Gas Exchange and Transport Gas Exchange in the Lungs and Tissues 18 Lower Alveolar P Decreases Oxygen Uptake O2 Diff usion Problems Cause Hypoxia Gas Solubility Aff ects Diff usion Gas Transport in the Blood Hemoglobin Binds to Oxygen Oxygen Binding Obeys the Law of Mass Action Hemoglobin Transports Most Oxygen to the Tissues P Determines Oxygen-Hb Binding O2 Oxygen Binding Is Expressed As a Percentage Several Factors Aff ect Oxygen-Hb Binding Carbon Dioxide Is Transported in Three Ways Regulation of Ventilation Neurons in the Medulla Control Breathing Carbon Dioxide, Oxygen, and pH Infl uence Ventilation Protective Refl exes Guard the Lungs Higher Brain Centers Aff ect Patterns of Ventilation The successful ascent of Everest without supplementary oxygen is one of the great sagas of the 20th century. — John B. West, Climbing with O’s , NOVA Online (www.pbs.org) Background Basics Exchange epithelia pH and buff ers Law of mass action Cerebrospinal fl uid Simple diff usion Autonomic and somatic motor neurons Structure of the brain stem Red blood cells and Giant liposomes hemoglobin of pulmonary Blood-brain barrier surfactant (40X) From Chapter 18 of Human Physiology: An Integrated Approach, Sixth Edition. Dee Unglaub Silverthorn. Copyright © 2013 by Pearson Education, Inc. All rights reserved. 633 Gas Exchange and Transport he book Into Thin Air by Jon Krakauer chronicles an ill- RUNNING PROBLEM fated trek to the top of Mt. Everest. To reach the summit of Mt. Everest, climbers must pass through the “death zone” T High Altitude located at about 8000 meters (over 26,000 ft ). Of the thousands of people who have attempted the summit, only about 2000 have been In 1981 a group of 20 physiologists, physicians, and successful, and more than 185 have died. What are the physiologi- climbers, supported by 42 Sherpa assistants, formed the American Medical Research Expedition to Mt. Everest. The cal challenges of climbing Mt. Everest (8850 m or 29,035 ft ), and purpose of the expedition was to study human physiology why did it take so many years before humans successfully reached at extreme altitudes, starting with the base camp at 5400 m the top? Th e lack of oxygen at high altitude is part of the answer. (18,000 ft) and continuing on to the summit at 8850 m (over Th e mechanics of breathing includes the events that cre- 29,000 ft). From the work of these scientists and others, we ate bulk fl ow of air into and out of the lungs. In this chapter we now have a good picture of the physiology of high-altitude focus on the two gases most signifi cant to human physiology, acclimatization. oxygen and carbon dioxide, and look at how they move between alveolar air spaces and the cells of the body. Th e process can be divided into two components: the exchange of gases between compartments, which requires diff usion across cell membranes, elevated concentrations of carbon dioxide. These two condi- and the transport of gases in the blood. Figure 18.1 presents tions are clinical signs, not diseases, and clinicians must gather an overview of the topics that we cover in this chapter. additional information to pinpoint their cause. Table 18.1 If the diff usion of gases between alveoli and blood is sig- lists several types of hypoxia and some typical causes. nifi cantly impaired, or if oxygen transport in the blood is inad- To avoid hypoxia and hypercapnia, the body uses sensors equate, hypoxia (a state of too little oxygen) results. Hypoxia that monitor arterial blood composition. Th ese sensors respond frequently (but not always!) goes hand in hand with hypercapnia , to three regulated variables: 1 Oxygen. Arterial oxygen delivery to the cells must be ad- equate to support aerobic respiration and ATP production. PULMONARY GAS EXCHANGE AND TRANSPORT 2 Carbon dioxide ( C O 2) is produced as a waste product dur- ing the citric acid cycle. Excretion of CO 2 by the lungs is CO2 O2 important for two reasons: high levels of CO2 are a cen- tral nervous system depressant, and elevated CO c a u s e s a Airways 2 state of acidosis (low pH) through the following reaction: + Δ Δ + + - Alveoli of lungs C O 2 H2O H2CO3 H HCO3 . 