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© Copyright 2012, John P. Fisher, All Rights Reserved

Introduction to Physiology: The Human Body

Adapted From:

Textbook Of Medical Physiology, 11th Ed. Arthur C. Guyton, John E. Hall

Chapter 1

John P. Fisher


Organization of the Body Anatomical Directions

Sagittal plane

Transverse plane

Inferior

Superior

Posterior

Frontal plane

Anterior

Lateral

Medial

Lateral

Inferior

Superior

Anterior Posterior

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Control Systems Negative Feedback Systems •  Most control systems of the body act by negative feedback

•  A stimulus causes a reaction that opposes the acting stimulus •  Increased CO2 causes increased pulmonary ventilation, which decreases CO2 •  Decreased arterial pressure activates the baroreceptor system which acts

increase heart rate and arterial constriction, which increases arterial pressure

•  The negative feedback system acts to maintain homeostasis

homeostasis

stimulus

response

negative feedback response


Control Systems of the Body Positive Feedback •  In a positive feedback control system, a stimulus causes a responses that promotes

the stimulus

•  In general, positive feedback systems lead to instability and therefore are not utilized as often as negative feedback systems

homeostasis

stimulus

response

positive feedback response

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Control Systems Gain of Control Systems •  The gain of a control system is a parameter which describes the degree of

effectiveness with which a control system can maintain constant conditions •  Gain = Correction / Error

•  Example •  In a normal person with a functioning baroreceptor control system, a defined

stimulus causes arterial pressure to increase from 100 mmHg to 125 mmHg •  Error is +25 mmHg - if the baroreceptor system provided perfect control, there

would be no change in arterial pressure •  A person with a non-functioning baroreceptor control system, the same stimulus

causes arterial pressure to increase from 100 mmHg to 175 mmHg •  Difference from the normal response is 50 mmHg •  Thus, the baroreceptor system provides a correction of -50 mmHg

•  Gain = -50 mmHg / +25 mmHg = -2 •  The baroreceptor system reduces the effect of the stimulus by two thirds


Mass Transport Law of Conservation •  Consider a stationary volume element

•  Rate of mass Acc = Rate of mass In - Rate of mass Out

•  Mass unit: ρ x v x a •  ρ = density (m/l3)

•  v = velocity (l/t) •  a = area (l2) •  ρ x v x a [=] m/t

ρvx x+Δx

ρvx x

ρvz z+Δz

ρvz z

ρvy y

ρvy y+Δy

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Mass Transport Diffusion Through a Membrane •  With different assumptions, Fick’s Second Law can

also be written as

•  Consider a steady state system where a membrane separates two large reservoirs of a dilute chemical, with a concentration of CL on the left (x = 0) and CR on the right (x = L), the above equation reduces to

•  Assuming a “perfect source” and a “perfect sink”, we can solve the above to find

diffusion cell

reservoir 1 reservoir 2

C = CL

C = CR

x = 0 x = L

C = CL

C = CR

conc

entr

atio

n

length

membrane

pCDtC

+∇−=∂

∂ 2

02

2

=∂

∂

tCD

( ) xLCCCC LR

L−

+= ( )RL CCLDJ −=and


Momentum Transport Conservation of Momentum •  Using this approach, we can develop x, y, and z components of the

momentum equation in rectangular coordinates

•  For example, the x component is the following

•  Assuming a Newtonian fluid with constant ρ and µ

xzxyxxxx

zx

yx

xx g

zyxxp

zvv

yvv

xvv

tv

ρτττ

ρ +⎟⎟⎠

⎞⎜⎜⎝

⎛

∂

∂+

∂

∂+

∂

∂−

∂

∂−=⎟⎟

⎠

⎞⎜⎜⎝

⎛

∂

∂+

∂

∂+

∂

∂+

∂

∂

xxxxx

zx

yx

xx g

zv

yv

xv

xp

zvv

yvv

xvv

tv

ρµρ +⎟⎟⎠

⎞⎜⎜⎝

⎛

∂

∂+

∂

∂+

∂

∂+

∂

∂−=⎟⎟

⎠

⎞⎜⎜⎝

⎛

∂

∂+

∂

∂+

∂

∂+

∂

∂2

2

2

2

2

2

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Momentum Transport Conservation of Momentum •  We can also develop the r, θ, and z components of the momentum equation

in cylindrical coordinates, assuming a Newtonian fluid with constant ρ and µ

ρ∂vz∂t

+ vr∂vz∂r

+vθr∂vz∂θ

+ vz∂vz∂z

"

#$

%

&'= −

∂p∂z+µ

1r∂∂r

r ∂vz∂r

"

#$

%

&'+1r2∂2vz∂θ 2

+∂2vz∂z2

"

#$

%

&'+ ρgz

ρ∂vr∂t

+ vr∂vr∂r

+vθr∂vr∂θ

−v2θr+ vz

∂vr∂z

"

#$

%

&'= −

∂p∂r+µ

∂∂r

1r∂∂rrvr

"

#$

%

&'+1r2∂2vr∂θ 2

−2r2∂vθ∂θ

+∂2vr∂z2

"

#$

%

&'+ ρgr

ρ∂vθ∂t

+ vr∂vθ∂r

+vθr∂vθ∂θ

−vrvθr

+ vz∂vθ∂z

"

#$

%

&'= −

1r∂p∂θ

+µ∂∂r

1r∂∂rrvθ

"

#$

%

&'+1r2∂2vθ∂θ 2

−2r2∂vr∂θ

+∂2vθ∂z2

"

#$

%

&'+ ρgθ

z

θ r


Momentum Transport Fluid Flow Between Parallel Plates

•  Consider a volume element in a fluid between two parallel plates separated by a height, H. The bottom plate is stationary, while the top plate is pulled to the right at a velocity of V0. The fluid between the plates will also begin to move to the right due to the momentum imparted by the upper plate. Here, we wish to describe the velocity of the fluid as a function of position (height) between the plates.

•  Our two boundary conditions state that the fluid next to the stationary plate is a rest (Vx = 0 at y = 0) and the fluid next to the plate in motion moves at the same velocity as the plate (Vx=V0 at y = H).

