Chapter 16

Lecture Outline

Copyright © 2016 McGraw-Hill Education. Permission required for reproduction or display. 1

I. The Respiratory System
 1. Introduction

1. Includes:
a. Ventilation (breathing) – mechanical process
that moves air into and out of the lungs
b. Gas exchange between blood and lungs and
between blood and tissues
c. Oxygen utilization by tissues to make ATP –
cellular respiration
2. Ventilation and gas exchange in lungs = external
respiration
3. Oxygen utilization and gas exchange in tissues =
internal respiration
 Introduction, cont

4. Gas exchange in lungs

a. Occurs via diffusion
b. O2 concentration is higher in the lungs than in
the blood, so O2 diffuses into blood.
c. CO2 concentration in the blood is higher than in
the lungs, so CO2 diffuses out of blood.
 Introduction, cont

5. Anatomically divided into:

a. Conduction zone: gets air to the respiratory
zone
b. Respiratory zone: site of gas exchange
 1. Structure of the respiratory system
1. Alveoli
a. Air sacs in the lungs where gas exchange
occurs
b. 300 million of them
1) Provide large surface area (760 square feet)
to increase diffusion rate
c. Each alveolus is one-cell layer thick
d. Form clusters at the ends of respiratory
bronchioles
 1. Alveolar Cells

1) Type I: 95−97% total surface area where gas

exchange occurs
2) Type II: secrete pulmonary surfactant and
reabsorb sodium and water, preventing fluid
buildup within the alveoli
Relationship between lung alveoli &
pulmonary capillaries
Micrographs of Alveoli

Blood
capillary

0.3 m
Type IV collagen protein

bronchiole
1. Pathway of air

Air travels down the nasal cavity 

Pharynx ( 咽 )
Larynx ( 喉 )(through the glottis and vocal cords) 
Trachea 
Right and left primary bronchi 
Secondary bronchi 
Tertiary bronchi  (more branching) 
Terminal bronchioles 
Respiratory zone (respiratory bronchioles) 
Terminal alveolar sacs
 Conducting and Respiratory Zones

Air sacs
Trachea and Respiratory Bronchi
 1. Functions of Conducting Zone

a. Transports air to the lungs

b. Warms, humidifies, filters, and cleans the air
1) Mucus traps small particles, and cilia move it
away from the lungs.
c. Voice production in the larynx as air passes over
the vocal folds
Larynx showing true & false vocal cords

聲門
食道
 1. Thoracic Cavity
1. Contains the heart, trachea, esophagus, and thymus within
the central mediastinum
2. The lungs fill the rest of the cavity.
a. The parietal pleura ( 體壁胸膜 ) lines the thoracic wall.
b. The visceral pleura ( 臟層胸膜 ) covers the lungs.
c. The parietal and visceral pleura are normally pushed
together, with a potential space between called the
intrapleural space (pleural cavity).
3. The diaphragm is a dome-shaped skeletal muscle of
respiration that separates the thoracic and abdominal
cavities
Thoracic Cavity Cross Section
X-ray of the Lungs
II. Physical Aspects of
Ventilation
 1. Introduction

1. Air moves from higher to lower pressure.

2. Pressure differences between the two ends of the
conducting zone occur due to changing lung
volumes.
3. Compliance, elasticity, and surface tension are
important physical properties of the lungs.

Compliance : Ease of which the lung can expand under

pressure
 B. Intrapulmonary and Intrapleural Pressures

1. Types of pressure
a. Atmospheric pressure: pressure of air outside
the body
b. Intrapulmonary or intraalveolar pressure:
pressure in the lungs
c. Intrapleural pressure: pressure within the
intrapleural space (between parietal and
visceral pleura); contains a thin layer of fluid to
serve as a lubricant
 1. Pressure Differences When Breathing

a. Inspiration (inhalation): Intrapulmonary pressure is

lower than atmospheric pressure.
1) Pressure below that of the atmosphere is called
subatmospheric or negative pressure
2) Generally about -3 mm Hg
b. Expiration (exhalation): Intrapulmonary pressure is
greater than atmospheric pressure.
1) Generally about +3mm Hg
Pressure Changes in Normal Breathing

-) -)
 1. Intrapleural Pressure

a. Lower than intrapulmonary and atmospheric

pressure in both inspiration and expiration
b. The difference between intrapulmonary and
intrapleural pressure is called the transpulmonary
pressure.
c. Keeps the lungs against the thoracic wall and
allows the lungs to expand during inspiration
 1. Boyle’s Law (V=K/P, 體積與壓力成反比 )

a. States that the pressure of a gas is inversely

proportional to its volume
b. An increase in lung volume during inspiration
decreases intrapulmonary pressure to
subatmospheric levels - Air goes in.
c. A decrease in lung volume during expiration
increases intrapulmonary pressure above
atmospheric levels - Air goes out.
 1. Physical Properties of the Lungs

