PATHOPHYSIOLOGY OF BURNS

Time temperature relationship is crucial.

Depth of burn is determined by :
1. temperature
2. length of exposure to the specific heat source producing the burn
Even low temperature (<44C) results in tissue death if exposure long enough.
Between 44 & 51C the rate of cell destruction doubles with each degree rise in temperature.
>70C tissue destruction instantaneous.
Immersion time to produce full thickness burns
Temperature (C)
Time
65
<1 second
60
2 seconds
55
10 seconds
50
30 seconds
47.5
1 minute
45
10 minutes
Skin has water as major component so has high specific heat and low thermal conductivity. Becomes
overheated slowly but cools slowly. Even after heat source removed, heat continues to penetrate deeper.
Immediate cooling may reduce underlying tissue damage (in vitro)

A. LOCAL EFFECTS
The effect of a burn depends on:
A) Temperature (and type) of burning substance,
B) Time that the burning substance is in contact with the skin.
The three zones of a burn (Jackson):
1. Zone of coagulation
2. Zone of Stasis (middle zone)
a. Stagnation of microvasculature flow:
i. Early (0 to 4 hours) - inner zone,
ii. Delayed (4 to 24 hours) - outer zone.
3. Zone of hypereamia (outermost zone)
a.

Epidermis: reversibly injured

b. Dermis: microvasculature dilated.

c. Minimal fluid loss.
Marked oedema, blanches on pressure, diminished aerobic metabolism and O2 consumption.

Causes of stasis:
1. Endothelial injury
2. Arteriolar (1-2 hours post burn) and venular (3-4 hours post burn) dilatation
3. RBC aggregation
4. WBC clumping (8-24 hours post burn)
5. Platelet thrombi formation
6. Increased blood viscosity (due to plasma loss and haemoconcentration)
7. Thromboplastin release.
Zone of stasis may progress with
1. inadequate resuscitation
2. infection
3. sepsis
4. wound dries out

B. FLUID SHIFTS
1. Locally at burn site:

- Due to oedema formation

- Loss to exterior
- Loss into blisters

2. In burns > 30% TBSA - Oedema of non-burned tissue

3. Systemic fluid shifts due to effects of hypovolaemic shock
1. LOCAL OEDEMA AT BURN SITE
Role of:
1. Dilatation of precapillary resistance vessels,
2. Increased interstitial osmolality (Bostwick) secondary to protein shifts.
3. Venular obstruction (RBC, WBC, platelets).
An increase in microvascular permeability is the predominant mechanism- Biphasic
(a) Immediate and transient phase- Histamine mediated, lasts 5-10 minutes, slight increase in
permeability with little contribution to oedema formation.
(b) Delayed prolonged phase - Begins + 2 hours post burn, lasts + 8 hours.

- Due to:

(1) Direct heat injury and destruction of vasculature.

(2) Mediators - arachidonic acid metabolites
- free oxygen radical
- kinins, serotonin, etc.

Oedema:

- Worsens oxygen delivery to the tissues.

- Peaks + 6 hours post burn (later in large burns).
- Starts resolving after about 24 hours. Resolves by end of first week.
- Magnitude depends on depth and extent of burn.
- Full thickness burns may result in less oedema due to coagulation of vessels.

Causes of oedema:
1. Increased microvascular permeability (as above), Hypoproteinaemia.
2. Direct destruction due to burn:
a. Endothelial cell destruction
b. Increased gaps between endothelial cells
c. Collagen denaturation - ground substance destruction results in increased negativity of
colloid osmotic pressure of interstitial fluid.
Reestablishment of blood flow to ischemic areas triggers a sequence of events that produce
irreversible damage.
The mechanism accounting for this increased vascular permeability is likely related to
polymorphonuclear leukocytes (PMN) and their adhesion to the endothelium. PMN have been
identified as contributing to the microvascular occlusion seen both systemically and locally
following burn injury.
The adherence of PMN to vascular endothelial cell surfaces creates a microenvironment in which
PMN-derived proteases and toxic oxygen radicals, hydrogen peroxide and hydroxyl radicals are
released by both endothelial cells and PMN. These radicals trigger peroxidation of lipids in cell
membranes and resultant cell lysis, to the detriment of vessel lining. Intercellular gap formation,
which increases the microvascular permeability, results in edema and thrombosis.
Fluid loss in burns due to:
1. evaporative losses
2. oedema third space losses
a. increased vessel permeability inflammatory cascade and direct damage

Early mediators include histamine, serotonin & various kinins.

