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Cormack: Ch. 6; Guyton and Hall: Chs. 38-44, 84; Michael and Rovick: Unit 6; vanWysberghe and Cooley: Cases 16-18

W. Crone (303 FTZ, 629-7439, cronewil@hvcc.edu, http://www.hvcc.edu/academ/faculty/crone/index.html) 2/28/00

possible web site: http://pulm.imed.missouri.edu/ (detailed case studies)

Pulmonary arterioles constrict when alveolar PAO2 is low and dilate as alveolar PAO2 is raised. This helps to match ventilation (V) to perfusion (Q). With gravity, there is not a perfect match anyhow, so that the V/Q ratio at the apex is high and at the base is low. So overall, even with (normally) very efficient transfer from alveolus to pulmonary capillary, alveolar PAO2 is 104 mm Hg, but arterial PaO2 is 100 mm Hg. Furthermore, slow replacement of alveolar air leads to prevent sudden changes in blood gas concentrations because of FRC (functional reserve capacity) and also dead-space air.1

REGULATION OF BREATHING: The motor neurons stimulating the respiratory muscles controlled by 2 major descending pathways: one for control of voluntary breathing and one for control of involuntary breathing. Voluntary breathing we're most familiar with when speaking or playing instruments (via corticospinal tract to spinal neurons for respiratory muscles).

Involuntary breathing is influenced by feedback from receptors that sense PaCO2, pH, and PaO2 in arterial blood. In the brainstem, there are three collections of cells responsible for rhythmic breathing: a dorsal respiratory group for inspiration in a ramp signal, a ventral respiratory group as an overdrive mechanism, and a pneumotaxic center (more pontine) that controls the rate and pattern of breathing.1 One form of receptor input are stretch receptors in the lungs, so that they inhibit the inspiratory drive to prevent the lungs from overexpansion: the Hering-Breuer reflex (not seen in normal tidal breathing).

Chemoreceptors responding to PaCO2, pH, PaO2:

1) central chemoreceptors in medulla oblongata. They are quite sensitive to changes in arterial PaCO2 that lead to [H+] changes in the CSF, and, in the ventral medulla oblongata are in synaptic communication with the neurons of the respiratory control centers.

2) peripheral receptors in aortic bodies in aortic arch and carotid bodies at the bifurcation of the common carotid into the internal/external carotids, which are sensitive to arterial pH.

The goal from chemoreceptors is to keep arterial PaCO2, pH, PaO2 at appropriate levels.

hypoventilation: rise in PaCO2 (hypercapnia), fall in pH (PaO2 not as affected since the big reservior of O2 attached to hemoglobin--remember from biochemistry?)

CO2 + H2O à H2CO3 à HCO3- + H+ via carbonic anhydrase

hyperventilation: fall in PaCO2 (hypocapnia), rise in pH (above reactions in opposite direction)

The central chemoreceptors do not pick up on the increased H+ from increased CO2, since the H+ does not cross the blood brain barrier. But the carbon dioxide in the arterial blood can cross the blood brain barrier, and can lower the pH of the CSF via the equation above. So, while ultimately the medullary chemoreceptors are responsible for 70-80% of the increased ventilation with high PaCO2, it takes a few minutes... for that quick response, one wants the peripheral chemoreceptors, which pick up on the lowered pH from the arterial blood (not arterial CO2 directly).1

Where does PaO2 play a role? One situation is in emphysema, where there is a chronic retention of CO2. The central chemoreceptors in the medulla oblongata respond to PaCO2 levels, while the peripheral chemoreceptors of the aortic and carotid bodies can respond to pH and PaO2 (not the total oxygen content of the blood). In fact, each of these factors can potentiate each other, so that a hypoventilating, hypoxic individual will have plenty of respiratory drive. Typically, the peripheral chemoreceptors won't register decreased PaO2 until it drops very low, e.g., 50-60 mm Hg--so it will take a while in the disease process to reach that point! In emphysema, alveolar tissue is destroyed, so fewer, larger alveoli, so less surface area for gas exchange (and less ability of bronchioles to remain open during expiration with tissue loss, so low FEV1.0).

Hypoxia: O2 deficiency in tissues.1

  1. Hypoxic hypoxia, reduced PaO2 in arterial blood, e.g., high altitudes. At altitude, atmospheric pressure is reduced (still 21% O2-right?), and so low PAO2, PaO2.
  2. Anemic hypoxia, with normal PaO2, but deficiency of hemoglobin.
  3. Stagnant (ischemic) hypoxia, where PaO2, hemoglobin are normal but circulation poor.
  4. Histotoxic hypoxia, where the tissue is poisoned (e.g., cyanide), even though PaO2, hemoglobin, and circulation are all normal.

