Blood flow Flashcards
What is the function of blood?
Transports:
Gases
Heat
Nutrients
Metabolites
Signals
Immune cells
The structure is adapted to its function.
What are the constituents of the blood?
Blood is a suspension of solid particles.
When coagulated and centrifuged the layers are:
Bottom - RBCs
Buffy coat, very thing late - white cells and platelets.
Plasma, made from proteins.
What is the cellular component of blood?
99% of the blood cells are red blood cells, which carry oxygen.
Platelets are small cell fragments for haemostasis.
White cells are for immunity and protection.
What are the constituents of plasma?
Na+ is most abundant cation then K+
Cl- and HCO3- are the most abundant anions.
Blood plasma is electroneutral
Na+, Cl- and HCO3- are the main osmotically active solutes.
What are the proteins in the plasma?
Albumin is the most abundant, made in the liver.
Then immunoglobulin, made by B cells.
Fibrinogen is also important.
What are the other components of plasma?
Lipids -
Cholesterol
Phospholipids
Triglycerides
Carbohydrates - mainly glucose, which is tightly regulated.
What is blood rheology?
The flow of matter, especially non-Newtonian flow of liquids and the plastic flow of solids.
Why is blood rheology studied?
It influences circulation.
It influences or is adapted to cellular function.
Abnormalities may relate to pathology
What properties are looked at in blood rheology?
Blood as a whole - resistance to flow and viscosity.
Cells in particular - deformability and adhesion.
How do the physical properties of vessels affect blood flow?
Small arteries are much bigger than RBCs, so blood is a liquid in arteries.
Arterioles - smaller, 10x bigger diameter than RBC. Cells and plasma flow change, RBCs go to centre, cell-free zone at the edges.
Capillaries are the same size or smaller than RBCs.
As vessels get smaller, the cells action have more of an impact.
How do the main drivers change with diameter?
When the diameter is much more than the blood cells, the blood component is blood viscosity.
When the diameter is less than the blood cells, the blood component is the cellular properties and plasma viscosity.
What is viscosity?
The characteristic resistance to flow, the friction within liquid.
What is the driving force for flow?
Flow is driven by the pressure gradient.
The heart pressurises that aorta.
As the elasticity squeezes in, blood moves around the body.
Blood moves from high pressure to low pressure.
What is the equation for flow?
Pressure gradient = the volumetric flow rate x resistance.
How is flow related to cardiac output?
Cardiac output = ABP / TPR
What is laminar flow?
A Newtonian fluid is a fluid where the viscosity does not change according to the flow rate.
The Newtonian fluid will flow through a straight tube at constant viscosity, but in layers.
Next to the wall, the liquid will have no velocity.
At the centre of the tube, the liquid will have very fast velocity.
What is the equation for resistance?
Resistance = 8 x viscosity x length / radius of the vessel ^4.
Resistance has 2 components:
Blood component - the blood viscosity.
Vascular component - the length of the vessel and the radius of the vessel.
Why is blood not a Newtonian fluid?
Blood is a non-Newtonian fluid because its viscosity changes depending on shear rate.
The blood vessels are not rigid and straight, instead curved and deform.
Blood flow is not constant but pulsatile.
What is the effect of increasing resistance?
If resistance increases (because blood viscosity increases) then to maintain flow rate pressure needs to increase.
If pressure doesn’t change and resistance increases, then cardiac output decreases.
What are the intrinsic factors controlling viscosity?
The structure of blood.
Major factors: Haematocrit - packed red cell volume
Plasma viscosity.
Minor factors: Red cell aggregation
Red cell deformation
What are the extrinsic factors controlling viscosity?
Flow conditions.
Viscosity depends on shear rate.
What is the relationship between haematocrit and viscosity?
As haematocrit increases viscosity increases, but is not linear.
Viscosity increases by 4% for each 1% increase in haematocrit.
What is the relationship between haematocrit and oxygen delivery?
The oxygen content is directly proportional to haematocrit, because this shows how many RBCs there are.
Proportional up to a certain point - because resistance goes up and flow becomes slower.
Haematocrit can become too high, and oxygen delivery inefficient = 40%, which is the value of haematocrit in healthy humans.
What are healthy haematocrit levels?
Men = 45%
Women = 4%
Neonates = 54%
How does pathology affect haematocrit levels?
Smoking increases haematocrit by 5%.
In anaemia, haematocrit decreases by 20%.
Polycythaemia vera is a blood cancer with overproduction of RBCs, haematocrit can increase over 60%.
What are the consequences of anaemia?
Reduced oxygen carrying capacity, and reduced haematocrit and therefore reduced viscosity.
TPR decreases, so to maintain arterial blood pressure cardiac output increases.
This limits the ability to exercise as cardiac output cannot increase much higher.
How does plasma viscosity affect blood viscosity?
Plasma viscosity depends on the protein concentration of albumin, immunoglobulin, and fibrinogen.
What is fibrinogen?
Fibrinogen is involved in blood clotting, as well as red cell aggregation - sticking together at low flow.
In inflammatory conditions - atherosclerosis, diabetes, smoking etc, fibrinogen levels increase, so increases red cell aggregation.
Increased erythrocyte sedimentation rate.
What do RBCs do at high flow rate?
RBC deform
Cells align with flow
Decreased viscosity with high shear rate.
What do RBCs do at low flow rate?
Red cells aggregate
Mediated by plasma proteins, mainly fibrinogen.
Increases viscosity at low shear.
What are hyperviscosity syndromes?
Very high blood viscosity.
Associated with spontaneous bleeding from mucous membranes.
Visual disturbances due to retinopathy.
Neurologic symptoms ranging from headache and vertigo to seizures and coma.
What are hyperviscosity syndromes caused by?
