Systemic Resonse to Burns

Original Editor - Carin Hunter based on the course by Carin Hunter
Top Contributors - Carin Hunter, Jess Bell and Kim Jackson

Overview of the Skin

Our skin, which is part of the integumentary system, is a cutaneous membrane that covers the surface of the body. It is the largest organ system in the human body in terms of weight and surface area. However, it is often overlooked and underappreciated for the role it plays in overall health.

Layers of the Skin

The skin has two principal layers: the epidermis and the dermis. The hypodermis is considered an extension of the skin by some sources, but not by others. Please see Figure 1 for an illustration of the layers of the skin - please note subcutis, or subcutaneous tissue, is another term for the hypodermis.

Figure 1. The layers of the skin

Epidermis	Superficial layer	Composed of five layers, provides a waterproof barrier and contributes to skin tone	Composed of epithelial tissue	Avascular
Dermis	Deeper, thicker layer	Composed of two layers	Contains blood vessels, nerves, glands and hair follicles	Highly vascularised
Hypodermis	Deepest layer	Storage for fat/ insulation Attaches to underlying facia	Made up of loose connective tissue and adipose tissue	Contains large blood vessels

For more information, please see Skin Anatomy, Physiology, and Healing Process, which provides a detailed discussion of the role of the skin, its layers and normal tissue healing.

Healing Process

When treating a burns patient, it is crucial to understand tissue healing. Your knowledge of tissue healing and the information gathered from your assessment will influence clinical decisions, including when to rest, exercise, stretch and strengthen during the recovery period. Please note that these timescales do vary in the literature, and are impacted by factors such as the size of the burn, surgical intervention and any other complicating factors. Clinical reasoning is essential when applying the following in practice.

The following table provides a summary of the four stages of healing. These stages are also illustrated in Figure 2.

Stage	Timescale	Process	Signs and Symptoms	Treatment
Haemostasis The process of the wound being closed by clotting	Begins when blood leaks out of the body, then blood vessels constrict to restrict the blood flow	The platelets aggregate and adhere to the sub-endothelium surface within seconds of the rupture of a blood vessel's epithelial wall. After that, the first fibrin strands begin to adhere in about sixty seconds. As the fibrin mesh begins, the blood is transformed from liquid to gel through pro-coagulants and the release of prothrombin. The formation of a thrombus or clot keeps the platelets and blood cells trapped in the wound area.		Reduce heat, oedema and pain. Prevent infection and disruption of  wound. Useful: Immobilisation,  positioning and splinting.
Inflammation	0-5 days	Vasoconstriction followed by vasodilatation and an influx of inflammatory mediators and white blood cells. Increased capillary  permeability. Exudate leaks into the tissues. Pus may be produced.	Redness, heat, swelling, pain	Reduce heat and  oedema and pain. Prevent infection and disruption of  the wound. Useful: Immobilisation,  positioning and splinting.
Proliferation  (Fibroplasia)	Begins day 3- 5. Lasts 2-6 weeks.	Fibroblasts synthesise collagen, which is laid down haphazardly.   Angiogenesis continues.	Moist red raised tissue over the wound	Early: Positioning  and   immobilisation Later: Gentle stress with splinting and exercise. Reduce oedema and prevent contractures.
Remodelling  (Maturation)	Begins week 4-6. Lasts up to 2  years.	Synthesis of collagen balanced by degradation. Organisation of collagen fibres along the lines of stress.	Wound closure. Red and raised scar, progresses to flat pale and pliable scar. Scar tissue tightens.	Optimise function, splinting, positioning, exercise, stretching, strengthening.

Tissue healing process following burn injury

File:4-STAGES-OF-WOUND-HEALING.png

Figure 2. The Four Stages of Wound Healing

For more information on the healing process, please see:

• Normal tissue healing
• Wound Healing
• Soft Tissue Healing

Systemic Response to Burns

Different factors contribute to the magnitude of the host response to a burn wound, including:

• burn severity (percentage total body surface area (TBSA) of the burn and burn depth)
• burn cause
• inhalation injury
• exposure to toxins
• other traumatic injuries
• patient-related factors
  • age
  • pre-existing chronic medical conditions
  • drug or alcohol intoxication
  • timing of presentation to care

Pathophysiology of Burn Wounds

In severe burn injuries (i.e. >30% TBSA), complex reactions occur both at the burn and away from the burn. Excess cytokines, chemokines and other inflammatory mediators are released, which results in extensive inflammatory reactions within a few hours of injury. As well as an inflammatory response, burn injuries, particularly severe burns, also cause an immune response, metabolic changes and distributive shock.

