Gas Exchange

1
Gas Exchange

• Chapter 16

2
Partial Pressure of Gases

• Partial pressure pressure that a particular gas
  in a mixture exerts independently
• Daltons Law total pressure of a gas mixture is
  the sum of partial pressures of each gas
• Atmospheric pressure at sea level is 760 mm Hg
• PATM PN2 P02 PC02 PH20 760 mm Hg

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3
Gas Exchange in Lungs

• Driven by differences in partial pressures of
  gases between alveoli capillaries

Fig 16.20
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4
Gas Exchange in Lungs continued

• Facilitated by surface area of alveoli, short
  diffusion distance between alveolar air
  capillaries, density of capillaries

Fig 16.21
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5
Partial Pressures of Gases in Blood

• When blood alveolar air are at equilibrium the
  amount of O2 in blood reaches a maximum value
• Henrys Law this value depends on solubility of
  O2 in blood (a constant), temperature of blood (a
  constant), partial pressure of O2
• The amount of O2 dissolved in blood depends
  directly on its partial pressure (PO2), which
  varies with altitude

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6
Blood PO2 PCO2 Measurements

• Provide good index of lung function
• At normal PO2 arterial blood has about 100 mmHg
  PO2
• PO2 is about 40 mmHg in systemic veins
• PC02 is 46 mmHg in systemic veins

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7
Fig 16.23
8
Disorders Caused by High Partial Pressures of
Gases

• Total atmospheric pressure increases by an
  atmosphere for every 10m below sea level
• Therefore, PP increases, and amt dissolved
  increases (Henrys Law).
• Too much dissolved oxygen becomes toxic.

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9
Disorders Caused by High Partial Pressures of
Gases

• At sea level, nitrogen is physiologically inert
• It dissolves slowly in blood
• Nitrogen narcosis resembles alcohol intoxication
• Amount of nitrogen dissolved in blood as diver
  ascends decreases due to decrease in PN2
• If ascent is too rapid, decompression sickness
  occurs (the bends)

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10
Brain Stem Respiratory Centers

• Automatic breathing is generated by a rhythmicity
  center in medulla oblongata
• Consists of inspiratory neurons that drive
  inspiration expiratory neurons that inhibit
  inspiratory neurons
• activity varies in a reciprocal way may be due
  to pacemaker neurons

Fig 16.25
Insert fig. 16.25
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11
Pons Respiratory Centers

• Activities of medullary rhythmicity center is
  influenced by centers in pons
• Apneustic center promotes inspiration by
  stimulating inspiratories in medulla
• Pneumotaxic center antagonizes apneustic center,
  inhibiting inspiration

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12
Chemoreceptors

• Automatic breathing influenced by activity of
  chemoreceptors monitor blood PC02, P02, pH
• Central chemoreceptors are in medulla
• Peripheral chemoreceptors are in large arteries
  near heart (aortic bodies) in carotids (carotid
  bodies)

Fig 16.26
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13
Effects of Blood PC02 pH on Ventilation

• Chemoreceptors modify ventilation to maintain
  normal CO2, O2, pH levels
• PCO2 is most crucial because of its effects on
  blood pH
• H20 C02 ? H2C03 ? H HC03-
• Hyperventilation causes low C02 (hypocapnia)
• Hypoventilation causes high C02 (hypercapnia)

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14
Effects of Blood PC02 pH on Ventilation
continued

• Brain chemoreceptors are responsible for greatest
  effects on ventilation
• H can't cross BBB but C02 can, which is why it
  is monitored has greatest effects
• Rate and depth of ventilation adjusted to
  maintain arterial PC02 of 40 mm Hg
• Peripheral chemoreceptors do not respond to PC02,
  only to H levels

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15
Fig 16.30
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16
Effects of Blood P02 on Ventilation

• Low blood P02 (hypoxemia) has little affect on
  ventilation
• Does influence chemoreceptor sensitivity to PC02
• P02 has to fall to about half normal before
  ventilation is significantly affected

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17
Effects of Pulmonary Receptors on Ventilation

• Lungs have receptors that influence brain
  respiratory control centers via sensory fibers in
  vagus
• Unmyelinated C fibers are stimulated by noxious
  substances such as capsaicin
• Causes apnea followed by rapid, shallow breathing
• Irritant receptors are rapidly adapting respond
  to smoke, smog, particulates
• Causes cough
• Hering-Breuer reflex is mediated by stretch
  receptors activated during inspiration
• Inhibits respiratory centers to prevent
  overinflation of lungs

