I now have comprehensive information from two authoritative sources. Here is a structured synthesis:
Pathophysiology of Hypovolemia in Burns
Overview: Burn Shock
Burn shock is a paradigm of ischemia/reperfusion injury and represents a unique combination of hypovolemic and distributive shock. It unfolds in two phases:
- Ebb phase (0–48 h): Hypodynamic, hypovolemic state — rapid intravascular fluid loss, decreased cardiac output
- Flow phase (>48 h): Hyperdynamic, hypermetabolic state driven by systemic inflammatory responses (DAMPs), persisting for months
— Miller's Anesthesia, 10e, p. 12308–12309
Two Core Mechanisms of Fluid Loss
1. Negative Imbibition Pressure (Primary Early Mechanism)
Thermal injury alters tissue integrins (which normally regulate interstitial hydrostatic pressure), generating a strongly negative interstitial pressure of –25 to –50 mmHg within burned tissue. This negative pressure acts as a "suction force," pulling water and crystalloid from the vasculature into the interstitium — a process distinct from osmotic or hydrostatic pressure gradients.
Key features:
- Most pronounced immediately after injury, lasting several hours
- Severity is proportional to burn size — larger burns generate greater negative pressure
- A paradoxical "creep" effect: the more fluid administered during resuscitation, the more negative the imbibition pressure becomes, increasing fluid demand further
- Resolves within 24–48 hours, though extravascular edema resorption takes much longer
— Miller's Anesthesia, 10e, p. 12310
2. Increased Vascular Permeability
Even a small 5% TBSA burn causes measurable increases in microvascular permeability, manifest as blistering. Mechanisms include:
- Histamine release from mast cells in burned skin disrupts venous tight junctions → protein and fluid efflux into the interstitium
- Liberation of proinflammatory cytokines causes systemic vasodilation, raising microcirculatory hydrostatic pressure (P_c in the Starling equation) → further fluid filtration into the interstitial compartment
- Platelet-activating factor, eicosanoids, and serotonin amplify vasoconstriction (pulmonary vascular resistance) and the permeability response
At burned sites: both protein and crystalloid are lost from the vasculature (full permeability breakdown).
At uninjured distant sites: capillary "protein sieving" occurs — only crystalloid is lost (oncotic gradient maintained to some degree).
— Miller's Anesthesia, 10e, p. 12309, 12311; Mulholland & Greenfield's Surgery, 7e, p. 729
Starling Forces in Burns
The Starling equation summarises the net fluid movement:
J_v = K_f [(P_c − P_i) − σ(π_c − π_i)]
In burns, multiple forces simultaneously worsen fluid filtration out of the vasculature:
| Variable | Change | Effect |
|---|
| P_c (capillary hydrostatic pressure) | ↑ (vasodilation) | Pushes fluid out |
| P_i (interstitial pressure) | ↓↓ (imbibition) | Pulls fluid out |
| π_c (plasma oncotic pressure) | ↓ (protein loss) | Reduces retention |
| π_i (interstitial oncotic pressure) | ↑ (protein leak) | Pulls fluid out |
The net result is massive, relentless fluid egress from the vasculature.
Mediators Driving Permeability
- Histamine (mast cell degranulation) — early mediator, disrupts tight junctions
- Serotonin & eicosanoids (platelet activation) — amplify vasoconstriction and permeability
- TNF-α, IL-6, IL-10 — systemic inflammatory amplification
- Complement activation — contributes to capillary leak
- Reactive oxygen species (ROS) — endothelial injury
— Mulholland & Greenfield's Surgery, 7e, p. 729; Miller's Anesthesia, 10e, p. 12311
Cardiovascular Consequences
Despite total-body fluid excess (extravascular overload), the patient is intravascularly depleted:
- Tachycardia and ↑ systemic vascular resistance
- ↓ Cardiac output (not cardiogenic — inflammatory mediators depress myocardial function directly)
- ↑ Pulmonary vascular resistance
- Hypercoagulable state (platelet-activating factor + clotting factor dysregulation → DIC-like picture), worsened by hypothermia
Burn shock is therefore correctly characterised as "intravascular hypovolemia despite total-volume hypervolemia."
— Mulholland & Greenfield's Surgery, 7e, p. 729
Timeline
| Time | Predominant Process |
|---|
| 0–8 h | Massive imbibition pressure–driven fluid shift; maximal permeability |
| 8–24 h | Ongoing capillary leak; edema formation continues |
| 24–48 h | Intravascular fluid loss plateaus; resuscitation restores output |
| >48 h | Hyperdynamic/hypermetabolic phase begins; edema slowly resorbs |
Clinical Implication
The dual mechanism (imbibition + permeability) is why standard Parkland formula resuscitation (4 mL/kg/% TBSA of lactated Ringer's over 24 h) targets the intravascular deficit — but over-resuscitation amplifies imbibition pressure and worsens edema ("fluid creep"), making titrated resuscitation essential.