechanisms of Local Injury

Immediate Effects (Seconds to Minutes) (PMID: 26808756):

1. Protein Denaturation

   • Begins at 43°C (slow)
   • Rapid above 60°C
   • Complete above 70°C
   • Collagen denaturation and contraction

2. Cell Membrane Disruption

   • Lipid bilayer melting
   • Ion channel dysfunction
   • Loss of membrane potential
   • Ca2+ influx → cell death

3. DNA Damage

   • Direct thermal denaturation
   • Strand breaks
   • Activation of apoptosis pathways

Early Inflammatory Phase (Hours) (PMID: 32061313):

1. DAMPs Release

   • HMGB1 (High Mobility Group Box 1)
   • Heat shock proteins
   • Mitochondrial DNA
   • ATP, uric acid

2. Complement Activation

   • Classical and alternative pathways
   • C3a, C5a anaphylatoxins
   • Membrane attack complex

3. Inflammatory Cell Infiltration

   • Neutrophils (first responders, peak 24-48 hours)
   • Macrophages (peak day 3-7)
   • Lymphocytes (later phase)

4. Cytokine Production

   • TNF-α (peak 2-4 hours)
   • IL-1β
   • IL-6 (major driver of acute phase response)
   • IL-8 (neutrophil chemotaxis)

Oxidative Stress:

1. Reactive Oxygen Species (ROS)

   • Superoxide (O2•-)
   • Hydrogen peroxide (H2O2)
   • Hydroxyl radical (OH•)
   • Peroxynitrite (ONOO-)

2. Sources

   • Activated neutrophils (respiratory burst)
   • Mitochondrial dysfunction
   • Xanthine oxidase (ischemia-reperfusion)
   • NADPH oxidase

3. Effects

   • Lipid peroxidation
   • Protein oxidation
   • DNA damage
   • Endothelial dysfunction

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Burn Depth Classification

Histological and Clinical Correlation

Superficial (First Degree) Burn

Histopathology:

• Epidermal injury only
• Basal layer intact
• Dermis unaffected
• Minimal inflammatory infiltrate

Clinical Features:

• Erythema (sunburn-like)
• Pain (intact nerve endings)
• No blistering
• Blanches with pressure

Healing:

• Spontaneous within 3-7 days
• No scarring
• Not included in TBSA calculation for fluid resuscitation

Superficial Partial-Thickness (Second Degree - Superficial)

Histopathology:

• Epidermal destruction
• Papillary dermis involvement
• Dermal appendages (hair follicles, sweat glands) preserved
• Epidermal-dermal separation (blister formation)
• Inflammatory infiltrate with neutrophils

Clinical Features:

• Blistering (tense, clear fluid)
• Moist, pink/red wound bed
• Extremely painful (exposed nerve endings)
• Brisk capillary refill
• Hair follicles intact

Healing:

• Spontaneous within 10-14 days
• Re-epithelialisation from dermal appendages
• Minimal scarring if no infection

Deep Partial-Thickness (Second Degree - Deep)

Histopathology:

• Extends into reticular dermis
• Partial destruction of dermal appendages
• Some appendage remnants deep in dermis
• Significant inflammatory infiltrate
• Vascular thrombosis in deep dermis

Clinical Features:

• Blistering may be absent or ruptured
• Mottled pink/white appearance
• Decreased sensation (partial nerve damage)
• Sluggish capillary refill
• Some hair follicles destroyed

Healing:

• Spontaneous healing possible in 3-8 weeks
• Re-epithelialisation from remaining appendages
• Significant scarring likely
• Often benefits from grafting

Full-Thickness (Third Degree) Burn

Histopathology:

• Complete destruction of epidermis and dermis
• Destruction of all dermal appendages
• May extend into subcutaneous tissue
• Coagulation necrosis with "ghost" cells
• Thrombosed vessels
• Collagen denaturation

Clinical Features:

• White, waxy, or brown/black (charred)
• Leathery or parchment-like texture
• Insensate (nerve endings destroyed)
• No capillary refill
• Thrombosed vessels visible
• Hair easily removed

Healing:

• Cannot heal spontaneously (no epithelial source)
• Requires surgical excision and grafting
• Heals only by contraction from wound edges (if small)

Fourth Degree Burn

Histopathology:

• Full-thickness skin destruction
• Extends through subcutaneous fat
• Involves fascia, muscle, tendon, or bone
• Carbonisation in electrical and severe flame burns

Clinical Features:

• Charred, dry, contracted tissue
• Visible deep structures
• Complete insensation
• Often associated with electrical injury

Treatment:

• Often requires amputation or extensive reconstruction
• Flap coverage needed

Burn Depth Estimation Methods

Clinical Assessment (PMID: 24279823):

• Appearance, texture, sensation, capillary refill
• Accuracy: 60-80% by experienced surgeons
• Difficult in first 24-48 hours (evolving injury)

Laser Doppler Imaging (LDI):

• Measures dermal blood flow
• Accuracy: 95% at 48-72 hours
• Predicts healing potential
• Available in major burn centres

Biopsy:

• Gold standard but rarely used clinically
• Adds morbidity
• Reserved for research

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TBSA Calculation Methods

Rule of 9s (Wallace)

Adult Values (PMID: 29288000):

Advantages:

• Rapid estimation
• Easy to remember
• Adequate for field and initial assessment

Limitations:

• Less accurate for children (head proportionally larger)
• Less accurate for obese patients
• Overestimates head, underestimates legs in children

Lund-Browder Chart

Age-Adjusted Values:

Advantages:

• Age-adjusted for accurate paediatric assessment
• More precise than Rule of 9s
• Standard in burn centres

Palm Method

Principle: Patient's palm (including fingers) ≈ 1% TBSA

Applications:

• Scattered burns
• Small burns
• Field estimation

Limitations:

• Less accurate for large burns
• Palm size varies with age

Practical Application

Key Principles:

1. Only include partial-thickness and full-thickness burns
2. Do NOT include superficial (first-degree) burns in TBSA for resuscitation
3. Reassess as burns evolve (especially at 24-48 hours)
4. Document clearly with diagrams
5. Photography useful for reassessment

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Systemic Response to Burns

Burn Shock Pathophysiology

Definition: Burn shock is a unique combination of hypovolaemic and distributive shock occurring after major burns (>20% TBSA), characterised by massive capillary leak, intravascular volume depletion, and myocardial depression (PMID: 24979134).

