Stephen C. Wood, Ph.D.

Medical Physiology

Metabolic Rate and Alveolar Ventilation Learning Objectives

1. Predict the effect of fever on resting oxygen uptake. 2. Explain the factors that limit maximum oxygen uptake. 3. Define the respiratory quotient (RQ) and respiratory exchange ratio (R); list values for metabolism of fat, carbohydrate, protein. 4. Describe how alveolar PO2 depends on inspired PO2, alveolar PCO2, and R. 5. Describe how arterial PCO2 depends of alveolar ventilation and CO2 output. 6. Diagnose hyperventilation and hypoventilation using arterial PCO2.

I. Pathway for Oxygen

A. Four Steps.
The pathway for oxygen from air to cells has four steps: 1) ventilation of lungs; 2) diffusion into blood; 3) perfusion of lungs; and 4) diffusion into cells. These steps are in series. This means that any one step can limit the rate of oxygen delivery to tissues.
O2

DL

B. Oxygen Cascade.

Each step in the pathway results in a decrease in the partial pressure of O2 called the oxygen cascade and shown in the figure below.

tissue

DT

The PO2 of the inspired air at sea level is quite a bit higher than the PO2 in the lungs due to the presence of CO2 in lung air. At higher altitudes (4540 m and 6700 meters above sea level) the PO2 is less in both outside air, lung air, and other steps in the cascade.

Why is there a smaller drop in PO2 from air to lungs at higher altitudes? Try to answer before turning the page.

Page 30

Stephen C. Wood, Ph.D. Medical Physiology

why does the PO2 step betweeen air and lungs get smaller at thigher altitudes?

breathing
carotid body response

increased ventilation

hypoxia

lower PCO2

II. Metabolic Rate = O2 Demand

A. Basal metabolic rate depends on body temperature.
Cellular metabolism (the fire of life) Metabolic Rate = O2 Uptake consumes O2 and produces CO2 . The Metabolic Rate = O2 Uptake minimum or resting value of O2 used is called the Basal Metabolic Rate (BMR). 20% 80% Non-mitochondrial BMR is influenced by hormonal factors Liver CNS (thyroxin, cathecholamines, steroids) and High affinity Low affinity by changes in body temperature. For each BMR = basal metabolic rate = VO2 250 ml per minute at 37 C (98.6 F) 1 C change in body temperature, BMR 275 ml per minute at 38 C (100.6 F) changes by 10%. This is important during 225 ml/min at 36 C (96.6 F) fever or hypothermia. This effect of hypothermia has clinical applications in neuro and cardiac surgery.
Oxidative phosphorylation

. B. Oxygen Uptake (VO2)

Adults consume about 15 liters of oxygen each hour or 250 ml each minute. Mitochondria account for about 80% of this resting oxygen uptake. Mitochondria have a very high affinity for O2 and can consume O2 at normal rates when there is severe hypoxia. Other, non-mitochondrial pathways; e.g., synthesis of the neurotransmitters, norepinephrine, dopamine, and serotonin as well as liver cell function, account for the other 20% of resting O2 uptake and are more susceptible to fail during hypoxia.

Page 31

Stephen C. Wood, Ph.D. Medical Physiology

. C. Maximum O2 uptake (VO2 max) in a healthy adult is about 15

VO2, L/min

times higher than BMR; i.e., 225 L/hour or 3.75 L/min (53.5 ml/kg/min). 2 VO . VO2 max is measured during exercise on a treadmill or bicycle ergometer. 0 The watt is the SI standard unit of The work level is increased in steps 0 100 200 300 power (energy per unit time, joules/sec). Work rate (watts) until O2 uptake no longer increases with increasing work. Notice that power produced by the cyclist at VO2 max is adequate to light a 250 VO2 max, ml/kg/min watt light bulb. It is far less than one horse power which is off the Steve Prefontaine, 84.4 US runner scale at 746 watts. Elite athletes Greg LeMond, in running, cycling and other 92.5 professional cyclist aerobic events usually have higher Matt Carpenter, than normal values of maximum O2 Pikes Peak 92.0 marathon course uptake. Greg Lemond, for example, record holder has a VO2 max of 6.5 L/min (92.4 ml/kg/min), among the highest ever Lance Armstrong, 83.0 professional cyclist measured. According to the Fick principal, maximum oxygen uptake = maximum cardiac output x maximum (arterial O2 venousO2). What makes elite athletes stand out is a large stroke volume and therefore very high maximum cardiac output. Maximum heart rates are normal, as are maximum arterial venous O2 difference.

