Fluid that collects in extracellular, extravascular spaces can be either exudative or transudative. Exudative fluid arises from inflammatory processes that make vessel walls more permeable to both fluid and proteins which allow them to exit the vessels and collect in the extravascular spaces. Transudative fluid exits the vessels due to a pressure differential between the intra and extravascular space (either hydrostatic or oncotic), but typically does not contain proteins since they are too large to squeeze out of the vessels. A fluid sample can be tested according to Light’s criteria to determine if it is exudative or transudative.
Exudates are from Enflammation (inflammation)
Light’s criteria – protein 5, LDH 6
(fluid protein:serum protein >0.5, fluid LDH:serum LDH>0.6)
Fluid can collect in extravascular, extracellular spaces. One of the most common examples would be a pleural effusion. The fluid originates from blood vessels and ends up in the extravascular space either because there is a pressure differential pushing or pulling fluid out of the vessels (transudate) or because the vessel walls have become very permeable and fluid is able to leak out (exudate). Whether the fluid is exudative or transudative will have implications for treatment. Exudates primarily result from inflammatory processes which loosen the junctions between vascular endothelial cells and allow fluid and proteins to leak out. For example, pneumonia can cause exudative pleural effusions. Examples of transudative pleural effusions would be those resulting from cirrhosis or heart failure.
Before we go on, it might be important to go back and review some physics principles because they will be important for understanding how transudates form. Now I’m no expert in physics, as a matter of fact I took it twice in high school and my mark wasn’t any higher the second time … nevertheless, we’ll give this a try. We need to understand the Starling equation. Basically, it describes the movement of fluids across permeable membranes as they are affected by hydrostatic and oncotic forces. Now proper physicists will tell you that what I’m about to say is not completely correct (and I believe them), but what I’ll say here is a helpful way to think about these things. Hydrostatic forces are those which result from the “pressure” of fluid on either side of the membrane. So in a capillary blood vessel, this would be the force the blood exerts on the vessel wall. If the patient has high blood pressure in that capillary, the hydrostatic pressure is high and forces fluid out into the extravascular space. Typically the hydrostatic force outside the blood vessel is low in comparison to the hydrostatic pressure inside the vessel. Hydrostatic forces are resisted by oncotic forces. Oncotic forces are those which draw fluid toward areas where there is a lot of protein. It’s a form of osmotic pressure which tries to make both sides of the membrane equally “dilute” (i.e. if there’s a lot of protein on one side of the membrane you need a lot of fluid to come over to that side to “dilute” it). Capillary blood typically contains more protein (mostly albumin) compared to the outside. This would tend to keep fluid inside the capillary (and thus resist the outward force from the hydrostatic pressure).
Now back to our pleural effusion case, think of an instance where there is high hydrostatic pressure in the lungs. Maybe left sided heart failure for example. All the blood is backing up from the left ventricle, into the left atrium, into the pulmonary veins, into the pulmonary vasculature. As those pulmonary vessels expand under the strain from all that blood volume, the pressure inside increases. This is hydrostatic pressure and eventually it outweighs the oncotic pressure and more fluid starts leaking out of the capillaries. Now let’s say instead of heart failure, the patient has cirrhosis. That would impair albumin production and suddenly there’s very little protein in the blood. Now the oncotic pressure in the vessels has dropped and even the slightest amount of hydrostatic pressure is enough to cause fluid to spill out into the extravascular space. These are the basic mechanisms behind the formation of transudates.
Exudates don’t really involve so much physics. Basically, exposure to histamine, inflammatory cytokines, and molecules such as VEGF (vascular endothelial growth factor) cause an increase in vascular permeability and allow fluid and proteins to leak out into the extravascular space. A good review of the topic can be found here. There is some debate as to the details of this process and whether or not it is related to the movement of leukocytes out of blood vessels and into the tissues. That process is called extravasation and may, or may not, allow fluid to travel along with the leukocytes as they migrate into the tissues.
It should be noted that cancer and pulmonary embolism are important causes of exudative pleural effusions. This is likely due to the influence of VEGF which is released from tumours or from platelets in the embolism.
Light and colleagues published a paper in 1972 outlining some criteria that could help distinguish exudative fluid from transudative fluid. Since exudates contain more protein and cellular components than transudates, simple measurement of protein and lactate dehydrogenase (an enzyme present in virtually every cell) can determine if an effusion is transudative or exudative. The list of these “Light’s criteria” are as follows:
- Fluid protein/serum protein ratio greater than 0.5
- Fluid lactate dehydrogenase (LDH)/serum LDH ratio greater than 0.6
- Fluid LDH level greater than two-thirds the upper limit of the laboratory’s reference range of serum LDH
Medscape has a great article on this topic as does Life in the Fast Lane.
Medscape’s take on Light’s criteria
Life in the Fast Lane’s post on pleural fluid analysis
Wikipedia’s Starling Equation