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-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.
Blood constituents
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) RBCsNormal (deformable) RBCs
Roggenkamp, et al., 1986Dr. Max Hardeman, with permission
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 Ratio of male to female mortality due to myocardial infarction, IHD, and cancer (Vital Statistics of the US) infarction, IHD, and cancer (Vital Statistics of the US)
0.0
1.0
2.0
3.0
4.0
5.0
6.0
7.0
10 20 30 40 50 60 70Age, years
Rat
io o
f m
orta
lity
Myocardial Infarction
IHD
Cancer
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)
20
25
30
35
40
45
50
Males Females
Hematocrit
40
50
60
70
80
90
100
110
120
Males Females
Systolic BPDiastolic BP
Number of teenagers with elevated blood Number of teenagers with elevated blood pressure (above 140/85 mm Hg)pressure (above 140/85 mm Hg)
765
53
705
40
100
200
300
400
500
600
700
800
Num
ber o
f stu
dent
s
MalesMales FemalesFemales
Number of teenagers with elevated hematocrit Number of teenagers with elevated hematocrit (Ht>50%) in the hypertensive groups(Ht>50%) in the hypertensive groups
53 50
4 10
10
20
30
40
50
60
Num
ber
of s
tude
nts
MalesMales FemalesFemales
Effect of hematocrit on blood viscosity20% difference in Ht causes ~90% and ~40% difference in low and
high shear viscosity
0
20
40
60
80
100
0.01 0.1 1 10 100 1000
Shear rate (1/s)
Vis
cosi
ty (
cP)
Ht=40%
Ht=48%
Fåhraeus and Fåhraeus-Lindquist effectsReduction 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.
0
20
40
60
80
100
120
Pres
sure
, mm
Hg
Aorta Arterioles CapillariesLarge
arteries and braches
Small arteries
RBC age distribution in male and female bloodRBC age distribution in male and female blood
0
10
20
30
40
50
60
Perc
ent
Young RBCs Middle age RBCs Old RBCs
MalesMales FemalesFemales
The picture is based on data published by Micheli et al. , 1984The picture is based on data published by Micheli et al. , 1984
Whole Whole bloodblood
CentrifugedCentrifuged
RBCsRBCs
Young RBCsYoung RBCs
Old RBCsOld RBCs
RBCsRBCs
PlasmPlasmaa
CentrifugedCentrifuged
0
20
40
60
80
100
120
140
160
180
200
"Young" RBCs "Old" RBCs
RBCRBCDeformabilityDeformability
RBCRBCSedimentationSedimentation
RateRate
Low Low ShearShear
ViscosityViscosity
RBCRBCMechanicalMechanical
FragilityFragility
p<0.05
p<0.001
p<0.05
p<0.001
Dif
fere
nce
(%
)
Mechanical properties of old and young red blood cellsMechanical properties of old and young red blood cells
Rheological parameters in male and premenopausal Rheological parameters in male and premenopausal female bloodfemale 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
Asymptotic Blood Viscosity, cP
Original hematocrit
4.8±0.4 5.9±0.5 p<0.001
Erythrocyte sedimentation rate, mm/hr Standard hematocrit Ht=40%
8.4±3.1
10.8±4.1
p=0.002
05
101520253035404550
Hem
atoc
rit,
%Difference in male (red) and female (green) hemorheological paraDifference in male (red) and female (green) hemorheological parametersmeters
p<0.001
50
60
70
80
90
100
110
RBC
def
orm
abili
ty, %
p<0.001
0
10
20
30
40
50
60
70
80
90
100
RB
C a
ggre
gatio
n,
diffe
renc
e (%
)
p<0.005
0
2
4
6
8
10
12
14
ESR
(mm
/hr)
p<0.01
Oxygen Delivery Index (hematocrit/blood viscosity )Oxygen Delivery Index (hematocrit/blood viscosity )
5
6
7
8
9
10
Male bloodFemale blood
p<0.001
Oxy
gen
Del
iver
y In
dex
Oxygen Delivery Index vs.Viscosity
2
3
4
5
6
7
8
9
10
15 20 25 30 35 40 45 50 55
Hematocrit, %
Vis
cosi
ty,
cP;
OD
I
Viscosity
ODI
3
4
5
6
7
8
9
10
35 40 45 50 55
Hematocrit, %
Blo
od v
isco
sity
(cP
); O
DI
Viscosity (women)ODI (women)Viscosity (men)ODI (men)
Asymptotic blood viscosity and oxygen delivery index Asymptotic blood viscosity and oxygen delivery index (ODI) vs. hematocrit for pre-menopausal women (ODI) vs. hematocrit for pre-menopausal women