Depending on the size of the burn injury, a patient's initial response is similar to the response that occurs after "other inflammatory conditions triggered by tissue destruction such as trauma or major surgery".

The pathophysiology of burn wounds can be summarised as follows.

The inflammatory response leads to rapid oedema formation (see more on this below). This is caused by:

• Increased microvascular permeability
• Increased hydrostatic microvascular pressure
• Vasodilation
• Increased extravascular osmotic activity

These reactions are caused by the direct effect of heat on the microvasculature and the chemical mediators of inflammation.

• The release of histamine tends to cause early vasodilation and increased venous permeability
• Prostaglandin is rapidly formed because of damage to the cell membranes
  • This damage is caused in part by oxygen-free radicals that are released from polymorphonuclear leucocytes
  • This activates the enzymes that catalyse the hydrolysis of prostaglandin precursor
• Prostaglandins inhibit the release of noradrenaline (norepinephrine) - this may have a modulatory impact on the adrenergic nervous system, which is activated by thermal injuries
• There are further changes in the structure of the blood-lymph barrier, such as an increase in the number of vacuoles and more open endothelial intercellular junctions
• There are changes in the interstitial tissue

• There is a continuous loss of fluid from the blood circulation, resulting in increased haematocrit levels and a fall in plasma volume - this leads to decreased cardiac output and hypoperfusion at the cellular level
• Burn shock occurs if fluid loss is not adequately restored. To learn more about the complexities of burn shock, please see: Burn Shock

The following sections describe some of the main systemic responses to severe burn wound injuries.

1. Effect on the Cardiovascular System

Cardiac Stress: The initial cardiovascular response to the catecholamine-mediated surge from a severe burn injury is hypovolemia with myocardial depression and reduced venous return. This leads to decreased cardiac output, increased heart rate, and peripheral resistance. In addition to the cardiac dysfunction, pulmonary resistance increases, which causes an increase in right- and left-ventricular workload. This then progresses to a "hyperdynamic-hypermetabolic phase with increased cardiac output." This second phase is characterised by tachycardia, increased myocardial oxygen consumption, and increased cardiac output. It is important to note that cardiac stress continues for at least two years after a burn injury.

Compromised cardiac function results in:

1. Organ hypoperfusion
2. Impaired peripheral microcirculation
3. Extension of the burn zone
4. Reduced resistance to bacterial infection at the wound site.

Burn Shock: "Burns exceeding 30% of total body surface area (TBSA) result in considerable hypovolemia coupled with formation and release of inflammatory mediators with subsequent systemic effect, namely a distinctive cardiovascular dysfunction known as burn shock."

• Burn shock is a complex process that affects the circulatory and microcirculatory systems and leads to oedema in traumatised and non-traumatised tissues.

• In burn shock, there is inadequate tissue perfusion, which results in insufficient delivery of oxygen and nutrients and an inability to remove waste from the tissues
• Even with appropriate fluid resuscitation and sufficient preload, there is increased pulmonary and systemic vascular resistance and myocardial depression
• This can further exacerbate the inflammatory response and add to the risk of organ failure

Key Definitions:

• Hypovolaemia is a decrease in blood volume
• Hypovolaemic shock occurs when there is a loss of approximately 1/5 or more of the normal amount of blood in the body
  • Caused by:
    • blood loss from bleeding (bleeding from a cut or internal bleeding)
    • loss of blood plasma due to severe burns (occurs because of skin loss and damage to the blood vessels)
    • dehydration, which may be from diarrhoea or vomiting (loss of a lot of body fluids may lead to a drop in the amount of circulatory blood)
  • Hypovolemic shock is treated by replacing the fluid and/or blood, usually through an IV line, and treating the cause

For more information on hypovolaemic shock, please see Burn Shock.

