Translational Research: Multi-Scale Models of the Pulmonary Circulation in Health and Disease - Multiscale Computer Modeling in Biomechanics and Biomedical Engineering - page 266

80-100 m 2 . The pulmonary capillary network forms a far denser mesh than that
found in the systemic microcirculation. Pulmonary capillaries are, on average,
shorter in length and smaller in diameter than their systemic counterpart and
because of this cellular transit through the circulations differs. Measurements of
pulmonary capillary morphometry have found a range of internal diameters from 1
to 15 lm, with an average of around 8 lm[ 1 ]. The density of pulmonary capil-
laries led in early studies to the approximation that blood flows as a sheet through
interconnected posts of connective tissue [ 60 ]. Later studies, using higher reso-
lution imaging techniques, demonstrated that pulmonary capillary blood does in
fact flow through discrete tubules [ 61 ], however the sheet-flow concept is still used
as a simplification in computational modeling studies (see below) and it remains a
physiologically meaningful description of the pulmonary microcirculation.
The gas exchange barrier separating alveolar gas from capillary blood has a
thickness of only around 0.1-0.3 lm. The passive diffusion capacity (gases
diffusing down a partial pressure gradient) correlates directly with the surface area
of contact and inversely with the thickness of the diffusion membrane. The
structure of this tissue barrier has been optimized to enable a thin enough layer for
adequate gas exchange while enabling structural integrity to be maintained over a
range of intravascular pressures. However, because of the fine balance of this
system the pulmonary capillaries are very sensitive to excessive increases in
pulmonary blood pressure. If capillary transmural pressure exceeds a critical limit
(around 24 mmHg) the blood-gas barrier may begin to rupture resulting in fluid
leakage into the alveolar units. This fluid accumulation (edema) is believed to
reduce the capacity for gas exchange by increasing the thickness of the diffusion
barrier within the lung [ 62 ].
In large blood vessels blood can be assumed to flow as a Newtonian fluid. That
is, while the viscosity of blood is shear-rate dependent (and hematocrit-dependent)
the relatively large fluid velocities in the largest vessels prevent formation of cel-
lular aggregates that would markedly change the blood viscosity, and hence vis-
cosity can be assumed constant. In contrast, in vessels less than approximately
300 lm in diameter the non-Newtonian properties of blood can no longer be
neglected. Red blood cells (RBCs) tend to preferentially migrate to the center of
small vessels and travel through at a faster rate than the rest of the blood at the
vessel periphery. This results in a decrease in RBC concentration and a dynamic
reduction in the apparent viscosity of blood whereby apparent viscosity decreases
with decreasing vessel diameter. These phenomena are known as the Fahraeus and
Fahraeus-Lindqvist effects, respectively [ 63 ], and are one of the key differences in
modeling macro- and micro-circulatory flow behavior. Another important aspect
when discussing cellular transport within the pulmonary capillaries is the transit of
neutrophils. Neutrophils are the most abundant white blood cell (WBC) in the body
and play an important role in immune response. Under normal conditions the
concentration of neutrophils in the lung is between 40 and 80 times higher than that
found in the systemic circulation [ 64 ]. This phenomenon is known as neutrophil
margination and is due to the relative size (6.8-8.3 lm[ 65 ]) and stiffness of
neutrophils in comparison to the capillaries through which they transit (typical