(n=47) and age-matched men(n=47) and age-matched men (n= (n=50) 50)
ODI
5.0
6.0
7.0
8.0
9.0
Females (n=47) Males (n=50) Cardiac patients(n=15)
Ox
yg
en
De
live
ry In
de
xOxygen Delivery Index in premenopausal women,
men and cardiac patients
SummarySummary• Male blood has higher viscosity due to higher Male blood has higher viscosity due to higher
hematocrit and RBC aggregation and lower RBC hematocrit and RBC aggregation and lower RBC deformability deformability
• Men possess a higher number of old RBCs and a Men possess a higher number of old RBCs and a fewer number of young RBCs than premenopausal fewer number of young RBCs than premenopausal womenwomen
• Old RBCs demonstrate an increased ability to Old RBCs demonstrate an increased ability to aggregate and decreased deformability as aggregate and decreased deformability as compared to young RBCscompared to young RBCs
• Oxygen delivery index is significantly lower Oxygen delivery index is significantly lower (p<0.001) for male blood than for blood of pre-(p<0.001) for male blood than for blood of pre-menopausal femalesmenopausal females
• Increased blood viscosity and aggregability of Increased blood viscosity and aggregability of RBCs and decreased deformability of RBCs are RBCs and decreased deformability of RBCs are known risk factors of cardiovascular diseases.known risk factors of cardiovascular diseases.
• The difference in the mechanical properties of The difference in the mechanical properties of male and female blood places men at higher risk male and female blood places men at higher risk of cardiovascular diseases than pre-menopausal of cardiovascular diseases than pre-menopausal womenwomen
• Blood donation or regular, small phlebotomy Blood donation or regular, small phlebotomy might help to improve rheological properties of might help to improve rheological properties of blood and reduce the risk of cardiovascular blood and reduce the risk of cardiovascular diseases in men and post-menopausal womendiseases in men and post-menopausal women
Summary (cont.)Summary (cont.)
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.
w w
Effect of exercises on RBC aggregation and microcirculation
References• Micheli V, Taddeo A, Vanni AL, Pecciarini L, Massone M and Ricci MG. Distribuzione
in gradiente di densita’ degli eritrociti umani: differenze lagate al sesso, Boll. Soc. Italiana Biol. Speriment. LX(3) (1984), 665–671.
• 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.• Vital Statistics of the United States 1990, Vol. 2, Mortality, U.S. Department of Health
and Human Services, Hyattsville, MD, 1994.• Kameneva MV. Effect of hematocrit on the development and consequences of some
hemodynamic disorders. In: "Contemporary Problems of Biomechanics," GG Chernyi and SA Regirer, (eds.). Mir. Publ., Moscow, USSR, CRC Press, Boca Raton, 1990, 111-26.
• Meyers DC, Strickland D, Maloley PA, Seburg JJ, Wilson JE and McManus BF. Possible association of a reduction in cardiovascular events with blood donation, Heart 78(2) (1997), 188–193.
• Kameneva MV, Garrett KO, Watach MJ, and Borovetz HS. Red blood cell aging and risk of cardiovascular diseases. Clinical Hemorheology and Microcirculation, 18(1):67-74, 1998.
• Kameneva MV, Watach MJ, and Borovetz HS. Gender difference in rheologic properties of blood and risk of cardiovascular diseases. Clinical Hemorheology and Microcirculation, 21(3-4):357-363, 1999.
• Kameneva MV, Watach MJ, and Borovetz HS. Rheologic dissimilarities in female and male blood: potential link to development of cardiovascular diseases. In: Advances in Experimental Medicine & Biology. Oxygen Transport to Tissue XXIV. JF Dunn and HM Swartz (Eds.), Kluwer Academic/Plenum Publisher, New York, 2003, vol. 530, pp 689-696.
Thank you!