Phase 1: Immediate Response (0-2 hours)

Mediator Release (PMID: 28333817):

1. Histamine

   • Released from mast cells within minutes
   • Increases vascular permeability (H1 receptors)
   • Vasodilation
   • Peak effect 30-60 minutes

2. Kinins (Bradykinin)

   • Kallikrein-kinin system activation
   • Potent vasodilation
   • Increased permeability
   • Pain signalling

3. Serotonin

   • Platelet release
   • Vasoconstriction in pulmonary circulation
   • Increased permeability

4. Prostaglandins and Leukotrienes

   • Arachidonic acid metabolism (COX and LOX pathways)
   • PGE2: vasodilation, fever
   • PGI2: vasodilation, antiplatelet
   • TXA2: vasoconstriction, platelet aggregation
   • LTB4: neutrophil chemotaxis
   • LTC4/D4/E4: increased permeability, bronchoconstriction

5. Complement Activation

   • C3a, C5a anaphylatoxins
   • Increased vascular permeability
   • Neutrophil activation
   • Mast cell degranulation

Phase 2: Capillary Leak Syndrome (2-24 hours)

Endothelial Injury Mechanisms (PMID: 31387720):

1. Glycocalyx Degradation

   • Proteoglycan and glycosaminoglycan loss
   • Increased permeability to proteins
   • Loss of mechanotransduction
   • Syndecan-1 released (marker of glycocalyx injury)

2. Intercellular Junction Disruption

   • VE-cadherin phosphorylation and internalisation
   • Tight junction disassembly
   • Adherens junction opening
   • Paracellular leak pathway

3. Transcytosis Increase

   • Caveolae-mediated transcytosis
   • Albumin transport to interstitium
   • Transcellular leak pathway

Consequences:

• Plasma protein loss to interstitium
• Loss of oncotic pressure gradient
• Massive third-spacing of fluid
• Oedema formation (local and systemic in >20% TBSA)
• Intravascular hypovolaemia

Time Course:

• Begins within minutes of injury
• Peak permeability at 8-12 hours
• Maximum oedema at 18-24 hours
• Permeability normalises by 24-48 hours
• Fluid shifts back to intravascular space (post-resuscitation diuresis)

Phase 3: Myocardial Depression

Myocardial Depressant Factors (PMID: 15590226):

1. Circulating Mediators

   • TNF-α (negative inotrope)
   • IL-1β
   • PAF (platelet-activating factor)
   • Nitric oxide

2. Direct Myocardial Effects

   • Reduced contractility
   • Diastolic dysfunction
   • Decreased ejection fraction
   • May persist 24-48 hours

3. Preload Reduction

   • Hypovolaemia from capillary leak
   • Reduced venous return
   • Exacerbates low output state

Clinical Significance:

• Cardiac output may be reduced despite adequate fluid resuscitation
• May require inotropic support in severe cases
• Typically resolves within 48-72 hours

Phase 4: Organ Hypoperfusion

Affected Organs:

1. Kidneys

   • Renal vasoconstriction
   • Reduced GFR
   • Pre-renal AKI if inadequate resuscitation
   • ATN if prolonged hypoperfusion

2. Gut

   • Splanchnic vasoconstriction
   • Mucosal ischaemia
   • Barrier dysfunction
   • Bacterial translocation (contributes to late sepsis)

3. Lungs

   • Pulmonary oedema (increased permeability)
   • ARDS in severe burns
   • Compounded by inhalation injury

Hypermetabolic Response

Definition: The hypermetabolic response is a catecholamine-driven state of increased metabolic rate, catabolism, and systemic inflammation that begins after resuscitation and can persist for up to 24 months (PMID: 19793552).

Ebb and Flow Phases (PMID: 23053123)

Ebb Phase (First 24-48 hours):

• Hypometabolic state during shock
• Decreased oxygen consumption
• Reduced core temperature
• Decreased cardiac output
• Focus on resuscitation

Flow Phase (Days to Months):

• Hypermetabolic state after resuscitation
• Metabolic rate 150-200% of baseline (proportional to burn size)
• Elevated core temperature (reset thermostat to 38-39°C)
• Hyperdynamic circulation
• Massive catabolism

Neuroendocrine Drivers

Catecholamines (PMID: 25183331):

• Epinephrine and norepinephrine elevated 10-20 fold
• Drives glycogenolysis, gluconeogenesis
• Stimulates lipolysis
• Increases metabolic rate

Cortisol:

• Elevated 3-5 fold
• Promotes gluconeogenesis
• Protein catabolism
• Immunosuppressive effects
• Impaired wound healing at excess levels

Glucagon:

• Elevated 3-4 fold
• Opposes insulin action
• Stimulates gluconeogenesis
• Glycogenolysis

Insulin:

• Absolute levels may be elevated
• BUT profound insulin resistance (post-receptor defect)
• Results in stress hyperglycaemia

Metabolic Consequences

Protein Catabolism:

• Skeletal muscle breakdown (autocannibalism)
• 200-250 g protein/day catabolised in major burns
• Provides amino acids for:
  • Acute phase proteins (CRP, fibrinogen)
  • Gluconeogenesis
  • Wound healing
• Negative nitrogen balance despite aggressive feeding
• 10% lean body mass loss increases mortality