•  Using this approach, we find that the velocity profile between the two plates is linear with position

yHVVx 0=

H

V0 y

z

x

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Chemical Reaction with an Enzyme •  Consider a substrate (S) reacting with an enzyme (E) to form a complex (C) that

then produces a product (P) and returns the enzyme and B react to produce C

•  Let s = [S], c = [C], e = [E], and p = [P] as well as define the mass balance for each as the following:

Biological Kinetics

EPCES k

k

k

+⎯→⎯⎯⎯←

⎯→⎯+

−

2

1

1

sekckdtds

11 −= − ckksekdtdc )( 121 −+−=

sekckkdtde

121 )( −+= − ckdtdp

2=


Competitive Inhibition •  Consider the Michaelis - Menton system, but with an inhibitor (I) which can disrupt

enzyme catalysis of the substrate reaction

•  The mass balances are defined as

Biological Kinetics

EPCES k

k

k

+⎯→⎯⎯⎯←

⎯→⎯+

−

2

1

1

1 23

3

CIEk

k

⎯⎯←

⎯→⎯+

−

sekckdtds

111 −= − 11211 )( ckksekdtdc

−+−=

iekckdtdi

323 −= − 2332 ckiekdtdc

−−=

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Lipid Barrier of the Cell Membrane •  All molecules may

eventually pass through the cell membrane, but the rate of transport varies greatly with the properties of the molecule

•  Small (<100 Da), hydrophobic, nonpolar, and neutral molecules all pass quickly

•  Larger, hydrophilic, and

charged molecules are highly impermeable •  These molecules may

pass through the membrane using protein channels

Chemical Composition of Extracellular and Intracellular Fluids

EXTRACELLULAR INTRACELLULAR

Hydrophobic Molecules O2, CO2, N2, Benzene

Large, Neutral, Polar Molecules H2O, Urea, Glycerol,

Glucose, Sucrose

Charges Molecules (Ions) H+, Na+, HCO3

-, K+, Ca++, Cl-, Mg++


Lipid Barrier of the Cell Membrane

Guyton & Hall. Textbook of Medical Physiology, 11th Edition

Transport Through the Cell Membrane

•  Many molecules, including ions and large molecules do not permeate the cell’s plasma membrane

•  Transport of these molecules occurs through a membrane bound protein

•  Transport can be accomplished by •  Diffusion

•  Simple diffusion •  Facilitated diffusion

•  Active transport

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Diffusion Facilitated Diffusion •  Model

•  Release is much faster than conformational change •  Intracellular solute concentration is low •  Equilibrium state is reached between S + P and C •  All membrane bound protein is either free or in a complex

C S*P S + P S* + P

PSESCPS kk

k

k

+⎯→⎯⎯→⎯⎯⎯←

⎯→⎯+

−

** 32

1

1

23 kk >>

0* ≈SCPS ←

→+

CPPT +=


Active Transport Types of Active Transport

•  Similar to facilitated transport, however energy is required •  Primary Active Transport: Energy is used directly, as in the consumption of ATP

to ADP •  Secondary Active Transport: Energy is derived from another source, such as a

concentration gradient established by primary active transport •  Transport can occur against the concentration gradient across the plasma membrane •  Transport typically utilizes membrane bound carrier proteins •  Transport can be regulated by the relative number of ligands and / or receptors

•  Therefore, transport can be saturated

ATP ADP

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Membrane Potentials Membrane Potentials Are Caused by Diffusion •  K+ is high inside a nerve fiber membrane,

but K+ is low outside the membrane

•  Ignoring other ions, the large K+ gradient causes K+ to diffuse outward through the membrane •  K+ carry positive electrical charges to

the outside, thus creating electropositivity outside the membrane and electronegativity inside because of negative anions that remain behind

•  The potential difference ultimately is balanced with the concentration difference and further K+ transport is stopped

•  In the normal mammalian nerve fiber, the potential difference created by the K+ concentration difference is about 94 mV, with negativity inside the fiber membrane



Membrane Potential Nernst Equation

•  The membrane potential, or Nernst potential, for a single ion is given as

•  Vs potential difference •  R gas constant •  T absolute temperature •  F Faraday’s constant •  z charge on the ion •  Sin intracellular ion concentration •  Sout extracellular ion concentration

RT zF

Vs = ln Sout

Sin ( )

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Membrane Potential Goldman-Hodgkin-Katz Equation

•  Under the influence of sodium, potassium, and chloride ions, the Nernst Equation expands to the Goldman-Hodgkin-Katz Equation

•  Notes about the GHK Equation •  K+, Na+, and Cl- are the most significant ions in nerve and muscle fibers •  Permeability controls significance •  Note sign convention •  Cl- does not change greatly during transmission of a nerve impulse, so it plays a

rather minor role in this phenomena

Vm = - ln RT F

PK+ CK+in + PNa+CNa+in + PCl- CCl-out ( ) PK+ CK+out + PNa+CNa+out + PCl- CCl-in


Membrane Potential Origin of Resting Membrane Potential •  Potassium Diffusion Potential

•  If K+ is the only ion to move through the membrane (channel), and since there is a high ratio of K+ inside to outside (35:1), the resting potential inside the fiber would be equal to -94 mV

•  Sodium Diffusion Potential •  There is a slight permeability of the nerve

membrane to Na+ due to the K+ Na+ leak channel

•  In addition, the ratio of Na+ from inside to outside the membrane is 0.1, and this gives a calculated Nernst potential for the inside of the membrane of +61 mV

•  Combining with the GHK equation, the resting potential is -86 mV


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Nerve Action Potential Voltage-Gated Na+ and K+ Channels

•  Voltage-gated Na+ channel drives the action potential

•  Voltage-gated K+ channel speeds the repolarization of the membrane

•  Voltage-Gated Na+ Channel •  Channel has two gates, one near the

outside of the channel called the activation gate and one near the inside called the inactivation gate

•  At rest (-90 mV) the activation gate is closed

•  When the membrane potential rises from -90 mV, at approximately -70 to -50 mV, the activation gate opens (activated state) increasing the Na+permeability as much as 500 to 5000 times



Nerve Action Potential Propagation of the Action Potential •  A local circuit of current flow from the

depolarized areas of the membrane to the adjacent resting membrane areas •  Positive charges are carried by the

inward-diffusing Na+ through the depolarized membrane and then for several millimeters in both directions along the core of the axon

•  Positive charges increase the voltage for a distance of 1 to 3 mm inside the large myelinated fiber to above the threshold voltage value for initiating an action potential

•  The action potential travels in all directions

away from the stimulus until the entire membrane has become depolarized


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Rhythmicity of Some Excitable Tissues Rhythmicity •  The membrane of the heart control

center does not depolarize immediately after it has become repolarized

•  Toward the end of each action potential, and continuing for a short period thereafter, the membrane becomes excessively permeable to K+

•  The excessive outflow of K+ carries tremendous numbers of positive charges to the outside of the membrane, leaving inside the fiber considerably more negativity than would otherwise occur



Eliciting the Action Potential Threshold for Excitation and Acute Local Potentials

•  The level required to elicit an action potential is called the threshold level

•  A weak negative electrical stimulus may not be able to excite a fiber •  These local potential changes are called

acute local potentials, and when they fail to elicit an action potential, they are called acute subthreshold potentials

•  A stronger stimulus induces a stronger acute local potential

•  When the voltage of the stimulus is increased, there comes a point at which excitation does take place


