Indian Institute of Technology Kharagpur, India Indian Institute of Technology Kharagpur, India - - 721302 721302

Science of Living Systems:

Science of Living Systems:

Bio
Bio
-
-
Thermal
Thermal
-
-
Fluid Sciences
Fluid Sciences
Lecture By
Prof.
Prof.
Suman
Suman

Chakraborty
Chakraborty
Department of Mechanical Engineering
Autumn 2010
Indian Institute of Technology Kharagpur, India Indian Institute of Technology Kharagpur, India - - 721302 721302
Major Differences in Transport Phenomena in
Major Differences in Transport Phenomena in
Engineering and Physiology
Engineering and Physiology
Wide Range of Reynolds Number:
Majority of flow in physiological system is laminar
High and low Reynolds Number Laminar regime
High Re: Large Arteries

and airways in lungs
Low Re: Small capillaries and Interstitial Flow
There are localized bursts of turbulence as well
Artery
Interstitial Flow (IF)
Blood vessels that carry blood away from the heart
into the tissue. This blood is normally oxygenated.
Percolating fluid flow through a 3D tissue spaces,
around embedded cells. IF drains out of blood vessels.
Interstitial Flow
Local Vortices in Bifurcation
Glossary
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Hierarchy of Blood Vessels
Hierarchy of Blood Vessels
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Unusual Multiplicity of Tube Branching

The branched
networks of tubes from the cardiovascular system

and
lungs are extremely intricate and complex.
Unusual Wall Properties of Containing Vessels

Networks of vessels containing blood flow and air flows
exhibit complicated distensibility. Walls of arteries are
complicated by viscoelasticity

and non-linear features.
Major Differences
Major Differences

.
.
Cardiovascular System
Viscoelasticity
Glossary
The circulatory system which includes the heart and the blood vessels and is
responsible for the transport of blood, dissolved oxygen, nutrient, metabolic
wastes throughout the body
Property of materials that exhibit both viscous (fluid) and elastic (solid)
characteristics when undergoing deformation
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Major Differences
Major Differences

.
.
Unusual Fluid Properties
Whole blood contains a suspension of 40-50% by
volume (hematocrit) of deformable bodies (mainly red
blood cells or RBCs) in a transparent plasma.
While the plasma obeys Newtonian behavior, the
whole blood is described by an effective viscosity
which increases substantially with decreasing rate of
strain due to increased formation of RBC aggregates
Air inhaled into lung is also a suspension of dust
particles which deposit at different levels in the
bronchial tree

depending upon particle size
Bronchial Tree
Blood Plasma
Bronchial Tree
Glossary
Blood plasma is the yellow liquid component of blood in which the blood cells
in whole blood are normally suspended. It makes up about 55% of the total
blood volume.
The branching of the bronchi (airway passages) of the lung, considered as a
structural and functional unit and designed to spread air over wide area.
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Major Differences
Major Differences

.
.
Unusual Pulsatility
Pulmonary

inspiration and expiration cause regular flow reversal in the
respiratory system
In the circulatory system, however, the arterial blood flow exhibits a
pulsatile characteristics
Attenuation of the pulse waves, due to deformable vessel walls, makes
such pulsatility

less important in microcirculation

and veins
Pulmonary
Microcirculation
Glossary
Related to lungs
Describes the small vessels in the vasculature which are embedded within
organs and are responsible for the distribution of blood within tissues; as
opposed to larger vessels in the macrocirculation

which transport blood to and
from the organs.
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Major Differences
Major Differences

