Red cells and rheology

Question 1

Factors controlling viscosity

Answer 1

• Intrinsic structure of blood: major factors = haematocrit and plasma viscosity, minor factors = red cell aggregation and red cell deformation
• Extrinsic, flow conditions: viscosity depends on shear rate, velocity gradient across vessel
• Haematocrit: non-linear relationship, haematocrit ↑, resistance ↑ disproportionally
• O2 flux for a given pressure: haematocrit ↑, O2 delivery ↑ to certain point, then becomes detrimental to have a high haematocrit due to high resistance
• Anaemia and polycythaemia vera (↑ in viscosity due to abnormal cell numbers) impact haematocrit levels
• Plasma viscosity: depends primarily on protein concentration
• Acute phase response: ↑ fibrinogen levels and ↑ plasma viscosity and red cell aggregation leading to ↑ erythrocyte sedimentation rate
• High flow rate = red cell deformation, cells align with flow, ↓ viscosity with high shear rate, low flow rates = red cells aggregate, mediated by plasma protein (mainly fibrinogen), and ↑ viscosity at low shear rate
• Hyperviscosity syndrome: symptoms of spontaneous bleeding from mucous membrane, visual disturbances due to retinopathy, and neurological symptoms
• Viscosity in intermediate sized vessels: haematocrit is lower in smaller vessels than large vessels due to Fahraeus effect
• ‘Apparent viscosity’ ↓ with ↓ vessel diameter, haematocrit in many arterioles is lower than systemic haematocrit, flow resistance lower than expected from systemic viscosity, however, resistance still depends on haematocrit
• Parabolic velocity profile: profile is blunted at haematocrits over 30%, occurs at low and high flow rates, white cells + platelets move towards edge of flow due to aggregation of red cells
• Atherosclerotic lesions: develop at focal points of disturbed flow, regions of vasculature have ↑ permeability to macromolecules, ↑ turnover, ↑ adhesiveness to monocytes, altered eNOS levels (lamina flow + endothelial shear stress = protective)

Question 2

Blood rheology and blood cell adhesion

Answer 2

• Difference in serum and plasma: plasma contains anti-coagulants to prevent clotting allows for isolation of plasma, serum allows for coagulation, turns liquid after centrifugation
• Albumin = most abundant, maintains oncotic pressure, important in fluid exchange across capillaries, fibrinogen = less abundant, roles in red cell aggregation and viscosity
• Rheology = branch of physics, deals with deformation and flow of matter, non-Newtonian flow of liquids, and plastic flow of solids (influence on circulation, adaptation to cellular function, and identify abnormalities
• Flow in large vessels: main property of flow resistance = viscosity friction in liquid
• Small vessel flow: main property = cellular properties + plasma viscosity
• Flow driving force = pressure gradient, heart pressurises aorta > moves blood
• Blood flow in circulation differs from constant flow of a Newtonian liquid in a rigid vessels, lamina flow is the steady flow of a Newtonian liquid
  * R= 8ƞl/(πr^4 ) (derived from Poiseuille^’ s law)
• Blood = non-Newtonian fluid, viscosity changes due to shear rate, tubes tapered and walls deform, blood flow is not constant but pulsatile (in arteries and arterioles)
• ↑ resistance + constant pressure gradient → flow will go down
• Maintain CO: if resistance ↑ then arterial blood pressure will increase
• Red cells: do not normally adhere, pathological adheres in some situations
• Leukocytes (adhere to exit microcirculation): physiological are protective inflammatory response and lymphocyte re-circulation, pathological is out of control, used in vascular occlusion and tissue damage
• Platelets: physiological in haemostasis, and pathological in thrombosis (occlusion)
• Leukocyte migration: margination (allows contact with vessel wall) → contact → capture → rolling slow cells (mediated by cell-surface selectins) → stop (by integrin activation activated by signals), spread, and migrate
• White cell rheology pathology: problems due to occlusion and/or tissue damage, mechanical abnormalities include vasculitis (autoantibodies activate neutrophils), smoking, and inflammatory mediators (septic shock)
• Uncontrolled adhesion: ischemia/reperfusion, chronic inflammation, graft rejection

Question 3

Red + white cell flow in capillaries

Answer 3

• For red cells to access vessels, they are highly deformable, occurs within a matter of milliseconds, but white cells are less deformable
• Microcirculation, less numerous white cells have a greater influence on blood flow
• Factors effecting cell flow: cell geometry of size and SA:V (degree of deformation required and ability to adapt shape), membrane deformation (resistance to deformation = rigidity and resistance to disruption = stability), cytoplasm and viscosity (cytoskeleton = dominant factor for white cells)
• Red cells create steady flow resistance in capillaries, white cells create intermittent flow affecting flow distribution, can take path of least resistance (white cells can influence flow by adhering to vessel wall – typically post capillary venules)
• Membrane = resistant structure for red cell, cytoplasm = white cell resistant structure
• Red cell membrane supported by network of spectrin (mutations associated with haemolytic anaemias), spectrin has spring-like structure, α-helices allow red cell membrane to stretch and reoil but not increase its surface area, is relatively impermeable to lipid bilayer, stabilised by underlying skeletal network, controls cell shape, flexible for reversible deformation, and stable to withstand flow stress, also contains specialised pumps and transporters for homeostasis and regulates volume
• Red cell pathology: genetic defects in membrane structure → haemolytic anaemia
• Mechanical abnormalities → sickle cell disease (haemoglobin S forms polymer at low oxygen) and malarial parasites (parasites within red cell causes increased rigidity and alters membrane structure)
• Adhesion abnormalities can also cause either sickle cell disease or malaria