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Physiologic Anatomy of Skeletal Muscle Skeletal Muscle Fiber

•  All skeletal muscles are composed of numerous fibers ranging from 10 to 80 µm in diameter

•  In most skeletal muscles, each fiber extends the entire length of the muscle

•  Most fibers are usually innervated by only one nerve ending, located near the middle of the fiber


muscle fiber

actin

myosin


Molecular Mechanism of Muscle Contraction Sliding Filament Mechanism of Muscle Contraction •  Sacromere exists in relaxed and contracted states

•  Relaxed: Ends of the actin filaments begin to overlap one another

•  Contracted: Ends of actin filaments overlap one another to their maximum extent

•  Z discs have been pulled by the actin filaments up to the ends of the myosin filaments

•  Actin filaments slide due to forces generated by dynamic bonds between myosin and actin filaments

•  When an action potential travels along the muscle fiber, this causes the sarcoplasmic reticulum to release Ca++ that rapidly surround the myofibrils

•  Ca++ activate the forces between the myosin and actin filaments, using ATP, and contraction begins


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Molecular Mechanism of Muscle Contraction Cross-bridges •  Each cross-bridge is flexible at two hinges

•  One where the arm leaves the body of the myosin filament

•  One where the head attaches to the arm

•  The hinged arms allow •  Heads either to be extended outward or to

be brought close to the body •  Hinged heads participate in the actual

contraction process

•  The myosin filament itself is quite twisted so that each successive pair of cross-bridges is axially displaced from the previous pair by 120°

•  Myosin head acts as an ATPase enzyme, cleaving ATP and using the energy to drive contraction


no myosin heads exist in the center

of the myosin filament


Molecular Mechanism of Muscle Contraction Walk-Along Theory of Contraction

•  After Ca++ activation, the heads of the cross-bridges from the myosin filaments become attracted to the active sites of the actin filament, and causes contraction to occur

•  Contraction is hypothesized to occur due to a walk-along mechanism •  When a cross-bridge head attaches to an active site,

the attachment causes the head to tilt toward the arm and drags actin filament - the power stroke

•  After tilting, the head then automatically breaks away from the active site

•  Next, the head returns to its extended direction •  The head then combines with a new active site farther

down along the actin filament •  The head tilts again to cause a new power stroke

•  Each cross-bridges acts independently •  Number of cross-bridges in contact with the actin

filament determines the force of contraction


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Myosin - Actin Overlap Determines Tension •  At no overlap, developed tension is zero •  As overlap increases, tension increases •  At a sarcomere length of 2.2 µm, the actin filament

has overlapped all the cross-bridges of the myosin filament but has not yet reached the center of the myosin filament

•  With further shortening, the sarcomere maintains full tension until 2.0 µm

•  Below 2.0 µm, the ends of the two actin filaments begin to overlap each other in addition to overlapping the myosin filaments •  Two Z discs of the sarcomere abut the ends of

the myosin filaments •  Ends of the myosin filaments are crumpled •  Strength of contraction decreases rapidly and

approaches zero

Molecular Mechanism of Muscle Contraction



Effect of Muscle Length on Force of Contraction •  Force generation in whole muscle is similar to a

single muscle fiber, although differences exist •  Whole muscle has a large amount of connective

tissue •  Sarcomeres in different parts of the muscle do

not always contract the same amount

•  When muscle is approximately at normal resting length (a sacromere length of 2.0 µm), it contracts with maximum force

•  At increased lengths, the increase in tension that occurs during contraction (active tension) decreases

Molecular Mechanism of Muscle Contraction


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Excitation of Skeletal Muscle Neuromuscular Junction

•  The nerve fiber forms a complex of branching nerve terminals that invaginate into the surface of the muscle fiber but lie outside the muscle fiber plasma membrane •  Structure is called the motor end plate •  Schwann cells insulate it from the

surrounding fluids •  Invaginated membrane is the synaptic

gutter or synaptic trough •  Space between the terminal and fiber is

the synaptic space or synaptic cleft •  Space is 20 to 30 nm •  Subneural clefts increase the

surface area for the synaptic transmitter



Excitation of Skeletal Muscle Propagation of Muscle Action Potential •  Skeletal muscle fibers are so large that

action potentials spreading along the surface membrane cause almost no current flow deep within the fiber

•  Excitation-contraction coupling •  Interior transmission of action

potentials occurs along transverse tubules (T tubules) that penetrate all the way through the muscle fiber from one side of the fiber to the other

•  T tubule action potentials cause release of Ca++ inside the muscle fiber in the immediate vicinity of the myofibrils, and these Ca++ then cause contraction


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Contraction and Excitation of Smooth Muscle Contraction Mechanisms in Smooth Muscle

•  Smooth muscle is irregular compared to skeletal muscle

•  Large numbers of actin filaments are attached to dense bodies •  Dense bodies are attached to the cell membrane and dispersed

inside the cell - they serve the same role as the Z discs in skeletal muscle

•  Some membrane bound dense bodies of adjacent cells are bonded together by intercellular protein bridges - these bonds transmit force from cell to cell

•  Myosin filaments are interspersed among actin filaments •  Approximately 15x less myosin than actin •  Myosin filaments have sidepolar cross-bridges, where the

bridges on one side hinge in one direction and those on the other side hinge in the opposite direction

•  Sidepolar cross-bridges allow myosin to pull an actin filament in one direction on one side while simultaneously pulling another actin filament in the opposite direction on the other side

•  This allows smooth muscle cells to contract as much as 80% of their length, compared to < 30% in skeletal muscle

Guyton & Hall. Textbook of Medical

Physiology, 11th Edition


The Heart and Circulatory System Introduction •  The heart is two separate pumps

•  A right heart that pumps blood through the lungs

•  A left heart that pumps blood through the peripheral organs

•  Each heart pump is a pulsatile two-chamber pump composed of an atrium and a ventricle •  The atrium is a weak primer pump, helping

to move blood into the ventricle •  The ventricle then supplies the main

pumping force that propels the blood •  Through the pulmonary circulation by

the right ventricle •  Through the peripheral circulation by

the left ventricle Guyton & Hall. Textbook of Medical Physiology, 11th Edition

superior vena cava

right atrium

pulmonary valve

tricuspid valve

right ventricle

inferior vena cava

aorta

pulmonary artery

lungs

pulmonary vein

left atrium

mitral valve

aortic valve

left ventricle

Upper body

lower body

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Action Potentials Cardiac Muscle Introduction •  The magnitude of an action potential recorded in a

ventricular muscle fiber averages about 105 mV

•  After the initial spike, the membrane remains depolarized for about 0.2 sec in a plateau, followed by abrupt repolarization

•  The action potential plateau causes ventricular contraction to last as much as 15 times as long in cardiac muscle as in skeletal muscle