.
.
Unusually Low Conduction of Heat Flux
In human body, maximum temperature is around
37C in the core region while minimum
temperature is around 34C at extremities
The temperature gradient is 0.1C/cm
Thermal conductivity of tissue is quite low ~ 0.06
W/m.K
The conduction heat flux ( ) ~ 0.06 W/m
2

is
low to disperse the BMR (Basal Metabolic Rate

~
72 kcal/hour) over our body surface area of 1.8 m
2

(for a normal 70kg adult)
T k q V
' '
~
Basal Metabolic Rate
Glossary
The minimum calorific requirement needed to sustain life in a resting
individual. It is the amount of energy expended while at rest in

a neutrally
temperate environment, in the post-absorptive state (i.e. the digestive system is
inactive, which requires about twelve hours of fasting in humans)
Indian Institute of Technology Kharagpur, India Indian Institute of Technology Kharagpur, India - - 721302 721302
Major Differences
Major Differences

.
.
Unusual Blood Cooling
When blood flows through tissues or organs, it functions not only as a carrier of nutrients
and metabolic

wastes but also as a coolant to remove the heat produced by metabolism
Blood gains heat which is transferred by circulation to the skin

where it is dissipated to the
environment
For maintaining body core temperature in the normal range, the blood transfusion cooling is
vital, because of the poor conduction flux
The blood cooling rate per unit volume may be estimated as
The unusual feature of blood cooling is the variability range of

cooling rate with mass flow

mass can be regulated by the vasomotor activity

of tissue vessels
For example, vasoconstriction

decreases the mass flux while vasodilation

increases it
( )
tissue blood arterial
~ T T C m q
p b vol

Metabolism
Glossary
Vasomotor
Vasoconstriction/dilation
The chemical processes occurring within a living cell or organism that are
necessary for the maintenance of life.
Vasomotor refers to actions upon a blood vessel which alter its diameter.
Vasoconstriction is the narrowing of the blood vessels resulting

from
contraction of the muscular wall of the vessels, particularly the large arteries,
small arterioles and veins. Vasodilation

refers to the widening of blood vessels
resulting from relaxation of smooth muscle cells within the vessel walls.
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Major Differences
Major Differences

.
.
Unusual Thermoregulatory Mechanisms
Skin Temperature (T
s

) is one of the most important factors in the regulation
of body temperature and it varies with a change in the environmental
conditions.
For a resting person in thermally steady state, metabolic heat generation
balances the heat loss by convection and radiation
However for sudden change in ambient temperature (T
amb

), T
s

and T
core

change, activating peripheral and central thermoreceptors

respectively.
Signals from thermoreceptors

are integrated by the thermorgulator

centers
(mainly located in Hypothalamus), which trigger the necessary regulatory
mechanisms.
The control mechanisms include
Vasomotor Systems (induce either vasodilation

or vasoconstriction)
Active regulation: sweating for T
amb

>T
s

and cold induced metabolic
heat generation (including shivering and non-shivering) for T
amb

<T
s
Thermoreceptor
Hypothalamus
Glossary
A thermoreceptor

is a sensory receptor, or more accurately the receptive
portion of a sensory neuron, that codes absolute and relative changes in
temperature.
Hypothalamus is an area of the brain that produces hormones that

control
body temperature, hunger, moods etc.
Indian Institute of Technology Kharagpur, India Indian Institute of Technology Kharagpur, India - - 721302 721302
Major Differences
Major Differences

.
.
Unusual Thermal Properties
Tissue thermal properties
are inhomogeneous,
anisotropic and age
dependent
Unusual Range of System
Size for Heat Transfer
Ranges from microheat

transfer in cellular scale

to
macro heat transfer on
system scales
Tissue

Organized
Cluster of Cells
Hierarchical Organization
of Life
Inner Architecture of a
Typical Animal Cell
Cellular Scale
Glossary
Typical length scale of an animal cell is 5-10 m. Mass Transport processes at
this scale is dominated by diffusion while heat transfer is dictated by the
enhanced surface area to volume ratio which scales as the inverse of the
characteristic length scale
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Blood Rheology
Blood Rheology

Blood Properties
Blood Properties
Human Plasma is transparent, slightly yellowish with

= 1.035
g/ml
It contains a solution of plasma proteins is an aqueous
medium
Proteins contain about 7% of total plasma volume and can be
classified into three major groups

