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Chapter 23 – Part 2 – Respiration Physiology!
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Chapter 23, Part 2!Respiration Physiology!
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SECTION 23-6!External respiration and internal respiration allow gaseous exchange within the body!
Chapter 23 – Part 2 – Respiration Physiology!
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Respiration Physiology Overview!
1. Pulmonary ventilation!• Exchange of gases between air and lungs
2. External respiration!• Exchange of gases between lungs and blood
3. Internal respiration!• Exchange of gases between blood and
tissuesCellular respiration (Chapter 25)!
• Use of oxygen and substrates by cells to produce ATP, CO2, H2O and heat!
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SECTION 23-7!External respiration and internal respiration allow gaseous exchange within the body!
Chapter 23 – Part 2 – Respiration Physiology!
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Boyle’s Law !
The volume of a fixed quantity of gas (at constant temperature) is inversely proportional to pressure.!
V α 1 ! P !
⎯ OR ⎯ Pi • Vi = Pf • Vf!
(V = volume; P = pressure; i = initial; f = final)
I.e. If volume goes up, pressure goes down.!https://www.grc.nasa.gov/www/k-12/airplane/boyle.html!!
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Pressure-Volume Relationships Figure 23-12!
Chapter 23 – Part 2 – Respiration Physiology!
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Ventilation Mechanisms Figure 23-13!
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Inspiration!Quiet breathing:!
• Diaphragm contracts, flattens!• Thoracic cavity volume increases!• Lung volume increases (see intrapleural
pressure, below)!• Alveolar (intrapulmonary) pressure decreases
below atmospheric pressure!• Air enters lungs (higher to lower pressure)!
Deep (forced) inspiration!• External intercostals pull ribs up and out!• Others: scalenes, sternocleidomastoids!
Chapter 23 – Part 2 – Respiration Physiology!
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Expiration!
Quiet breathing:!1. Diaphragm relaxes, resumes dome shape!2. Thoracic cavity and lung volumes decrease:!
a) Change in diaphragm shape!b) Elastic recoil of thoracic wall and lungs!
Forced breathing:!Contractions of internal intercostals, external obliques, internal obliques, transversus abdominis, rectus abdominis!
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Intrapleural pressure!
= Pressure between the two pleural membranes!Intrapleural pressure is always negative with
respect to atmospheric pressure and intrapulmonary (alveolar) pressures
Keeps lungs inflated, attached to body wall!Pneumothorax causes atelectasis:!Puncture of body wall →!Air enters intrapleural space (= pneumothorax)!
Intrapleural pressure = atmospheric pressure!Lung collapses or doesn’t fully inflate !
Chapter 23 – Part 2 – Respiration Physiology!
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Second!
Third!
First:!Diaphragm contracts!
Pressure Changes During Breathing Figure 23-14!Note units on scale; Blue arrow = atmospheric pressure
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Lung Compliance!
High compliance means lungs and thoracic cage are easily expanded!
Low compliance = not easily expanded!Compliance normally high:!
1. Elastic fibers of lung tissue!2. Surfactant decreases surface tension in small
airways and somewhat decreases the work necessary to inflate the lungs!
Decreased compliance:!• Scar tissue (tuberculosis), excess tissue fluid
(pulmonary edema), decreased surfactant (respiratory distress syndrome)!
Chapter 23 – Part 2 – Respiration Physiology!
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Respiratory Rates and Volumes!
Respiratory minute volume!= volume of air moved (exchanged) per minute!= breaths/min x tidal volume (volume/breath)!
.!VE = f x VT!
Alveolar ventilation rate!= volume of air actually entering alveoli every minute!= breaths/min x (tidal volume - anatomical dead space)!
.!VA = f x (VT - anatomical dead space)!
(the • above the “V” (or any other physiological symbol) indicates a rate, such as volume per minute.)!
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Lung Volumes!
1. Tidal volume - about 500 ml (VT)!• Volume in and out during quiet breathing!
2. Anatomical dead space - about 150 ml!• Volume of air in conducting airways!• This air does not participate in gas exchange!
.!3. Respiratory minute volume (VE) - about 6 l/min!