Memories from biochemistry....remember the oxyhemoglobin dissociation curve, which is sigmoidal, so that in the steep part of the curve one can have venous unloading of O2 to tissues?"4-5-6, 7-8-9" (40 - 60 mm Hg PaO2 matching up to 70 - 90% O2 saturation, respectively).

Large amounts of carbonic anhydrase in red blood cells form carbonic acid, as favored by high PaCO2 in tissue capillaries. As the carbonic acid dissociates, H+ ions are released. These are buffered by deoxyhemoglobin in the red cells, so that more bicarbonate diffuses into the plasma than does H+. Hence, with all these H+ on board of the red cells, and the HCO3- moving out, there is an attraction for Cl- to move in, or the (infamous?) chloride shift. Overall, this process accounts for about 70% of CO2 carrying in the bloodstream.

acidosis: arterial blood pH < 7.35

alkalosis: arterial blood pH > 7.45

Hypoventilation, not enough blowing off of CO2, and so high PaCO2, high carbonic acid production, and respiratory acidosis.

Hyperventilation, arterial PaCO2 decreases, so low carbonic acid production, and respiratory alkalosis.

You can imagine how this plays out... e.g., someone with metabolic acidosis (example: diabetes) will hyperventilate to have a secondary respiratory alkalosis to compensate. So a combination of a low pH and low PaCO2 as a result. Interim acid/base summary: in respiratory problems, the increase/decrease of CO2 creates an increase/decrease in H+. In metabolic problems, the increase/decrease of H+ leads to a respiratory adjustment.

a quick look at arterial blood gas normal values (or range thereof):


7.35 - 7.45


85 - 100 (mm Hg, or may see term torr)


35 - 48 (mm Hg)


94 - 98% (O2 saturation of hemoglobin)


23 - 28 mEq/L (will discuss significance during renal lectures)


Muscles respire anaerobically when cardiovascular system is still adjusting, and we can get a"second wind" after adjustment, or put ourselves into oxygen debt with anaerobic activity. As one way to replenish the high levels of ATP needed for contraction (all of those myosin cross-bridges, right?), phosphocreatine can be utilized for rapid donation to ADP. While we're exercising those muscles, some of you may notice that some muscles may fatigue more quickly than others, depending on the amount of fast-twitch vs. slow-twitch muscles. Training will help to increase the ability of muscles to increase energy uptake, e.g., more mitochondria for more b -oxidation of fatty acids. There's a set amount of glycogen storage that you have--ask any marathoner"hitting the wall" at 20 miles.

With exercise, ventilation (rate, depth of breathing) increases, but arterial PaCO2, pH, PaO2 held constant, or what is called hyperpnea. Sensory nerve input from exercising limbs/cerebral cortex input seem to account for this adjustment.1

cardiovascular side of exercise: as exercise progresses, vasodilation and increased skeletal muscle blood flow occur because of intrinsic metabolic control. At rest, there is a high level of a 1-mediated vasoconstriction throughout skeletal muscle, but during exercise, local factors can prevail. These local metabolic factors include more CO2, lowered pH from carbonic acid and lactic acid, lowered O2, etc., so that skeletal muscle can receive much more blood flow during exercise. Note that rhythmic, pumping contractions allow more blood flow, but when you're doing an isometric contraction, blood flow slows and stops (think about being tired about holding one position for a while). On the flip side, during exercise, resistance to flow through visceral organs increases: a 1-mediated vasoconstriction (without local factors to overcome it).

Also in exercise, the cardiac output can go way up (e.g., up to 25 L/min), due to an increase in heart rate. But there is a maximum value of heart rate increase, depending on age. Stroke volume (SV) can also be increased by training. How can SV go up, if there is less time to fill between the quickened beats? End-diastolic volume is maintained with improved venous return from skeletal muscle pumps and increased respiratory efforts. Therefore SV is improved by increased contractility from sympathetic stimulation.

Also, afterload is decreased with peripheral resistance decreased from skeletal muscle vasodilation. Training: lowering of resting heart rate (inhibition of SA node by vagus) and increase in resting stroke volume (increase in blood volume). So, it's the large cardiac output that is the ultimate factor in improved oxygen delivery to skeletal muscles as a result of endurance training.


  1. AC Guyton, JE Hall, Textbook of Medical Physiology, 9th ed. (WB Saunders, Philadelphia, 1996), pp. 485, 493, 504, 525, 526, 532, 542.

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