Transcript Microcirculation

Microcirculation
(The middle ground.)
The 'scale' of the microcirculation
 Larger than cells
and individual
elements (e.g.
Krogh tissue
cylinder).
 Smaller than
organs
What it looks like …
HUMAN ANATOMY, 3rd. ed., Martini et al., Fig. 22-4, p.567
Microcirculation Issues
What is it (structure, mechanism)?
What are its important functions?
How does it arise, develop, adjust, and
repair?
What we think it does:
Supports metabolism of tissues.
Maintains 'appropriate' hydrostatic/oncotic
pressure balance.
Both of these are transport functions that are
either, or both:
 Gravimetric – transport of substances
necessary for material/energy functions
 Informatic – transport of materials that carry
information.
Transport Issues – Diffusive Movement
 Intravascular – unimportant at capillary level.
Skalak R,, Bra°nemark P-I. 1969. Deformation of red blood cells in
capillaries. Science 164:717–19.
Copyright [1969] American Association for the Advancement of Science.)
Skalak's early calculation of RBC shape
in capillaries
Vascular wall
 Principal discriminant of what passes.
Differs from tissue to tissue (e.g. Bloodbrain barrier). Trans-cellular movement,
movement at 'tight junctions'.
Extravascular space
 Deterministic models in 'organized'
tissues, e.g. Krogh cylinder applied to
muscle.
 What is the functional extravascular
space? Which capillaries are open and
what is the rate of flow through them?
And what to do in 'disorganized' structures?
Transport Issues – Convective Movement
 Starling-Landis hypothesis.
 Overall balance between oncotic and
hydrostatic pressure.
Excess of hydrostatic over oncotic pressure
at arteriolar end causes outflow.
Excess of oncotic over hydrostatic pressure
at venous end causes (return) inflow.
Extra-capillary flow 'washes' tissue and
augments diffusive transport.
Starling-Landis components
Starling-Landis "In action"
Good discussion and slides:
http://141.106.8.23/medphy/chout/Lectures/Lecture20&21.pdf
Starling-Landis models:
 Models "work" but have not been
clinically useful because their parameters
are hard to determine for individual
patients and pathologies:
Capillary pressure and gradient
Tissue pressure
Tissue oncotic pressures
How does the microcirculation develop?
The microcirculation is a stochastic* structure that is
difficult to parameterize. Some kind of abstracting
model with distributions and defined parameters is
always needed to describe its development.
In some tissues the stochasticity is limited and
deterministic models help. In others?
* a process involving a randomly determined sequence of observations
each of which is considered as a sample of one element from a
probability distribution.
Types of models (R. Thomas)
What models permit observed behavior?
What models impose observed behavior?
What interactions and constraints are
common to all models?
What are the simplest modifications of an
existing model to conform it to new facts?
Stochastic aspects of the microcirculation
 Anatomy
Spatio-temporal variability
Regulation
The WBC anomaly
 Consequences of stochasticity in
anatomy and spatio-temporal behavior
Flow
Transport (convective and diffusive)
Fractal Model of Anatomy
Branching Models
Effect of branching on flow (predicted)
Measured regional flow distributions
Flow distribution is fractal?
How does this tissue develop?
 ab initio?
 in response to activity and development
of surrounding tissue? [W. Schreiner]
 in response to injury?
Will Genomic Approaches Help?
 Classical physiology proceeds by induction:
conclusions, though supported by the premises,
do not necessary follow from them.
 Genomics-driven physiology proceeds (tries to
proceed) by deduction: conclusions follow
necessarily from the premises presented so that
the conclusions cannot be false if the premises
are true.
What could happen
when the
microcirculation
becomes disturbed
in different places?
Happy Easter!