1. How is the mechanism of pulmonary edema?

INCREASED PRESSURE EDEMA

 Increased Microvascular Hydrostatic Pressure. Congestive heart failure is the most common cause of
increased pressure edema. That is why increased pressure edema is often called “cardiogenic,” even though the
heart is not always primarily involved. Elevated pressures in the pulmonary microvasculature are usually due to
left-sided heart failure, with elevated left atrial pressures transmitted retrograde into the pulmonary circulation.
Common causes are left ventricular dysfunction (e.g., caused by acute myocardial infarction, severe coronary
insufficiency, tachyarrhythmias, bradyarrhythmias, cardiomyopathies, constrictive pericarditis, aortic stenosis or
regurgitation, mitral regurgitation, coarctation of the aorta, rupture of chordae tendineae or intraventricular
septum, systemic hypertension) or mechanical obstruction of the left atrial outflow tract (e.g., mitral stenosis,
left atrial myxoma). Left atrial and pulmonary microvascular pressures can also be elevated by severe fluid
volume overloading in a patient with a normal or diseased heart.
 Decreased Perimicrovascular Hydrostatic Pressure. The sum of driving pressures would increase if
perimicrovascular hydrostatic pressure was greatly diminished, thereby resulting in an increase in fluid and
protein filtration at the microvascular barrier in the lungs. Pulmonary edema has been described in
circumstances in which this might happen.
 Decreased Transmural Protein Osmotic Pressure Difference. The sum of driving pressures would be
increased if the protein osmotic pressure difference opposing the hydrostatic pressure difference across the
microvascular barrier was decreased, either by lowering plasma protein concentration or by raising interstitial
protein concentration, resulting in an increase in the sum of driving pressures for fluid and protein flow into the
lungs.
 Alveolar Barrier Function. If interstitial hydrostatic pressure was raised or if alveolar hydrostatic pressure or
the osmotic pressure difference across the alveolar barrier was lowered, driving pressure for fluid and protein
flow across the alveolar barrier would be elevated, resulting in increased pressure edema. Interstitial hydrostatic
pressure rises as interstitial edema accumulates in the lungs.4,35 Increased interstitial hydrostatic pressure
would raise the sum of driving pressures across the alveolar barrier and could drive edema formation across the
alveolar or airway epithelium.

INCREASED PERMEABILITY EDEMA

Increased permeability pulmonary edema (Fig. 62-4) is caused by an increase in liquid and protein conductance across
the barriers in the lungs. The essential feature of this edema is that the integrity of the barriers to fluid and protein flow
into the lung interstitium and alveoli is altered from lung parenchymal damage. Increased permeability edema is
sometimes called noncardiogenic pulmonary edema, and the resulting clinical syndromes in humans—when explicitly
defined (see later)—are referred to as acute lung injury (ALI) or, when severe, the acute respiratory distress syndrome
(ARDS).

If the rate of fluid and protein accumulation from lung endothelial and epithelial barrier injury exceeds the rate at which
it can be removed, increased permeability edema results. Because the barriers limiting fluid and protein flow into the
lungs do not function normally when the lungs are injured, the lungs are not protected against edema by the usual safety
factors. Although increases in fluid and protein filtration across the barriers are removed by lymphatics and drained away
from the alveolar walls as in increased pressure edema, much more fluid and protein are filtered at any given sum of
driving pressures because the barriers to their flow are much less restrictive than normal. Edema formation in injured
lungs becomes extremely sensitive to driving pressures.22 Driving pressures are often increased when the lungs are
injured because of the vasoconstrictive effects of inflammatory mediators such as thromboxanes, which may shift the
main site of resistance to postcapillary venules, thus increasing hydrostatic pressure at the microvascular fluid exchange
sites,67 or because of effects on the heart as well as on the circulation. For example, elevated left atrial pressure,
pulmonary venoconstriction, and an increase in cardiac output in sepsis can increase hydrostatic pressure at the
microvascular fluid exchange sites.41
The consequences of increased permeability edema on lung mechanics and gas exchange depend on how much edema
accumulates and how severe the causative lung injury is.43 As with increased pressure edema, the major effects on
pulmonary mechanics follow alveolar flooding
Physiology of Microvascular Fluid Exchange in the Lung.
In the normal lung (Panel A), fluid moves continuously outward from the vascular to the interstitial
space according to the net difference between hydrostatic and protein osmotic pressures, as well as to
the permeability of the capillary membrane.
The following Starling equation for filtration of fluid across a semipermeable membrane describes
the factors that determine the amount of fluid leaving the vascular space: Q = K[(Pmv-Ppmv) -
(πmv-πpmv)], where Q is the net transvascular flow of fluid, K is the membrane permeability, Pmv
is the hydrostatic pressure in the microvessels, Ppmv is the hydrostatic pressure in the
perimicrovascular interstitium, πmv is the plasma protein osmotic pressure in the circulation, and
πpmv is the protein osmotic pressure in the perimicrovascular interstitium. When hydrostatic
pressure increases in the microcirculation, the rate of transvascular fluid filtration rises (Panel B).
When lung interstitial pressure exceeds pleural pressure, fluid moves across the visceral pleura,
creating pleural effusions. Since the permeability of the capillary endothelium remains normal, the
filtered edema fluid leaving the circulation has a low protein content. The removal of edema fluid
from the air spaces of the lung depends on active transport of sodium and chloride across the alveolar
epithelial barrier.
The primary sites of sodium and chloride reabsorption are the epithelial ion channels located on the
apical membrane of alveolar epithelial type I and II cells and distal airway epithelia. Sodium is
actively extruded into the interstitial space by means of the Na+/K+–ATPase located on the
basolateral membrane of type II cells. Water follows passively, probably through aquaporins, which
are water channels that are found predominantly on alveolar epithelial type I cells.6 Noncardiogenic
pulmonary edema (Panel C) occurs when the permeability of the microvascular membrane increases
because of direct or indirect lung injury (including the acute respiratory distress syndrome), resulting
in a marked increase in the amount of fluid and protein leaving the vascular space.
Noncardiogenic pulmonary edema has a high protein content because the more permeable
microvascular membrane has a reduced capacity to restrict the outward movement of larger
 molecules such as plasma proteins. The degree of alveolar flooding depends on the extent of
interstitial edema, the presence or absence of injury to the alveolar epithelium, and the capacity of
the alveolar epithelium to actively remove alveolar edema fluid. In edema due to acute lung injury,
alveolar epithelial injury commonly causes a decrease in the capacity for the removal of alveolar
fluid, delaying the resolution of pulmonary edema.

2. How to differentiate cardiogenic and non cardiogenic pulmonary edema?