The Cardiac Cycle Diastole and Systole

•  The cardiac cycle consists of a period of relaxation called diastole, during which the heart fills with blood, followed by a period of contraction called systole

Guyton & Hall. Textbook of Medical Physiology, 11th

Edition

know and understand this

figure

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The Cardiac Cycle Semilunar Valves vs. A-V Valves •  The high pressures in the arteries at the end of

systole cause the semilunar (aortic and pulmonary) valves to snap to the closed position •  A-V (tricuspid and mitral) valves close

more softly

•  Blood ejection velocity is great through the semilunar valves •  Velocity is much lower through the A-V

valves

•  Due to rapid closure and ejection, the edges of the semilunar valves are subjected to significant mechanical abrasion

•  Semilunar valves are not supported •  A-V valves are supported by the chordae

tendineae

Semilunar Valves Aortic Valve

Pulmonary Valve

A-V Valves Tricuspid Valve

Mitral Valve



Work Output of the Heart Graphical Analysis of Ventricular Pumping

•  Consider the pumping mechanics of the left ventricle

•  The diastolic pressure curve is determined by filling the heart with progressively greater volumes of blood and then measuring the diastolic pressure immediately before ventricular contraction occurs, which is the end-diastolic pressure of the ventricle

•  The systolic pressure curve is determined by recording the maximum systolic pressure achieved during ventricular contraction at each volume of filling, and without any outflow of blood from the heart Guyton & Hall. Textbook of Medical Physiology, 11th Edition


figure

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Regulation of Heart Pumping Frank-Starling Mechanism

•  Fundamental Concept: The amount of blood pumped by the heart each minute (venous return) is determined by the rate of blood flow into the heart •  Peripheral tissue controls blood flow

•  The greater the heart is stretched during filling, the greater it contracts and the greater quantity of blood is pumped into the aorta

•  The intrinsic ability of the heart to adapt to increasing volumes of inflowing blood is called the Frank-Starling Mechanism


Guyton & Hall. Textbook of Medical

Physiology, 11th Edition


Specialized Excitatory and Conductive System Introduction

•  The sinus node (also called sinoatrial or S-A node) generates the normal rhythmical impulse

•  The internodal pathways that conduct the impulse from the sinus node to the atrioventricular (A-V) node

•  The A-V bundle conducts impulses from the atria into the ventricles

•  The left and right bundle branches of Purkinje fibers conduct the cardiac impulse to all parts of the ventricles


figure


sinus node

A-V node A-V bundle

left bundle branch

Purkinje fibers right bundle branch

internodal pathways

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Specialized Excitatory and Conductive System Organization of the A-V Node

•  The A-V node is located in the posterior wall of the right atrium immediately behind the tricuspid valve

•  After traveling through the internodal pathways, an impulse reaches the A-V node about 0.03 sec after its origin in the sinus node

•  There is a delay of another 0.09 sec before the impulse enters the penetrating portion of the A-V bundle, where it passes into the ventricles

•  A final delay of another 0.04 sec occurs mainly in this penetrating A-V bundle, which is composed of multiple small fascicles passing through the fibrous tissue separating the atria from the ventricles •  The total delay in the A-V nodal and A-V bundle

system is about 0.13 sec •  A total delay of 0.16 sec occurs before the excitatory

signal finally reaches the contracting muscle of the ventricles



Specialized Excitatory and Conductive System Summary of Cardiac Impulse Transmission


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The Normal Electrocardiogram Characteristics of the ECG •  The normal ECG has a P wave, QRS

complex, and a T wave •  The QRS complex is normally

composed of a Q wave, R wave, and S wave

•  P wave is caused by electrical potentials generated by atrial depolarization

•  QRS complex is caused by potentials generated by ventricular depolarization

•  T wave is caused by potentials generated by ventricular repolarization



The Normal Electrocardiogram Electrocardiographic Leads •  Standard bipolar limb leads, on each arm and the left

leg, provide 3 different measurements

•  Lead I: Negative terminal at right arm and positive terminal at left arm •  Positive measurement means right arm is

electronegative with respect to left arm

•  Lead II: Negative terminal at right arm and positive terminal at left leg

•  Lead III: Negative terminal at left arm and positive terminal at left leg


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Electrocardiographic Interpretation Principles of Vector Analysis in Electrocardiograms •  Similarly, a vector representing the instantaneous mean direction of current flow may

be projected onto all three leads to determine their relative contributions

+

II

III -

I -

+ +

-


Electrocardiographic Interpretation Principles of Vector Analysis in Electrocardiograms •  Finally, this vector analysis may be applied to ventricular vectors during

depolarization and compared to the ECG’s QRS wave



figure

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Electrocardiographic Interpretation Vector Analysis During Atrial Depolarization and

Repolarization •  Again, a similar analysis may be performed during

atrial depolarization and the P wave as well as repolarization and the atrial T wave

•  Important concepts here include •  Depolarization begins in the sinus node •  The direction of the electrical potential vector

is slightly to the right of the atrial septum •  This direction persists throughout

depolarization •  This direction is almost the same as the

vector for ventricular depolarization •  Thus, the P wave is positive

•  Repolarization also begins in the sinus node •  Opposite to ventricular repolarization •  Thus vector is in the opposite direction •  Thus, the atrial T wave is negative



Electrocardiographic Interpretation Current of Injury •  Consider a current of injury due to ischemia located in the base of the left ventricle


Notice the definition of the J point

J

J

J

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Cardiac Arrhythmias & Electrocardiograms Abnormal Impulse Conduction •  Atrioventricular block can occur in a number of ways

•  Ischemia of the AV node or AV bundle •  Compression of the AV bundle •  Inflammation of the AV bundle •  Excessive parasympathetic stimulation

•  First Degree Block •  The typical P-R (same as P-Q) interval is 0.16 sec, and this decreases with

increased heart rate and increases with decreased heart rate •  At a normal heart rate, a P-R interval of 0.20 sec is said to be a first degree

incomplete heart block



Overview of Circulation Functional Parts of the Circulation

•  Arteries •  Transport blood under high pressure

•  Arterioles •  Acts as control valves through which blood is

transported into the capillaries

•  Capillaries •  Allows exchange of fluid, nutrients,

electrolytes, hormones, and other substances

•  Venules •  Collect blood from the capillaries

•  Veins •  Conduits for transport of blood from tissues

back to the heart and reservoir of blood Guyton & Hall. Textbook of Medical Physiology, 11th Edition