1. Lung compliance
a. Lungs can expand when stretched.
b. Defined as the change in lung volume per
change in transpulmonary pressure:
ΔV/ΔP
c. The ease with which the lungs expand under
pressure
d. Reduced by factors that produce a resistance to
distention such as the infiltration of connective
tissue proteins in pulmonary fibrosis
 1. Elasticity

a. Lungs return to initial size after being stretched

(recoil)
b. Lungs have lots of elastin fibers.
c. Because the lungs are stuck to the thoracic wall,
they are always under elastic tension.
d. Tension increases during inspiration and is
reduced by elastic recoil during expiration
 1. Surface Tension

a. Resists distension
b. Exerted by fluid secreted on the alveoli
c. Fluid is absorbed by active transport of Na + and
secreted by active transport of Cl -
d. Raises the pressure of the alveolar air as it acts to
collapse the alveolus
e. People with cystic fibrosis have a genetic defect
that causes an imbalance of fluid absorption and
secretion
 1. Law of Laplace

1) Pressure is directly proportional to surface tension

and inversely proportional to radius of alveolus.
2) Small alveoli would be at greater risk of collapse
without surfactant.
Law of Laplace
 D. Surfactant & Respiratory Distress Syndrome

1. Surfactant – surface active agent

a. Secreted by type II alveolar cells
b. Consists of hydrophobic protein and phospholipids
c. Reduces surface tension between water
molecules by reducing the number of hydrogen
bonds between water molecules
d. More concentrated as alveoli get smaller during
expiration
e. Prevents collapse
f. Allows a residual volume of air to remain in lungs
Production of Pulmonary Surfactant
 1. Respiratory Distress Syndrome (RDS)

a. Production of surfactant begins late in fetal

life, so premature babies may be born with
a high risk for alveolar collapse called
respiratory distress syndrome (RDS);
treated with surfactant
b. A similar problem may occur in adults
caused by septic shock, reduced lung
compliance and reduced surfactant – acute
respiratory distress syndrome (ARDS); is
not treatable with surfactant
III. Mechanics of Breathing
 1. Introduction

1. Breathing is also called pulmonary ventilation

a. Inspiration: breathe in
b. Expiration: breathe out
2. Accomplished by changing thoracic cavity/ lung
volume
3. Thorax must be rigid enough for protection yet
flexible enough to act as bellows for breathing
Changes in lung volume during breathing

Expiration Inspiration
 1. Inspiration and expiration
1. Muscles involved in breathing
a. Diaphragm most important.
1) Contracts in inspiration – lowers, making the
thoracic cavity larger
2) Relaxes in expiration – raises, making the
thoracic cavity smaller
b. External intercostal muscles – raises the rib
cage during inspiration
c. Internal intercostal muscles – lowers the rib
cage during forced expiration
d. Parasternal intercostal muscles – works with the
external intercostals
 Muscles Involved in Breathing

胸鎖骨乳突肌

Contracts
斜角肌

Contracts
Contracts

Contracts

Contracts
 Muscles involved in breathing, cont

1. The scalenes ( 斜角肌 ), pectoralis minor ( 胸小肌 ), and

sternocleidomastoid ( 胸鎖骨乳突肌 ) are used for forced
inspiration
2. Quiet expiration occurs with the relaxation of the
inspiratory muscles (passive process)
3. Abdominal muscles are also used for forced
expiration
 1. Mechanisms of Breathing

a. Inspiration: Volume of thoracic cavity (and lungs) increases

vertically when diaphragm contracts (flattens) and laterally
when parasternal and external intercostals raise the ribs.
1) Thoracic & lung volume increase  intrapulmonary
pressure decreases  air in
b. Expiration: Volume of thoracic cavity (and lungs) decreases
vertically when diaphragm relaxes (dome) and laterally
when external and parasternal intercostals relax for quiet
expiration or internal intercostals contract in forced
expiration to lower the ribs.
1) Thoracic & lung volume decrease  intrapulmonary
pressure increases  air out
Quiet (Normal) vs. Forced Ventilation
Mechanisms of Pulmonary Ventilation
1. Pulmonary Function Tests

1. Spirometry( 肺功能量計 ): Subject breathes into and out

of a device that records volume and frequency of
air movement on a spirogram.
a. Measures lung volumes and capacities
b. Can diagnose restrictive and disruptive lung
disorders
 1. Lung Volume Measurements

a. Tidal volume (TV): amount of air expired or

inspired in quiet breathing (500 mL)
b. Expiratory reserve volume (ERV): amount of air
that can be forced out after tidal volume (1100
mL)
c. Inspiratory reserve volume (IRV): amount of air
that can be forced in after tidal volume (3000 mL)
d. Residual volume (RV): amount of air left in lungs
after maximum expiration (1100 mL)
 1. Lung Capacity Measurements