Carbohydrate Metabolism:

• Increased gluconeogenesis
• Glycogenolysis
• Insulin resistance
• Hyperglycaemia (10-15 mmol/L common)
• Glucose intolerance

Lipid Metabolism:

• Increased lipolysis
• Elevated free fatty acids
• Hepatic steatosis
• Triglyceride elevation

Clinical Implications:

• Massive nutritional requirements (30-35 kcal/kg/day)
• High protein intake needed (1.5-2.0 g/kg/day)
• Temperature management (ambient 28-33°C)
• Glycaemic control (target 6-10 mmol/L)
• Anabolic agents may have role (oxandrolone, propranolol)

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Immunosuppression and Infection

Biphasic Immune Response

SIRS (Systemic Inflammatory Response Syndrome) (PMID: 17356352):

Initial hyper-inflammatory phase:

• Cytokine storm (TNF-α, IL-1β, IL-6, IL-8)
• Complement activation
• Neutrophil activation
• Endothelial activation
• Coagulation activation

CARS (Compensatory Anti-inflammatory Response Syndrome) (PMID: 24703487):

Counter-regulatory phase:

• IL-10 elevation (anti-inflammatory)
• TGF-β production
• Prostaglandin E2
• Suppression of pro-inflammatory responses

In major burns, CARS often predominates → Immunoparalysis

Cellular Immune Dysfunction

Neutrophil Dysfunction (PMID: 27150165):

• Impaired chemotaxis (reduced migration to infection site)
• Defective phagocytosis
• Reduced respiratory burst (impaired killing)
• Delayed apoptosis (tissue damage)
• NET formation (collateral tissue damage)

Monocyte/Macrophage Dysfunction:

• Reduced HLA-DR expression (marker of immunoparalysis)
• Impaired antigen presentation
• Defective cytokine production
• Inability to activate adaptive immunity

T-Cell Dysfunction:

• Th1 → Th2 shift
• Reduced cell-mediated immunity
• Increased regulatory T-cells (Tregs)
• Anergy (unresponsive T-cells)
• Reduced IL-2 and IFN-γ production

B-Cell Dysfunction:

• Reduced immunoglobulin production
• Impaired antibody responses
• Complement consumption

Infection Risk Factors

Host Factors (PMID: 32792490):

• Loss of skin barrier (primary defence)
• Immunosuppression
• Protein malnutrition
• Gut barrier dysfunction
• Central venous catheters
• Urinary catheters
• Endotracheal tubes

Wound Factors:

• Avascular eschar (cannot deliver antibiotics/immune cells)
• Moist, protein-rich environment
• Extensive surface area for colonisation
• Biofilm formation

Microbial Factors:

• Initially colonised by Gram-positive organisms (S. aureus)
• Gram-negative organisms predominate after 5-7 days (P. aeruginosa)
• Fungi in prolonged ICU stay (Candida, Aspergillus)
• Antibiotic resistance selection

Sepsis in Burns

Definition (PMID: 28404221):

American Burn Association criteria (2007) recognise that baseline SIRS is present in burn patients. Sepsis diagnosis requires:

• Documented infection AND
• 3+ of:
  • Temperature >39°C or <36.5°C
  • Progressive tachycardia (>110 bpm in adults)
  • Progressive tachypnoea (>25 in adults) or MV >12 L/min
  • Thrombocytopenia <100,000 or >25% drop from peak
  • Hyperglycaemia (>200 mg/dL in non-diabetics) or insulin requirement >7 units/hr
  • Enteral feeding intolerance (>24 hr)
  • Plus a physiological or laboratory parameter

Gut-Derived Sepsis:

• Splanchnic hypoperfusion during shock
• Mucosal atrophy
• Loss of tight junctions
• Bacterial translocation to mesenteric lymph nodes and bloodstream
• Major contributor to late sepsis

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Inhalation Injury

Definition and Epidemiology

Definition: Inhalation injury is damage to the airways and/or lungs from inhaled smoke, toxic gases, or heat. It has three components: thermal upper airway injury, chemical lower airway injury, and systemic toxicity (PMID: 30210330).

Epidemiology:

• Present in 20-35% of burn unit admissions
• More common in enclosed-space fires
• Increases mortality 2-3 fold at any given TBSA
• Independent predictor of mortality

Components of Inhalation Injury

1. Thermal Injury (Upper Airway)

Mechanism:

• Heat injury to structures above the glottis
• Air is a poor conductor of heat
• Upper airway efficiently absorbs thermal energy
• Larynx rarely injured by heat alone

Pathophysiology:

• Direct epithelial damage
• Mucosal oedema
• Blistering
• Airway obstruction

Time Course:

• May present immediately or delayed up to 24 hours
• Oedema peaks at 12-24 hours
• Maximal swelling may cause complete obstruction

Clinical Features:

• Facial burns
• Singed nasal/facial hair
• Oropharyngeal erythema/blistering
• Hoarseness, stridor
• Carbonaceous sputum

2. Chemical Injury (Lower Airway)

Mechanism:

• Smoke contains 200+ toxic compounds
• Particles <1 μm reach alveoli
• Chemical pneumonitis

Toxic Compounds:

Pathophysiology (PMID: 17255302):

• Tracheobronchial epithelial necrosis
• Ciliary dysfunction
• Mucus hypersecretion
• Bronchospasm
• Cast formation (sloughed epithelium, fibrin, mucus)
• Small airway obstruction
• V/Q mismatch
• ARDS

Time Course:

• May be delayed 24-48 hours
• Progressive over 72-96 hours
• Resolution over 1-2 weeks if survive

