July 12, 2016

How the spleen keeps blood healthy

At a Glance

  • Researchers used computer modeling to show how the spleen maintains the quality of red blood cells in the bloodstream.
  • The findings may provide insights into conditions that lead to anemia, such as certain hereditary disorders, infectious diseases, and cancers.
Illustration of spleen in human body, The spleen is located under the rib cage. It removes unhealthy, old, and misshapen red blood cells from circulation.Nerthuz/iStock/Thinkstock

The spleen helps keep harmful microorganisms out of the bloodstream. It holds key components of the body’s immune system. The spleen also removes unhealthy, old, and misshapen red blood cells from circulation.

Red blood cells carry oxygen throughout the body and remove carbon dioxide (a waste product). These disc-shaped cells are filtered by the spleen based on their physical characteristics. They can only reenter the bloodstream if they’re able to pass through a tiny splenic structure called the interendothelial slit. When the red blood cells’ size, shape, or ability to deform is altered, they can’t pass through.

Under certain conditions, such as hereditary spherocytosis, misshapen red blood cells can get trapped in the spleen, leading to anemia. In addition, some diseases — such as malaria, leukemia, and lymphomas — may cause enlargement of the spleen and lead it to filter out not only abnormal cells but also healthy red blood cells.

Studying how the human spleen filters faulty red blood cells has been challenging. The anatomy and physiology of the human spleen differ from that of common laboratory animal models. And invasive procedures, such as a biopsy or needle aspiration, can cause dangerous bleeding. A team of researchers led by Dr. Subra Suresh at Carnegie Mellon University and Dr. Ming Dao at MIT approached the problem by using computational simulation tools. Their work was funded in part by NIH’s National Heart, Lung, and Blood Institute (NHLBI). The study was published online in Proceedings of the National Academy of Sciences on June 27, 2016.

The team developed computational simulations of the mechanics of red blood cells as they pass through the spleen. The researchers determined that cells deform significantly as they cross the narrow splenic slit. This is in contrast, they found, to the simple bullet-shaped deformation that occurs in narrow blood capillaries.

Illustration of red blood cells in a blood vesselHealthy red blood cells are disc-shaped and look like doughnuts without holes in the center. rasslava/iStock/Thinkstock

The analyses revealed the limits of surface area and volume within which red blood cells can cross the spleen. The work showed how the splenic slit determines the size and shape distributions of healthy red blood cells. The team’s predictions were consistent with independent experimental results using healthy, artificially modified, and infected human red blood cells.

“The computational and analytical models from this work, along with a variety of experimental observations, point to a more detailed picture of how the physiology of the human spleen likely influences several key geometrical characteristics of red blood cells,” Suresh says.

“We have presented results showing that the spleen is the main organ that defines the shape of the circulating red blood cells,” Dao adds.

This work may lead to a better understanding of the spleen’s role in various disease states. The findings could have implications for future therapeutic approaches.

—by Harrison Wein, Ph.D.

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Reference: Biomechanics of red blood cells in human spleen and consequences for physiology and disease. Pivkin IV, Peng Z, Karniadakis GE, Buffet PA, Dao M, Suresh S. Proc Natl Acad Sci U S A. 2016 Jun 27. pii: 201606751. [Epub ahead of print]. PMID: 27354532.

Funding: NIH’s National Heart, Lung, and Blood Institute (NHLBI); National Science Foundation; US Department of Energy; Swiss Platform for Advanced Scientific Computing; and Singapore-MIT Alliance for Research and Technology.