1. Vital capacity (VC=IRV+TV+ERV): maximum

amount of air that can be forcefully exhaled after a
maximum inhalation
2. Total lung capacity (TLC=IC+FRC): amount of gas
in the lungs after a maximum inspiration
3. Inspiratory capacity (IC=TV+IRV): amount of gas
that can be inspired after a normal expiration
4. Functional residual capacity (FRC=ERV+RV):
amount of gas left in lungs after a normal
expiration
4. Relationship between lung volume and capacity

1. Vital capacity = inspiratory reserve volume +

expiratory reserve volume + tidal volume
2. Functional residual capacity = residual volume
+ expiratory reserve volume
3. Total minute volume = tidal volume X breaths
per minute (~ 6L/min)
 Lung Volumes and Capacities

Spirogram:

(VC=IRV+TV+ERV)
(IRV)

(TV) (ERV)

(RV) (FRC=ERV+RV)
Ventilation Terminology

呼吸暫停
呼吸困難

氣胸
5. Restrictive and Obstructive Disorders

a. Restrictive: Lung tissue is damaged. Vital capacity

is reduced, but forced expiration is normal.
1) Examples: pulmonary fibrosis and emphysema
(inhalation that fills the lungs far less than would be expected in a
healthy person)
b. Obstructive: Lung tissue is normal. Vital capacity
is normal, but forced expiration is reduced.
1) Example: asthma
(obstruction defined by exhalation that is slower and shallower than in
someone without the disease.)
Restrictive vs Obstructive Lung Disease

https://medizzy.com/feed/156472
c. Forced Expiratory Volume (FEV1) Test

1. Obstructive lung disorders are usually

diagnosed by doing forced expiratory volume
tests.
 D. Pulmonary Disorders

1. Asthma
a. Symptoms: dyspnea (shortness of breath) and
wheezing
b. Caused by inflammation, mucus secretion, and
constriction of bronchioles
c. Often called airway hyperresponsiveness
 Asthma, cont

d. Allergic (atopic) asthma: triggered by allergens

stimulating T lymphocytes to secrete cytokines and
recruit eosinophils and mast cells, which contribute
to inflammation
1) Can also be triggered by cold or dry air,
exercise, or aspirin
2) Causes production of IgE antibodies
3) Reversible with bronchodilator, such as
Albuterol
 2. Emphysema

a. Destruction of alveoli
b. Reduces surface area for gas exchange
c. With fewer alveoli to put pressure on bronchioles,
they collapse during expiration.
d. Smoking is the most common cause. It triggers
inflammation and destruction of alveoli by
immune cells
Emphysema destroys lung tissue

Normal Emphysema
 3. Chronic Obstructive Pulmonary Disease
(COPD)

a. Chronic inflammation, narrowing of the airways,

and alveolar destruction
b. Includes emphysema and chronic obstructive
bronchiolitis
c. Accelerated decline in FEV1
d. Inflammation involves macrophages, neutrophils,
and cytotoxic T cells
e. Excessive mucus production and inflammation
triggered by smoking
Chronic Obstructive Pulmonary Disease (COPD), cont

f. Most people with COPD smoke.

g. Smoking also promotes the infiltration of
obstructing fibrous tissue and muscle in the
airways and remodeling of blood vessels in the
lungs, leading to pulmonary hypertension.
h. May develop cor pulmonale – pulmonary
hypertension with hypertrophy and eventual failure
of the right ventricle
i. There is no cure.
j. 5th leading cause of death (estimated to move to
3rd by 2020)
 4. Pulmonary Fibrosis

a. Some people accumulate fibrous tissues in the

lungs when alveoli are damaged.
b. May be due to inhalation of small particles
c. Example: black lung (anthracosis) in miners
IV. Gas Exchange in the
Lungs
 1. Introduction