3. Systemic Toxicity

Carbon Monoxide (CO) (PMID: 27217020):

Mechanism:

• CO binds haemoglobin with 200-250× affinity of O2
• Forms carboxyhaemoglobin (COHb)
• Left-shifts oxygen-haemoglobin dissociation curve
• Impairs O2 delivery to tissues
• Binds cytochrome oxidase (impairs cellular respiration)
• Binds myoglobin (cardiac and skeletal muscle dysfunction)

Clinical Features:

• Headache, confusion, coma
• Cherry-red colour (rarely seen)
• Metabolic acidosis
• Cardiac ischaemia
• Normal PaO2 (dissolved O2 unaffected)
• SpO2 unreliable (reads COHb as HbO2)

Diagnosis:

• Co-oximetry (arterial blood gas with COHb measurement)
• COHb levels:
  • "Non-smokers: <2%"
  • "Smokers: 5-10%"
  • "Symptomatic: >15-20%"
  • "Severe: >40%"
  • "Lethal: >60%"

Treatment:

• 100% O2 (reduces half-life from 320 min to 60-90 min)
• Hyperbaric O2 (reduces half-life to 20-30 min)
• HBO indications: COHb >25%, neurological symptoms, pregnancy, cardiac ischaemia

Hydrogen Cyanide (CN) (PMID: 29153421):

Source:

• Combustion of synthetic materials (plastics, polyurethane, nylon, wool, silk)

Mechanism:

• Inhibits cytochrome c oxidase
• Blocks mitochondrial electron transport chain
• Prevents oxidative phosphorylation
• Cells cannot use O2 despite adequate delivery

Clinical Features:

• Altered consciousness, seizures
• Lactic acidosis (often >10 mmol/L)
• Normal PaO2, high SvO2 (O2 not extracted)
• Cardiovascular collapse

Treatment:

• Hydroxocobalamin (Cyanokit) - first line
• Binds CN to form cyanocobalamin (vitamin B12)
• Safe in smoke inhalation (unlike sodium nitrite)
• Dose: 5-10g IV

Diagnosis of Inhalation Injury

Clinical Suspicion (PMID: 26116314):

• Enclosed-space fire
• Altered consciousness at scene
• Facial burns
• Singed nasal/facial hair
• Carbonaceous sputum
• Hoarseness, stridor
• Dyspnoea
• Circumferential neck/chest burns

Investigations:

• Fibreoptic bronchoscopy (gold standard for direct visualisation)
• Chest X-ray (often normal initially)
• ABG with co-oximetry
• Lactate (cyanide suspicion)
• CT chest (assess parenchymal injury)

Bronchoscopy Grading:

Management of Inhalation Injury

Airway Management:

• Early intubation if signs of impending obstruction
• Use largest tube possible (secretion clearance)
• Avoid tracheostomy in acute phase (stomal burns)
• Awake fibreoptic intubation if time permits

Ventilation:

• Lung-protective ventilation (6-8 mL/kg IBW)
• PEEP to prevent atelectasis
• May require bronchoscopy for cast removal
• Nebulised therapies (heparin, N-acetylcysteine) - variable evidence

Systemic Toxicity:

• High-flow O2 for all smoke inhalation
• Co-oximetry (do not rely on SpO2)
• Hydroxocobalamin if CN suspected
• HBO for severe CO poisoning

---

Fluid Resuscitation

Principles

Goals (PMID: 32061313):

• Restore intravascular volume
• Maintain organ perfusion
• Prevent burn wound conversion
• Avoid under- and over-resuscitation

Timing:

• Most critical in first 24-48 hours
• During capillary leak phase
• Fluid requirements decrease after 24-48 hours

Parkland Formula

Formula:

Total crystalloid in first 24 hours = 4 mL × weight (kg) × %TBSA burned

Administration:

• Half (50%) in first 8 hours from time of burn (NOT from arrival)
• Remainder (50%) over next 16 hours
• Titrate to urine output

Example: 70 kg patient with 40% TBSA burn:

• Total = 4 × 70 × 40 = 11,200 mL in 24 hours
• First 8 hours: 5,600 mL (700 mL/hour)
• Next 16 hours: 5,600 mL (350 mL/hour)

Resuscitation Endpoints

Urine Output Targets:

• Adults: 0.5-1.0 mL/kg/hour
• Children: 1.0-1.5 mL/kg/hour
• Electrical injury: 1.0-1.5 mL/kg/hour (myoglobinuria)

Other Parameters:

• Heart rate <120 bpm
• MAP >65 mmHg
• Lactate normalisation
• Base deficit improvement
• Pulse pressure variation <13% (if mechanically ventilated)

Modified Formulas

Modified Brooke Formula:

Total crystalloid = 2 mL × weight (kg) × %TBSA
Plus colloid after 24 hours

Advantages: Less total fluid, potentially less oedema Disadvantages: May under-resuscitate severe burns

Colloid Use:

• Controversial
• May reduce total fluid requirements
• Consider after 8-12 hours when leak decreasing
• Albumin 5% most commonly used
• No proven mortality benefit

Fluid Creep

Definition: Administration of resuscitation fluid in excess of Parkland formula predictions (PMID: 27918244).