• Volume inhaled and exhaled each minute!• = breaths/min x tidal volume!
4. Inspiratory Reserve Volume (IRV)!• Additional volume that can be inhaled after a
normal inspiration!
Chapter 23 – Part 2 – Respiration Physiology!
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Lung Volumes – 2!
5. Expiratory Reserve Volume (ERV)!• Additional volume that can be exhaled after a normal
expiration!6. Residual Volume!
• Volume of air in lungs that cannot be exhaled!7. Vital capacity!
• IRV + VT + ERV!8. Total lung capacity - just what it says!9. Functional Reserve (Residual) Volume or
Capacity (FRV)!• Volume of air in lungs after a normal expiration!
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Spirometer!
Life, Purvis et al.
Chapter 23 – Part 2 – Respiration Physiology!
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Respiratory Volumes/Capacities Figure 23-16!
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Importance of FRV!
Air reaching lungs = TV - anatomical dead space!• 500 ml - 150 ml = 350 ml!
This volume added to air that is already in lungs!• 350 ml new air added to FRV!
New volume = 2400 ml (FRV) + 350 ml = 2750 ml!• Percent new air = 350/2750 = about 13%!
So only about 13% of air in the lungs is “new air” during quiet breathing!
• This helps maintain relatively constant concentration gradients for O2 and CO2 diffusion between lung air and blood.!
Chapter 23 – Part 2 – Respiration Physiology!
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SECTION 23-8!Gas exchange depends on the partial pressures of gases and the diffusion of molecules!
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Gas Laws!
Charles’ Law - gases expand when heated!• Oh, really? J !• But this is important because air is warmed
on its way to the lungs!!
Dalton’s Law of Partial Pressures:!• Each gas in a mixture of gases exerts its own
(partial) pressure to the total pressure!Total atmospheric pressure (PB): !
PB = PO2 + PCO2 + PN2 + PH2O + Pothers!
Chapter 23 – Part 2 – Respiration Physiology!
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Dalton’s Law Calculations!
At sea level on a cool, dry day!• PO2 = 20.9% x 760 torr = 160 torr!• PCO2 = 0.04% x 760 torr = 0.3 torr!
But air entering the lungs (about to enter alveoli) is saturated with water vapor!• PH20 at 37 °C = 47 torr!
PO2 of air about to enter alveoli is 20.9%(760-47) = 150 torr!
PCO2 of air about to enter alveoli is 0.04%(760-47) = 0.3 torr!
PGas = [Gas] x total pressure!
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Henry’s Law (of Solubility)!• The volume of gas dissolved in a solution at
constant temperature is proportional to its solubility (α) and its partial pressure!
i.e. Vgas = αgas x Pgas!!
Solubility coefficients: ml/(dl ⋅ mmHg)!αCO2 = 0.067; αO2 = 0.003; αN2 = 0.0015!
The bottom line is that only CO2 is transported in solution to any great extent.!
CO2 bubbles come out of a can of pop when it is opened because the total pressure (and therefore the partial pressure) goes down when the seal is broken.!
Chapter 23 – Part 2 – Respiration Physiology!
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Henry’s Law – 2 Figure 23-17!
Partial pressure in the liquid is the same as the partial pressure in the gas when the two are in equilibrium.!
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Gas Exchange at the Alveolus Depends Upon Diffusion – 1!
Fick’s Law (again) Diffusion Rate = Flux = D • A • ΔC! L!
So diffusion is maximized when:!1. Diffusion distance (L) is small!2. Cross-sectional area (A) is large!3. A (large) concentration difference is
maintained!
Chapter 23 – Part 2 – Respiration Physiology!
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Gas Exchange at the Alveolus Depends Upon Diffusion – 2!
4. Gases are lipid soluble!5. Blood flow and air flow are synchronized!
• High PO2 in alveoli → high blood flow!• Low PO2 in alveoli → low blood flow!• Note that this is just the opposite of what one
sees in the systemic circulation.!
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Alveolar Adaptations That Maximize Diffusion!