1. Measuring pressure
a. Atmospheric pressure can be measured using
a barometer
b. At sea level, the atmospheric pressure is 760
mmHg or one atmosphere
Measurement of Atmospheric Pressure
 2. Dalton’s Law

a. The total pressure of a gas mixture is equal to the

sum of the pressures of each gas in it.
b. Partial pressure: the pressure of an individual gas;
can be measured by multiplying the % of that gas
by the total pressure
1) O2 makes up 21% of the atmosphere, so partial
pressure of O2 = 760 X 20% = 159 mmHg.
 Dalton’s Law, cont

c. Total pressure
1) Nitrogen makes up 78% of the atmosphere, O2
21%, and CO2 1%.
Pdry = PN2 + PO2 + PCO2 = 760 mmHg

d. When air gets to our lungs, it is humid, so the

calculation changes to:
Pwet = PN2 + PO2 + PCO2 + PH2O= 760 mmHg
 3. Calculation of PO2

a. Addition of water vapor also takes away from the

total atmospheric pressure when calculating partial
pressure O2.
1) Pressure of water at 37°C is a constant 47
mmHg.
2) Partial pressure O2 at sea level:
0.21(760 − 47) = 150 mmHg
 1. Result of Gas Exchange

a. In the alveoli, the percentage of oxygen decreases

and CO2 increases, changing the partial pressure
of each.
Partial Pressure of Gases
 Partial Pressure Oxygen

Changes with altitude and location

玉山 : 12,970 呎
1. Partial Pressure of Gases in Blood

1. Alveoli and blood capillaries quickly reach

equilibrium for O2 and CO2.
a. This helps maximize the amount of gas
dissolved in fluid.
b. Henry’s Law predicts this.
1. Henry’s Law

a. The amount of gas that can dissolve in liquid

depends on:
1) Solubility of the gas in the liquid (constant)
2) Temperature of the fluid (more gas can
dissolve in cold liquid); doesn’t change for
blood
3) Partial pressure of the gases, the
determining factor
Relationship Between Alveoli and Capillaries
Blood Gas Measurement
 C. Significance of blood PO2 and PCO2
measurements

1. Only measures oxygen dissolved in the blood

plasma. It will not measure oxygen bound to
hemoglobin in red blood cells.
2. It does provide a good measurement of lung
function.
3. When lungs are functioning properly, PO2 of
systemic arterial blood is only 5mm Hg less than
PO2 of alveolar air
a. At normal PO2 of about 100mmHg, hemoglobin
is almost completely filled with O2
b. Oxyhemoglobin saturated of 97%
 Significance of blood PO2 and PCO2 measurements,
cont

c. Adding more O2 will not significantly change the

amount of O2 in RBCs, but can increase the
amount of dissolved oxygen
d. Since O2 must dissolve in the plasma before it
can be delivered to tissues, the rate of O2
diffusion would increase
4. Blood gas measurement of venous blood is not
very useful
Partial Pressure of Gas in Blood
D. Pulmonary Circulation & Ventilation/Perfusion

1. The rate of blood flow through the lungs is equal

to that through the systemic circuit (5.5 L/minute
cardiac output).
2. Systemic circulation pressure difference is about
100mm Hg (arterial pressure:100 mmHg; right
atrium: 0 mmHg)
3. The pressure difference between the left atrium
and the pulmonary artery is only 10 mmHg.
4. Vascular resistance must be very low.
a. Low pressure/low resistance pathway
b. Reduces possibility of pulmonary edema (less
filtration pressure)
右心房→右心室→肺動脈→小動脈→肺部微血管→肺靜脈→左心房→左心室
 Pulmonary Circulation & Ventilation/Perfusion, cont

5. Pulmonary arterioles constrict when alveolar

partial pressure O2 is low and dilate when partial
pressure O2 is high.
a. Blood flow to alveoli is increased when they are
full of oxygen and decreased when not.
Pulmonary Circulation & Ventilation/Perfusion, cont

b. Opposite of systemic arterioles that constrict

when partial pressure O2 in tissues is high. This
ensures that only tissues that need oxygen are
sent blood.

(supply more blood an

oxygen to the tissues)
 6. Arteriole Response to O2

a. Low oxygen depolarizes smooth muscle cells of

the arteriole wall by inhibiting outward flow of K+.
b. This opens voltage-gated Ca2+ channels, which
stimulate contraction.
c. The response of pulmonary arterioles to low
oxygen levels makes sure that ventilation (O2 into
lungs) matches perfusion (blood flow).
 Lung Ventilation/Perfusion Ratios

Overventilated

Underventilated
 1. Disorders Caused by High Partial
Pressure of Gases

1. Problems for deep-sea divers

2. Oxygen toxicity: 100% oxygen is dangerous at 2.5
atmospheres; due to oxidation of enzymes
3. Nitrogen narcosis: occurs if nitrogen is inhaled
under pressure; results in dizziness and
drowsiness
4. Decompression sickness: When a diver comes to
the surface too fast, nitrogen bubbles can form in
the blood and block small vessels.
5. Can also happen if an airplane suddenly loses
pressure
Nitrogen narcosis
V. Regulation of Breathing
 1. Introduction

