High-Speed Video Footage Solves One of the Great Mysteries of Human Blood Flow
A key theory of blood dynamics has been overturned by video evidence showing how red blood cells can make blood less viscous.
Red blood cells are flexible biconcave discs that spend their lives suspended in blood plasma. They are by far the largest component of ordinary blood and consequently play a hugely important role in the way it flows through the body.
In ordinary conditions, red blood cells stack together to form structures called rouleaux like cylindrical packs of coins. These constantly form and break up but they can also become tangled. When this happens, the blood becomes thicker and eventually clots.
But it’s easy to imagine that these rouleaux structures can cause problems as blood vessels get smaller—the smallest vessels being little bigger than the red blood cells themselves.
But hematologists have long known that this doesn’t happen. It turns out that blood has a unique property that prevents this kind of snarl-up—it becomes thinner and runnier when it passes through smaller channels. Just why this happens is something of mystery.
But today, Manouk Abkarian and at the University of Montpellier in France and a few pals say they have worked out what’s going on. These guys have used high-speed video cameras to record the behavior of red blood cells in the same conditions the cells experience in the human body. And they say their results overthrow conventional thinking about the role of red blood cells in the blood.
First some background. The property that makes blood thinner when it flows through smaller vessels is known as shear thinning. It comes about when the forces in one part of a liquid differ from those in another, causing shear stress. Physicists call liquids that behave like this non-Newtonian fluids.
Shear stresses happen naturally in the flow through any vessel. That’s because the fluid nearest the surface of the vessel moves more slowly than the fluid in the middle and this sets up a shear stress. But how does shear stress make blood runnier?
Part of the puzzle is that biologists have long known that blood plasma is a Newtonian fluid—its viscosity is unaffected by shear stress. So any non-Newtonian behavior must be caused by the red blood cells, which are suspended in blood plasma and make up to 45 percent of blood.
In the 1970s, hematologist began to study the behavior of these cells suspended in aqueous solutions of dextran polysaccharides, which was thought to mimic conditions in the body. They found that red blood cells flip like coins when the shear stress is low. But as the shear stress increases, the cells orient themselves with the flow and become stable. Indeed, the cells elongate in the direction of flow forming oblate ellipsoids.
This led to an influential theory of blood flow. This theory suggested that in these circumstances red blood cells behave like liquid droplets. In other words, blood behaves like an emulsion.
But a cell can only behave like a droplet if its membrane behaves like a fluid as well. And that has some important consequences.
When the cells form oblate ellipsoids, the shear forces cause them to rotate. The cytoplasm inside the cell is more viscous than the fluid outside, so the membrane must rotate more rapidly than the cytoplasm inside. From the side this would look like the movement of a tank track.
So-called tank-treading has become a seemingly well-known phenomenon for red blood cells moving inside small blood vessels.
But Abkarian and co now say this theory of red blood cell behavior is wrong. For a start, they point out that the early solutions of dextran polysaccharides did not accurately reproduce conditions within the body. They also say that red blood cell membranes cannot behave like a liquid and that tank-treading is therefore impossible.
Instead, they use high speed video cameras to record the behavior of red blood cells in microchannels at body temperature in dextran solutions that mimicked the viscosity, osmolarity, and pH of blood. They then varied the shear stress experienced by the red blood cells by controlling the flow rate.
The results make for interesting reading. Abkarian and co say that blood viscosity undergoes a series of remarkable transformations as the shear stresses increase and that these are the result of complex changes in the behavior of red blood cells.
At first red blood cells tumble like flipped coins in blood. But as the shear stresses increase, this tumbling changes to a rolling motion. The cells appear to roll on their sides, like runaway tires. And as the proportion of cells that do this increases, the viscosity of the fluid falls.
But rolling is very different to tank treading, which requires the membrane to act like a fluid. Indeed, Abkarian and co says key feature of the behavior is that red blood cell membranes do not act like fluids.
As the shear stresses increase further, the cells begin to become squashed which presents a smaller surface area to the flow. “This leads to a further shear-thinning,” say Abkarian and co.
And as the shear stress increases still further, the red blood cells become distorted in shape, developing three or six lobes. Exactly how this happens isn’t clear but it contributes to shear thinning by allowing the cells to fold and so reduce their surface area even more.
The team back up their observations by creating a computer model of the cells, which reproduces this behavior when the same shear stresses are applied.
That’s an interesting result. It means that the liquid droplet theory of red blood cells is wrong and blood does not behave like an emulsion. Indeed, the observed behavior is only possible if the red blood cell membrane does not become fluid and so separates the plasma more effectively from the cytoplasm inside the cell. “The lack of membrane fluidity for high viscosity contrast between inner and outer fluids is the key feature which controls red blood cells behavior,” say Abkarian and co.
The new thinking has some important implications. Hematologists have used the idea of blood as an emulsion to explain various physiological phenomenon. For example, tank treading is a key part of a theory that explains how red blood cells release ATP. “Our study questions the relevance of a droplet-like analogy for red blood cell dynamics to explain these phenomena,” say the researchers.
Living fluids like the blood are hugely important. So a better understanding of their behavior will inevitably help researchers handle it more effectively. It’ll be interesting to see how the overturning of this conventional thinking will impact this field.
Ref: arxiv.org/abs/1608.03730: A New Look at Blood Shear-Thinning