Causes:

• Inhalation injury (increased requirements)
• Delayed resuscitation
• Over-reliance on urine output
• Deep sedation (opioid effects on urine output)
• Electrical injury

Consequences:

• Pulmonary oedema
• ARDS
• Abdominal compartment syndrome
• Extremity compartment syndrome
• Escharotomy requirements
• Orbital compartment syndrome
• Increased morbidity and mortality

Prevention:

• Use formula as starting point, titrate to endpoints
• Regular reassessment
• Consider colloids
• Avoid over-sedation
• Early recognition of compartment syndromes

---

Organ Dysfunction in Major Burns

Cardiovascular

Acute Phase (0-48 hours):

• Hypovolaemia
• Myocardial depression
• Increased systemic vascular resistance

Hypermetabolic Phase:

• Hyperdynamic circulation
• Cardiac output 10-15 L/min
• Tachycardia
• Peripheral vasodilation

Respiratory

ARDS Risk Factors:

• Inhalation injury
• Sepsis
• Large TBSA burn
• Over-resuscitation

Pathophysiology:

• Inflammatory mediators
• Capillary leak
• Surfactant dysfunction
• Similar to other causes of ARDS

Renal

AKI Incidence: 25-40% of major burns

Causes:

• Pre-renal (hypovolaemia)
• ATN (prolonged hypoperfusion)
• Myoglobinuria (electrical/deep burns)
• Nephrotoxic drugs
• Sepsis

Prevention:

• Adequate resuscitation
• Avoid nephrotoxins
• Early dialysis if indicated

Hepatic

Early Phase:

• Ischaemic hepatitis (shock liver)
• Transient transaminase elevation

Late Phase:

• Hepatic steatosis
• Drug metabolism alterations
• Synthetic dysfunction in severe cases

Coagulation

Early:

• Procoagulant state
• Consumptive coagulopathy possible
• DIC in severe burns/sepsis

Later:

• Hypercoagulable
• DVT/PE risk (immobility, central lines, inflammation)
• Prophylaxis essential

Gastrointestinal

Curling's Ulcer:

• Stress ulceration
• Historical: significant cause of morbidity/mortality
• Now rare with PPI prophylaxis and early feeding

Ileus:

• Common in major burns
• Enteral feeding important for gut integrity
• Prokinetics may be needed

Gut Barrier Dysfunction:

• Bacterial translocation
• Contributes to late sepsis/MODS

---

Special Burn Types

Electrical Burns

Pathophysiology (PMID: 28257855):

• Current follows path of least resistance
• Nerve, blood vessels, muscle conduct well
• Bone conducts poorly (heats adjacent tissues)
• Surface burns underestimate deep injury

Unique Features:

• Entry and exit wounds
• Deep tissue injury (iceberg effect)
• Rhabdomyolysis
• Arrhythmias
• Neurological injury

Management:

• Aggressive fluid resuscitation (myoglobinuria)
• Target UO 1-1.5 mL/kg/hr
• ECG monitoring
• Compartment syndrome surveillance
• Delayed fasciotomy/escharotomy often required

Chemical Burns

Pathophysiology:

• Acids: coagulative necrosis (limits penetration)
• Alkalis: liquefactive necrosis (progressive penetration)
• Duration of contact is critical

Management:

• Immediate copious irrigation (minimum 30 minutes)
• Remove contaminated clothing
• NO neutralising agents (exothermic reactions)
• Specific antidotes for some agents (calcium gluconate for HF)

Cold Injury (Frostbite)

Pathophysiology:

• Direct cellular freezing
• Microvascular injury
• Reperfusion injury
• Progressive ischaemia

Zones (similar to thermal):

• Zone of coagulation (irreversible)
• Zone of stasis (potentially salvageable)

---

SAQ Practice

SAQ 1: Burns Pathophysiology

Question: A 35-year-old male is brought to the Emergency Department following a house fire. He has sustained 45% TBSA mixed partial and full-thickness burns to his trunk and limbs. He was found in an enclosed space with reduced level of consciousness.

(a) Describe the Jackson zones model of burn wound injury and their clinical significance. (6 marks)

(b) Outline the pathophysiology of burn shock, including mediators and time course. (8 marks)

(c) Calculate the fluid resuscitation requirements using the Parkland formula. He weighs 80 kg and the burn occurred 2 hours ago. (6 marks)

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Model Answer:

(a) Jackson Zones (6 marks)

Douglas Jackson (1953) described three concentric zones based on tissue viability (PMID: 13059150):

Zone of Coagulation (2 marks)

• Central area of irreversible coagulative necrosis
• Direct thermal protein denaturation (>60°C)
• No blood flow (avascular)
• Will require debridement and grafting
• Cannot be salvaged

Zone of Stasis (2 marks)

• Surrounds zone of coagulation
• Reduced but present perfusion
• Cells initially viable but threatened
• Microvascular changes: vasoconstriction, platelet aggregation, microthrombi
• Potentially salvageable - key therapeutic target
• Vulnerable to secondary insults: hypotension, hypothermia, infection
• If not rescued, converts to zone of coagulation (burn deepening)

Zone of Hyperemia (2 marks)

• Outermost layer
• Vasodilation from inflammatory mediators
• Increased blood flow, viable tissue
• Will recover spontaneously in 7-10 days
• Rarely progresses to necrosis unless severe sepsis

Clinical Significance: Optimal resuscitation aims to preserve zone of stasis. Inadequate fluid resuscitation, hypotension, or delayed treatment causes burn wound conversion and deepening of injury.