2. Effect on the Respiratory System

• Heat Injury to the Upper Airway
  • The result of a heat injury to airway structures includes extensive swelling of the tongue, epiglottis, and aryepiglottic folds, which causes an accompanying obstruction.
• Chemical Injury to the Lower Airway
  • Most commonly, following smoke inhalation, inflammatory mediators are released in the lungs, leading to bronchoconstriction, pulmonary oedema and acute respiratory distress syndrome (ARDS).
• Systemic Toxicity
  • Inhalation of chemicals, cytotoxic liquids, fumes, mist and gases can cause systemic toxic changes. Smoke can combine with these toxins and cause increased mortality due to tissue hypoxia, metabolic acidosis, decreased oxygen supply to the brain and decreased metabolism.

For more information, please read Inhalation Injury.

3. Effect on the Renal System

Early kidney injury is due to:

• low blood volume
• inflammatory mediators
• increased release of protein in the bloodstream
• extensive tissue damage
• medications that are toxic to the kidneys

The renal system is affected by changes in the cardiovascular system caused by a burn injury. Blood flow to the kidneys is decreased due to hypovolaemia, reduced cardiac output and the effects of angiotensin, vasopressin and aldosterone. This marks the beginning of kidney failure. Appropriate fluid resuscitation can help prevent these issues. The rehabilitation team should always keep an eye out for decreased urine output (oliguria) as this is an early sign of renal compromise.

4. Effect on the Endocrine System

The endocrine system is made up of glands in the body, which secrete hormones. Following a burn trauma, there are distinct responses in the endocrine system.

Trauma can affect the HPA Axis (hypothalamic-pituitary-adrenal axis), which controls the interaction between the hypothalamus, pituitary gland, and adrenal glands. The hypothalamus and pituitary gland are located just above the brainstem, while the adrenal glands are found on top of the kidneys.

Burn injuries commonly cause patients to have an elevated sympathetic drive. This is due to an increase in the release of cortisol and glucagon. These hormones affect the metabolic system (see below). Prolonged excess cortisol can result in hypercortisolemia. This is associated with increased infection rates in burn patients and lengthened durations of severe infection. Secondly, oxytocin production is decreased, which can have long-term effects.

5. Effects on the Metabolic System

For around 72-96 hours post-burn, the metabolic state is initially suppressed by the effects of acute shock. This can cause:

• impaired gastrointestinal motility
• impaired digestion and absorption
• increased intragastric pH
• feeding difficulties

Hypermetabolism (an increase in the metabolic rate, often up to a 100% to 150% increase) begins approximately five days post-burn in patients with severe burns. The cause of hypermetabolism is a complex process that is not clearly defined. It is most likely activated and sustained by stress-induced hormonal releases and inflammation. Decreased perfusion of the organs in the abdominal cavity necessitates early and aggressive enteral feeding to decrease catabolism and maintain gut integrity. Hypermetabolism causes muscle wasting, mucosal atrophy, reduced absorptive capacity, and increased surface permeability. Effects can be seen for up to two years post-burn.

Hypermetabolism causes:

• increased body temperature
• increased oxygen and glucose consumption
• increased CO2 and minute ventilation
• increased heart rate for up to two years post-burn  

Catabolism occurs when food is digested and the large, complex molecules in the body are broken down into smaller, simple molecules that can be used as energy.

6. Immunological Changes

As mentioned above, following a burn injury, individuals commonly have an elevated sympathetic drive, causing the release of cortisol. Prolonged excess cortisol can result in hypercortisolaemia, which is associated with infection rates in post-burn patients and lengthened durations of severe infection.

Patients also have a high risk of  infection while wounds are open.

7. Oedema formation

Oedema formation is a characteristic response to burn injuries. It has two phases:

• in the first hour after the burn, there is an increase in water content of the affected tissue
• in the second phase, there is a gradual increase in "fluid flux of both burned and intact skin and soft tissues 12-24 hours post-burn"

Rapid oedema formation is caused by:

• strongly negative interstitial fluid pressure developing
• greater microvascular permeability
• loss of glycocalyx
• endothelial activation

Fluid resuscitation (in terms of type, timing, total amount) will affect these shifts in fluid.