Blood constituents
-Erythrocytes (red blood cells)
-Leukocytes (white blood cells)
-Thrombocytes (platelets)
-Plasma (55-60% of volume):
a). water (90-91%)
b). proteins (6.5-8.5%)
c). electrolytes, anions, etc.
Determinants of blood viscosity
• RBC concentration (hematocrit)
• Plasma viscosity (Newtonian fluid)
• RBC deformability (at high hear rates)
• RBC aggregation (at low hear rates)
Normal (deformable) RBCs
Dr. Max Hardeman, with
permission
Roggenkamp, et al., 1986
Pathologies related to significantly
increased RBC aggregation
•
•
•
•
•
•
Cardiovascular diseases
Diabetes
Obesity
Hypertension
Atherosclerosis
Shock
Methods of evaluation
• Blood viscosity (viscometers; rheometers)
• RBC deformability (asymptotic blood viscosity;
ektacytometry)
• RBC aggregation (low shear blood viscosity,
erythrocyte sedimentation rate, aggregometers)
Results obtained by the most of these methods strongly
depend on hematocrit
Ratio of male to female mortality due to myocardial
infarction, IHD, and cancer (Vital Statistics of the US)
Myocardial Infarction
7.0
IHD
Ratio of mortality
6.0
Cancer
5.0
4.0
3.0
2.0
1.0
0.0
10
20
30
40
50
Age, years
60
70
Hypotheses
• The higher level of the circulating ovarian
hormones (estrogens) that produce a
vasodilatory effect mediated by NO on coronary
arteries protect women of reproductive age
(however, the increase in risk of heart disease
was found to be essentially the same in women
with surgically induced menopause regardless of
ovary removal)
• Our hypothesis was that rheological properties
of the premenopausal female blood are
optimized by a monthly blood loss to maximize
gas transport
Correlation between hematocrit and blood pressure
Study of a large group of 17-18 years old teenagers
(756 males and 705 females)
50
Systolic BP
Diastolic BP
120
Hematocrit
45
110
100
40
90
80
35
70
30
60
25
50
40
20
Males
Females
Males
Females
Number of teenagers with elevated blood
pressure (above 140/85 mm Hg)
Number of students
800
765
705
700
600
500
400
300
200
100
53
4
0
Males
Females
Number of teenagers with elevated hematocrit
(Ht>50%) in the hypertensive groups
Number of students
60
53
50
50
40
30
20
4
10
0
Males
1
Females
Effect of hematocrit on blood viscosity
20% difference in Ht causes ~90% and ~40% difference in low and high
shear viscosity
100
Ht=40%
Viscosity (cP)
80
Ht=48%
60
40
20
0
0.01
0.1
1
10
Shear rate (1/s)
100
1000
Fåhraeus and Fåhraeus-Lindquist effects
Reduction of RBC concentration and apparent viscosity in microvessels
(less than 0.5 mm diameter) due to development of the near-wall cell free
layer and “plasma skimming” effect. The plasma layer increases the
resistance for O2 diffusion and decreases vessel wall shear stresses.
120
Pressure, mmHg
100
80
60
40
20
0
Aorta
Large
arteries and
braches
Small
arteries
Arterioles
Capillaries
RBC age distribution in male and female blood
60
Young RBCs
Middle age RBCs
Old RBCs
50
Percent
40
30
20
10
0
Males
Females
The picture is based on data published by Micheli et al. , 1984
Whole blood
Centrifuged
Centrifuged
Young RBCs
Plasma
RBCs
RBCs
Old RBCs
Mechanical properties of old and young red blood cells
"Young" RBCs
"Old" RBCs
p<0.001
200
p<0.001
180
160
Difference (%)
p<0.05
140
120
p<0.05
100
80
60
40
20
0
RBC
Deformability
RBC
Sedimentation
Rate
Low
Shear
Viscosity
RBC
Mechanical
Fragility
Rheological parameters in male and premenopausal
female blood
Women
n=47
Men
n=50
Level of
statistical
significance
Age, years
25.7±4.8
26.2±5.1
n.s.
