Science of Living Systems:

Bio-Thermal-Fluid Sciences
Lecture By

Prof. Suman Chakraborty

Department of Mechanical Engineering

Autumn 2010

Indian Institute of Technology Kharagpur, India - 721302

 Major Differences in Transport Phenomena in
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

Interstitial Flow Glossary

Blood vessels that carry blood away from the heart Artery
into the tissue. This blood is normally oxygenated.
Percolating fluid flow through a 3D tissue spaces,
Interstitial Flow (IF)
around embedded cells. IF drains out of blood vessels.
Local Vortices in Bifurcation

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 Hierarchy of Blood Vessels

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 Major Differences ….
• 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.

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

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

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 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

Related to lungs
Glossary

Describes the small vessels in the vasculature which are embedded within
Pulmonary
organs and are responsible for the distribution of blood within tissues; as Microcirculation
opposed to larger vessels in the macrocirculation which transport blood to and
from the organs.

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 Major Differences ….
• Unusually Low Conduction of Heat Flux
– In human body, maximum temperature is around
37ºC in the core region while minimum
temperature is around 34ºC at extremities

– The temperature gradient is 0.1ºC/cm

– Thermal conductivity of tissue is quite low ~ 0.06

W/m.K

– The conduction heat flux (q ~ kT ) ~ 0.06 W/m2 is

low to disperse the BMR (Basal Metabolic Rate ~
72 kcal/hour) over our body surface area of 1.8 m2
(for a normal 70kg adult)
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
Basal Metabolic Rate
temperate environment, in the post-absorptive state (i.e. the digestive system is
inactive, which requires about twelve hours of fasting in humans)

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 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
qvol ~ m bC p Tarterial blood  Ttissue 

– 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

The chemical processes occurring within a living cell or organism that are
necessary for the maintenance of life. Glossary
Vasomotor refers to actions upon a blood vessel which alter its diameter. Metabolism
Vasoconstriction is the narrowing of the blood vessels resulting from Vasomotor
contraction of the muscular wall of the vessels, particularly the large arteries, Vasoconstriction/dilation
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 ….
• Unusual Thermoregulatory Mechanisms
– Skin Temperature (Ts) 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 (Tamb), Ts and Tcore
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 Tamb>Ts and cold induced metabolic
heat generation (including shivering and non-shivering) for Tamb<Ts
Glossary
A thermoreceptor is a sensory receptor, or more accurately the receptive
portion of a sensory neuron, that codes absolute and relative changes in Thermoreceptor
temperature.
Hypothalamus
Hypothalamus is an area of the brain that produces hormones that control
body temperature, hunger, moods etc.

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 Major Differences ….
• Unusual Thermal Properties
– Tissue thermal properties
are inhomogeneous,
anisotropic and age
dependent Tissue – Organized
Cluster of Cells

• Unusual Range of System

Size for Heat Transfer Inner Architecture of a
Typical Animal Cell
– Ranges from microheat
transfer in cellular scale to
macro heat transfer on Hierarchical Organization
system scales of Life

Glossary
Typical length scale of an animal cell is 5-10 µm. Mass Transport processes at
this scale is dominated by diffusion while heat transfer is dictated by the Cellular Scale
enhanced surface area to volume ratio which scales as the inverse of the
characteristic length scale

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 Blood Rheology – Blood Properties
• Human Plasma is transparent, slightly yellowish with ρ = 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 O2, dissolved
CO2

• 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/mm3  40-45% by
volume of whole blood  Hematocrit
• Typical dimensions of RBC  7.8 µm in diameter (Biconcave
Disc), 2 µm thick and 88 µm3 in volume
• Function  Transport of Oxygen
• Less number of RBC  Anaemia

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 Blood Properties ….
• Size of WBC varies from 16-22 µm for
monocytes to 6-12 µm 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 µm
• Platelet : RBC = 1 : 10 (number
concentration) RBC

• Platelets and WBCs are actively ordinarily

not enough to influence the flow
WBC
characteristics
• However, platelets play important role in
forming blood clots that may severely Platlets
interfere with flow

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 Standard Rheological Behaviors

Bingham Plastic    0   B 

Power law    ; n  1

n

µ = Viscosity
 Newtonian    

Stress
Power law    ; n  1
n

Apparent Viscosity (µapp ):


 Strain Rate  app 


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 Blood Properties – 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 - 721302

 Unusual Hydrodynamics …. 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.

