Mrs. V is 62-year-old woman with leg edema for the past 2 weeks.
|What is the differential diagnosis of edema? How would you frame the differential?|
Edema is defined as an increase in the interstitial fluid volume and is generally not clinically apparent until the interstitial volume has increased by at least 2.5–3 L. It is useful to review some background pathophysiology before discussing the differential diagnosis:
Distribution of total body water
67% intracellular; 33% extracellular
Extracellular water: 25% intravascular; 75% interstitial
Regulation of fluid distribution between the intravascular and interstitial spaces
There is constant exchange of water and solutes at the arteriolar end of the capillaries
Fluid is returned from the interstitial space to the intravascular space at the venous end of the capillaries and via the lymphatics.
Movement of fluid from the intravascular space to the interstitium occurs through several mechanisms
Capillary hydrostatic (hydraulic) pressure pushes fluid out of the vessels
Interstitial oncotic pressure pulls fluid into the interstitium
Capillary permeability allows fluid to escape into the interstitium
Movement of fluid from the interstitium to the intravascular space occurs when opposite pressures predominate
Intravascular (plasma) oncotic pressure from plasma proteins pulls fluid into the vascular space
Interstitial hydrostatic pressure pushes fluid out of the interstitium
In skeletal muscle, the capillary hydrostatic pressure and the intravascular oncotic pressure are the most important.
There is normally a small gradient favoring filtration out of the vascular space into the interstitium; the excess fluid is removed via the lymphatic system.
Edema formation occurs when there is
An increase in capillary hydrostatic pressure (for example, increased plasma volume due to renal sodium retention)
An increase in capillary permeability (for example, burns, angioedema)
An increase in interstitial oncotic pressure (for example, myxedema)
A decrease in plasma oncotic pressure (for example, hypoalbuminemia)
Although it is possible to construct a pathophysiologic framework (Figure 15–1) for the differential diagnosis of edema, it is more useful clinically to combine anatomic, pathophysiologic, and organ/system frameworks:
Generalized edema due to a systemic cause and manifested by bilateral leg edema, with or without presacral edema, ascites, pleural effusion, pulmonary edema, periorbital edema
Systolic or diastolic dysfunction, or both
Advanced renal failure of any cause
The most common systemic causes of edema are cardiac, renal, and hepatic diseases as well as anemia.
Antidepressants: Monoamine oxidase inhibitors
Calcium channel blockers, especially dihydropyridines
Direct vasodilators (hydralazine, minoxidil)
Nonselective nonsteroidal antiinflammatory drugs (NSAIDs) and cyclooxygenase-2 inhibitors
Limb edema due to a venous or lymphatic cause, manifested by unilateral or bilateral edema
Deep venous thrombosis (DVT) (see Chapter 14, Dyspnea for a full discussion of lower extremity DVT)
Lymphatic obstruction (lymphedema)
Primary (idiopathic, often bilateral)
Lymphedema praecox (onset in puberty) or tarda (onset after age 20)
Secondary (more common, generally unilateral)
Surgery (especially, following mastectomy)
Miscellaneous (tuberculosis, recurrent lymphangitis, filariasis)
Figure 15–2 outlines the diagnostic approach to edema.
Mrs. V was well until a couple of months ago when she began feeling a bit more tired than usual, despite continuing to sleep well. She has had no shortness of breath or chest pain. She has noted intermittent vague abdominal pain, not related to eating, position, or bowel movements. She has been a bit constipated and feels bloated. Over the last 2 weeks, she has noted swelling in her feet and lower legs and has not been able to wear her regular shoes. As she tells you this, you note that she is wearing house slippers, and that her socks have produced a significant indentation above her ankles.
Her past medical history is notable for hypertension and diabetes, both well controlled. She had a blood transfusion during a cholecystectomy 25 years ago. Her current medications include hydrochlorothiazide, lisinopril, rosiglitazone, simvastatin, and aspirin. She has no history of heart or kidney disease, or tobacco or alcohol use.
|At this point, what is the leading hypothesis, and what are the active alternatives? What other tests should be ordered?|
Pathophysiology of edema. (Adapted with permission from Cho S et al. Peripheral edema. Am Med. 2002;V113:581. Copyright © 2002 Excerpta Medica, Inc.)
Diagnostic approach: edema.
Even before examining Mrs. V, you can see that she has significant bilateral leg edema, a pivotal point in her presentation. Although there are some local diseases that can present with bilateral leg edema, the first step in such patients is always to look for systemic causes. While the history and physical are often not sensitive or specific enough to make a diagnosis, they are a good starting point for organizing the differential. So the first question to ask is, “Does Mrs. V have any signs or symptoms pointing to a cardiac, hepatic, or renal cause of her edema?” The answers to this question would be additional pivotal points. Mrs. V's history of a blood transfusion puts her at risk for chronic hepatitis and cirrhosis, and her vague abdominal complaints raise the possibility of ascites, more commonly seen with cirrhosis than heart failure (HF) or renal failure. She is certainly at risk for both cardiac and renal disease because of her history of hypertension and diabetes. While most patients with heart failure complain of shortness of breath, some describe only fatigue. Medication should be considered as a cause, since rosiglitazone frequently causes edema; hypothyroidism does not ...