Later mediators, acting via PMNs and the arachidonic acid cascade, include
thromboxanes, prostaglandins & leukotrienes

b. osmotic gradient Starlings forces (venous obstruction, protein shifts)

3. cellular swelling failure of ATPase channels
2. NON BURNED TISSUE
> 25% TBSA- Generalised oedema of all body tissues, (Intact skin, muscle, organs distant from burn).
Arturson: General increase in capillary permeability mediated by some circulatory factor (what ?).
Demling: Hypoproteinaemia is the main cause. Effect of burns is increased flow to CNS, heart, liver
and adrenals and diminished flow to skin, muscle, gut and kidneys.
3. SYSTEMIC EFFECTS - HYPOVOLAEMIC SHOCK
Effects of shock:
(1) Cellular Hypoxia, therefore:
1. Failure of Na-K ATPase pump - cellular swelling - cell death.
2. Anaerobic metabolism - lactic acidosis
3. Mitochondrial calcium depletion - myocardial depression
4. Cellular damage - cytokine release
(2) Compensatory Mechanisms:
1. Collapse, hyperventilation
2. Microcirculatory changes (resorption of fluid from interstitial & intracellular spaces)
3. Neurohumoral changes
4. Splanchnic vasoconstriction

- hepato-renal dysfunction
- ileus, gut ischaemia and translocation

(3) Decompensation, if overwhelming shock

1. Cellular failure (Na-K pump, mitochondria, lysozomal and cellular lysis)
2. Microcirculatory failure (massive fluid leak from vasculature)
3. Organ failure - MOF
C. IMMUNOLOGICAL RESPONSE TO BURNS
Suppression of host defence mechanisms contributing to susceptability to infections in the burned
patient. Infection is the primary or major cause of death in 75% of all burn deaths.

1. INTEGUMENT
EARLY - Skin damage results in loss of protection against microbial invasion. Inhalational burns
destroy respiratory tract mucosa. Intestinal mucosa is affected by splanchnic vasoconstriction
occuring as a result of hypovolaemic shock and shunting of blood away from the gut. This results in
translocation, increased systemic bacterial and endotoxin load and all its effects.
LATE - Coagulated skin and eschar form an ideal growth media for micro-organisms.
2. NON SPECIFIC IMMUNITY Early acute inflammatory response.
Mediator release:

* Vasoactive amines (Histamine and Serotonin)

* Arachidonic Acid Metabolites (PG's, PGI2, TxA2, LT's)
* TNF
* Interleukins (1, 2, 6)
* Interferons (gamma)
* Colony stimulating factors
* Free oxygen radicals

Diminished neutrophil function (chemotaxis, opsonisation, phagocytosis, killing).

Diminished macrophage function (opsonisation, phagocytosis, killing).
Activation and consumption of C' factors.
Depletion of fibronectin.
Circulatory immunosuppressive factors: (autoantibodies, immune complexes, toxins, globulins)
3. HUMORAL IMMUNITY
Immunoglobulins are depleted due to: Decreased synthesis
Capillary leakage
Increased catabolism
Haemodilution.
IgG

- Most affected. The most important opsonic Ab for both G-ve and G+ve bacteria.
- Level of depletion can be correlated prognostically with septic complications.

IgM

- Because of its size, is least affected.

4. CELL MEDIATED IMMUNITY

Cell mediated immunity is depressed by burns:
- Blast transformation and lymphocyte proliferation is impaired.

- Decreased T-helper : T-suppressor cell ratio.

- Diminished activity of T-helper and T-killer cells.
Suppressor cells proliferate maximally at about 7 to 14 days post injury, coinciding with the
appearance of septic complications. There is an increased risk of infection (well documented), but
also other changes in cellular immunity have been noted such as
-

Impaired response to antigens

Prolonged allograft survival

Diminished resistance to tumours.

