Blood flow and rheology Lecture 3

Question 1

What are reticulocytes?

Answer 1

Immature RBCs released from the bone marrow that still have endoplasmic reticulum

Question 2

Describe cellular mechanical factors affecting deformation and circulation

Answer 2

RBCs are highly deformable as the capillary diameter is similar in size to the RBC. White cells move more slowly in capillaires and affect flow distribtion due to intermittent flow. (Can influence flow by adhering to vessel wall)

Cell geometry:

Size determines the level of deformation required

SA:V (surface area:volume ratio) determines the ability to adapt shape

Membrane:

Resistance to deformation determines rigidity

Resistance to disruption determines stability

Cytoplasm

Viscosity, cytoplasm, inclusions, organelles

Question 3

How do RBCs and WBCs affect microcirculation?

Answer 3

RBCs capillary entry- msec whilst WBC- sec

WBCs 1000x slower, 1000x more resistance

RBCs have a steady resistance to flow

WBCs- intermittent flow and affects flow distribution Can influence flow by adhering to a vessel

Question 4

Describe how the cellular mechanisms affect WBC and RBCs

Answer 4

WBCs have a spherical shape but a folded membrane, the excess membrane allows sufficient deformation to fit into capillaries- the cytoskeleton (1000x more viscose than RBC) of the dominant resistance factor for WBCs

RBCs have a biconcave shape with excess membrane and its cytoplasm has lower viscosity with no cytoskeleton or organelles- membrane rigidity is the dominant factor for resistance for RBCs

Question 5

Describe RBC membrane structure and function

Answer 5

RBC membrane is supported by a network of spectrin. If this skeleton is affected, then RBCs are prone to lysis. Spectrin allows deformation and has good elasticity.

Has external glycolipids and glycoproteins attached on to the outer phospholipid leaflet and integral proteins for recognition and adhesion

Peripheral proteins also attached to integral proteins and also to spectrin tetramers that form the membrane skeleton - No cytoskeleton

Elastic membrane skeleton allows the easy deformation when the RBC is stretched in high flow or to enter capillaries

It controls the cell shape- requires ATP

Provides flexibility, stability

Contributes to homeostasis by regulating the contents and volume

Question 6

Describe how blood cells behave in physiological conditions and pathological conditions

Answer 6

RBCs- don’t adhere normally- will in some disorders

Leucocytes- protective inflammatory, lymphocytes re-circulation

Can be out of control cause vascular occlusion and tissue damage

Platelets- haemostasis vs thrombosis

Question 7

Describe leukocyte migration

Answer 7

1) Contact via seletins which have weak interactions in order to slow the white cells down as a result they roll.
2) Capture via rolling
3) Stop- integrin activation by activatory signals in endothelium which form a firm adhesion.
4) Spread over the endothelial cells
5) Migrate through endothelium
6) Spread under the endothelial cells and casues Chemotaxis to infection via chemokines

Question 8

Describe how sickle cell and malaria affects blood rheology

Answer 8

Sickle cell forms a haemoglobin S polymer in deoxygenated conditions. So less deformable than RBCs

Malaria makes the cytoplasm more viscos and the membrane more rigid

Both make the RBCs more adhesive

Question 9

Describe pathological WBC rheology

Answer 9

Abnormalities:

Vasculitis- autoantibodies activate neutrophils and become less deformable

Smoking alters shape and affects ridigty

Inflammatory mediators

Uncontrolled adhesion:

Myocardial infarction (uncontrolled inflammation and adhesion)

Shock, chronic inflammation, graft rejection, vasculitis