---

(b) Burn Shock Pathophysiology (8 marks)

Burn shock is a unique combination of hypovolaemic and distributive shock (PMID: 24979134):

Mediators (3 marks)

• Immediate (minutes): Histamine, bradykinin, serotonin from mast cells and platelets
• Early (hours): Prostaglandins (PGE2, PGI2), thromboxane A2, leukotrienes (LTB4, LTC4)
• Pro-inflammatory cytokines: TNF-α, IL-1β, IL-6, IL-8 from macrophages
• Complement activation: C3a, C5a anaphylatoxins
• DAMPs: HMGB1, heat shock proteins from necrotic cells

Capillary Leak Syndrome (3 marks)

• Endothelial glycocalyx degradation
• VE-cadherin internalisation (adherens junction disruption)
• Increased transcytosis and paracellular permeability
• Plasma protein extravasation to interstitium
• Loss of oncotic pressure gradient
• Massive third-spacing: 4-6 mL/kg/%TBSA in first 24 hours
• Oedema both local (burn wound) and systemic (>20% TBSA burns)

Time Course (2 marks)

Additional Features:

• Myocardial depressant factors (TNF-α, PAF) reduce contractility
• Increased SVR initially (compensatory vasoconstriction)
• Reduced cardiac output despite fluid loading (combined hypovolaemic-distributive pattern)

---

(c) Parkland Formula Calculation (6 marks)

Formula (2 marks): Total crystalloid in 24 hours = 4 mL × weight (kg) × %TBSA = 4 × 80 × 45 = 14,400 mL in 24 hours

Administration (2 marks):

• First 8 hours (from time of burn): 7,200 mL
• But 2 hours have elapsed, so remaining 6 hours: 7,200 mL
• Rate for next 6 hours = 7,200/6 = 1,200 mL/hour
• Next 16 hours: 7,200 mL = 450 mL/hour

Titration (2 marks):

• Parkland is a starting estimate only
• Titrate to urine output 0.5-1.0 mL/kg/hour (40-80 mL/hr for this patient)
• Monitor: HR <120, MAP >65, lactate normalising
• Expect increased requirements with inhalation injury (present - enclosed space)
• Avoid fluid creep (over-resuscitation causes oedema complications)

---

SAQ 2: Inhalation Injury

Question: A 28-year-old female is retrieved by helicopter from a remote industrial fire. She has 30% TBSA burns and suspected inhalation injury. She is intubated and ventilated.

(a) Describe the three components of inhalation injury and their pathophysiology. (9 marks)

(b) Outline the diagnosis and grading of inhalation injury. (5 marks)

(c) Describe the management of carbon monoxide and cyanide toxicity. (6 marks)

---

Model Answer:

(a) Three Components of Inhalation Injury (9 marks)

(PMID: 30210330)

1. Thermal Injury - Upper Airway (3 marks)

• Heat injury to structures above the glottis (supraglottic)
• Air is poor heat conductor - upper airway absorbs thermal energy
• Direct epithelial damage with mucosal oedema
• Blistering and sloughing of mucosa
• Delayed presentation - oedema peaks 12-24 hours
• Can cause complete airway obstruction
• Clinical signs: facial burns, singed nasal hair, hoarseness, stridor

2. Chemical Injury - Lower Airway (3 marks)

• Smoke contains >200 toxic compounds
• Particles <1 μm reach terminal bronchioles and alveoli
• Common toxins: acrolein, hydrogen chloride, phosgene, ammonia, aldehydes
• Pathophysiology:
  • Tracheobronchial epithelial necrosis
  • Ciliary dysfunction (impaired mucociliary clearance)
  • Mucus hypersecretion
  • Bronchospasm
  • Cast formation (sloughed epithelium, fibrin, mucus)
  • Small airway obstruction
  • V/Q mismatch
  • ARDS development

3. Systemic Toxicity (3 marks)

• Carbon Monoxide (CO):

  • Binds haemoglobin 200-250× affinity of O2
  • Forms carboxyhaemoglobin, left-shifts ODC
  • Binds cytochrome oxidase (impairs cellular respiration)
  • Tissue hypoxia despite normal PaO2

• Hydrogen Cyanide (CN):

  • From combustion of synthetics (plastics, foam, nylon)
  • Inhibits cytochrome c oxidase
  • Blocks mitochondrial electron transport
  • Prevents oxidative phosphorylation
  • Severe lactic acidosis

---

(b) Diagnosis and Grading (5 marks)

Clinical Suspicion (2 marks):

• Enclosed-space fire
• Altered consciousness at scene
• Facial/perioral burns
• Singed nasal/facial hair
• Carbonaceous sputum
• Hoarseness, stridor, dyspnoea

Investigations (1.5 marks):

• Fibreoptic bronchoscopy (gold standard) - direct visualisation
• Chest X-ray (often normal initially)
• ABG with co-oximetry (COHb measurement)
• Lactate >10 mmol/L suggests cyanide toxicity
• CT chest (parenchymal assessment)

Bronchoscopy Grading (1.5 marks):

Higher grades predict worse outcomes and prolonged ventilation.

---

(c) Management of CO and CN Toxicity (6 marks)

Carbon Monoxide Management (3 marks) (PMID: 27217020):

• Remove from exposure
• 100% oxygen immediately (reduces half-life from 320 min to 60-90 min)
• Monitor with co-oximetry (SpO2 unreliable - cannot distinguish COHb)
• Supportive care (cardiac monitoring for ischaemia)

Hyperbaric Oxygen (HBO) Indications:

• COHb >25%
• Neurological symptoms (confusion, LOC, seizures)
• Cardiac ischaemia/arrhythmia
• Pregnancy
• Reduces half-life to 20-30 minutes
• Controversial benefit for long-term neurological sequelae

Cyanide Management (3 marks) (PMID: 29153421):

• Suspect if: smoke inhalation + altered consciousness + severe lactic acidosis (>10 mmol/L) + cardiovascular collapse
• Normal PaO2 but high SvO2 (O2 not extracted)

Antidote - Hydroxocobalamin (Cyanokit):

• First-line treatment
• Binds cyanide → cyanocobalamin (vitamin B12)
• Renally excreted
• Dose: 5g IV over 15 minutes, may repeat 5g
• Safe in smoke inhalation (unlike older agents)

Other Antidotes (rarely used in smoke inhalation):

• Sodium nitrite + sodium thiosulfate (cyanide kit)
• Contraindicated with CO poisoning (worsens methaemoglobinaemia)
• Dicobalt edetate (historical, cardiac toxic)

---

Viva Scenarios

Viva 1: Local and Systemic Burns Pathophysiology

Stem: "A 45-year-old man has sustained 55% TBSA mixed-depth burns from a workplace explosion. Discuss the pathophysiology of his burn injury."