5. OTHER FACTORS AFFECTING IMMUNITY

1. Extremes of age
2. Concomittant disease (eg. Diabetes)
3. Poor nutritional status
4. Drugs (Antibiotics, topical agents, steroids)
5. Blood transfusions
6. Surgery
D. METABOLIC ALTERATIONS CAUSED BY BURNS
Cuthbertson (1930) - Biphasic metabolic response to injury:
EBB PHASE (Hypofunction/hypometabolic state)
1. CVS

Decreased intravascular volume (hypovolumia), Low cardiac output

2. Pulm

hypoventilation

3. Renal

Oliguria

4. CNS

Agitation

5. Endocrine

Catabolism, decreased O2 consumption

6. GIT

Ileus

7. Skin

Poor tissue perfusion

FLOW PHASE: (Hyperfunction)

Hypermetabolic phase following successful resuscitation from ebb phase.
1. CVS

Hyperdynamic, Increased cardiac output

2. Pulm

Hyperventilation

3. Renal

Diuresis

4. CNS

Depression

5. Endocrine

Anabolism, Increased oxygen consumption

6. GIT

Hypermotility

7. Skin

Hyperemia

Persists until remodelling is complete- Many months.

Increase BMR/Energy expenditure (2-3X increase in 60% TBSA burn)

Increased nitrogen losses (via normal channels and from burn directly)

This response is mediated by the hypothalamic-pituitary axis which receives neuronal (pain, fear,
anxiety, hypoxia, hypotension) and humoral (prostoglandins, interleukins, C', endotoxins) signals.
Volume, chemo, osmo and baro receptors act on the hypothalamus resulting in a neurohumoral
response is with an increase in:

- Adrenergic outflow
- Anti-insulin hormones:
- ACTH and Catecholamines
- Glucagon
- Growth Hormone
- Insulin

(Diminished levels initially)

(Hours or days post burn, insulin levels rise)
(Insulin resistance occurs)

- Renal hormones:
- ADH
- Renin/Angiotensin
- Aldosterone
- Other hormonal mediators:
- TSH
- Endorphins
- Interleukins
The effect of this neuro-humoral cascade on substrate mobilisation is as follows:
1. GLUCOSE METABOLISM
1. Increased glycolysis
2. Increased gluconeogenesis
3. Hyperglycaemia due to insulin resistance

4. Increased utilization and oxidation of glucose

5. Increased futile cycles (Cori and glucose-alanine cycles)
2. FAT METABOLISM
1. Increased lipolysis
2. Increased cycling (TG FFA + Glycerol)
- Increasingly recognised role of fats in immunological function:
* Prostinoid substrates
* Lipoproteins
* Cell membranes
- Dietary fat supplementation is important.
3. PROTEIN METABOLISM
Massive proteolysis and muscle catabolism occur leading to a negative N balance.
Urinary nitrogen losses may approach 30 gm per day in the fasting severely burned patient.
Exudative wound protein losses can be 150 gm per day.
Average 70 kg male has: 4500 gm of skeletal muscle protein and 8500 gm of visceral, plasma and
bone protein. Loss of > 40% of body protein is fatal.
Protein is also mobilised from other tissues (eg, gut, leading to translocation), which is used for:
Gluconeogenesis
Acute phase proteins
Components of immune system: cells, Ig, clotting factors, etc.
Wound repair.
With excess mobilisation and depletion of the body's protein, problems may arise:
weakness, myopathy, wasting and LOW
impaired mobilisation
impaired respiratory function
impaired immunity
poor wound healing
The aim of the body's metabolic response to a severe burn is to provide an effective physiological
response to fluid depletion, shifts and hypovolaemia; to mount a protective immunological barrier to

micro-organism invasion and infection and to mobilise the body's substrate resources so as to allow
effective wound healing and a return to health.

Systemic inflammatory response syndrome (SIRS)

a syndrome that encompasses the features of systemic inflammation without end-organ damage,
identifiable bacteremia, and the need for pharmacologic support.
SIRS is separate and distinct from sepsis, severe sepsis, and septic shock.
key transition from SIRS to sepsis according to definition is the presence of an identified pathogen.
pathophysiology is complex and involves all of the multiple interlacing and interacting systems that are
involved in inflammation and the response to an immune or perfusion challenge. These systems include:
1. complement
2. cytokine cascades
3. arachidonic acid metabolites
4. cell-mediated immunity
5. clotting cascade
6. humoral immune mechanisms.
hallmark of SIRS is the creation of a proinflammatory state that is marked by tachycardia, tachypnea or
hyperpnea, hypotension, hypoperfusion, oliguria, leukocytosis or leukopenia, pyrexia or hypothermia, and
the need for volume infusion.
SIRS may affect all organ systems and may lead to multiple organ dysfunction syndrome (MODS).
trigger for SIRS is unclear, but prominent investigators in the field have advanced multiple competing
theories. These theories include the second-hit hypothesis, the intestine as the motor of SIRS, chaos
theory, and immunologic inflammation.