Albumin, Globulin and
Fibrinogen
Plasma also contains emulsified fats (or lipids), cholesterol,
free fatty acids, hormones (adrenalin), dissolved O
2

, dissolved
CO
2
Whole blood consists of a suspension of RBCs

(erythrocytes),
WBCs

(White Blood Cells or Leukocytes) and Platlets

in an
aqueous solution
RBC count is approximately 5 million/mm
3

40-45% by
volume of whole blood Hematocrit
Typical dimensions of RBC 7.8 m in diameter (Biconcave
Disc), 2 m thick and 88 m
3

in volume
Function Transport of Oxygen
Less number of RBC Anaemia
Indian Institute of Technology Kharagpur, India Indian Institute of Technology Kharagpur, India - - 721302 721302
Blood Properties
Blood Properties

.
.
Size of WBC varies from 16-22 m for
monocytes

to 6-12 m for lymphocytes and
granulocytes
WBC protects body from disease
Normal WBC:RBC concentration = 1:1000
Abnormal rise in WBC number ~ Leukemia
Platelets are smaller than RBC and WBC:
Diameter ~ 2-3 m
Platelet : RBC = 1 : 10 (number
concentration)
Platelets and WBCs

are actively ordinarily
not enough to influence the flow
characteristics
However, platelets play important role in
forming blood clots that may severely
interfere with flow
RBC
WBC
Platlets
Indian Institute of Technology Kharagpur, India Indian Institute of Technology Kharagpur, India - - 721302 721302
Standard Rheological Behaviors
Standard Rheological Behaviors
Bingham Plastic
( ) t t

B
+ =
0
Newtonian ( ) t

=
Power law
( ) 1 ; < = n
n
t

Power law
( ) 1 ; > = n
n
t

t

Stress
Strain Rate
= Viscosity
Apparent Viscosity (
app

):

=
app
Indian Institute of Technology Kharagpur, India Indian Institute of Technology Kharagpur, India - - 721302 721302
Blood Properties
Blood Properties

Unusual Hydrodynamics
Unusual Hydrodynamics
Fahraeus

Lindquist Effect: Tendency of blood cells to move away
from the wall
At wall, they leave a layer of low viscosity
The effect is more pronounced for reduced capillary diameter (d)
Hence, apparent viscosity decreases with the reduction in capillary
diameter
Apparent Viscosity increases with increasing volume percentage of
RBC (Hematorcrit)
Indian Institute of Technology Kharagpur, India Indian Institute of Technology Kharagpur, India - - 721302 721302
Unusual Hydrodynamics
Unusual Hydrodynamics

. Disease
. Disease
Shape of RBC changes with flow
rate
At abnormally high flow rate and
in constricted region of
circulatory system, RBCs

may
deform and burst
Change in effective/apparent viscosity with volume
percentage of RBC (also Packed Cell Volume or
PCV) is manifested in several diseases like Anaemia

or Polycythaemia
Anaemia: A decrease in normal number of red blood
cells (RBCs) or less than the normal quantity of
hemoglobin in the blood.
Polycythaemia: A disease state in which the
proportion of blood volume that is occupied by red
blood cells i.e. hematocrit

increases.
Indian Institute of Technology Kharagpur, India Indian Institute of Technology Kharagpur, India - - 721302 721302
Blood Properties
Blood Properties

Unusual Rheology
Unusual Rheology
Often Represented by a Pseudoplastic

behavior (apparent viscosity
decreases with increasing shear rate)
Blood is also sometimes modeled as a Bingham plastic fluid with
0
~
0.1 dyn/cm
2
However, the deviation from this model may be significant, typically at
low shear rates
Casson

model is an empirically modified Bingham plastic model to
give a better fit to measured
app

data for lower shear rates. As per the
model
0
t t + =

c
k
Cassons Viscosity
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Lump Parameter Modeling of Compartmental
Lump Parameter Modeling of Compartmental
System with Flow Regulation
System with Flow Regulation
Compartment = An organ or tissue
Q Volumetric Flow Rate
C Concentration
V Volume
m Mass = CV
V
C(t)
Q
C
i

