Leukocytes rolling on blood vessel walls
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Leukocytes rolling on blood vessel walls
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[post_date] => 2025-01-09 07:49:32
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[post_content] => Practice Passage (Question 1-5)
*This passage is the property of Khan Academy and has been reformatted into an AAMC-style interface in their entirety by MedLife Mastery. MedLife Mastery does not endorse and is not an affiliate of Khan Academy.
Leukocytes in the circulatory system have the remarkable ability to migrate to particular areas of the body. They adhere to the endothelium, or inner wall, of post-capillary venules before entering the appropriate tissues. During the first stage of this process, leukocytes roll along the vascular endothelium. Rolling adhesion is mediated by selectin adhesion: weak, transitory interactions between selectins, proteins on the vascular endothelium, and oligosaccharides on the surface of the leukocytes. Selectins are only present in post-capillary blood vessels: primarily in venules and rarely in larger veins.
Physiological variables, such as shear stress, affect the ability of leukocytes to engage in rolling adhesion. Shear stress is applied along the endothelial surface by blood flow and is measured as force per unit area. It is applied in the same direction as blood flow. Generally, higher numbers of leukocytes are able to adhere at lower levels of shear stress. In vivo shear stress can be calculated by the following equation:
Where 𝒯 is shear stress, μ is blood viscosity, 𝒗 is mean blood velocity, and d is blood vessel diameter. Shear stress levels vary throughout the circulatory system.
Figure 1: Shear Stress Values in Various Vessels
A team of researchers explored the function of a CD-62, a selectin involved in rolling adhesion, at varying levels of shear stress. They utilized a flow chamber in which leukocytes rolled along a flat, artificial endothelium containing CD-62 at varying densities.
Figure 2: Leukocyte Rolling Velocity as a Function of CD-62 Density and Shear Stress. Rolling velocity values represent means of adherent cell rolling velocities. CD-62 were incorporated into the artificial endothelium at the indicated density (50, 200, or 400) in sitesμm-2 . Nonadherent cell velocities were too fast (>1700 μms-1 ) to be accurately measured.
Passage and figures adapted from: Papaioannou, Theodoros G., and Christodoulos Stefanadis. "Vascular wall shear stress: basic principles and methods." Hellenic J Cardiol 46, no. 1 (2005): 9-15; Lawrence, Michael B., and Timothy A. Springer. "Leukocytes roll on a selectin at physiologic flow rates: distinction from and prerequisite for adhesion through integrins." Cell 65, no. 5 (1991): 859-873.
[post_title] => Leukocytes rolling on blood vessel walls
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[question] => Which of the following physiological changes can be inferred to increase the number of leukocytes that are able to adhere to the vascular endothelium?
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[answer] => 1
[description] => Reason for the Correct Answer:
The passage says, “Generally, higher numbers of leukocytes are able to adhere at lower levels of shear stress.” You need to choose the answer that the lowers shear stress levels.
When you examine the provided equation, you can see that increasing blood viscosity and blood velocity increase the shear stress levels. Eliminate these options.
The equation shows that shear stress decreases when vessel diameter increases. Therefore, wider venules would decrease shear stress and increase the number of adherent leukocytes.
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[answers] => Array
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[each_answer] => A. Wider post-capillary venules
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[each_answer] => B. Faster blood flow
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[each_answer] => C. Higher blood viscosity
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[each_answer] => D. Lower density of CD-62
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[1] => Array
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[quiz_unique_key] => 3873426850
[question] => What is the primary cause of the difference in capillary and arteriolar shear stress levels, assuming that effects related to blood viscosity are negligible?
[value] => Array
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[answer] => 1
[description] => Reason for the Correct Answer:
First, you need to determine relative shear stress levels in capillaries and arterioles. Figure 1 shows that shear stress levels are lower in capillaries than in arterioles.
From your knowledge of the circulatory system, you know that capillaries are smaller and have slower blood flow than arterioles. Eliminate the answers that are simply false.
The remaining answers are “Capillaries have a smaller diameter” and “Blood flow is slower in capillaries.” Both of these will have an effect on shear stress, but you can look at the provided equation to determine how each would affect shear stress.
