Rheology For Clinicians
Rheology For Clinicians
Rheology For Clinicians
Introduction
The physiology and pathophysiology of the cardiovascular system are taught and integrated into clinical reasoning (diagnosis and therapy). The relevance of the present day teaching strategy in this domain can be questioned
because there is little teaching on the microvasculature and even less on
blood rheology. One example to illustrate these assertions is the cristalloids
versus colloids controversy for resuscitation of critically ill patients (1-3).
The question being asked is whether there is a benefit (in terms of improved survival) for colloids versus cristalloids when resuscitating a variety of
critical illnesses such as hemorrhagic or septic shock. The answer to this
question, for the moment is no (1-3) but the explanations to this lack of
measurable effect are not clear.
Part of the difficulty to find explanations arises from the fact that the
physiology, pathophysiology, as well as monitoring of microcirculation and
especially rheology are not well known by the clinicians. The goal of this
article is to present and explain several features of the physiology and pathophysiology of blood rheology. We will focus in this article on only two
mechanisms of shock: hemorrhagic and septic.
Department of Anesthesia and Intensive Care, Hpital Bichat-Claude Bernard 46, rue
Henri Huchard, 75877 Paris Cedex 18; Laboratoire INSERM U698, Universit Ren
Descartes, Paris VII, France
Department of Anesthesia and Intensive Care, Hpital Brabois-Adultes, 4, rue du
Morvan 54500 Vandoeuvre-les-Nancy, France
Laboratoire dingenierie cellulaire et tissulaire, physiologie et pharmacologie articulaires UMR 7561, Universit Henri Poincar-Nancy 1, France
Address correspondence to: Professor Dan Longrois, Department of Anesthesia and Intensive Care, Hpital Bichat-Claude Bernard, 46, rue Henri Huchard, 75877 Paris Cedex
18, France, e-mail: dan. [email protected]
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The sequential goals of resuscitation in hemorrhagic shock are (i) restoration of circulating volume (and consequently of cardiac output and arterial
pressure); (ii) restoration of microvascular perfusion and oxygen supply to
vital organs; (iii) to prevent or correct end organ damage due to cardiac
output redistribution (to protect the heart and the brain at the expense of
splanchnic organs such as the liver or the kidney as well as other territories
such as skeletal muscles or skin).
Despite controversy concerning the best diagnostic tools to assert restoration of the circulating blood volume and the critical level of hemoglobin,
these goals are fairly well integrated into clinical practice. On the contrary,
restoration of microvascular perfusion and oxygen supply to vital organs is
a more difficult task.
A model of micro-circulation
Organ and tissue blood flow is controlled by the vascular tone of resistance
vessels (small arteries and arterioles) that modify their diameter thus regulating flow as well as by the pressure drop across the microvascular bed (4).
Downstream from the resistance vessels, flow is passively distributed within
the capillary network (4). Two main factors control flow in the capillary
network: the resistance (in its turn the result of the interaction between
diameter and length) and rheology (that mainly depends on whole blood
and plasma viscosity as well as red blood cells or RBC deformability). In the
capillaries, RBC flow single line and must undergo deformation in order to
progress through capillaries with smaller diameters. It was proposed that
the most important factor accounting for capillary heterogeneity are the
rheological properties of blood (4). This model of microcirculation has several characteristics among which the fact that there is integration to ensure
that oxygen delivery meets oxygen demand. The mechanisms responsible for
this integration are complex and it has been suggested that the endothelial cells, by way of intercellular communications, could represent a major
integrator (4). The second integrator could be the RBCs themselves. It has
been suggested that RBCs could release ATP and nitrosothiols in response to
increased PO2 gradients and mechanical deformation (4,5). Decreased RBC
deformability (a method-dependent measurement )(6) could be due to decreases of membrane viscosity, or, more probably, to increased RBC shear
elastic modulus, as a result of oxidative damage, increased cytosolic calcium
triggering changes of RBC membrane skeletal proteins (6). Decreased RBC
deformability, probably potentiated by decreased white blood cells deforRecomandri i Protocoale n Anestezie, Terapie Intensiv i Medicin de Urgen
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animals total blood flow was maintained, but capillary flow distribution was
varied from 60/30/10% (normal/fast/stopped) in control to 33/33/33% (normal/fast/stopped) in average sepsis and 25/25/50% (normal/fast/stopped)
in extreme sepsis (28). Using a sophisticated mathematical model, the same
authors found approximately two- and fourfold increases in tissue VO2 in
average and extreme sepsis, respectively. Average (minimum) tissue oxygen
tension (PtiO2) decreased from 43 (40) mmHg in control to 34 (27) and 26
(15) mmHg in average and extreme sepsis, respectively, and clustering fastflow capillaries (increased flow heterogeneity) reduced minimum PtiO2 to
14.5 mmHg. The mechanisms responsible for stopped-flow in the capillaries
could be activation and structural changes of endothelial cells, activation of
coagulation, activation of leukocytes, decreased deformability of RBC and
possibly microthrombi (4). There are two additional changes in the microcirculation of septic animals, as compared to shams: (i) the population of
continuously perfused vessels is characterized by a greater proportion of
capillaries with high velocities (27); (ii) there are many capillaries with intermittent flow and large low-frequency flow reversals (oscillations about
zero velocity)(27).
There are many arguments that support the hypothesis that alteration
of tissue O2ER is mainly, and at least initially, the result of maldistribution
of O2 delivery and not of inability to utilize O2 (27). It has been proposed
that maldistribution of microvascular blood flow leads to a mismatching
of O2 supply and demand, analogous to the mismatching of ventilation and
perfusion in the lung (27). It has been suggested that the degree of stopped capillary flow could be considered as one index of the microvascular
dysfunction (27).
One important issue raised by the observations concerning the relationship between capillary heterogeneity and impaired O2ER concerns the mechanisms of this alteration. Indeed, the expected response to a fall in RBC
haemoglobin saturation (SO2) values in the normal-velocity capillaries would be diverting excess flow to these vessels to increase their O2 supply and
thus compensate for the loss of perfused capillaries. The presence of low
SO2 levels in capillaries suggests that in septic animals, the microvasculature is unable to properly redistribute O2 delivery in response to the local
metabolic requirements of the tissue. This inability to redistribute flow has
been attributed to alteration of the communications between capillaries
and arterioles as well as to alterations of the vasoreactivity of arterioles. It
is probable that alteration of arteriolar vasoreactivity could be that main
factor accounting for the inability to redistribute flow to capillaries with
low SO2 levels. The altered arteriolar vasoreactivity could explain the obserTimioara 2010
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