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18
Hemoglobin (Hb) 02 Transport

• Loading of Hb with O2 occurs in lungs unloading
  in tissues
• Affinity of Hb for O2 changes with a number of
  physiological variables

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19
Hemoglobin (Hb) 02 Transport

• Each Hb has 4 globin polypeptide chains 4 heme
  groups that bind 02
• Each heme has a ferrous ion that can bind 1 02
• So each Hb can carry 4 02s

Fig 16.33
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20
Hemoglobin (Hb) 02 Transport continued

• Most 02 in blood is bound to Hb inside RBCs as
  oxyhemoglobin
• Each RBC has about 280 million molecules of Hb
• Hb greatly increases 02 carrying capacity of blood

Insert fig. 16.32
Fig 16.32
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21
Hemoglobin (Hb) 02 Transport continued

• Methemoglobin contains ferric iron (Fe3) -- the
  oxidized form
• Lacks electron to bind with 02
• Blood normally contains a small amount
• Carboxyhemoglobin is heme combined with carbon
  monoxide
• Bond with carbon monoxide is 210 times stronger
  than bond with oxygen
• So heme can't bind 02

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22
Hemoglobin (Hb) 02 Transport continued

• 02-carrying capacity of blood depends on its Hb
  levels
• Anemia Hb levels are below normal
• Polycythemia Hb levels are above normal
• Hb production controlled by erythropoietin (EPO)
• Production stimulated by low P02 in kidneys
• Hb levels in men are higher because androgens
  promote RBC production

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23
Hemoglobin (Hb) 02 Transport continued

• High P02 of lungs favors loading low P02 in
  tissues favors unloading
• Ideally, Hb-02 affinity should allow maximum
  loading in lungs unloading in tissues
• The extent to which 02 will be loaded or unloaded
  depends on
• P02 of the environment
• Affinity between hemoglobin and 02

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24
Oxyhemoglobin Dissociation Curve

• of Hb sites that have bound 02 at different
  P02s
• Reflects loading unloading of 02
• In steep part of curve, small changes in P02
  cause big changes in saturation

Fig 16.34
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25
Oxyhemoglobin Dissociation Curve

• Hb-02 affinity is affected by changes in pH
  temp
• Affinity decreases when pH decreases (Bohr
  Effect) or temp increases
• Occurs in tissues where temp, C02 acidity are
  high
• Causes Hb-02 curve to shift right more
  unloading of 02

Fig 16.35
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26
Effect of 2,3 DPG on 02 Transport

• RBCs have no mitochondria cant perform aerobic
  respiration
• 2,3-DPG is a byproduct of glycolysis in RBCs
• production is increased by low 02 levels
• Causes Hb to have lower 02 affinity, shifting
  curve to right
• In anemia, total blood Hb levels fall, causing
  each RBC to produce more DPG
• Fetal hemoglobin (HbF) has 2 g-chains in place of
  b-chains of HbA
• HbF cant bind DPG, causing it to have higher 02
  affinity
• Facilitates 02 transfer from mom to baby

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27
Sickle-cell Anemia

• Sickle-cell anemia affects 8-11 of African
  Americans
• HbS has valine substituted for glutamic acid at 1
  site on b chains
• At low P02, HbS crosslinks to form a
  paracrystalline gel inside RBCs
• Makes RBCs less flexible more fragile

Fig 16.36
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Thalassemia

• Thalassemia affects primarily people of
  Mediterranean descent
• Has decreased synthesis of a or b chains
  increased synthesis of g chains

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Myoglobin

• Is a red pigment found exclusively in striated
  muscle
• Slow-twitch skeletal cardiac muscle fibers are
  rich in myoglobin

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30
Myoglobin

• Has only 1 globin binds only 1 02
• Has higher affinity for 02 than Hb is shifted to
  extreme left
• Releases 02 only at low P02
• Serves in 02 storage, particularly in heart
  during systole

Insert fig. 13.37
Fig 16.37
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C02 Transport

• C02 transported in blood as dissolved C02 (10),
  carbaminohemoglobin (20), bicarbonate ion,
  HC03-, (70)
• In RBCs carbonic anhydrase catalyzes formation of
  H2CO3 from C02 H2O