---

Examiner: "Describe the local pathology at the burn wound site."

Candidate: "The burn wound can be described using Jackson's zones model from 1953:

Zone of Coagulation:

• Central area closest to heat source
• Irreversible coagulative necrosis from protein denaturation
• Occurs when tissue temperature exceeds 60°C
• Complete cellular destruction - no blood flow
• Will require surgical debridement and grafting

Zone of Stasis:

• Surrounds the central zone
• Tissue is initially viable but under ischaemic stress
• Reduced blood flow due to:
  • Vasoconstriction (thromboxane A2, endothelin-1)
  • Platelet aggregation and microthrombi
  • Fibrin deposition
  • Endothelial swelling
• This zone is critically important because it can be salvaged with optimal resuscitation, or convert to necrosis with inadequate treatment
• 'Burn wound conversion' deepens the injury

Zone of Hyperemia:

• Outermost area
• Characterised by vasodilation from inflammatory mediators
• Tissue is viable with increased blood flow
• Will heal spontaneously in 7-10 days"

---

Examiner: "What mediators are involved in the early inflammatory response?"

Candidate: "Multiple inflammatory mediators are released within minutes to hours:

Immediate Release (seconds to minutes):

• Histamine from mast cell degranulation - increases vascular permeability
• Bradykinin from kallikrein-kinin system activation - vasodilation, pain
• Serotonin from platelet activation

Early Phase (minutes to hours):

• Arachidonic acid metabolites via COX and LOX pathways:
  • Prostaglandins (PGE2, PGI2) - vasodilation, fever
  • Thromboxane A2 - vasoconstriction, platelet aggregation
  • Leukotrienes (LTB4) - neutrophil chemotaxis
  • Leukotrienes (LTC4, D4, E4) - increased permeability, bronchoconstriction

Cytokine Phase (hours):

• TNF-α peaks at 2-4 hours - drives systemic response
• IL-1β - fever, acute phase response
• IL-6 - major acute phase protein driver
• IL-8 - neutrophil chemotaxis

DAMPs (Damage-Associated Molecular Patterns):

• HMGB1, heat shock proteins, mitochondrial DNA
• Released from necrotic cells
• Activate pattern recognition receptors
• Drive sterile inflammation"

---

Examiner: "Explain the pathophysiology of burn shock."

Candidate: "Burn shock is a unique combination of hypovolaemic and distributive shock that develops in major burns, typically greater than 20% TBSA.

Capillary Leak Syndrome: The hallmark of burn shock is massive increase in microvascular permeability:

1. Endothelial glycocalyx degradation - the protective carbohydrate layer is stripped by inflammatory mediators, exposing endothelium

2. Adherens junction disruption - VE-cadherin is phosphorylated and internalised, opening intercellular gaps

3. Increased transcytosis - vesicular transport of proteins across endothelium increases

4. Consequence - plasma proteins, especially albumin, leak into interstitium, losing the oncotic pressure gradient and causing massive fluid shifts

Time Course:

• Leak begins within minutes
• Peak permeability at 8-12 hours
• Maximum oedema at 18-24 hours
• Capillary integrity restored by 24-48 hours
• This explains why we give half the Parkland volume in the first 8 hours

Myocardial Depression:

• Circulating myocardial depressant factors (TNF-α, PAF)
• Reduced contractility and ejection fraction
• May persist 24-48 hours
• Contributes to low output state despite fluid loading

Global Effect:

• Intravascular hypovolaemia despite massive total body water increase
• Reduced venous return and cardiac output
• Organ hypoperfusion if not adequately resuscitated"

---

Examiner: "This patient has burns >50% TBSA. What is the hypermetabolic response?"

Candidate: "The hypermetabolic response is a catecholamine-driven state of massively increased metabolism that occurs after the initial resuscitation phase.

Phases:

1. Ebb Phase (first 24-48 hours):

   • During shock and resuscitation
   • Hypometabolic state
   • Decreased oxygen consumption
   • Decreased core temperature

2. Flow Phase (days to months):

   • After resuscitation
   • Hypermetabolic state begins
   • Metabolic rate increases to 150-200% of normal
   • Proportional to burn size - 55% TBSA would cause near-maximal response

Neuroendocrine Drivers:

• Catecholamines elevated 10-20 fold (epinephrine, norepinephrine)
• Cortisol elevated 3-5 fold
• Glucagon elevated 3-4 fold
• Profound insulin resistance despite elevated insulin levels

Metabolic Consequences:

Protein Catabolism:

• Skeletal muscle breakdown (autocannibalism)
• Up to 250 g protein per day catabolised
• Provides amino acids for acute phase proteins and gluconeogenesis
• Negative nitrogen balance despite aggressive feeding
• 10% lean body mass loss increases mortality significantly

Carbohydrate Metabolism:

• Increased gluconeogenesis
• Stress hyperglycaemia (10-15 mmol/L common)
• Insulin resistance at post-receptor level

Lipid Metabolism:

• Increased lipolysis
• Elevated free fatty acids
• Hepatic steatosis

Duration: Can persist for 12-24 months post-injury

Clinical Implications:

• Nutritional requirements 30-35 kcal/kg/day
• Protein 1.5-2.0 g/kg/day
• Warm environment (28-33°C ambient)
• Glycaemic control (target 6-10 mmol/L)
• May benefit from anabolic agents (oxandrolone, propranolol)"

---

Viva 2: Fluid Resuscitation and Complications

Stem: "A 60-year-old woman weighing 70 kg has sustained 40% TBSA burns from a kitchen fire. She arrives at your hospital 3 hours after the injury."