1. Contraction and relaxation of breathing muscles is

controlled by motor neurons from two areas of the
brain.
a. Voluntary breathing: from cerebral cortex
b. Involuntary breathing: from respiratory control
centers of the medulla oblongata and pons
 1. Brain stem Respiratory Centers

1. Motor neurons
a. Those that innervate the diaphragm from the
phrenic nerve and arise from the cervical region
of the spinal cord.
b. Those that innervate the other breathing
muscles arise from the thoracolumbar region of
the spinal cord.
c. Regulated by descending neurons from the
brain.
 1. Medulla Oblongata
a. Rhythmicity center: four types of neurons
identified for different stages of breathing
1) Dorsal respiratory group: made up of
inspiratory neurons (I neurons) that stimulate
neurons of the phrenic nerve
2) Ventral respiratory group: made up of
inspiratory neurons that stimulate spinal
respiratory neurons and expiratory neurons (E
neurons) that inhibit the phrenic nerve
b. Activity of I and E neurons vary in a reciprocal way
to produce the rhythmic pattern of breathing
 1. Pons

a. Influences medulla activity

b. Apneustic center: promotes inspiration
c. Pneumotaxic center: inhibits inspiration

4. Brainstem respiratory centers control breathing

largely via the phrenic nerve from C3-C6 spinal
nuclei
Brain Stem Respiratory Centers
 1. Chemoreceptors

a. Automatic control of breathing is influenced by

feedback from chemoreceptors, which monitor pH
of fluids in the brain and pH, PCO2 and PO2 of the
blood.
1) Central chemoreceptors in medulla
2) Peripheral chemoreceptors in carotid and aorta
arteries
 1. Aortic and Carotid Bodies

1) Aortic body sends feedback to medulla along

vagus nerve.
2) Carotid body sends feedback to medulla along
glossopharyngeal nerve.
Sensory Input From Aortic and
Carotid Bodies
Regulation of Ventilation by the CNS

vagus nerve
glossopharyngeal nerve
 C. Effects of pH and PCO2 on Ventilation

1. When ventilation is inadequate, CO2 levels rise

and pH falls. (hypercapnia 高碳酸血症 )
CO2 + H2O  H2CO3  H+ + HCO3-
2. In hyperventilation, CO2 levels fall and pH rises.
(hypocapnia)
3. Oxygen levels do not change as rapidly because
of oxygen reserves in hemoglobin, so O 2 levels are
not a good index for control of breathing.
4. Ventilation is controlled to maintain constant levels
of CO2 in the blood. Oxygen levels naturally
follow.
Effects of PCO2 on Ventilation
 1. Chemoreceptors in the Medulla

a. When increased CO2 in the fluids of the brain

decrease pH, this is sensed by chemoreceptors in
the medulla, and ventilation is increased.
b. Senses CO2, not H+ which does not cross the
blood-brain barrier
c. Takes longer, but responsible for 70−80% of
increased ventilation
Chemoreceptors in the Medulla
 1. Peripheral Chemoreceptors

a. Aortic and carotid bodies respond to rise in H +

due to increased CO2 levels.
b. Respond much quicker
Chemoreceptor Control of Breathing
D. Effect of Blood PO on Ventilation
2

1. Indirectly affects ventilation by affecting

chemoreceptor sensitivity to PCO2
2. Low blood O2 makes the carotid bodies more
sensitive to CO2.
3. Hypoxic drive – carotid bodies respond directly
to low oxygen dissolved in the plasma (below
70mmHg)
 ventilation

Hypoxia
European Respiratory Journal 2008 32: 1386-1398; DOI: 10.1183/09031936.00056408
Comparing the effects of blood CO2
and O2 on breathing

hypercapnic drive

hypoxic drive
Sensitivity of Chemoreceptors to Changes
in Blood Gases and pH
E. Effects of Pulmonary Receptors on Ventilation

1. Unmyelinated C fibers in the lungs: affected by

capsaicin ( 辣椒素 ); produce rapid shallow breathing
when a person breathes in pepper spray
2. Receptors that stimulate coughing:
a. Irritant receptors: in wall of larynx; respond to
smoke, particulates, etc.
b. Rapidly adapting receptors: in lungs; respond to
excess fluid
Effects of Pulmonary Receptors on Ventilation, cont

3. Hering-Breuer reflex: stimulated by pulmonary

stretch receptors
a. Inhibits respiratory centers as inhalation
proceeds
b. Makes sure you do not inhale too deeply
VI. Hemoglobin and Oxygen
Transport
 1. Introduction

1. Plasma O2 concentration in systemic arteries is

about 0.3mL/100mL blood
2. Total O2 content of blood depends on PO2 and
hemoglobin concentration
Oxygen Content of Blood
1. Hemoglobin