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32
Chloride Shift

• High C02 levels in tissues causes the reaction
  C02 H2O ? H2C03 ? H
  HC03- to shift right in RBCs
• Results in high H HC03- levels in RBCs
• H is buffered by proteins
• HC03- diffuses down concentration charge
  gradient into blood causing RBC to become more
• So Cl- moves into RBC (chloride shift)

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33
Chloride Shift
Fig 16.38
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34
Reverse Chloride Shift

• In lungs, C02 H2O ? H2C03 ? H HC03-, moves
  to left as C02 is breathed out
• Binding of 02 to Hb decreases its affinity for H
• H combines with HC03- more C02 is formed
• Cl- diffuses down concentration charge gradient
  out of RBC (reverse chloride shift)

Fig 16.39
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35
Acid-Base Balance in Blood

• Blood pH is maintained within narrow pH range by
  lungs kidneys (normal 7.4)
• Most important buffer in blood is bicarbonate
• H20 C02 ? H2C03 ? H HC03-
• Excess H is buffered by HC03-
• Kidney's role is to excrete H into urine

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36
Effect of Bicarbonate on Blood pH
Fig 16.40
Insert fig. 16.40
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37
Acid-Base Balance in Blood continued

• 2 major classes of acids in body
• A volatile acid can be converted to a gas
• E.g. C02 in bicarbonate buffer system can be
  breathed out
• H20 C02 ? H2C03 ? H HC03-
• All other acids are nonvolatile cannot leave
  blood
• E.g. lactic acid, fatty acids, ketone bodies

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Acid-Base Balance in Blood continued

• Acidosis is when pH lt 7.35 alkalosis is pH gt
  7.45
• Respiratory acidosis caused by hypoventilation
• Causes rise in blood C02 thus carbonic acid
• Respiratory alkalosis caused by hyperventilation
• Results in too little C02

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39
Acid-Base Balance in Blood continued

• Metabolic acidosis results from excess of
  nonvolatile acids
• E.g. excess ketone bodies in diabetes or loss of
  HC03- (for buffering) in diarrhea
• Metabolic alkalosis caused by too much HC03- or
  too little nonvolatile acids (e.g. from vomiting
  out stomach acid)

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Acid-Base Balance in Blood continued

• Normal pH is obtained when ratio of HCO3- to C02
  is 20 1
• Henderson-Hasselbalch equation uses C02 HCO3-
  levels to calculate pH
• pH 6.1 log HCO3-
  0.03PC02

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41
Respiratory Acid-Base Balance

• Ventilation usually adjusted to metabolic rate to
  maintain normal CO2 levels
• With hypoventilation not enough CO2 is breathed
  out in lungs
• Acidity builds, causing respiratory acidosis
• With hyperventilation too much CO2 is breathed
  out in lungs
• Acidity drops, causing respiratory alkalosis

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42
Ventilation During Exercise

• During exercise, arterial PO2, PCO2, pH remain
  fairly constant

Fig 16.41
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43
Ventilation During Exercise

• During exercise, breathing becomes deeper more
  rapid, delivering much more air to lungs
  (hyperpnea)
• 2 mechanisms have been proposed to underlie this
  increase
• With neurogenic mechanism, sensory activity from
  exercising muscles stimulates ventilation and/or
  motor activity from cerebral cortex stimulates
  CNS respiratory centers
• With humoral mechanism, either PC02 pH may be
  different at chemoreceptors than in arteries
• Or there may be cyclic variations in their values
  that cannot be detected by blood samples

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Lactate Threshold

• Is maximum rate of oxygen consumption before
  blood lactic acid levels rise as a result of
  anaerobic respiration
• Occurs when 50-70 maximum 02 uptake has been
  reached
• Endurance-trained athletes have higher lactate
  threshold, because of higher cardiac output
• Have higher rate of oxygen delivery to muscles
  greater numbers of mitochondria aerobic enzymes

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Acclimatization to High Altitude

• Involves increased ventilation, increased DPG,
  increased Hb levels
• Hypoxic ventilatory response initiates
  hyperventilation which decreases PC02 which slows
  ventilation
• Chronic hypoxia increases NO production in lungs
  which dilates capillaries there
• NO binds to Hb is unloaded in tissues where may
  also increase dilation blood flow
• NO may also stimulate CNS respiratory centers
• Altitude increases DPG, causing Hb-02 curve to
  shift to right
• Hypoxia causes kidneys to secrete EPO which
  increases RBCs

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