A. Measurement

1. Radial or Brachial Arteries
2. 22 gauge or smaller needle
3. Expel air bubbles
4. <1 mL blood into a heparinized tube
5. Transport rapidly on ice

B. Normal Values

1. PaO2 = 90±10 mm (80-100mm) breathing room air (FiO2 ~21%)
2. PaCO2 = 36-46 mmHg
3. pH 7.35 - 7.45

C. Acid-Base Abnormalities

1. Henderson-Hasselbach Equation: pH = pKa - Log{[H2CO3]÷ [HCO3-]}
2. pKa refers to the major buffering system, which is bicarbonate
   1. pKa is normally 6.1
   2. If HCO3- and CO2 concentrations are in mmol/L, [CO2] can be replaced by PaCO2x0.03
   3. For PaCO2 = 40 and HCO3- = 24 (normal ranges), pH = 6.1 + log (24÷ 0.12) = 7.4
3. The body will attempt to maintain pH within 7.35-7.45 range
4. Anomalies on either respiratory or metabolic side be (partially) corrected by the other side
5. pH > 7.45 is Alkalosis
   1. Respiratory alkalosis: pCO2 <35 mm Hg (hyperventilation)
   2. Metabolic alkalosis: [HCO3-] > 25mM (hypochloremic, volume contraction)
6. pH < 7.35 is Acidosis
   1. Respiratory acidosis: pCO2 >45 mm (hypoventilation, V/Q mismatch)
   2. Metabolic acidosis: [HCO3-] <18mM (hyperacidity, lactate, ketosis, etc.)
7. Rules for contribution of respiratory component to acid-base abnormalities
   1. Acute change in pCO2 of 10mm causes pH delta 0.08 units change
   2. Chronic change in pCO2 of delta 10mm causes pH delta 0.04 units change

D. Primary Acid-Base Disorders

1. Oxygen Partial Pressure in Alveoli = PAO2 = FiO2·(Patm-Pw) - [PACO2÷ R]
   1. R is the respiratory coefficient (ratio of oxygen consumed to CO2 produced)
   2. R is a constant ~ 0.8 at rest (decreases with exercise)
   3. Patm=atmospheric pressure (760mm Hg sea level); Pw=water vapor pressure (~47mm)
   4. FiO2 is the fraction of inspired oxygen (0.21 for room air)
2. This equation can be used to calculate Alveolar-arterial oxygen gradient:
   1. A-a Gradient = PAO2 - PaO2 where PaO2 is the measured arterial oxygen concentration
   2. A normal A-a Gradient is 10-15mm Hg for young persons; increases with age
3. Normal PAO2 (from room air) = 21% · (760-47) - 40/0.8 ~ 100mm Hg
4. Therefore, normal PaO2 is ~90mm Hg = 100mm - 10mm
5. The normal A-a gradient is due to ventilation - perfusion (V/Q) mismatch
   1. Note that normal V/Q ~ 1 where V~6L/min=Ve and Q~6L/min=cardiac output
   2. The difference between Ve and Va (see below) is dead space ventilation
   3. Lung dead space is ventilated but there is no blood supply (no perfusion)
   4. Therefore, the dead space volume (Vds) is useless for gas exchange
   5. In addition, there is a normal "physiologic" shunt of about 30% of cardiac output
   6. Shunt is another form of V/Q mismatch, but is usually considered separately

F. Hypoxemia - Causes [2]

1. Decreased Alveolar Tension of Oxygen or Poor Oxygen Exchange
2. Increased arterial pCO2 is always seen with reduced arterial pO2
3. Four Classes of Causes
   1. Hypoventilation
   2. Ventilation - Perfusion (V/Q) Mismatch
   3. Shunts
   4. Nonpulmonary: Low cardiac output conditions, low environmental O2, methemoglobinemia
4. Hypoventilation
   1. Often in the presence of normal lungs
   2. Nearly always causes both hypoxemia and hypercapnia
   3. If hypoventilation is sole pulmonary problem, than A-a gradient will be normal
   4. Poor CNS function - stroke, sedation, anesthesia will decrease respiratory rate
   5. Decline in muscle function - myositis, myasthenia, others will decrease tidal volume
   6. Rigid spine syndrome - proximal muscle weakness, joint contractures, scoliosis, rigid spin
5. V/Q Mismatch (V/Q >>1)
   1. Lung is ventilated but not perfused
   2. Therefore, no gas exchange can occur
   3. Pulmonary embolism is the classic example
6. Shunts
   1. Blood bypasses alveoli, no gas exchange occurs, V/Q = 0
   2. Includes areas of impaired O2 diffusion (DLCO increases) and underperfused lung
   3. Cardiac septal defects are the classic examples
   4. Pulmonary arteriovenous malformations can also cause shunting
7. Low Cardiac Output Conditions
   1. Low mixed venous oxygen (high tissue extraction)
   2. Increased V/Q mismatch
8. Low O2 environment including high altitude
9. Methemoglobinemia (see below)