max

1 HP

III. CO2 Output

A. Respiratory Exchange Quotient/Ratio

C6H12O6 + 6O2 = 6CO2 + 6H2O RQ =

VCO2 VO2

=6 =1 6

The ratio of CO2 output to O2 RQ = TISSUE R = LUNG uptake is called respiratory quotient (RQ) in the tissues and respiratory exchange ratio (R) in the lungs. When carbohydrates are metabolized R = RQ = 1.0. When fats are metabolized, R = RQ = 0.7 (fasting metabolism). For most proteins, R = RQ 0.8.

B. Steady State
Steady state is defined as normal quiet breathing at rest when R = RQ. This means that gas exchange is exactly matched in the lungs and tissues.

Page 32

Stephen C. Wood, Ph.D. Medical Physiology

Non steady state conditions occur during exercise, breath holding, crying, hyperventilation, hypoventilation, etc.

IV. Clinical Calculations Used in Pulmonary Medicine

You need to be able to interpret arterial blood gases; i.e., arterial PO2, PCO2, and pH. These 3 values, combined with plasma [HCO3-] tell you about oxygenation, ventilation, and acid base status of a patient. The PO2 of arterial blood must be interpreted relative to the PO2 available in the lungs and outside air; e.g. it will be lower at high altitude. You will not be required to solve these equations on Ross exams, but be able to predict what will happen to the dependent variable (y) if the independent variables change; e.g., what will happen to inspired PO 2 if the level of inspired oxygen increases or if barometric pressure decreases.

A. Inspired PO2
Inspired PO2 (PIO2) is calculated to find out how much oxygen is in the inspired air. It is the PO2 of air in the trachea and airways after you inhale.
H20

Inspired PO2 Inspired PO2

P I O 2 = (P B P H2 0 ) x F O2

Sea level
CO2 CO2 O2 O2

P I O 2 = (7 4 7 4 7 ) x .2 1 = 1 4 7
m m Hg

The value depends on two P O = (3 4 7 4 7 ) x .2 1 = 6 3 m m Hg things: the concentration of O2 in the air (normally 21% O2) and the barometric pressure (PB). (For calculation the fraction instead of %O2 is used: FIO2 = .21)
I 2

20,000 feet

The equation is:

Inspired PO2 = (PBaro PH2O) x FIO2.

Using a value of 747 mm Hg for barometric pressure, the PIO2 at sea level is: PIO2 = (747 47) x .21 = 147 mm Hg. At higher altitudes, the value of inspired PO2 will decrease because barometric pressure decreases. For a local example, at 20,000 ft. above sea level the PB 347 mm Hg. The inspired PO2 of a climber at this Alveolar PO2 Alveolar PO2 altitude is calculated to be: PIO2 = (347 47) x .21 = 63 mm Hg. For PIO2 = (PB PH20) x FO2 patients on ventilators or breathing H20 PAO2 = ? supplemental O2, the concentration of O2 CO2 O2 being administered must be known CO in order to calculate PIO2. The FIO2 needed to provide a normal PIO2 can be calculated by rearranging the above equation; e.g., if P B is 373 (half of sea
2

O2

Page 33

Stephen C. Wood, Ph.D. Medical Physiology level 747), the FIO2 for a normal PIO2 of 147 would be FIO2 = 147/(373 47) = 0.45 (45% O2).

B. Alveolar PO2 (PAO2)

PAO2 is calculated to find out how much oxygen is available to venous blood delivered to alveoli. It is lower than inspired PO2 because of the large volume of FRC (3 L or so) in the lungs and because O2 is continuously removed from alveolar gas and CO2 is continuously added to alveolar gas. Therefore, the alveolar PO2 is less than inspired PO2 according to the Alveolar Gas Equation:
Alveolar PCO2 - how to calculate it Alveolar PCO2 - how to calculate it

PAO2 = PIO2 (PACO2/R)