1. Diffusion distance is small (see slide #60)!
A. Alveolar and capillary epithelia are simple squamous!
B. Basement membranes often fused so diffusion distance is only about 0.5 µm!
2. Cross-sectional area is enormous!A. About 500 million alveoli/lung !(Ochs et al., American Journal of Respiratory and
Critical Care Medicine Vol 169. pp. 120-124, 2004)!B. Total exchange area about 70 m2!
3. Concentration gradients are maintained!
Chapter 23 – Part 2 – Respiration Physiology!
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Surfactant!
Alveoli are not shaped like soap bubbles as shown in some textbooks!!
(Laplace’s law and the alveolus: a misconception of anatomy and a misapplication of physics, HD Prange. Advances in Physiology Education, 1 March 2003 Vol. 27no. 34-40DOI: 10.1152/advan.00024.2002)
• They have flat walls and are held open by connective tissue elements.!
• Surfactant does not magically keep alveoli from collapsing by reducing surface tension.!
Surfactant is important for reducing surface tension in small conducting airways and somewhat reduces the work of inflating the lungs.!
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An Overview of Partial Pressures Figure 23-18!
External respiration!• lung air ↔ blood!
Internal respiration!• blood ↔ tissues!
You should be very familiar with this figure and its meaning.
♥ **
** Thebesian veins!
Chapter 23 – Part 2 – Respiration Physiology!
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Partial Pressures and Gas Exchange!
Gases diffuse down their partial pressure gradients!
Why aren’t the values for lung air and air entering the lungs the same?!
Air ENTERING alveoli!
Air !IN !
alveoli!
Mixed Venous blood!
Arterial blood!
PO2! 150 torr! 100 torr! 40 torr! 95 torr!
PCO2! 0.3 torr! 40 torr! 45 torr! 40 torr!
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Air Entering Lungs vs. Air In Lungs!
The partial pressures are different because:!1. Lung air is a mixture of “new” air and “old”
air (see FRV)!• Only about 13% of the air in the lungs is
“new” air added with each breath at rest!2. Lung air is giving up O2 to the blood!3. Lung air is taking up CO2 from the blood!
Chapter 23 – Part 2 – Respiration Physiology!
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SECTION 23-9!Most oxygen is transported bound to hemoglobin; and carbon dioxide is transported in three ways: as carbonic acid, bound to hemoglobin, or dissolved in plasma!
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Gas Transport – Oxygen!
O2 has low solubility in plasma (Henry’s Law)!• Little (1.5% of total) can be transported in
solution!• Transport requires a carrier: hemoglobin!
O2-saturated blood carries:!• 20 ml O2/100 ml blood!• a.k.a. 20 vol%!
Hemoglobin:! Hb + O2 ↔ HbO2!
(deoxyhemoglobin) (oxyhemoglobin)!
Chapter 23 – Part 2 – Respiration Physiology!
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The Hb–O2 Saturation Curve Figure 23-19!
← Dissolved O2!
Vol % (m
l O2 / 100 m
l blood)!
Perc
ent O
2 sat
urat
ion
of H
b!
PO2 (mmHg) to which Hb is exposed!
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How is such a curve constructed?
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Oxygen-Hemoglobin Dissociation Curves!
Percent saturation of Hb is related to PO2!Reaction is reversible (Hb + O2 ↔ HbO2)!
• Increased PO2 shifts this reaction to the right!• Decreased PO2 shifts this reaction to the left!
Graph is a sigmoid curve, not a straight line!• Binding of the first O2 molecule makes
binding of 2nd O2 molecule easier; binding of 2nd O2 facilitates binding of the 3rd. !
• Adding the 4th is more difficult. But so is giving it up.!
Chapter 23 – Part 2 – Respiration Physiology!
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Oxygen-Hemoglobin Dissociation Curves – 2!
Note in the next figure (23-19):!1. % saturation of arterial blood about 98%!2. % saturation of venous blood about 75%!3. This is called the A-V O2 difference!
• A-V O2 difference at rest is about 25%!• This is the O2 given up to the tissues
under resting conditions!• So at rest, the “average” Hb is giving up!
Note that we are referring to % saturation, not PO2.!____ O2 as it goes through capillaries.!
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Oxygen-Hemoglobin Dissociation Curves – 3!