---

Examiner: "How would you calculate her fluid requirements?"

Candidate: "I would use the Parkland formula as a starting point:

Parkland Formula: Total crystalloid in 24 hours = 4 mL × weight (kg) × %TBSA = 4 × 70 × 40 = 11,200 mL in first 24 hours

Administration:

• Half (5,600 mL) should be given in first 8 hours from time of burn
• She is now 3 hours post-burn, so 5 hours remain of this period
• Rate for next 5 hours = 5,600 ÷ 5 = 1,120 mL/hour
• Remaining half (5,600 mL) over next 16 hours = 350 mL/hour

Crystalloid Choice:

• Hartmann's solution or Plasmalyte preferred (balanced crystalloid)
• 0.9% saline acceptable but risk of hyperchloraemic acidosis

Titration: The formula is only a starting estimate. I would titrate to:

• Urine output 0.5-1.0 mL/kg/hour (35-70 mL/hour for this patient)
• Heart rate <120 bpm
• Mean arterial pressure >65 mmHg
• Improving lactate and base deficit

If inhalation injury is present, expect to exceed Parkland predictions by 20-50%."

---

Examiner: "What are the methods for calculating TBSA?"

Candidate: "There are three main methods:

1. Rule of 9s (Wallace): For adults:

• Head and neck: 9%
• Each upper limb: 9%
• Anterior trunk: 18%
• Posterior trunk: 18%
• Each lower limb: 18%
• Perineum: 1%

Advantages: Quick, easy to remember, adequate for initial assessment Disadvantages: Less accurate in children (proportionally larger head) and obese patients

2. Lund-Browder Chart: Age-adjusted body surface area chart that accounts for the changing proportions from infant to adult.

• In children, the head is larger (19% at birth vs 7% in adult)
• Legs are smaller (13% at birth vs 18% in adult)
• Most accurate method, standard in burn centres

3. Palm Method: Patient's palm including fingers represents approximately 1% TBSA Useful for scattered burns or small burns

Important Principles:

• Only count partial-thickness and full-thickness burns
• Do NOT include superficial (first-degree) burns in TBSA for resuscitation
• Reassess at 24-48 hours as injury evolves
• Document with clear diagrams"

---

Examiner: "What is 'fluid creep' and how would you manage it?"

Candidate: "Fluid creep refers to the administration of resuscitation fluid significantly in excess of Parkland formula predictions, leading to complications from over-resuscitation.

Causes:

• Inhalation injury (truly increased requirements)
• Delayed resuscitation initiation
• Over-reliance on urine output as sole endpoint
• Opioid-induced oliguria (appears under-resuscitated)
• Deep sedation
• Electrical burns with myoglobinuria

Complications of Fluid Creep:

Respiratory:

• Pulmonary oedema
• Worsening oxygenation
• ARDS

Abdominal:

• Abdominal compartment syndrome (IAP >20 mmHg with organ dysfunction)
• Bowel oedema
• Decreased abdominal wall compliance

Extremity:

• Compartment syndrome in burned and unburned limbs
• Increased escharotomy requirements

Other:

• Orbital compartment syndrome
• Cerebral oedema
• Wound oedema (impairs perfusion to zone of stasis)

Prevention Strategies:

1. Use Parkland as starting point, not target
2. Titrate to multiple endpoints (not just urine output):
   • MAP >65 mmHg
   • Heart rate <120 bpm
   • Lactate clearance
   • Base deficit improvement
3. Consider colloids after 8-12 hours when capillary leak decreasing
4. Early recognition and treatment of compartment syndromes
5. Avoid excessive opioids (mask true fluid status)
6. Hourly fluid balance review

If Suspected:

• Measure intra-abdominal pressure (bladder pressure)
• Assess for compartment syndrome clinically and with compartment pressures
• May need escharotomy, fasciotomy, or decompressive laparotomy"

---

Examiner: "Describe the immunological changes after major burns."

Candidate: "Major burns cause profound immunosuppression through a biphasic response:

Initial Phase - SIRS (Systemic Inflammatory Response Syndrome):

• Cytokine storm with TNF-α, IL-1β, IL-6
• Complement activation (C3a, C5a)
• Neutrophil activation and sequestration
• This phase drives the capillary leak and early organ dysfunction

Counter-regulatory Phase - CARS (Compensatory Anti-inflammatory Response Syndrome):

• Anti-inflammatory mediators (IL-10, TGF-β, PGE2)
• Attempt to limit inflammatory damage
• BUT in major burns, CARS predominates
• Results in immunoparalysis

Cellular Dysfunction:

Neutrophils:

• Present in high numbers BUT dysfunctional
• Impaired chemotaxis (cannot migrate to infection)
• Defective phagocytosis
• Reduced respiratory burst (impaired killing)
• Delayed apoptosis (contribute to tissue damage rather than bacterial clearance)

Monocytes/Macrophages:

• Reduced HLA-DR expression (hallmark of immunoparalysis)
• HLA-DR <30% is associated with high infection risk
• Impaired antigen presentation
• Cannot activate T-cells effectively

T-Lymphocytes:

• Shift from Th1 (cell-mediated immunity) to Th2 (humoral)
• Reduced IL-2 and IFN-γ
• Increased regulatory T-cells (Tregs)
• T-cell anergy

Clinical Consequences:

• Burn wound colonisation → infection → sepsis
• High susceptibility to nosocomial infections
• Difficult to clear infections once established
• Gram-positive organisms early, Gram-negative later
• Fungal infections in prolonged ICU stay

Contributing Factors:

• Loss of skin barrier
• Avascular eschar (cannot deliver immune cells or antibiotics)
• Hypermetabolism and catabolism (protein/energy depletion)
• Gut barrier dysfunction with bacterial translocation"