(t)
Q
C
e

(t)
Control Volume (CV)
e i CV
m m
dt
dm

= ( )
e i
QC QC V C
dt
d
=
Note Note
i. V = Const. (Const. volume of organ) i. V = Const. (Const. volume of organ)
ii. ii. C C
e e

= = C(t C(t) ) QC QC
e e

= = QC(t QC(t) )
( ) 0 ) 0 ( condition initial with ) (
) (
= = C t C C Q
dt
t dC
V
i
( )
t Compartmen the of Constant Time /
1 ) ( : soln.
/
Q V
e C t C
t
i
=
=

t
t
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Compartmental Systems in Parallel and Series
Compartmental Systems in Parallel and Series
V
1
C
1

(t)
V
2
C
2

(t)
Q
C
i

(t)
Q
C
e

(t)
Q
1

, C
i1

(t) Q
1

, C
e1

(t)
Q
2

, C
i2

(t)
Q
2

, C
e2

(t)
( ) ) (
) (
1 1 1
1
1
t C C Q
dt
t dC
V
i
=
( ) ) (
) (
2 2 2
2
2
t C C Q
dt
t dC
V
i
=
2 1
Q Q Q + =
2 2 1 1 i i i
C Q C Q QC + =
) ( ) (
2 2 1 1
2 2 1 1
t C Q t C Q QC
C Q C Q QC
e
e e e
+ =
+ =
Q
C
i

(t)
Q
C
2

(t)
V
1
C
1

(t)
V
2
C
2

(t)
Q
C
1

(t)
( ) ) (
) (
1
1
1
t C C Q
dt
t dC
V
i
=
( ) ) ( ) (
) (
2 1
2
2
t C t C Q
dt
t dC
V =
Indian Institute of Technology Kharagpur, India Indian Institute of Technology Kharagpur, India - - 721302 721302
Compartmental Systems in Body
Compartmental Systems in Body
During systolic phase of a heartbeat cycle, blood is
pumped from the heart to one end of the aorta and
walls of the aorta stretch to accommodate the blood
Assume: ap V p V + =
0
) (
Volume of Aorta Pressure of Blood
bp Q
e
= and
During the diastolic phase, there is
no blood flow into the aorta. The
walls of the aorta contract, squeezing
blood out of the aorta around the
circulatory network of the body
Heart
Q
i
Aorta
V,p
Q
e
Circulatory Network
For Illustration of the Cardiac Cycle, please see Next Slide
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Cardiac Cycle
Cardiac Cycle
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Mass Conservation
of Aorta:
( )
e i
Q Q
dt
dV
= bp Q
dt
dV
i
= bp Q
dt
dp
a
i
=
Assume:
ap V p V + =
0
) (
Volume of Aorta Pressure of Blood
bp Q
e
=
and
Assume:
)
`

=
phase systolic during , sin
phase diastolic during , 0
t A
Q
i
e
Assume:
0
) 0 ( p t p = =
1 1
) / ( p t t p = = = e t
Aortic pressure at the
beginning of systolic phase
Aortic pressure at the end of
systolic phase
Solution:
( )
( )
2 2 2
0
cos sin / exp
/ exp
e
e e e
a b
t a t b a bt a
A a bt p p
systolic
+
+
+ =
( ) | | a t t b p p
systolic
/ exp
1 1
=
Compartmental Systems in Body
Compartmental Systems in Body
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Some Diseases with Fluid Mechanics Relevance
Some Diseases with Fluid Mechanics Relevance
Air Embolism: Cavitation

of Bubbles creates
destructive action to the blood components
(RBCs

typically). This can trigger coagulation
mechanisms that produce blood clots
Thrombus is stationary clot while Embolus is
moving clot
Hemolysis: Refers to loss (damage) of RBCs

and is a measure of cell trauma. This may be
due to the diseased condition or in presence
of prosthetic devices such as valves.
Hemolysis

is triggered by
Wall-RBC interaction
Prolonged Exposure to intermediate shear
stress (1000-2000 dynes/cm
2
)
Short Exposure to high shear stress (> 40,000
dynes/cm
2
)
Indian Institute of Technology Kharagpur, India Indian Institute of Technology Kharagpur, India - - 721302 721302
Diseases
Diseases