4. Below a PO2 of about 40 torr, the curve becomes very steep!• That means that small changes in PO2 lead to
large changes in the amount of O2 hemoglobin can carry (or give up to the tissues)!
• This results in more O2 being released when tissue PO2 is low (i.e., when tissues are using O2)!
Chapter 23 – Part 2 – Respiration Physiology!
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The Hb–O2 Saturation Curve Figure 23-19!
Vol % (m
l O2 / 100 m
l blood)!Pe
rcen
t O2 s
atur
atio
n of
hem
oglo
bin!
PO2 (mmHg)!
VenousPO2
ArterialPO2
A-V O2difference
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High affinity: Hb hanging onto O2 tightly!Low affinity: Hb not hanging onto O2 as tightly!P50 indicates hemoglobin’s affinity for O2!
• Normal human P50 is about 28 torr!• A higher P50 means lower affinity!
(It takes a higher PO2 to reach 50% saturation)!• A lower P50 indicates higher affinity!
P50 Indicates the Hb’s Affinity for O2!
Definition: P50 is defined as the PO2 at which hemoglobin is 50% saturated with 02. It is also known as the half-saturation value.!
Chapter 23 – Part 2 – Respiration Physiology!
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P50 – Changes in Hb’s Affinity for O2 – 2!
Decreased affinity!• Hb-O2 dissociation curve shifted to the right!• Easier for Hb to give up O2 to the tissues!
Increased affinity - Opposite!!
To remember factors that decrease affinity (shift the curve to the right) think of exercising muscle!• You would “want” hemoglobin to have a
lower affinity for O2 (i.e., to give it up to the tissues) during exercise. Right?!
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Factors Affecting Affinity – 1!
Exercising muscle is:!1. Acidic!
• Lactic acid ↔ lactate + H+ (?)!• ATP → ADP + Pi + H+!
2. Has a high PCO2!• Carbonic acid is produced from CO2
released by aerobic metabolism!• You certainly remember this:!
H2O + CO2 ← carbonic anhydrase → H2CO3 ↔ H+ + HCO3-!
Chapter 23 – Part 2 – Respiration Physiology!
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Factors Affecting Affinity – 2!
Effects of increased H+ and CO2:!H+ binds to Hb, changes Hb’s shape, causes
Hb to release O2!• A change in Hb affinity due to pH change
is called the Bohr effect!!CO2 also binds directly to Hb and lowers its
affinity for O2. (CO2 binding to hemoglobin forms carbaminohemoglobin). This change in affinity is called the Haldane effect (discussed later).!
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Effects of pH – the Bohr Effect Figure 23-20a!
P50s!
50% saturation!
Chapter 23 – Part 2 – Respiration Physiology!
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Effects of Temperature Figure 23-20b!
3. Exercising muscle is hot!• Metabolism
produces heat!• Higher temperature
weakens the bond between Hb and O2! P50s!
50% saturation!
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Other Factors Affecting Hb–O2 Affinity!
4. 2, 3-bisphosphoglycerate (BPG)!• RBCs produce BPG via anaerobic metabolism!• Increased BPG decreases Hb affinity!• Takes hours for effect to occur!
5. Fetal Hemoglobin!• Adult Hb has two α and two β polypeptides!• Fetal Hb has two α and two γ polypeptides!• Fetal Hb has a higher affinity for O2 (lower P50) than
does maternal Hb!6. Myoglobin - has higher affinity than hemoglobin!• “Stores” O2 in muscle cells!
Chapter 23 – Part 2 – Respiration Physiology!
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Fetal vs. Adult Hemoglobin Figure 23-21!
50% saturation!
P50s!
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Carbon Dioxide Transport!CO2 transport and elimination is just as important as
O2 uptake (Why?) Hint: H2O + CO2 ↔H2CO3 ↔ H+ + HCO3-
Resting conditions: 52 vol% transported in venous blood!Forms of transport!
1. Dissolved CO2 in plasma!• About 7% of total (recall high solubility (α))!
2. Bound to Hb = carbaminohemoglobin!• About 23% of total!• Binds amino acids on Hb!• Higher PCO2 → more carbaminohemoglobin!