R is used because if R is less than 1.0,

PACO2 =
Do it yourself equation builder

VCO2 VA

x 863 VA

C = Amt/Vol

more O2 being removed from alveolar gas P CO than the amount of CO2 being added. For VCO this reason subtracting PCO2 from Inspired O2 would overestimate the actual PO2. Using a value of 147 mm Hg for inspired PO2 and normal values of 40 mm Hg for PaCO2 and 0.8 for R gives the normal alveolar PO2: PAO2 = 147 (40/.8) = 147 50 = 97 mm Hg.
A
2

CO2

C. Alveolar PCO2 (PACO2)

PACO2 is calculated to find out how well the alveoli are ventilated. It is the PCO2 in the alveoli and is assumed to be the same value as arterial PCO2. Alveolar PCO2 increases when CO2 is added to alveolar gas and decreases when CO2 is eliminated by ventilation. You calculate PACO2 using the equation

PACO2 =

V CO2/ V A x 863

863 is a correction factor needed because CO2 is measured in STPD and A is measured in BTPS and because FCO2. With normal values of
. VCO2 and

is used instead of

A, PACO2 = 200/4315 x 863 = 40 mm Hg.

D. Alveolar Ventilation ( V A) - the supply of O2

V A can be calculated from the above equation to find out the effective
ventilation of the lungs (effective = gets rid of CO 2). The above equation is rearranged to solve for alveolar ventilation where

V A = V CO2/PACO2 x 863
Page 34

Stephen C. Wood, Ph.D. Medical Physiology

This form of the equation is called the Alveolar Ventilation Equation. .

1. Hyperventilation is defined as ventilation in excess of what is

needed to maintain a normal PACO 2. As a result, the arterial PCO2 is decreased and alveolar PO2 is increased. As shown in the graph, doubling alveolar ventilation reduced the PaCO 2 from 40 to 20 mm Hg. A PaCO2 << 40 mm Hg in a patient is a diagnosis of hyperventilation. The cause of hyperventilation may be primary; e.g., aspirin toxicity, high altitude hypoxia, progesterone (pregnancy), anxiety, etc. or 80 secondary as a compensation for PaCO2 exercise mmHg metabolic acidosis. 1 Hyperpnea is defined 40 as increased frequency VCO2 = 560 rest ml/min and/or tidal volume; as 20 2 in exercise. VCO = 280
2

ml/min 0 3 6 12 24

2. Hypoventilation is
defined as ventilation

Alveolar Ventilation, L/min

not adequate to maintain a normal P ACO2. The resulting alveolar and arterial PCO2 are increased and alveolar PO2 is decreased. If CO2 output is constant and alveolar ventilation is halved, from 6 to 3 L/min, PaCO2 will double, from 40 to 80 mm Hg. A PaCO2 >> 40 mm Hg in a patient is diagnostic of hypoventilation. The cause may be primary; e.g., barbiturate overdose or secondary as a compensation for metabolic alkalosis.

3. Effect of Exercise. Ventilation increases when you exercise,

but this is not hyperventilation. The ventilation increases exactly the right amount to keep arterial PCO2 at the normal value of 40 mm Hg. In this figure, the CO2 output was doubled from 280 ml/min to 560 ml/min from exercise. In this case, the alveolar ventilation would also double but this is NOT hyperventilation because the arterial PCO 2 remains at 40 mm Hg. Hyperventilation will occur during exercise only if the exercise intensity crosses the anaerobic threshold (and lactic acidosis stimulates excess ventilation).

E. Alveolar arterial PO2 difference

(A-a)PO2

(A-a)PO2 is calculated to find out if gas exchange in the lungs is normal. This difference is normally 5 to 15 mm Hg Arterial PO2 in healthy subjects due to normal anatomical shunts as well as mismatching of Page 35

Stephen C. Wood, Ph.D. Medical Physiology

ventilation and perfusion. A small drop is saturation due to shunting or V/Q mismatch results in a larger drop in PO 2. The alveolar-arterial PO2 will be discussed in more detail in the lecture on mechanisms of hypoxemia.