3 pH. Maintaining pH homeostasis is critical to prevent de- CO2 O2 naturation of proteins. The respiratory system monitors 6 CO 2 enters alveoli 1 Oxygen enters the at alveolar-capillary blood at alveolar- plasma pH and uses changes in ventilation to alter pH. interface. CO2 O2 capillary interface. Th is process is discussed later along with renal contribu- Pulmonary tions to pH homeostasis. circulation 2 Oxygen is trans- ported in blood Th e normal values for these three parameters are given in dissolved in plasma Table 18.2 . In this chapter we will consider the mechanisms or bound to hemoglobin inside by which oxygen and CO2 move from the lungs to the cells and 5 CO2 is trans- RBCs. back again. ported dissolved, bound to hemoglobin, or – Systemic as HCO3 . CO2 circulation O2 Gas Exchange in the Lungs and Tissues 4 CO2 diffuses 3 Oxygen diffuses out of cells. into cells. Breathing is the bulk fl ow of air into and out of the lungs. Once CO O air reaches the alveoli, individual gases such as oxygen and CO Cells 2 2 2 Cellular diff use from the alveolar air space into the blood. Recall that dif- respiration fusion is movement of a molecule from a region of higher con- ATP determines Nutrients centration to one of lower concentration. metabolic CO2 production. Fig. 18.1 634 Gas Exchange and Transport Table Classifi cation of Hypoxias 18.1 Type Defi nition Typical Causes Hypoxic hypoxia Low arterial P High altitude; alveolar hypoventilation; O2 decreased lung diffusion capacity; abnormal ventilation-perfusion ratio Anemic hypoxia Decreased total amount of O2 bound to Blood loss; anemia (low [Hb] or altered hemoglobin H b O 2 binding); carbon monoxide poisoning Ischemic hypoxia Reduced blood flow Heart failure (whole-body hypoxia); shock (peripheral hypoxia); thrombosis (hypoxia in a single organ) Histotoxic hypoxia Failure of cells to use O2 because cells Cyanide and other metabolic poisons have been poisoned cells has a P of 100 mm Hg. Because P is lower in the cells, O2 O2 18 Table oxygen diff uses down its partial pressure gradient from plasma 18.2 Normal Blood Values in Pulmonary Medicine into cells. Once again, diff usion goes to equilibrium. As a result, venous blood has the same PO2 as the cells it just passed. Arterial Venous Conversely, PCO2 is higher in tissues than in systemic cap- illary blood because of CO2 production during metabolism P 95 mm Hg 40 mm Hg O2 ( Fig. 18.2 ). Cellular PCO2 in a person at rest is about 46 mm Hg, (85–100) compared to an arterial plasma PCO2 of 40 mm Hg. Th e gradient causes CO t o d i ff use out of cells into the capillaries. Diff usion P 40 mm Hg 46 mm Hg 2 CO2 goes to equilibrium, and systemic venous blood averages a P (35–45) CO2 of 46 mm Hg. pH 7.4 (7.38–7.42) 7.37 At the pulmonary capillaries, the process reverses. Venous blood bringing waste CO2 from the cells has a PCO2 o f 46 mm Hg. Alveolar PCO2 is 40 mm Hg. Because PCO2 i s h i g h e r When we think of concentrations of solutions, units such in the plasma, CO2 moves from the capillaries into the alveoli. as moles/liter and milliosmoles/liter come to mind. However, By the time blood leaves the alveoli, it has a PCO2 of 40 mm Hg, respiratory physiologists commonly express plasma gas con- identical to the PCO2 of the alveoli. centrations in partial pressures to establish whether there is a In the sections that follow we will consider some of the concentration gradient between the alveoli and the blood. Gases other factors that aff ect the transfer of gases between the alveoli move from regions of higher partial pressure to regions of lower and the body’s cells. partial pressure. Figure 18.2 shows the partial pressures of oxygen and CO2 in air, the alveoli, and inside the body. Normal alveolar PO2 Concept Check Answers: End of Chapter at sea level is about 100 mm Hg. Th e PO2 o f “ d e o x y g e n a t e d ” v e - nous blood arriving at the lungs is 40 mm Hg. Oxygen therefore 1. Cellular metabolism review: which of the following three metabolic pathways—glycolysis, the citric acid cycle, and the electron transport diff uses down its partial pressure (concentration) gradient from system—is directly associated with (a) O consumption and with the alveoli into the capillaries. Diff usion goes to equilibrium, 2 (b) CO2 production? and the PO2 of arterial blood leaving the lungs is the same as in the alveoli: 100 mm Hg. 2. Why doesn’t the movement of oxygen from the alveoli to the plasma decrease the P of the alveoli? When arterial blood reaches tissue capillaries, the gradient O2 is reversed. Cells are continuously using oxygen for oxida- 3. If nitrogen is 78% of atmospheric air, what is the partial pressure of this tive phosphorylation. In the cells of a person at rest, intra- gas when the dry atmospheric pressure is 720 mm Hg? cellular PO2 averages 40 mm Hg. Arterial blood arriving at the 635 Gas Exchange and Transport GASES DIFFUSE DOWN CONCENTRATION GRADIENTS RUNNING PROBLEM Dry air = 760 mm Hg Hypoxia is the primary problem that people experience when ascending to high altitude.