12/12/12

26


Elementary Fluid Mechanics Flow Through a Cylindrical Tube

•  Consider flow through a cylindrical tube

§  Velocity Profile, Volumetric Flow Rate, and Resistance to Flow

Hagen-Poiseuille Flow

( )⎟⎟⎠

⎞⎜⎜⎝

⎛−

−= 2

220 14 R

rLRPPv L

z η

( ) 40

8R

LPPQ L π

η−

= 4

8RL

πη

=Ω

R

z

L

θ r

00 == zatPP

LzatPP L ==

Rratvz == 0

00 ==∂

∂ ratrvz


Overview of Circulation Blood Flow

•  Fahraeus-Lindquist Effect •  As vessel diameter decreases, the

apparent viscosity of blood decreases

•  Marginal wall viscosity is less than the central core viscosity

•  As vessel diameter decreases, marginal wall proportion increases

•  Less than 4 – 6 microns, apparent viscosity increases

•  A vessel of 2.7 microns is the smallest a RBC can enter

tube diameter (µm)

1 10 100

visc

osity

( ) 40

8R

LQPP L

apparent πη−

=

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Vascular Distensibility Arterial Pressure Pulsations

•  Arterial compliance allows for blood flow during diastole

•  Difference between systolic and diastolic pressure is the pulse pressure

•  Pulse pressure is determined by •  Stroke volume output •  Arterial compliance

•  Factors changing pulse pressure include •  Arteriosclerosis (Inc PP) •  Aortic stenosis (Dec PP) •  Aortic regurgitation (Dec PP)


120

80

40

0

Pres

sure

(m

mH

g)


Vascular Distensibility Hydrostatic Pressure •  A column of liquid exerts pressure due to the

weight of the liquid •  Pressure rises 1 mmHg for each 13.6 mm

below the liquid surface

•  Thus, a person standing still has •  Right atrial pressure = 0 mmHg •  Venous pressure in the feet = 90 mmHg •  Venous pressure in the hands = 35 mmHg

•  Also, a standing person also has collapsed neck veins (0 mmHg) due to atmospheric pressure •  Veins in the skull do not collapse •  Sagittal sinus = -10 mmHg


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Vascular Distensibility Venous Valves and Venous Pumps •  Veins contain small “valves” that allow blood to

flow towards the right atrium and prevents it flow back into the arterial system

•  A standing person would have a +90 mmHg pressure in the feet •  However, skeletal muscle and other

movements compresses the veins, moves blood unidirectionally through the valve system - venous pump

•  Pressure in walking feet is + 25 mmHg

•  Standing without movement allows venous pressure to rise, movement of fluid into the interstitial space, loss of circulating blood volume - and eventually unconsciousness

•  Varicose veins result from valve dysfunction and result in edema



Microcirculation and the Lymphatic System Nutrient Exchange •  Nutrient exchange from the capillary to the

interstitial fluid is dominated by passive diffusion induced by thermal fluctuations (Brownian Motion)

•  Lipid soluble molecules (oxygen and carbon dioxide) can diffuse directly through endothelial cell membranes

•  Water soluble molecules (water, Na+, Ca++, and glucose) must pass through capillary pores •  Diffusion is incredibly fast •  Water diffuses through the capillary

membrane 80x faster than the rate of plasma flow along the capillary!!!

•  The transport of molecules through the capillary pore depends upon molecule size and molecular concentration gradient


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Microcirculation and the Lymphatic System Fluid Exchange Through the Capillary Membrane •  Four forces affect the movement of fluid

between the capillaries and the interstitial spaces

•  Capillary pressure (Pc) •  Tends to drive fluid to the interstitial

space •  Interstitial fluid pressure (Pif)

•  Tends to drive fluid to the capillary •  Can also pull fluid to the interstitial space

•  Plasma osmotic pressure (Πp) •  Tends to cause osmosis of fluid to the

capillary •  Interstitial fluid osmotic pressure (Πif)

•  Tends to cause osmosis of fluid to the interstitial space

Understand these forces !!!



Microcirculation and the Lymphatic System The Lymphatic System •  The lymphatic system provides a vital pathway

for the recirculation of large proteins

•  Lymphatic capillaries contain endothelial cells that use attaching filaments to connect to surrounding connective tissue

•  A minute valve is formed that opens to the interior of the capillary

•  Interstitial fluid, with suspended particles, push the valves open and move fluid into the lymphatics


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Local Control of Blood Flow Acute Blood Flow Control •  Autoregulation of Blood Flow

•  An increase in blood pressure, increases blood flow, but within a minute blood flow returns to normal - autoregulation

•  Metabolic Theory •  Arterial pressure increases, blood flow

increases, nutrition is too high, blood vessels contract, flow decreases

•  Myogenic Theory •  Sudden pressure increase causes a

stretch of small blood vessels and smooth muscles to contract, causing vasoconstriction, and reduced blood flow

•  Such a theory implies a possible positive feedback loop and a potential viscous cycle leading to death

•  Thus theory likely only applicable to a few tissues and in limited circumstances

Effect of increasing arterial pressure on blood flow through a muscle. The solid curve shows the effect when change occurs quickly (minutes), the dashed curve shows

the effect when change occurs slowly (weeks).



Nervous Regulation of Blood Flow Introduction •  Nervous regulation occurs almost entirely through the autonomic nervous system

•  The autonomic nervous system acts through the sympathetic and parasympathetic systems

•  Sympathetic System •  Nerve fibers leave the spinal cord through all the thoracic and the first two

lumbar spinal nerves •  Sympathetic nerves innervate the vasculature of the internal viscera and

heart •  Spinal nerves innervate the vasculature of the peripheral areas

•  Innervation of small arteries acts to increase resistance and decrease blood flow

•  Innervation of large arteries acts to decrease vessel volume

•  Parasympathetic System •  Little effect beyond innervation of the vagus nerves in the heart, where

stimulation causes a decrease in cardiac output

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Nervous Regulation of Blood Flow Sympathetic Vasoconstrictor System •  Under normal conditions, the vasomotor

center sends signals that act to maintain sympathetic vasoconstrictor tone

•  Blockage by spinal anesthesia causes a loss of vessel tone, and thus arterial pressure

•  Stimulation by norepinephrine restores tone, until hormone is consumed



Nervous Regulation of Blood Flow Reflex Mechanisms of Arterial Pressure Maintenance Baroreceptors

•  Arterial pressure has a significant effect upon the rate of impulse transmission in Hering’s nerve

•  At normal arterial pressure, a slight change in pressure causes a significant change in the autonomic reflex •  Steep slope

•  Also, the rate of autonomic reflect is directly related to the rate of change in arterial pressure •  Linear relationship

Response of the baroreceptors at different levels of arterial pressure

Guyton & Hall. Textbook of Medical Physiology, 11th

Edition

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Integrated System for Pressure Control Long Term Arterial Pressure Maintenance •  As long as the renal output curve for

water and salt as well as the line of net water and salt intake remain constant, long term arterial pressure will remain at 100 mmHg