Hematocrit, %
40.0±2.4
45.8±2.7
p<0.001
Plasma viscosity, cP
1.73±0.09
1.74±0.08
n.s.
Low shear blood viscosity (0.277 s-1), cP
Original hematocrit
35.2±4.8
55.4±11.1
p<0.001
Low shear blood viscosity (0.277 s-1), cP
Standard hematocrit Ht=40%
35.59±3.73
41.7±4.3
p<0.001
4.8±0.4
5.9±0.5
p<0.001
8.4±3.1
10.8±4.1
p=0.002
Asymptotic Blood Viscosity, cP
Original hematocrit
Erythrocyte sedimentation rate, mm/hr
Standard hematocrit Ht=40%
Difference in male (red) and female (green) hemorheological parameters
110
100
p<0.001
p<0.001
RBC deformability, %
Hematocrit, %
50
45
40
35
30
25
20
15
10
5
0
60
50
40
30
20
10
0
80
70
60
14
p<0.005
12
ESR (mm/hr)
RBC aggregation,
difference (%)
70
90
50
90
80
100
10
8
6
4
2
0
p<0.01
Oxygen Delivery Index (hematocrit/blood viscosity )
Oxygen Delivery Index
10
9
8
7
6
5
p<0.001
Male blood
Female blood
Oxygen Delivery Index vs.Viscosity
Viscosity, cP; ODI
10
9
8
7
6
5
Viscosity
4
ODI
3
2
15
20
25
30
35
40
Hematocrit, %
45
50
55
Asymptotic blood viscosity and oxygen delivery index
(ODI) vs. hematocrit for pre-menopausal women
(n=47) and age-matched men (n=50)
Blood viscosity (cP); ODI
10
9
8
7
6
5
Viscosity (women)
ODI (women)
Viscosity (men)
ODI (men)
4
3
35
40
45
Hematocrit, %
50
55
Oxygen Delivery Index in premenopausal women,
men and cardiac patients
ODI
Oxygen Delivery Index
9.0
8.0
7.0
6.0
5.0
Females (n=47)
Males (n=50)
Cardiac patients
(n=15)
Summary
• Male blood has higher viscosity due to higher
hematocrit and RBC aggregation and lower RBC
deformability
• Men possess a higher number of old RBCs and a
fewer number of young RBCs than premenopausal
women
• Old RBCs demonstrate an increased ability to
aggregate and decreased deformability as
compared to young RBCs
• Oxygen delivery index is significantly lower
(p<0.001) for male blood than for blood of premenopausal females
Summary (cont.)
• Increased blood viscosity and aggregability of
RBCs and decreased deformability of RBCs are
known risk factors of cardiovascular diseases.
• The difference in the mechanical properties of
male and female blood places men at higher risk
of cardiovascular diseases than pre-menopausal
women
• Blood donation or regular, small phlebotomy
might help to improve rheological properties of
blood and reduce the risk of cardiovascular
diseases in men and post-menopausal women
RBC aggregation promotes a formation of the near-wall plasma layer in
microvessels reducing wall shear stresses, shear-induced vasodilation and
intracapillary hematocrit.
Due to exercises, increased blood flow decreases RBC aggregation and, thus,
reduces the near wall plasma layer and plasma skimming at bifurcations. This
leads to an increase in wall shear stresses, vasodilation, number of functioning
capillaries, and concentration of RBCs in capillaries enhancing delivery of O2
and removal of metabolites.
tw
tw
Effect of exercises on RBC aggregation and microcirculation
References
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Micheli V, Taddeo A, Vanni AL, Pecciarini L, Massone M and Ricci MG. Distribuzione
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Kameneva MV and Timofeev VF. Increased hematocrit as a risk factor for arterial
hypertension. Cardiologiya 10 (1986), 105–106.
Lowe GDO, editor. Clinical Blood Rheology. CRC Press, Boca Raton, Florida, 1988.
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risk of cardiovascular diseases. Clinical Hemorheology and Microcirculation,
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Thank you!