G. Ventilation Equation

1. Ve = Vd + VA or VA = Ve - Vd or VA = Ve·(1-Vds/Vt)
   1. Ve= total ventilation; Vd = dead space ventilation; VA = alveolar ventilation
   2. Vds = dead space volume; Vt = total lung volume; Vds/Vt = fraction of dead space
2. Another way to measure "alveolar" ventilation is from concentration of CO2 expired
   1. Since no gas exchange occurs in anatomic dead space, there is no CO2 at end inspiration
   2. Thus, all CO2 expired must come from alveolar gas
   3. VCO2 is the production of CO2 from normal metabolism (~200ml/min)
3. So VCO2 = VA x %CO2/100; Partial Pressure of CO2 (PaCO2) is proportional to %CO2/100
   1. So PCO2 = K x VCO2 where K is a constant relating CO2 fraction to its partial pressure
   2. Thus, VA = VCO2 x K ÷ PaCO2 (K = 0.863 mm for conversions in liters)
   3. Normal VA = 0.86 x 1000 x 0.2L/min ÷ 40mm Hg (PaCO2) ~ 4.3 L / min
4. Now since VA = Ve·(1-Vds/Vt) and VA = VCO2 x K ÷ PaCO2, obtain:
5. PaCO2 = K x VCO2 ÷ {Ve·(1-Vds/Vt)}
   1. This says that arterial CO2 levels depend on four factors:
   2. VCO2 - production of CO2 by body tissues
   3. Ve - total ventilation, which is Ve = respiratory rate x tidal volume
   4. Vds/Vt - proportion of lung volume which is dead space (unventilated lung)
6. This alveolar ventilation equation can be used to understand changes in CO2 levels

H. Hypercapnia

1. Causes of high CO2 (PaCO2) follow from the alveolar ventilation equation
2. Because PaCO2 = K·VCO2 ÷ VA, hypercapnia is most often due to alveolar hypoventilation
3. Alveolar Hypoventilation
   1. Decreased Minute Ventilation (Ve)
   2. Increased Dead Space (Vds) including V/Q Mismatch (increased effective dead space)
4. Increased CO2 production (VCO2)
5. By increasing Ve, a person can compensate for changes in Vds and VCO2
6. Increased PaCO2 leads to reduced PaO2 (at fixed FiO2) by the alveolar gas equation

I. Hyperventilation

1. Usually results in decreased PaCO2 levels
2. However, may be used to compensate for increased Vds and/or increased VCO2
3. Pain or anxiety
4. Central Nervous System lesion
5. Metabolic Acidosis
   1. Septic / Lactate acidosis
   2. Diabetic Ketoacidosis
   3. Hyperchloremic Acidosis
6. Respiratory Center Stimulants: Theophylline, Progestins, Salicylates
7. Liver Failure

J. Diffusing Capacity

1. Measurement of rate of transfer of gas from alveolus to capillary
2. Measured in relation to the driving pressure of the gas across alveolar-capillary membrane
3. Carbon monoxide (CO) is used because it permeates membranes extremely efficiently
4. The major determinant of diffusing capacity is alveolar-capillary membrane surface area
5. Three categories of disease in which DLCO (diffusing limit of CO) is decreased:
   1. Emphysema
   2. Interstitial lung disease
   3. Pulmonary Vascular Disease (due to reduced pulmonary capillary blood volume)

K. Methemoglobinemia [1]

1. Rare consequence of exposure of normal red cells to various oxidizing substances
2. Methemogloblin is oxidized hemoglobin (Hb) that cannot properly carry oxygen
3. Normal levels of methemoglobin are 0.4-1.5%
4. Methemoglobin is normally reduced back to Hb by NADH-dependent cytochrome b5-methemoglobin reductase system
5. Several drugs associated with methemoglobinemia
   1. Dapsone
   2. Nitrates - nitroglycerin, nitroprusside
   3. Sulfonamides
   4. Primaquine
   5. Benzocaine
6. Increased risk of methemoglobinemia in patients with G6PD deficiency
7. Treatment
   1. Oxygen and drug-binding agents
   2. Methylene blue should be given if symptomatic but not to G6PD deficient persons
   3. Methylene blue reduces methemoglobin to Hb rapidly

References

1. Janssen WJ, Dhaliwal G, Collard HR, Saint S. 2004. NEJM. 351(22):2429 (Case Discussion)
2. Janssen WJ, Collard HR, Saint S, Weinberger SE. 2005. NEJM. 353(18):1956 (Case Discussion)