•  Equilibrium can only be changes by shifting one of the two relationships

•  Thus, long term arterial pressure is determined by •  The degree of shift of the renal

output curve •  The level of the water and salt

intake line



Integrated System for Pressure Control Hypertension •  Hypertension due to reduced

renal mass and increase in salt intake

•  Reduction of kidney mass reduces the ability of the kidney to remove salt, thus increasing arterial pressure - shifting the renal function curve to the right

•  The intake of both salt and water also causes increased arterial pressure - shifting the water and salt intake line up Guyton & Hall. Textbook of Medical Physiology, 11th Edition


figure

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Integrated System for Pressure Control Hypertension •  Again, the effects of reduced renal mass

and increased salt & water intake is examined

•  Initially, peripheral resistance falls in an attempt to keep arterial pressure low (baroreceptor mechanism) •  After this fails, pressure rises

•  Then, long term blood flow autoregulation takes over, where resistance increases, while fluid volume, blood volume, and cardiac output decrease

•  Hypertension induces an increase in peripheral resistance



figure


Integrated System for Pressure Control Renin-Angiotensin System •  Renin is a small protein produced by the kidneys and

released in response to a fall in arterial pressure

•  Once released, renin acts on angiotensinogen to form angiotensin I

•  Angiotensin II, a fragment of angiotensin I, is then formed by cleavage

•  Angiotensin II is a powerful vasoconstrictor (increasing resistance and therefore pressure) and inhibitor of renal excretion of salt and water (increasing volume and therefore pressure)

•  System actively maintains arterial pressure in response to significant changes in salt intake

•  Angiotensin II is inactivated by angiotensinase Guyton & Hall. Textbook of

Medical Physiology, 11th Edition


figure

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34


Integrated System for Pressure Control Summary •  Arterial pressure is regulated by a variety of

mechanisms

•  Trauma leading to severe blood loss causes •  Efforts to return arterial pressure, then •  Efforts to return blood volume

•  Acute changes are dominated by the nervous control system

•  Kidneys dominate long term control system

•  However, other systems do participate



Balance of Fluid Intake and Fluid Output Measurement of Fluid Volumes

•  Total Body Water •  Add a bolus of radioactive water and measure concentration after a few hours

•  Extracellular Fluid Volume •  Add a bolus of radioactive sodium and measure concentration after a few hours

•  Intracellular Fluid Volume •  Equals total body water minus extracellular fluid volume

•  Plasma Volume •  Add a bolus of radioactive serum albumin and measure concentration after a few

hours •  Interstitial Fluid Volume

•  Equals extracellular fluid volume minus plasma volume •  Total Blood Volume

•  Equals plasma volume / (1 - hematocrit*) •  *Here hematocrit is total blood cell volume

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Fluid Regulation in Abnormal States Example: Patient in Water Deficit

•  What is the effect on extracellular and intracellular fluid volumes when 2 liters of a hypertonic 2.9% sodium chloride solution is administered to a 70 kg patient with an initial osmolarity of 280 mOsm/liter

•  Using the basic assumptions •  Extracellular osmolarity = 280 mOsm/l x 14 liters = 3,920 mOsm •  Intracellular osmolarity = 280 mOsm/l x 28 liters = 7,840 mOsm •  Total body fluid osmolarity = 280 mOsm/l x 42 liters = 11,760 mOsm

•  Next, 2 liters of a 29 g/l sodium chloride (58 g/mol) solution provides 1 mole or 2 osmoles (2,000 mOsm) of sodium chloride

•  The instantaneous change would be •  Extracellular concentration = (3,920 + 2,000) mOsm / 16 liters = 370 mOsm/l •  Intracellular concentration remains constant = 280 mOsm/l

•  The long term change would be •  Total body fluid concentration = 13,760 mOsm / 44 liters = 312.7 mOsm/l •  Extracellular volume = 5,920 mOsm / 312.7 mOsm/l = 18.9 liters •  Intracellular volume = 7,840 mOsm / 312.7 mOsm/l = 25.1 liters


Fluid Regulation in Abnormal States Prevention of Edema

•  Three major safety factors prevent fluid accumulation in the interstitial space •  Low compliance of the interstitium when

interstitial fluid pressure is negative •  The ability of the lymph flow to increase

10 to 50 fold •  Washdown of interstitial fluid protein

•  Low Compliance of the Interstitum •  Interstitial fluid hydrostatic pressure is

slightly negative, about -3 mmHg •  Once interstitial fluid pressure rises

above 0 mmHg, compliance increases and fluids rapidly accumulate

•  Safety factor is about 3 mmHg


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Kidneys: Glomerular Filtration Physiological Anatomy of the Kidneys

•  Blood flow to the kidneys is normally 21% of cardiac output (1200 ml/min)

•  Blood enters the kidney through the renal artery, and then branches progressively to form interlobar arteries, arcuate arteries, interlobular arterioles, and afferent arterioles

•  Afferent arterioles lead to the glomerular capillaries, which then coalesce to form efferent arterioles, and then the peritubular capillaries •  Glomerular capillaries are the site of

fluid and solute filtration •  Efferent arterioles regulate pressure



Kidneys: Glomerular Filtration Nephron, the Function Unit of the Kidney

•  Each kidney contains about 1 million nephrons, which form urine

•  In renal disease, there is a decline in the number of functional nephrons •  After age 40, total nephron function

falls 10% every 10 years

•  Each nephron has two major components •  Glomerulus through which large

amounts of fluid are filtered from the blood

•  Tubule in which the fluid is converted into urine on its way to the pelvis of the kidney


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Kidneys: Glomerular Filtration Urine Formation

•  The rate of at which substances are excreted into the urine depends upon three factors •  Glomerular filtration •  Reabsorption of substances from

the renal tubules into the blood •  Secretion of substances from the

blood into the renal tubules

•  Urinary excretion rate = filtration rate - reabsorption rate + secretion rate



Kidneys: Glomerular Filtration Determinants of Glomerular Filtration •  The GFR is determined by net filtration

pressure and capillary filtration coefficient, such that •  GFR = Kf x net filtration pressure

•  Net filtration pressure •  Favored by glomerular hydrostatic

pressure (PG) and Bowman’s capsule colloid osmotic pressure (πB)

•  Typically, πB ~ 0 •  Opposed by glomerular capillary colloid

osmotic pressure (πG) and Bowman’s capsule hydrostatic pressure (PB)

•  Net filtration pressure = PG - PB - πG + πB

•  Thus, GFR = Kf x (PG - PB - πG + πB) Guyton & Hall. Textbook of Medical Physiology, 11th Edition

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Kidneys: Glomerular Filtration Determinants of Glomerular Filtration •  Changes in glomerular hydrostatic pressure are

the primary mechanism for the physiological regulation of GFR •  Increases in glomerular hydrostatic pressure

cause an increase in GFR •  Glomerular hydrostatic pressure is determined

by •  Arterial pressure

•  Increased arterial pressure increases glomerular hydrostatic pressure and thus increases GFR