Summary
1. Transfer of oxygen from the air to cells requires 4 steps that are in series: ventilation, diffusion into pulmonary capillary blood, circulation, diffusion into tissues. CO2 is removed with the same 4 steps. 2. Metabolic rate is determined at rest by body size and body temperature (basal metabolic rate). Exercise increases metabolic rate up to a maximum (VO2 max). 3. The respiratory quotient (RQ) is the ratio of CO2 output to O2 uptake at the cellular level. Respiratory exchange ratio (R) is the same ratio in the lungs. The ratio depends on fuel type 0.7 for fat; 0.83 for protein; 1.0 for carbohydrates. R = RQ at steady state. 4. Alveolar PO2 (PAO2) is the PO2 that drives diffusion into pulmonary capillary blood. It is determined by inspired PO 2 and alveolar PCO2 and the value of R using the equation: PAO2 = PIO2 - PACO2/R 5. Alveolar PCO2 is determined by two factors: CO2 output and alveolar ventilation. Hypoventilation results in increased PCO 2. Hyperventilation

.
. .
rearranged for PaCO2 = V CO2/ V A x 863.

results in reduced PCO2. The equation is: V A = V CO2/PaCO2 x 863;

6. The alveolar-arterial PO2 difference (A-a)PO2 is a measure of the efficacy of gas exchange. Arterial PO2 is normally 5-15 mm Hg less than alveolar PO2 due to normal shunts and V/Q mismatch. Alveolar PO 2 does not change with age but arterial PO2 declines gradually, so the (A-a)PO2 difference gets wider with age.

References/Reading Assignment
Rhodes and Tanner http://www.accessmedicine.com/content.aspx?aID=706398

Page 36

Stephen C. Wood, Ph.D. Medical Physiology

STUDY QUESTIONS
1a) The worlds highest summit (Mt. Everest) is 29,035 ft. and the barometric pressure is 247 mm Hg. As of 2007, 2000 climbers have reached the summit and 200 have died trying. On May 8, 1978, Reinhold Messner and Peter Habeler achieved what was thought to be impossible, the first ascent of Mt. Everest without oxygen. The inspired PO2 of these climbers at the summit would be about: (click here to read more about Everest without oxygen) A. B. C. D. 42 mm Hg 66 mm Hg 34 mm Hg 147 mm Hg

1b) If Messener and Habeler had not hyperventilated, their arterial PCO2 would be at the sea level value of 40 mm Hg. Assuming that R = 1, their alveolar PO2 would be about: A. 16 mm Hg B. 34 mm Hg C. 2 mm Hg D. 11mm Hg 2) What fraction of oxygen would they have needed to have a normal value of 150 mm Hg for inspired PO2? A. 1.0 (100%) B. 0.74 (74%) C. 0.50 (50%) D. 0.21 (21%) 3) A 15-year-old student complaining of dyspnea was admitted to the ER. Because he appeared cyanotic, an arterial blood gases were determined. The results were: PCO2 = 52 mm Hg, PO2 = 70 mm Hg, pH = 7.3. The metabolic rate (oxygen uptake) was 250 ml/min and R = 0.8. The calculated alveolar ventilation was approximately: A. 5650 ml/min B. 4322ml/min C. 4568 ml/min D. 3319 ml/min 4a) A patient in the intensive care unit is connected to a metabolic cart for measurement of basal metabolic rate. His CO 2 output is found to be 300 ml/min. Page 37

Stephen C. Wood, Ph.D. Medical Physiology

Assuming that his alveolar ventilation is 4000, his arterial PCO 2 is calculated to be about: A. 15 mm Hg B. 40 mm Hg C. 120 mm Hg D. 65 mm Hg 4b) If this patient developed a fever (body temperature = 38 C), the predicted CO2 output at rest would be about: A. 333 ml/min B. 350 ml/min C. 267 ml/min D. 250 ml/min 5. A volunteer in the physiology lab is preparing to do a maximum oxygen uptake test. His metabolic rate is measured at rest and he is found to have an oxygen uptake of 250 ml/min and a carbon dioxide output of 200 ml/min (R = 0.8). He begins pedaling and after a few minutes his oxygen uptake is 600 ml/min and his carbon dioxide output is also 600 ml/min (R = 1). If there is no change in inspired O2 or in his alveolar PCO2, his alveolar PO2 would be expected to: A) not change B) decrease C) increase D) decrease, then increase E) decrease, then go back to normal Click on or go to the link below for answers to questions http://rossmedphysiology.com/answerstostudyquestion.pdf

Page 38