3. Bicarbonate ions - about 70% of total!
Chapter 23 – Part 2 – Respiration Physiology!
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Carbon Dioxide Transport in Blood Figure 23-22!
Does this HCO3
-/Cl- transporter look familiar?!
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CO2 Uptake in Tissues and HCO3- Transport!
1. CO2 diffuses into RBCs!2. H+ and HCO3
- formed!
H2O + CO2 ← carbonic anhydrase → H2CO3 ↔ H+ + HCO3-!
(gas)!!• First step would be slow without the enzyme!
3. Bicarbonate leaves RBC in exchange for Cl-!• Facilitated diffusion!
• “Chloride shift” maintains electrical neutrality!4. Bicarbonate transported in plasma!
Chapter 23 – Part 2 – Respiration Physiology!
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CO2 Release From Blood Into Lung Air!
1. Essentially the reverse of:!H2O + CO2 ← carbonic anhydrase → H2CO3 ↔ H+ + HCO3
-!2. Haldane Effect!
• Binding of O2 to Hb displaces CO2!• Note in Figure 23-24 that Hb acts as a buffer!• Hb•H + O2 ↔ Hb•O2 + H+!I.e. when O2 binds Hb, Hb gives up H+, then…!• H+ + HCO3
- → H2CO3 → H2O + CO2 (gas)!When PCO2 rises in blood, CO2 moves into lung air!
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A Summary of Gas Transport Figure 23-23!
Higher!PO2!
Lower!PO2!
Lower!PCO2!
Higher!PCO2!
Chapter 23 – Part 2 – Respiration Physiology!
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SECTION 23-9!Neurons in the medulla oblongata and pons, along with respiratory reflexes, control respiration!
We will skip the remainder of the chapter for now. We may come back to it at the end of
the term.!
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Regulation of Respiration!
Nervous control by respiratory center!1. Medullary rhythmicity area!2. Pneumotaxic area (pons)!3. Apneustic area (pons)!
Chapter 23 – Part 2 – Respiration Physiology!
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Medullary Rhythmicity Center!1. Medullary rhythmicity center!
Inspiratory center (dorsal respiratory group)!• Sets basic rhythm for quiet breathing!• Inherent action potentials signal diaphragm!• Active 2 sec, inactive 3 sec!
Expiratory center (ventral respiratory group)!• Inactive during quiet breathing!• I.e. expiration is passive!• During labored breathing, receives excitation
from inspiratory area!Signals expiratory muscles!
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Basic Regulatory Patterns of Respiration!Figure 23-24!Reciprocal inhibition
Chapter 23 – Part 2 – Respiration Physiology!
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Pneumotaxic and Apneustic Areas - Pons!Pneumotaxic area!
• Inhibits inspiratory area!Limits duration of inspiration!
• Prevents over-inflation of lungs!• Breathing rate more rapid!
Inhibits apneustic area!Apneustic area!
• Stimulates inspiratory area when pneumotaxic area is active!Prolongs inspiration; Inhibits expiration!
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Respiratory Centers and Reflexes Figure 23-25!
Chapter 23 – Part 2 – Respiration Physiology!
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Chemical Regulation of Respiration!
Central chemoreceptors - medulla!• Monitor pH, PCO2 in CSF!
Peripheral chemoreceptors!• Carotid bodies, aortic body!• Monitor pH, PCO2, PO2!
Note: PO2 not important stimulus to breathe until blood PO2 < 60 torr!
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Chemoreceptor Response to PCO2 Figure 23-26!
Chapter 23 – Part 2 – Respiration Physiology!
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Proprioceptors and Baroreceptors!
Proprioceptors!• Signal inspiratory area in medulla!
Baroreceptors!• Hering-Breuer (Inflation) Reflex!• Receptors in walls of bronchi and bronchioles!• Stretch signals inspiratory and apneustic
areas via vagus!• Inhibits inspiration!
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The Respiratory Membrane Figure 23-10d!
Respiratory membrane!• Site of gas exchange!• Blood on one side, air on
the other side!1. Capillary (endothelial) wall!2. Fused basement membranes!
a) Epithelial (alveolar)!b) Capillary !
3. Alveolar epithelium!