•  Afferent arteriolar resistance •  Increased resistance reduces glomerular

hydrostatic pressure and thus decreases GFR

•  Efferent arteriolar resistance •  Increased resistance (up to a point!)

reduces glomerular capillary outflow, increases glomerular hydrostatic pressure and thus increases GFR

Understand this effect



Kidneys: Tubular Processing of Glomerular Filtrate Reabsorption and Secretion Along the Nephron •  The concentration of molecules along the

nephron are a result of both the individual molecules’ transport as well as the transport of water

•  Sodium is highly transported, but its concentration does not change as water is also highly removed

•  Glucose concentration falls dramatically, as it is transported much more quickly than water

•  Creatinine and urea increase in concentration

•  Toxic substances are highly filtered and secreted, and little reabsorption occurs


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Kidneys: Tubular Processing of Glomerular Filtrate Summary of Tubular Reabsorption and Secretion


know this

figure


Carbohydrate Metabolism ATP Formation From Glucose •  During glycolysis, 4 molecules of ATP are formed, and 2 are expended to cause the

initial phosphorylation of glucose - giving a net gain of 2 molecules of ATP •  During each citric acid cycle, 2 molecules of ATP are formed, 1 from each pyruvic

acid molecules formed from glucose •  During glucose breakdown, a total of 24 hydrogen atoms are released during

glycolysis and the citric acid cycle •  20 H atoms are oxidized in oxidative phosphorylation, with the release of 3 ATP

molecules per 2 atoms of hydrogen metabolized, giving 30 ATP molecules •  4 H atoms hydrogen atoms are released by their dehydrogenase in oxidative

phosphorylation; 2 ATP molecules are usually released for every 2 H atoms oxidized, thus giving 4 ATP molecules

•  Thus a maximum of 38 ATP molecules formed for each molecule of glucose degraded to carbon dioxide and water •  Thus, 456,000 calories of energy can be stored as ATP, whereas 686,000

calories are released from glucose, giving an overall maximum efficiency of 66%

•  The remaining 34% becomes heat

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Lipid Metabolism Transport of Lipids in the Body Fluids •  Almost all fats, broken down into monoglycerides and fatty acids, are absorbed from

the intestines and into the intestinal lymph

•  In intestinal epithelial cells, triglycerides are reformed and dispersed as chylomicron droplets, with the protein apoprotein B decorating their surface •  Chylomicrons contain 87% triglycerides, 9% phospholipids, 3% cholesterol, 1%

apoprotein B •  After eating, chylomicrons constitute 1 - 2% of plasma volume

•  The capillary endothelium of the liver and adipose tissue contain lipoprotein lipase, which hydrolyzes triglycerides within the chylomicrons and thus releasing fatty acids and glycerol •  Constituents are absorbed by surrounding cells and resynthesized into

triglycerides


Protein Metabolism Transport and Storage •  Upon food digestion, almost all proteins are digested and absorbed in the form of

amino acids - rarely are polypeptides or proteins absorbed into the blood

•  The normal blood concentration of amino acids is between 35 and 65 mg/dl •  Concentration rises only slightly after eating, due to

•  Digestion and absorption occur over the course of hours •  Amino acid uptake by tissues, especially the liver, is quick

•  Amino acids are too large for diffusion through cell membranes, thus are taken up by facilitated transport or active diffusion

•  In the kidneys, amino acids are actively reabsorbed by the proximal tubular epithelium

•  Absorbed amino acids are quickly reused in protein synthesis, thus storage of amino acids is low •  Cells do contain small quantities of amino acids, releasable during deficiency •  The liver contains proteins that are easily broken down for use as a amino acids •  Excess amino acids can be converted into energy, fat, or glycogen

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Liver Physiology •  The liver is the largest internal organ of the body,

weighing about 1.5 kg •  The functional unit of the liver is the liver lobule, a

cylindrical structure 2 - 3 mm in length and 1 - 2 mm in diameter •  A human liver contains 50,000 - 100,000

lobules

•  Briefly, blood enters the lobule from the portal vein (1050 ml/min) and hepatic artery (300 ml/min)

•  Blood then empties into the central vein, the hepatic vein, and then into the vena cava

•  Kupffer cells remove substances and bacteria from the blood, with the filtrate entering into Space of Disse and then into the lymphatic system

•  Liver cells, hepatocytes, also remove unwanted substances, with the filtrate entering the bile canaliculi and the bile duct



Liver Bilirubin •  Bilirubin is absorbed through the hepatic cell

membrane, released from albumin and then conjugated •  80% forms bilirubin glucuronide •  10% forms bilirubin sulfate •  10% forms other substances

•  Finally, most of these conjugated forms of bilirubin are excreted •  In the intestine, bacteria convert some into

urobilinogen, which is taken back up into the blood

•  Most returns to the liver, but about 5% leaves through the kidneys as urine


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Energetics Introduction



Energetics Metabolic Rate •  A 70 kg man in bed consumes 1650 kcal per day •  Eating and digestion consumes an additional 200

kcal per day •  Sitting without exercising consumes an additional

150 to 400 kcal per day •  Thus, a sedentary man consumes about 2000

kcal per day

•  The minimal amount of energy needed to exist is defined as the basal metabolic rate (BMR) and accounts for 50 - 70% of daily energy needs in a sedentary person •  Normal BMR is 65 - 70 kcal per hour •  Skeletal muscle accounts for 20 - 30% of

BMR •  BMR falls dramatically with age, following the

loss in skeletal muscle


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Respiration: Ventilation, Circulation, & Transport

Adapted From:

Textbook Of Medical Physiology, 11th Ed. Arthur C. Guyton, John E. Hall

Chapters 37, 38, 39, & 40

John P. Fisher


Pulmonary Ventilation Alveolar Ventilation

•  There are about 16 generations of conducting airways •  The trachea (Z = 0), which bifurcate into the two main

bronchi •  The bronchi (Z = 1), which divide into the lobar,

segmental and 4 to 5 further divisions of cartilaginous bronchi

•  The next eight generations (Z = 8 - 15) constitute progressively smaller, ciliated noncartilaginous bronchioles, the last of which is the terminal bronchiole which is about 0.5 mm in diameter

•  Total number of airways is approximately 216, or 65,000 •  An adult contains 300 million to 1 billion alveoli, with a

total alveolar surface area of 70 m2 •  The tracheal cross sectional area is about 2.5 cm2 and this

cross sectional area is approximatley constant until the third generation •  Cross sectional area then increases by approximately

7/5 per generation to 180 cm2 at the 16th generation

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Pulmonary Ventilation Pulmonary Volumes

•  Four volumes may be measured by spirometry •  Tidal Volume (VT)- the volume of air

inspired or expired with each normal breath (typically 500 ml)

