Ep 171: A 19-Year-Old Woman with Lower Extremity Edema

The first episode in the series, “Physiology at the Bedside” discussing the mechanisms of lower extremity edema.

Read more on this topic in Harrison's.

Harrison's Principles of Internal Medicine, 22nd Edition

Transcript

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[Ms. Heidhausen] This is Katerina Heidhausen, executive editor of Harrison's Principles of Internal Medicine. Harrison's Podclass is brought to you by McGraw Hill's AccessMedicine, the online medical resource that delivers the latest content from the best minds in medicine. And now, on to the episode. 

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[Dr. Handy] Hi, everyone. Welcome back to Harrison's Podclass. We're your co-hosts. I'm Dr. Cathy Handy. 

[Dr. Wiener] And I'm Dr. Charlie Weiner, and we're joining you from the Johns Hopkins School of Medicine. 

[Dr. Handy] Welcome to Harrison's Podclass. Today's episode is about a 19-year-old woman with lower extremity edema. 

[Dr. Wiener] Cathy, hold on to your seat. Today, we're kicking off a series of episodes that we're calling Physiology at the Bedside. These cases will all focus on physiology or pathophysiology that's relevant to the direct care of patients. 

[Dr. Handy] That sounds great, and I'm really excited about this series. It is easy to lose sight of the importance of understanding mechanisms of disease with all of our clinical pathways and strong reliance on technology. So it's good to have some throwbacks to first and second year of medical school. So let's get right to the case. 

[Dr. Wiener] So today's patient is a 19-year-old woman with a many-year history of anorexia nervosa who's admitted to your hospital's eating disorder center for supervised refeeding. Her BMI has been less than 18 for over six months. On physical examination, her vital signs are notable for a temperature of 38 degrees centigrade, a heart rate of 66, a blood pressure of 90/60, a respiratory rate of 12, with an oxygen saturation of 97% on room air. She's markedly malnourished on physical examination, and now her BMI is 16. She clearly has lost muscle mass, and she's also lost subcutaneous fat. She has thin hair that is falling out, brittle nails, and she has pitting edema to her knees. 

[Dr. Handy] All right, based on that history and physical exam, it sounds like she has severe malnutrition. We did discuss refeeding syndrome in episode 112, so I'll refer you back to that, but what's the question for today? 

[Dr. Wiener] So the question asks, which of the following is the mechanism for her lower extremity pitting edema? And the options are: A. low intravascular hydrostatic pressure; B. low intravascular oncotic pressure; C. low protein reflection coefficient; or D. high interstitial hydrostatic pressure. 

[Dr. Handy] This is great and clinically very useful. It relates to the Starling equation named after the British physiologist, Ernest Starling, who lived and worked in the late 1800s and early 1900s, mostly in London. 

[Dr. Wiener] I know our cardiology friends often talk about the Frank-Starling relationship between preload and cardiac output, but I assume this is another of his seminal contributions. What exactly is the Starling equation? 

[Dr. Handy] The Starling equation describes the movement of fluid across a semipermeable membrane. So in our case, that would be a systemic or pulmonary capillary based on the balance of hydrostatic and oncotic forces on both sides of the membrane. For a capillary, the net fluid movement equals the filtration coefficient, that describes the capillary's permeability in surface area, multiplied by the hydrostatic gradient to force fluid out of the capillary minus the oncotic gradient to keep fluid in the capillary. Importantly, the oncotic gradient is multiplied by the protein reflection coefficient, which is a dimensionless number between zero and one that characterizes how well the membrane retains proteins, and thus can exert an oncotic pressure. In systemic capillaries, that number is very high. So oncotic pressure is important for keeping fluids inside the capillary. 

[Dr. Wiener] And for a capillary, the relevant hydrostatic or oncotic pressure gradient is the intravascular minus the interstitial pressure, right? 

[Dr. Handy] Correct. 

[Dr. Wiener] So let's get back to our question and let's go through the options. 

[Dr. Handy] Well, option A. is a low hydrostatic pressure. That will tend to lessen fluid flow across the membrane. While not an option in this question, a high hydrostatic pressure, such as in heart failure, is the most common cause of pedal edema and transudative pleural effusions. In those cases, the hydrostatic pressures overwhelm the oncotic pressure's ability to keep fluid in the vessel, but the protein reflection coefficient is still high, and that's why heart failure edema or effusions have a low protein concentration. 

[Dr. Wiener] What about option D. which also talks about hydrostatic pressure? 

[Dr. Handy] Similarly, option D. a high interstitial hydrostatic pressure will also tend to keep fluid in the capillary. This is likely how compression stockings reduce pedal edema. 

[Dr. Wiener] Okay, so options A. and D. are false. How about option B. the low intravascular oncotic pressure? 

[Dr. Handy] That's the correct answer. The low intravascular oncotic pressure is less effective at keeping fluid in the vessel. So for any hydrostatic pressure, fluid will leak across. Remember, our patient is markedly malnourished, so has a very low serum albumin and other serum proteins. Albumin is the major intravascular protein that exerts an oncotic pressure. This is a common finding in patients with low serum albumin. 

[Dr. Wiener] It's also true for patients with chronic liver disease, right? 

[Dr. Handy] Yes, this is the mechanism for ascites with a high SAAG or serum albumin to ascites gradient. 

[Dr. Wiener] Okay, so let's finish up with option C. We know the low protein reflection coefficient is a false response. 

[Dr. Handy] Protein reflection coefficient is really interesting. Remember, it determines how effective the capillary is at exerting an oncotic pressure. A low protein reflection coefficient will allow proteins to leak across the membrane. It turns out, this is what happens in many inflammatory states where protein-rich fluid leaks out of the capillary. 

[Dr. Wiener] Is that clinically relevant? 

[Dr. Handy] Absolutely. It's the mechanism for exudative pleural effusions and ascites with a low SAAG. In those cases, the effusion or ascites have a high protein because the inflammation in the lung or the peritoneum allows exudate out of the capillaries. This also explains why many patients with sepsis have pedal or dependent edema even before they get fluids or when they're being kept relatively dry. 

[Dr. Wiener] Great. So the teaching point in today's case is that fluid fluxes across capillaries or other semipermeable membranes are controlled by the components of the Starling equation. Understanding hydrostatic pressures, oncotic pressures, permeability, surface area, and the protein reflection coefficient are helpful in understanding the mechanisms of edema formation and allow you to best craft appropriate therapy. 

[Dr. Handy] You can find this question and other questions like it on Harrison's Self-Review, and then you can also learn more about this topic on the chapter on malnutrition and edema. Visit the show notes for links to helpful resources, including related chapters and review questions from Harrison's, available exclusively on AccessMedicine. If you enjoyed this episode, please leave us a review, so we can reach more listeners just like you. Thanks so much for listening. 

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