. Thrombosis
. Thrombosis
Thrombosis: Formation of a clot or thrombus (an
abnormal clot) in ant part of the vascular or
lymphatic system. The thrombus bump or clot is a
coagulation of blood elements or a growth of cells
formed in the heart, blood vessel or lymphatic
system.
Once a clot has developed, the continued flow of
blood past the clot may break it away from its
attachment. Such freely flowing clots are called
Emboli (Embolus in singular). These may continue
flowing until coming to a narrow point in the
circulatory system
Formation of thrombus or embolus is favored by
Any roughened endothelial surface of a vascular or
lymphatic vessel which may be caused by
Atherosclerosis, Infection or Trauma
Very slow rate of Blood Flow
Indian Institute of Technology Kharagpur, India Indian Institute of Technology Kharagpur, India - - 721302 721302
Diseases
Diseases

. Atherosclerosis
. Atherosclerosis
Atherosclerosis: Disease of large arteries in which lipid deposits called Atheromatous

plaques

appear in the subintimal

layer

of the arteries. These plaques are rich in
Cholesterol.
Calcium often precipitates with lipids to form calcified plaques.
In later stage, progressive sclerosis

of the arteries occurs due to the infiltration of
fibroblasts

in the degenerative area. When both reactions take place, arteries become
extremely hard Arteriosclerosis (Hardening of Arteries).
These plaques often protrude into the flowing blood and their surface roughness may
cause clots to develop. When a small clot has developed, platelets become entrapped and
cause more clots to develop (thrombus) or the clot breaks away (Embolus) and plugs a
smaller vessel further downstream.
This is the mechanism for most coronary occlusions.
Interestingly, the presence of flow separation at branching points and bifurcation is
considered to be one form of hydrodynamic disturbance that contributes to Atherogenesis

at these sides.
Subintimal Plaque
Glossary
Sclerosis Fibroblast
The layer situated beneath the intima

i.e. the innermost layer of an artery or vein.
A deposit of fat and other substances that accumulate in the lining of the artery
wall.
Sclerosis or sclerotization

is a hardening of tissue and other anatomical
features.
A fibroblast is a type of cell that synthesizes and maintains the structural
framework (stroma) for connective tissues such as skin, tendons, ligaments etc.
Indian Institute of Technology Kharagpur, India Indian Institute of Technology Kharagpur, India - - 721302 721302
Illustration of Atherosclerosis
Illustration of Atherosclerosis
Indian Institute of Technology Kharagpur, India Indian Institute of Technology Kharagpur, India - - 721302 721302
Indian Institute of Technology Kharagpur, India Indian Institute of Technology Kharagpur, India - - 721302 721302
Diseases
Diseases

.
.
Stenosis
Stenosis

from Atherosclerosis
from Atherosclerosis
Abnormal narrowing of lumen is
called as Stenosis
There are three primary methods of
treating Atherosclerosis
Arterial Bypass: This is created to
restore flow to distal tissue by
bypassing the obstraction. The graft
may be synthetic (made from polymer
materials such as Dacron) or natural
(uses arteries or veins from other
vascular parts of the patient)
Balloon Angioplasty: Dilatation of a
balloon-tipped catheter within the
stenosis

to expand the lumen
Stenting: To hold open the diseased
region by using a metallic stent
Arterial Bypass
Balloon Angioplasty
Stenting
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Blood Flow and Cell Adaptation
Blood Flow and Cell Adaptation
Endothelial Cells (ECs) that line the inner (Luminal)
surface of the vasculature are sensitive to flow induced
shear stress
Large arteries appear to vasoconstrict

or vasodilate

via
smooth muscle contraction and relaxation so as to
maintain wall shear stress (
w