1. Most of the oxygen in blood is

bound to hemoglobin.
a. 4 polypeptide globins (2 alpha
and 2 beta chains) and 4 iron-
containing hemes
b. Each hemoglobin can carry 4
molecules O2.
c. 280 million hemoglobin/RBC
d. Each RBC can carry over a
billion O2 molecules
Structure of Hemoglobin
 1. Forms of Hemoglobin

a. Oxyhemoglobin/reduced (deoxyhemoglobin)
hemoglobin: Iron is in reduced form (Fe2+) and can
bind with O2.
b. Methemoglobin: Oxidized iron (Fe3+) can’t bind to
O2.
1) Abnormal; some drugs cause this.
c. Carboxyhemoglobin: Hemoglobin is bound with
carbon monoxide; has a stronger bond with CO
than with O2
d. Each type has a unique color and absorption
spectrum
(Fe2+)
(Fe3+)
 1. % Oxyhemoglobin Saturation

1. % oxyhemoglobin to total hemoglobin

2. Measured to assess how well lungs have
oxygenated the blood
3. Normal is 97%
4. Measured with a pulse oximeter or blood– gas
machine
 1. Hemoglobin Concentration

a. Oxygen-carrying capacity of blood is measured

by its hemoglobin concentration.
1) Anemia: below-normal hemoglobin levels
2) Polycythemia: above-normal hemoglobin
levels; may occur due to high altitudes

b. Erythropoietin made in the kidneys stimulates

hemoglobin/RBC production in red bone marrow
when O2 levels are low.
 1. Loading and Unloading

a. Loading: when hemoglobin binds to oxygen in the

lungs
b. Unloading: when oxyhemoglobin drops off oxygen in
the tissues

deoxyhemoglobin + O2 oxyhemoglobin
c. Direction of reaction depends on PO2 of the
environment and affinity for O2.
1) High PO2 favors loading.
2) Strong bond favors loading and inhibits unloading
 1. The oxyhemoglobin dissociation curve
1. Oxygen unloading
a. Systemic arteries have a PO2 of 100 mmHg.
1) This makes enough oxygen bind to get 97%
oxyhemoglobin.
2) 20 ml O2/100 ml blood
b. Systemic veins have a PO2 of 40 mmHg.
1) This makes enough oxygen bind to get 75%
oxyhemoglobin.
2) 15.5 ml O2/100 ml blood
c. 22% oxygen is unloaded in tissues
PO2 and % Oxyhemoglobin
 Oxygen Dissociation Curve, cont

2. Oxygen remaining in veins serves as an oxygen

reserve.
3. The curve is sigmoidal (S-shaped) – at high P O2,
changes in PO2 have little effect on loading
4. At the steep part of the curve, small changes
produce large changes in % saturation
5. Oxygen unloading during exercise is even greater:
a. 22% at rest
b. 39% light exercise
c. 80% heavy exercise
Oxygen Dissociation Curve

22%
 1. Effect of pH and Temperature on
Oxygen Transport

1. pH and temperature change the affinity of

hemoglobin for O2.
a. This ensures that muscles get more O2 when
exercising.
2. Affinity decreases at lower pH and increases at
higher pH = Bohr effect.
a. More unloading occurs at lower pH.
b. Increased metabolism = more CO2 = lower pH
c. More O2 unloading
d. Curve shifts to the right
Effect of pH and Temperature on Oxygen
Transport
 Effect of pH and Temperature on Oxygen
Transport, cont

3. Hemoglobin affinity for O2 is decreased at

increased temperatures.
a. This further enhances the amount of O2
unloaded to muscles during exercise.
b. Curve shifts to the right
 1. Effect of 2,3-DPG on Oxygen Transport

1. RBCs obtain energy from the anaerobic

metabolism of glucose (has no nucleus or
mitochondria)
a. During this process, 2,3 diphosphoglyceric acid
(2,3-DPG) is made.
b. Inhibited by oxyhemoglobin
c. 2,3-DPG is produced if a person is anemic or at
high altitude.
d. This increases oxygen unloading.
e. Shifts the oxyhemoglobin dissociation curve to
the right
Effect of 2,3-DPG on Oxygen Transport
Factors That Affect the Affinity of
Hemoglobin for O2
 1. Anemia

a. Total blood hemoglobin decrease

b. Adult hemoglobin (hemoglobin A) can bind to 2,3-
DPG, but fetal hemoglobin (hemoglobin F) cannot.
1) Hemoglobin F has 2 gamma chains instead of 2
beta chains
2) Fetal hemoglobin therefore has a higher affinity
for O2 than the mother, so oxygen is transferred
to the fetus.
 1. Inherited Hemoglobin Defects