•  Inspiratory Reserve Volume (IRV) - the extra volume of air that may be inspired in excess of the tidal volume (typically 3000 ml)

•  Expiratory Reserve Volume (ERV) - the extra volume of air that may be expired in excess of the tidal volume (typically 1100 ml)

•  Residual Volume (RV) - the volume of air remaining in the lungs after forceful expiration (typically 1200 ml)

•  Also, Minute Respiratory Volume is the tidal volume times the respiratory rate •  Typically, 500 ml/b x 12 b/min = 6 l/min



Pulmonary Circulation Blood Distribution

•  Thus, 3 zones of blood flow have been described •  Zone 1: No blood flow during the entire cardiac

cycle, as alveolar capillary pressure is never greater than alveolar air pressure

•  Zone 2: Intermittent blood flow, as only systolic pressures are high enough to push blood through the alveolar air pressure

•  Zone 3: Continuous blood flow, as alveolar capillary pressure is always higher than alveolar air pressure

•  A healthy, standing person has zone 2 flow in the apex and zone 3 flow in the lung base

•  A healthy person lying down has entirely zone 3 flow •  During exercise, pulmonary vascular pressure rise

high enough to ensure only zone 3 flow


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Pulmonary Circulation Blood Distribution

•  The movement of substances through the lung capillary membranes is similar to that observed in the peripheral tissues however •  Pulmonary capillary pressure is low (7

mmHg) •  Interstitial fluid pressure is lower than in

the peripheral tissue •  Pulmonary capillaries are leaky, so colloid

osmotic pressure is twice that observed in peripheral tissue, approaching 14 mmHg

•  Alveolar walls are extremely thin

•  When fluid forces are summed, a +1 mmHg filtration pressure is found, meaning that there is a slight movement of fluid from the capillaries into the lymphatic system



Pulmonary Gas Exchange Composition of Alveolar Air

•  The changing composition of air as it moves through respiration is provided below

•  Notes •  Atmospheric air is mostly nitrogen and oxygen •  Inspired air is almost completely humidified (relative humidity)

•  Humidification dilutes other gases’ concentrations •  Alveolar air is low in oxygen and high in carbon dioxide compared to both

humidified and expired air

Atmospheric Air Humidified Air Alveolar Air Expired Air Nitrogen, N2 597.0 mmHg 78.62% 563.4 mmHg 74.09% 569.0 mmHg 74.90% 566.0 mmHg 74.50% Oxygen, O2 159.0 mmHg 20.84% 149.3 mmHg 19.67% 104.0 mmHg 13.60% 120.0 mmHg 15.70% Carbon Dioxide, CO2 0.3 mmHg 0.04% 0.3 mmHg 0.04% 40.0 mmHg 5.30% 27.0 mmHg 3.60% Water, H2O 3.7 mmHg 0.50% 47.0 mmHg 6.20% 47.0 mmHg 6.20% 47.0 mmHg 6.20% Total 760.0 mmHg 100.0% 760.0 mmHg 100.0% 760.0 mmHg 100.0% 760.0 mmHg 100.0%

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Pulmonary Gas Exchange Diffusion Through the Respiratory Membrane

•  Some respiratory units lack for adequate blood flow, while others lack for adequate air flow - even though total ventilation and total pulmonary blood flow is normal

•  This imbalance may be described by the ventilation-perfusion ratio •  Here, alveolar ventilation (VA) and blood

flow (Q) are compared •  VA/Q = 0 means no alveolar ventilation •  VA/Q = ∞ means no blood flow

•  As VA/Q falls below normal, inadequate ventilation is observed: physiological shunt

•  As VA/Q rises above normal, inadequate blood flow is observed: physiological dead space •  This takes anatomical dead space into

account



Transport of Gas in Blood and Tissues Transport of Oxygen from Lungs to Tissues

•  Once in the systemic circulation and capillary bed, blood PO2 falls from 95 mmHg to 40 mmHg as the interstitial fluid takes up oxygen through pressure driven transport

•  Transport is a function of blood flow rate, with increasing rates increasing oxygen transport into the interstitial fluid up to the 95 mmHg limit

•  Transport is also a function of tissue consumption, with increasing consumption decreasing interstitial fluid PO2 or requiring a significant increase in flow to maintain interstitial fluid PO2

•  Cellular PO2 is low due to the cell’s consumption of oxygen, but still in great excess to the cell’s minimum level of 1 to 3 mmHg Guyton & Hall. Textbook of Medical Physiology,

11th Edition

12/12/12

47



•  Carbon dioxide moves in opposition to oxygen, but diffuses approximately 20 times as quickly •  Thus small pressure differences in carbon

dioxide are observed between cellular and interstitial space, interstitial space and capillary blood, and arterial and venous blood

•  Again, only one third of the capillary length is needed for “complete” carbon dioxide transport

•  Again, a decrease in blood flow increases interstitial fluid carbon dioxide pressure - and an increase in blood flow decreases interstitial fluid carbon dioxide pressure

•  Again, a increase in metabolism increases interstitial fluid carbon dioxide pressure and a decrease in metabolism decreases interstitial fluid carbon dioxide pressure




•  Normally, 97% of oxygen is carried by hemoglobin, while 3% is dissolved in the water solvent in blood

•  As blood PO2 increases, hemoglobin saturation increases, typically resting at about 97% under normal conditions •  Normally, 100 ml of blood carries 15 gm

hemoglobin which can bind oxygen at 1.34 ml / gm •  Thus, 100 ml of blood carries 20 ml of oxygen

bound to hemoglobin •  This is described as 20 volumes %

•  Upon passing through the capillaries, blood “gives up” about 5 ml of oxygen to the tissues •  25% utilization

•  During heavy exercise, up to 15 ml of oxygen is transported from the blood to the tissues •  75% utilization


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Transport of Gas in Blood and Tissues Transport of Carbon Dioxide

•  PCO2 of venous blood is 45 mmHg and contains 2.7 ml CO2/dl blood, while PCO2 of arterial blood is 40 mmHg and contains 2.4 ml CO2/dl blood •  Thus, for 100 ml of blood, only 0.3 ml of carbon

dioxide is transported in the dissolved form, or about 7% of total carbon dioxide

•  RBC produce an enzyme, carbonic hydrolase, which catalyzes the reaction of carbon dioxide with water, forming carbonic acid •  Carbonic acid dissociates to H+ and HCO3

-

•  H+ bind with hemoglobin •  HCO3

- diffuse into the plasma, exchanging with Cl-

•  Carbonic acid mechanism accounts for 70% of normal carbon dioxide transport

•  Carbon dioxide also binds with amine radicals of hemoglobin, forming carbaminohemoglobin •  Carbamino transport accounts for about 20% of

normal carbon dioxide transport Guyton & Hall. Textbook of Medical Physiology, 11th Edition

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