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 Blood Properties – 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 τ0 ~

0.1 dyn/cm2
• 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 µapp data for lower shear rates. As per the
model

  kc    0
Casson’s Viscosity

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 Lump Parameter Modeling of Compartmental
System with Flow Regulation

Compartment = An organ or tissue

Q V Q Q  Volumetric Flow Rate
Ci(t) C(t) Ce(t) C  Concentration
V  Volume
m  Mass = C×V
Control Volume (CV)

Note
 mi  me  C  V   QCi  QCe
dm d
CV
  i. V = Const. (Const. volume of organ)
dt dt ii. Ce = C(t)  QCe = QC(t)

 QCi  C (t )  with initial condition C (0)  0

dC (t )
V
dt

soln. : C (t )  Ci 1  e  t / 
  V / Q Time Constant of the Compartment

Indian Institute of Technology Kharagpur, India - 721302

 Compartmental Systems in Parallel and Series
 Q1 Ci1  C1 (t ) 
dC1 (t )
Q1, Ci1(t) Q1, Ce1(t)
V1
V1 dt
C1(t)
 Q2 Ci 2  C2 (t ) 
dC2 (t )
V2
Q Q dt
Ci(t) Ce(t) Q  Q1  Q2 QCi  Q1Ci1  Q2Ci 2
V2
QCe  Q1Ce1  Q2Ce 2
Q2, Ci2(t) C2(t) Q2, Ce2(t)
 QCe  Q1C1 (t )  Q2C2 (t )

 QCi  C1 (t ) 
dC1 (t )
V1
Q dt
Q V1 V2 Q
 QC1 (t )  C2 (t ) 
C1(t) dC2 (t )
Ci(t) C1(t) C2(t) C2(t) V2
dt

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 Compartmental Systems in Body
For Illustration of the Cardiac Cycle, please see Next Slide

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: V ( p )  V0  ap and Qe  bp
Volume of Aorta Pressure of Blood

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

Aorta Qe
Heart
Qi V,p

Circulatory Network

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 Cardiac Cycle

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 Compartmental Systems in Body

Assume: V ( p )  V0  ap and Qe  bp
Volume of Aorta Pressure of Blood

Mass Conservation
of Aorta:

dV
 
  Qi  Qe 
dV
 Qi  bp  a
dp
 Qi  bp
dt dt dt
 0, during diastolic phase 
Assume: Qi   
 A sin  t , during systolic phase 
Assume: p (t  0)  p0 p (t  t1   /  )  p1
Aortic pressure at the Aortic pressure at the end of
beginning of systolic phase systolic phase

a exp  bt / a   b sin t  a cos t

Solution: p systolic  p0 exp  bt / a   A
b 2  a 2 2
p systolic  p1 exp bt  t1  / a 

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 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/cm2)
– Short Exposure to high shear stress (> 40,000
dynes/cm2)

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 Diseases …. 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

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 Diseases …. 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.

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. Glossary
Sclerosis or sclerotization is a hardening of tissue and other anatomical Subintimal Plaque
features.
Sclerosis Fibroblast
A fibroblast is a type of cell that synthesizes and maintains the structural
framework (stroma) for connective tissues such as skin, tendons, ligaments etc.

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 Illustration of Atherosclerosis

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Indian Institute of Technology Kharagpur, India - 721302
 Diseases …. Stenosis from Atherosclerosis
• Abnormal narrowing of lumen is
called as Stenosis

• There are three primary methods of

Arterial Bypass
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

Stenting
region by using a metallic stent Balloon Angioplasty

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 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 (τw) 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 (PGI2)
– Vasoconstrictors: Endothelin-1 (ET-1) and
Thromboxene (TXA2)
– An important research goal is to correlate the
endothelial production of these molecules with τw

• In general as τw is increased (e.g. during exercise), the

endothelium produces more vasodilators to increase the
lumen area and thereby restores τw to its normal value.
The converse occurs when shear stress is decreased by
a decreased flow

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Fluid Shear Stress – Schematic Depiction

Flow field

Cell
Membrane

Cell-Substrate
y Adhesion

x Cell
z

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 Cell Culture in Parallel Plate Channel: The Flow Physics

Fully developed flow is non-accelerating:

 p    
pdy   p  dx dy  dx    dy dx  0
 x   y 
p 
  0
x y  v u 
       
 x y 
Assume Newtonian Fluid: u
   as v  0 (fully developed flow)
y
p   u 
Combining two relations:     Hence, each term = const. = C
x y  y  Also µ = const.
Function of x only Function of y only

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 The Flow Physics ….

p   u  u  0 at y  0
Integrating     With boundary conditions
x y  y  u  0 at y  H

Poiseuille Flow
u( y) 
2  dx

1 dp 2
y  Hy  (named in honor of French physician J. Poiseuille
who studied pressure-flow relations for blood flow)

Average Velocity: uavg

1
H
  udy 
1 dp  H 3 / 6   
dp

12 u avg
H 0 2  dx H dx H2

du H dp H  12 uavg  6 uavg
Wall Shear Stress:  w   y 0      2
 
dy 2 dx 2  H  H
6 uavg H   6 2  uavg H
w       Re
2 
Re   Reynolds Number
H  H  H  

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 Adaptivity of Adhering Cells
• Prima Foci of Shear Stress Apical Cell Membrane
– Apical Cell Membrane
– Focal Adhesion Points at Lipid Raft
Basal Surface
– Events related to these are
inter-connected !!!
Rearrangement of Focal Adhesion
Points Elicits Changes in Apical
Cell Membrane, which leads to
 Reduction of Lipid Rafts Focal Adhesion Points at Basal Surface
(Relatively Rigid Nanodomains
of Cell Membrane)
 Increase in Membrane Open Question: What are the
Fluidity  Stress Adaptation distinctive features of shear-adaptive
process kinetics of cancer cells in
very narrow confinements like inside
microchannels?

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