1. Sickle-cell anemia: found in 8−11% of African

Americans
a. The affected person has hemoglobin S with a
single amino acid difference.
b. Deoxygenated hemoglobin S polymerizes into
long fibers, creating a sickle-shaped RBC.
c. This hinders flexibility and the ability to pass
through small vessels.
 Sickle-cell anemia, cont

d. Blood flow to organs is restricted, and RBCs

hemolyse.
e. Treated with hydroxyurea; stimulates production
of fetal hemoglobin without the defect
f. This defect imparts a high resistance to malaria
Sickle-cell Anemia
 Inherited Hemoglobin Defects, cont

2. Thalassemia: found mainly in people of

Mediterranean heritage
a. Production of either alpha or beta chains is
defective.
b. Increased synthesis of gamma chains
c. Many mutations are possible giving a wide
range of symptoms
 1. Muscle Myoglobin

1. Red pigment found in skeletal and cardiac muscles

2. Similar to hemoglobin, but with 1 heme, so it can
only carry 1 oxygen molecule
3. Higher affinity to oxygen; oxygen is only released
when PO2 is very low
4. Stores oxygen and serves as go-between in
transferring oxygen from blood to mitochondria
Myoglobin and Hemoglobin
Dissociation Curves
VII. Carbon Dioxide Transport
 1. Introduction

1. Carbon dioxide is carried in the blood in three

forms:
a. Dissolved in plasma (more soluble than O2)
b. As carbaminohemoglobin attached to an amino
acid in hemoglobin
c. As bicarbonate ions (accounts for the majority
of transport)
 Introduction, cont

2. Carbonic anhydrase
a. Carbon dioxide readily reacts with water in the
RBC of the systemic capillaries and plasma
b. Carbonic anhydrase is the enzyme that
catalyzes the reaction to form carbonic acid at
high PCO2

H2O + CO2 H 2CO3

 3. Formation of Bicarbonate and H+

a. Carbonic acid is a weak acid that will dissociation

into bicarbonate and hydrogen ions. This reaction
also uses carbonic anhydrase as the catalyst

H2CO3 H+ + HCO3−
 1. Chloride Shift

1. Once bicarbonate ion is formed in the RBC, it

diffuses into the plasma
2. H+ in RBCs attach to hemoglobin and attract Cl−.
3. The exchange of bicarbonate out of and
Cl− into RBCs is called the chloride shift.
Carbon Dioxide Transport & the Chloride Shift

Carbonic anhydrase
 1. Bohr Effect

a. Bonding of H+ to hemoglobin lowers the affinity for

O2 and helps with unloading.
b. This allows more H+ to bind, which helps the blood
carry more carbon dioxide.
 1. Reverse Chloride Shift

1. In pulmonary capillaries, increased PO2 favors the

production of oxyhemoglobin.
2. This makes H+ dissociate from hemoglobin and
recombine with bicarbonate to form carbonic acid:

H+ + HCO3− H2CO3

3. Chloride ion diffuses out of the RBC as

bicarbonate ion enters.
 Reverse Chloride Shift, cont

4. In low PCO2, carbonic anhydrase converts carbonic

acid back into CO2 + H2O:

H2CO3 CO2 + H2O

5. CO2 is exhaled.
Reverse Chloride Shift in the Lungs

Carbonic anhydrase
VIII. Acid- Base Balance of the
Blood
 A. Principles of Acid-Base Balance

1. Maintained within a constant range by the actions

of the lungs and kidneys
a. pH ranges from 7.35 to 7.45.
b. Since carbonic acid can be converted into a gas
and exhaled, it is considered a volatile acid;
regulated by breathing.
c. Nonvolatile acids (lactic, fatty, ketones) are
buffered by bicarbonate; can not be regulated
by breathing, but rather the kidneys
 2. Bicarbonate as a Buffer

a. Bicarbonate ion is a weak base and is the major

buffer in the blood
excess H+ + HCO3-  H2CO3

b. Buffering cannot continue forever because

bicarbonate will run out.
c. Kidneys help by releasing H+ in the urine and by
producing more bicarbonate.
Bicarbonate as a Blood Buffer
 1. Blood pH: Acidosis

a. Acidosis: when blood pH falls below 7.35

1) Respiratory acidosis: caused by

hypoventilation; rise of CO2 which increases
H+ (lowers pH)
2) Metabolic acidosis: caused by excessive
production of acids or loss of bicarbonate
(diarrhea)
 1. Blood pH: Alkalosis

a. Alkalosis: when blood pH rises above 7.45

1) Respiratory alkalosis: caused by
hyperventilation; “blow off” CO2, H+ decreases,
pH increases
2) Metabolic alkalosis: caused by inadequate
production of acids or overproduction of
bicarbonates, loss of digestive acids from
vomiting
b. Respiratory component of blood pH measured by
plasma CO2
c. Metabolic component measured by bicarbonate
Terms Used in Acid Base Balance
Classification of Metabolic & Respiratory
Components of Acidosis & Alkalosis
 1. Henderson-Hasselbalch Equation

a. Normal blood pH is maintained when bicarbonate

and CO2 are at a ratio of 20:1.

