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Gas transport
Introduction
For successful cell respiration to occur, multiple systems must work in unison for the transport of oxygen (O 2 ) and carbon dioxide (CO 2 ):
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Respiratory system
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Hematologic system
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Cardiovascular system
Both O 2 and CO 2 traverse these systems (blood, alveoli, and tissues) via simple diffusion.
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O 2 : air → alveoli → pulmonary capillaries → systemic circulation → tissue
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CO 2 : tissue → systemic veins → pulmonary arteries → alveoli → air
System structure: Oxygen reservoirs and hemoglobin
To begin, we first ask: How much oxygen demand does the body actually have?
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Each 100 mL of arterial blood contains a mass of oxygen equivalent to about 20 mL.
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With a cardiac output of 6 L/min, we can calculate that approximately 1200 mL of oxygen is delivered to the body per minute.
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Of the 1200 mL of O 2 /min, the body tissues consume 300 mL/min and the remaining 900 mL flows back to the heart each minute in the venous blood.
To keep up with this level of oxygen demand, a majority of blood oxygen content must be bound to hemoglobin (Hb) inside red blood cells, with only a small remainder dissolved in the plasma in free solution (see Genetics Box 15.1 , Development Box 15.1 , Environmental Box 15.1 , Pharmacology Box 15.1 and Fast Fact Box 15.1 ).
GENETICS BOX 15.1
Patients with mutations in the CYB5R3 gene have autosomal recessive methemoglobinemia, a condition in which there is impaired conversion of methemoglobin (hemoglobin in the ferric Fe +++ state) to ferrohemoglobin (the ferrous Fe ++ state). The Fe +++ ions cannot reversibly bind oxygen, and the affinity of any remaining Fe ++ ions is increased, consequently left shifting the O 2 dissociation curve, limiting tissue delivery of O 2 . Type I disease affects only erythrocytes, while type II affects all cells.
DEVELOPMENT BOX 15.1
Patients affected by type I methemoglobinemia have cyanosis, dyspnea on exertion, and may have headaches and fatigue. Patients with type II disease have failure to thrive, developmental delay, and cognitive impairment.
ENVIRONMENTAL BOX 15.1
In addition to hereditary methemoglobinemia, there are acquired versions because of drugs (e.g., dapsone, benzocaine, and inhaled nitric oxide). Chemicals, such as aniline and other dyes, pesticides, the naphthalene chemical in moth balls, benzene-derived solvents, and hydrogen peroxide, are among the numerous agents that may be used in work settings and can cause methemoglobinemia.
PHARMACOLOGY BOX 15.1
The cyanosis of type I hereditary methemoglobinemia can be treated with methylene blue, riboflavin, and ascorbic acid. Unfortunately, these treatments have not proved effective in preventing the cognitive impairment and developmental delay of type II disease. For acquired methemoglobinemia, removal of the causative agent is of primary import, although methylene blue and ascorbic acid are often used as well. In the specific case of dapsone-induced disease, cimetidine is effective in the long term for patients who must remain on that drug.
Fast Fact Box 15.1
Oxygen extraction varies from organ to organ. A 25% oxygen extraction rate is an average of the body; the heart extracts almost all oxygen it receives, while the kidneys only extract a small percentage.
Oxygen reservoirs
What if oxygen were only carried in free solution?
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Henry’s law states that amount of gas dissolved in any liquid is proportional to its partial pressure.
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There is only 0.003 mL of dissolved O 2 per 100 mL of blood for each mmHg of PO 2 .
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If PO 2 around 100 mm Hg (normal), 100 mL of blood only contains 0.3 mL of dissolved O 2 (not nearly enough!)
To load the blood with the O 2 we need, the blood must contain an O 2 reservoir, Hb, which binds dissolved O 2 molecules and removes them from free solution.
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This prevents the plasma from reaching its saturation point (0.3 mL O 2 /100 mL blood).
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Thus more O 2 can diffuse out of alveolar gas into solution.
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This tends to increase the O 2 -carrying capacity of blood by over 60-fold (1.39 mL O 2 per g of saturated Hb).
To calculate the total O 2 content in the blood, or CaO 2 (measured in mL O 2 per 100 mL blood), we can rearrange Henry’s law to yield:
where SpO 2 is the O 2 saturation in the arterial blood, and P a O 2 is the partial pressure of O 2 in the arterial blood.
Hemoglobin structure and cooperativity
Recall from Chapter 7 that Hb possesses a unique structure that facilitates its interaction with O 2 ( Fig. 15.1 ).
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Two α and two β polypeptide chains.
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Each subunit contains a heme group, a porphyrin ring with a central iron atom that can reversibly bind oxygen.
Hb switches between two major conformational states: tense (T) and relaxed (R ) ( Fig. 15.2 ).
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T form (also known as, reduced Hb or deoxyhemoglobin)
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In the absence of oxygen, the four subunits are tightly bound to each other with electrostatic interactions.
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Relatively low affinity for oxygen.
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R form
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O 2 noncovalently binds to the central iron atom of the porphyrin ring of one subunit, producing a conformational shift.
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Because the subunits are in close apposition, the change in one subunit to the R conformation induces all of the other subunits to change to the R form via mechanical and electrostatic interactions.
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The R form has 500 times higher affinity for oxygen than the T form and displays cooperativity (i.e., binding of O 2 to one subunit makes it easier for the other three to bind O 2 ).
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This sequence essentially occurs in reverse when O 2 is unloaded into peripheral tissues after being carried through the arterial system.
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