From the equation, smaller diameter (d) is expected to increase shear stress. A slower velocity (𝒗) is expected to decrease shear stress. Therefore, the reason why capillaries have lower shear stress levels is because “blood flow is slower in capillaries.”
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[0] => Array
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[each_answer] => A. Blood flow is slower in capillaries
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[each_answer] => B. Capillaries have a smaller diameter
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[each_answer] => C. Arterioles have a smaller diameter
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[each_answer] => D. Blood flow is slower in arterioles
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[quiz_unique_key] => 83407773
[question] => In Figure 2, the rolling velocity is proportional to the shear stress at low shear stresses (0-2 dynes/cm2), and begins to plateau (flatten) at higher shear stresses. Which of the following effects can explain this data pattern?
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[answer] => 4
[description] => Reason for the Correct Answer:
The plateau of the lines indicates that an increase in shear stress at higher levels does not increase the rolling velocity of the leukocytes as much as it did at lower shear stress levels.
This indicates that at greater shear stress levels, there is more adhesion (stickiness), between the leukocytes and the endothelium. Greater adhesion prevents the leukocyte from speeding up as much in response to an increase in shear stress.
Flattening of leukocytes against the endothelium could cause more adhesion, because there would be more contact and more interactions between a flattened leukocyte and the endothelium. All the other choices would cause less adhesion.
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[answers] => Array
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[each_answer] => A. Destruction of CD-62 molecules at greater shear stresses
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[each_answer] => B. Lower selectin-ligand binding affinity at greater shear stresses
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[each_answer] => C. Detachment of leukocytes from the endothelium at greater shear stresses
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[each_answer] => D. Flattening of leukocytes against the endothelium at greater shear stresses
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[quiz_unique_key] => 2261298308
[question] => When designing the experiment shown in Figure 2, why did researchers increase shear stress levels to 14.3 dynes/cm2 but no higher?
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[answer] => 4
[description] => Reason for the Correct Answer:
The passage says that rolling adhesion occurs mostly in venules.
In Figure 1, the shear stress values in the venules are shown to be ~15 dynes/cm².
This approximately matches the highest value in the experiment, indicating that researchers intended to match physiological levels of shear stress in the venules.
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[each_answer] => A. To disrupt laminar flow and create turbulence
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[each_answer] => B. To test the limit of leukocyte adhesion abilities
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[each_answer] => C. To match physiological levels of shear stress
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[each_answer] => D. To cause greater numbers of nonadherent cells
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[quiz_unique_key] => 574431310
[question] => A competing explanation for leukocyte rolling along vascular endothelia is shear flow tumble: any object carried along by laminar fluid flow will tend to roll when traveling along a vessel wall because the flow rate close to the wall is less than the flow rate far from the wall, generating a torque on the object. Which finding would provide the strongest support for shear flow tumble over selectin adhesion as the best explanation for leukocyte rolling?
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[answer] => 3
[description] => Reason for the Correct Answer:
If selectin adhesion is the correct explanation, then we would predict that leukocytes would demonstrate different behaviors depending on whether selectins were present. Most likely, we would expect leukocytes to roll more slowly with selectins because of adhesion.
The passage mentions that selectins are present on venular endothelia (not on the arteriolar endothelia).
If shear flow tumble is the correct explanation, we would predict that leukocytes would demonstrate similar rolling behaviors and velocities along any endothelia, regardless of whether or not they contained selectins. In other words, leukocytes would “demonstrate similar rolling behaviors along both arteriolar and venular endothelia.”
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[0] => Array
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[each_answer] => A. Leukocytes roll on venular endothelia at velocities slower than theoretically predicted shear flow tumble velocities.
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[each_answer] => B. Leukocytes roll on arterioral endothelia at velocities similar to theoretically predicted shear flow tumble velocities.
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[each_answer] => C. Leukocytes demonstrate similar rolling behaviors along both arteriolar and venular endothelia.
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[each_answer] => D. Leukocytes demonstrate rolling behavior only along venular endothelia.
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