HCO3−
Ka: dissociation constant

pH = 6.1 + log -------------

0.03PCO2
b. Respiratory acidosis or alkalosis occurs with
abnormal CO2 concentration
c. Metabolic acidosis or alkalosis occurs with
abnormal bicarbonate concentration
 B. Ventilation and Acid-Base Balance

1. Ventilation controls the respiratory component of

acid-base balance.
a. Hypoventilation: Ventilation is insufficient to
“blow off” CO2. PCO2 is high, carbonic acid is
high, and respiratory acidosis occurs.
b. Hyperventilation: Rate of ventilation is faster
than CO2 production. Less carbonic acid forms,
PCO2 is low, and respiratory alkalosis occurs.
 Ventilation and Acid-Base Balance, cont

2. Ventilation can compensate for the metabolic

component.
a. A person with metabolic acidosis will
hyperventilate; “blow off” CO2, H+ decreases,
pH rises
b. A person with metabolic alkalosis will
hypoventilate; slow respiration, build up CO2, H+
increases, pH lowers
Effect of Lung Function on Blood Acid-Base Balance
IX. Effect of Exercise and High
Altitude on Respiratory
Function
 1. Ventilation During Exercise

1. Exercise produces deeper, faster breathing to

match oxygen utilization and CO2 production.
a. Called hyperpnea

2. Neurogenic and humoral mechanisms control this.

 1. Proposed Neurogenic Mechanisms

a. Sensory nerve activity from exercising muscles

stimulates respiration via spinal reflexes or brain
stem respiratory centers.
b. Cerebral cortex stimulates respiratory centers.
c. Helps explain the immediate increase in ventilation
at the beginning of exercise
 1. Humoral Mechanisms

a. Rapid and deep breathing continues after exercise

is stopped due to humoral (chemical) factors.
1. PCO2 and pH differences at sensors
2. Cyclic variations that are not detected by blood
samples that affect chemoreceptors
Effect of exercise on arterial blood gases & pH
 1. Lactate Threshold

a. Ventilation does not deliver enough O2 at the

beginning of exercise.
1) Anaerobic respiration occurs at this time.
2) After a few minutes, muscles receive enough
oxygen.
b. If heavy exercise continues, lactic acid
fermentation will be used again.
1) The lactate threshold is the maximum rate of
oxygen consumption attained before lactic acid
levels rise.
 Lactate Threshold, cont

c. Occurs when 50−70% maximum oxygen uptake is

reached
1) Due to aerobic limitations of the muscles, not
the cardiovascular system (still at 97% oxygen
saturation)
2) Endurance exercise training increases
mitochondria and Krebs cycle enzymes in the
muscles
Changes in Respiratory Function During Exercise
 1. Acclimation to High Altitude

1. Adjustments must be made to compensate for

lower atmospheric PO2.
a. Changes in ventilation ()
b. Hemoglobin affinity for oxygen ()
c. Total hemoglobin concentration
Blood Gas Measurements at
Different Altitudes
 1. Changes in Ventilation

a. Hypoxic ventilatory response: Decreases in PO2

stimulate the carotid bodies to increase ventilation.
1) Hyperventilation lowers PCO2, causing
respiratory alkalosis.
2) Kidneys increase urinary excretion of
bicarbonate to compensate.
3) Chronically hypoxic people produce NO in the
lungs, a vasodilator that increases blood flow.
4) NO bound to sulfur atoms (SNOs) in
hemoglobin may stimulate the rhythmicity
center in the medulla.
 3. Affinity of Hemoglobin for Oxygen

a. Oxygen affinity decreases, so a higher proportion

of oxygen is unloaded.
b. Occurs due to increased production of 2,3-DPG
c. At extreme high altitudes, effects of alkalosis will
override this, and affinity for oxygen will increase.
 1. Increased Hemoglobin Production

a. Kidney cells sense decreased PO2 and produce

erythropoietin.
1. This stimulates bone marrow to produce more
hemoglobin and RBCs.
2. Increased RBCs can lead to polycythemia, which
can produce pulmonary hypertension and more
viscous blood.
Changes During Acclimatization to High Altitude
 Respiratory Adaptations to High Altitude

① Changes in ventilation
② Hemoglobin affinity for oxygen
③ Total hemoglobin concentration