Increase in plasma viscosity - Hyperglobulinaemia, where immunoglobulins are elevated in myeloma and macroglobulinaemia.
Increase in viscosity due to abnormal cell numbers - polycythaemia vera and hyperleukotic leukaemia.
What is disturbed flow?
There is disturbed flow at bifurcations of blood vessels - where they branch into two.
These areas are vulnerable to atherosclerosis, where plaques form and can lead to heart attacks or stroke.
What are the features of athero-susceptible regions?
Increased permeability of macromolecules.
Increased turnover.
Increased adhesiveness to monocytes.
Altered levels of nitric oxide synthase.
What levels are measured in blood related to health?
Red blood cell count.
Haemoglobin concentration (Hgb).
Haematocrit (Hct).
Mean cell volume (MCV), mean cell haemoglobin (MCH) and mean cell haemoglobin concentration (MCHC) can then be calculated from these.
What is the shape of RBCs?
RBCs are highly deformable.
Can squeeze easily and quickly through small spaces.
This is important as the capillary diameter is similar in size to the RBCs.
What is the shape of white cells?
White blood cells are not deformable, so they move very slowly through capillaries.
This then impacts the flow of RBCs.
There are few white cells in microcirculation but they have a big influence on blood flow.
How does activation change the shape of white blood cells?
The state of white cell affects how it moves.
In healthy individuals white cells will be spherical, quiescent.
If stimulated, will change shape, become adhesive and less deformable.
e.g. in septic shock where there are many cytokines in circulation.
What are the factors affecting deformation and circulation?
Cell geometry.
Membrane deformability
Cytoplasm and viscosity
How does cell geometry affect cell deformation?
Diameter to volume ratio, which affects the degree of deformation required.
Surface area to volume ratio, which affects the ability to adapt its shape.
What is the shape of RBCs?
Has a biconcave shape so there is spare surface area, to change into a different shape to get through a space, and maintain surface area.
What is the shape of white cells?
White cells are spherical but have extra membrane on its surface, so can change shape, and use the spare membrane to fit over the volume.
How does membrane deformability affect deformability and circulation?
RBC membrane has a skeleton which gives the membrane structure, rigidity and resilience, which helps the cell survive the large amount of deformability it has to do.
This rigidity creates resistance to going through small spaces.
How does the cytoplasm and viscosity affect deformation?
RBCs have no organelles, only contain haemoglobin, so are adapted to transport oxygen, so resistance to flow is not affected by viscosity. Instead its membrane provides resistance.
White cells have a cytoskeleton and organelles which needs reorganisation in order to squeeze through a small diameter - the cytoplasm is major resistive element to flow.
What are the comparisons of white cells and red cells?
RBCs enter in milliseconds, white cells in seconds.
RBCs have steady resistance to flow in capillaries, white cells have intermittent flow, and affect the distribution of other things.
White cells can adhere to the vessel wall.
What is the structure of RBCs?
Biconcave disc
Anucleate
No organelles
Plasma membrane supported by spectrin
What is spectrin?
A network of proteins just under the membrane.
It is anchored to the membrane by integral membrane proteins.
What is the structure of spectrin?
Have an a-helical structure.
They stretch and recoil to allows RBC to stretch and return to biconcave shape.
Mutations in how it is attached to the plasma membrane are associated with haemolytic anaemia, where RBCs are fragile, usually genetic.
What is the membrane in RBCs?
Relatively impermeant lipid bilayer, stabilised by underlying skeletal network.
It controls cell shape, is flexible so has reversible deformation, and provides stability to withstand stress.
It also contains specialised pumps and transporters.
So homeostasis can regulate contents and volume of the RBCs.
What are mechanical abnormalities in red cells?
Sickle cell disease - haemoglobin S forms polymer at low oxygen, cells sickle, affects ability to flow through vessels.
Malarial parasites - causes increased rigidity and alters membrane structure.
These diseases can also cause adhesion abnormalities.
What is the adhesion of RBCs?
Healthy RBCs do not usually adhere.
What is the adhesion of leukocytes?
White cells protect in inflammation and infection.
White cells deliver lymphocytes, so need to be able to move out of blood vessels.
So they can adhere.
What is the pathology of leukocytes?
If they are excessively activated and change shape inside blood vessels, it causes vascular occlusion and damages the tissues.
What is the adhesion of platelets?
Function in haemostasis, so adhere.
Can cause thrombosis and occlusion.
What are the stages of white cell migration?
Margination
Rolling
Adhesion
Extravasation
What is margination of white cells?
RBC aggregation in the centre of the vessel causes white cells and platelets to move towards the edge of the flow - margination.
To leave the vessel, white cells need to be at the edge of the vessel, so margination helps with this, enables contact with the wall.
What is the process of leukocyte migration out of circulation after margination?
Rolling - selectin proteins make low affinity interactions with the white cels and slows it down.
Signals in the endothelium stimulated by cytokines allows upregulation of integrins, which allows adhesion.
The cells then spread out and elongate, and leave the endothelium into the tissues.
What are the problems needing solving in leukocyte migration?
Need to catch a fast moving cell.
Stabilise adhesion.
Present activating agents - chemokines.
Guide migration into the tissue.
What are mechanical abnormalities in white cells?
Vasculitis - autoantibodies which activate neutrophils.
Smoking
Inflammatory mediators - septic shock.
These over activate white cells.
What is uncontrolled adhesion in white cells?
Ischaemia, and then reperfusion when blood flow returns, causes adhesion.
Chronic inflammation e.g., in rheumatoid arthritis.
Graft rejection
If a 1% increase in haematocrit causes a 4% in viscosity – what % change in viscosity does smoking cause?
Smoking changes haematocrit by 5%.
so do 1.04 ^5, to get a 22% increase in viscosity.