) of 1.5 Pa under all
conditions
The vasomotion

is controlled partly by endothelial
productions of vasoactive

molecules such as
Vasodilators: Nitric Oxide (NO), Prostacyclin

(PGI
2

)
Vasoconstrictors: Endothelin-1 (ET-1) and
Thromboxene

(TXA
2

)
An important research goal is to correlate the
endothelial production of these molecules with
w
In general as
w

is increased (e.g. during exercise), the
endothelium produces more vasodilators to increase the
lumen area and thereby restores
w

to its normal value.
The converse occurs when shear stress is decreased by
a decreased flow
Indian Institute of Technology Kharagpur, India Indian Institute of Technology Kharagpur, India - - 721302 721302
F
l
o
w

f
i
e
l
d
Cell
Cell
Membrane
Cell-Substrate
Adhesion
y
x
z
Fluid Shear Stress
Fluid Shear Stress

Schematic Depiction
Schematic Depiction
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Cell Culture in Parallel Plate Channel: The Flow Physics
Cell Culture in Parallel Plate Channel: The Flow Physics
Fully developed flow is non-accelerating:
0
0
=
c
c
+
c
c

=
|
|
.
|

\
|
c
c
+ +
|
.
|

\
|
c
c
+
y x
p
dx dy
y
dx dy dx
x
p
p pdy
t
t
t t
Assume Newtonian Fluid:
flow) developed (fully 0 as =
c
c
=
|
|
.
|

\
|
c
c
+
c
c
= =
v
y
u
y
u
x
v
t
t

Combining two relations:
|
|
.
|

\
|
c
c
c
c
=
c
c
y
u
y x
p

Function of x only Function of y only

Hence, each term = const. = C
Also

= const.
Indian Institute of Technology Kharagpur, India Indian Institute of Technology Kharagpur, India - - 721302 721302
|
|
.
|

\
|
c
c
c
c
=
c
c
y
u
y x
p

The Flow Physics

The Flow Physics

.
.
Integrating With boundary conditions
H y u
y u
= =
= =
at 0
0 at 0
( ) Hy y
dx
dp
y u =
2
2
1
) (

Poiseuille

Flow
(named in honor of French physician J. Poiseuille

who studied pressure-flow relations for blood flow)
( )
H
H
dx
dp
udy
H
u
H
avg
6 /
2
1 1
3
0

= =
}

2
12
H
u
dx
dp
avg

=
Wall Shear Stress:
H
u
H
u
H
dx
dp H
dy
du
avg avg
y w

t
6 12
2 2
2
0
=
|
|
.
|

\
|
= = =
=
Re
6 6
2
2
|
|
.
|

\
|
= =
H H
H u
H
avg
w

t
Number Reynolds Re = =

H u
avg
Average Velocity:
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Adaptivity
Adaptivity
of Adhering Cells
of Adhering Cells
Prima Foci of Shear Stress Prima Foci of Shear Stress
Apical Cell Membrane Apical Cell Membrane
Focal Adhesion Points at Focal Adhesion Points at
Basal Surface Basal Surface
Events related to these are Events related to these are
inter inter- -connected !!! connected !!!
Apical Cell Membrane
Focal Adhesion Points at Basal Surface
Rearrangement of Focal Adhesion
Points Elicits Changes in Apical
Cell Membrane, which leads to

Reduction of Lipid Rafts
(Relatively Rigid Nanodomains

of Cell Membrane)

Increase in Membrane
Fluidity Stress Adaptation
Open Question: What are the
distinctive features of shear-adaptive
process kinetics of cancer cells in
very narrow confinements like inside
microchannels?
Lipid Raft