Interpretation of Arterial Blood Gases and Acid-Base Disorders Niki Paphitou, MD, FRCPC, FCCP Critical Care-Infectious Diseases, NGH ICU

Normal Arterial Blood Gas Values* pH 7.35-7.45 PaCO2 35-45 mm Hg PaO2 70-100 mm Hg** SaO2 95-100% HCO3- 22-26 mEq/L % MetHb <2.0% %COHb <3.0% CaO2 16-22 ml O2/dl * At sea level, breathing ambient air ** Age-dependent

Gas Exchange: 3 Key Equations For Evaluation Of 1) PaCO2 equation : Evaluating alveolar ventilation… 2)Alveolar gas equation: Evaluating oxygen transfer at the alveolar level… 3)Oxygen content equation: Evaluating oxygen transfer at the tissue level…

PaCO2 equation: PaCO2 reflects ratio of metabolic CO2 production to alveolar ventilation VCO2 x 0.863 VCO2 = CO2 production PaCO2 = ----------------- VA = VE – VD VA VE = minute (total) ventilation VD = dead space ventilation 0.863 converts units to mm Hg Condition State of PaCO2 in blood alveolar ventilation >45 mm Hg Hypercapnia Hypoventilation 35 - 45 mm Hg Eucapnia Normal ventilation <35 mm Hg Hypocapnia Hyperventilation

Hypercapnia VCO2 x 0.863 PaCO2 = ------------------ VA The only physiologic reason for elevated PaCO2 is inadequate alveolar ventilation (VA) for the amount of the body’s CO2 production (VCO2). Since alveolar ventilation (VA) equals minute ventilation (VE) minus dead space ventilation (VD), hypercapnia can arise from insufficient VE, increased VD, or a combination.

Hypercapnia PaCO2 = ------------------ VCO2 x 0.863 PaCO2 = ------------------ VA VA = VE – VD Examples of inadequate VE leading to decreased VA and increased PaCO2: sedative drug overdose; respiratory muscle paralysis; central hypoventilation Examples of increased VD leading to decreased VA and increased PaCO2: chronic obstructive pulmonary disease; severe pulmonary embolism, pulmonary edema.

Physiologic effects of hypercapnia 1) An elevated PaCO2 will lower the PAO2 (see Alveolar gas equation), and as a result lower the PaO2. 2) An elevated PaCO2 will lower the pH (see Henderson-Hasselbalch equation). 3) The higher the baseline PaCO2, the greater it will rise for a given fall in alveolar ventilation, e.g., a 1 L/min decrease in VA will raise PaCO2 a greater amount when baseline PaCO2 is 50 mm Hg than when it is 40 mm Hg.

PCO2 vs. Alveolar Ventilation The relationship is shown for metabolic carbon dioxide production rates of 200 ml/min and 300 ml/min (curved lines). A fixed decrease in alveolar ventilation (x-axis) in the hypercapnic patient will result in a greater rise in PaCO2 (y-axis) than the same VA change when PaCO2 is low or normal. This graph also shows that, if alveolar ventilation is fixed, an increase in carbon dioxide production will result in an increase in PaCO2.

Alveolar Gas Equation PAO2 = PIO2 - 1.2 (PaCO2) where PAO2 is the average alveolar PO2, and PIO2 is the partial pressure of inspired oxygen in the trachea PIO2 = FIO2 (PB – 47 mm Hg) FIO2 is fraction of inspired oxygen and PB is the barometric pressure. 47 mm Hg is the water vapor pressure at normal body temperature.

Alveolar Gas Equation If FIO2 and PB are constant, then as PaCO2 increases both PAO2 and PaO2 will decrease (hypercapnia causes hypoxemia). If FIO2 decreases and PB and PaCO2 are constant, both PAO2 and PaO2 will decrease. If PB decreases (e.g., with altitude), and PaCO2 and FIO2 are constant, both PAO2 and PaO2 will decrease (mountain climbing causes hypoxemia).

P(A-a)O2 P(A-a)O2 is the alveolar-arterial difference in partial pressure of oxygen. It is commonly called the “A-a gradient”. It results from gravity-related blood flow changes within the lungs (normal ventilation-perfusion imbalance). Normal P(A-a)O2 ranges from 5 to 25 mm Hg breathing room air (it increases with age). A higher than normal P(A-a)O2 means the lungs are not transferring oxygen properly from alveoli into the pulmonary capillaries. Except for right to left cardiac shunts, an elevated P(A-a)O2 signifies some sort of problem within the lungs.

Physiologic causes of low PaO2 NON-RESPIRATORY P(A-a)O2 Cardiac right to left shunt Increased Decreased PIO2 Normal RESPIRATORY Pulmonary right to left shunt Increased Ventilation-perfusion imbalance Increased Diffusion barrier Increased Hypoventilation (increased PaCO2) Normal

Ventilation-Perfusion imbalance A normal amount of ventilation-perfusion (V-Q) imbalance accounts for the normal P(A-a)O2. By far the most common cause of low PaO2 is an abnormal degree of ventilation-perfusion imbalance within the hundreds of millions of alveolar-capillary units. Virtually all lung disease lowers PaO2 via V-Q imbalance, e.g., asthma, pneumonia, atelectasis, pulmonary edema, COPD. Diffusion barrier is seldom a major cause of low PaO2 (it can lead to a low PaO2 during exercise).

SaO2 and oxygen content How much oxygen is in the blood? Oxygen content = CaO2 (mlO2/dl). CaO2 = quantity O2 bound + quantity O2 dissolved to hemoglobin in plasma CaO2 = (Hb x 1.34 x SaO2) + (.003 x PaO2) Hb = hemoglobin in gm%; 1.34 = ml O2 that can be bound to each gm of Hb; SaO2 is percent saturation of hemoglobin with oxygen; .003 is solubility coefficient of oxygen in plasma: .003 ml dissolved O2/mm Hg PO2.

Oxygen dissociation curve: SaO2 vs. PaO2 Also shown are CaO2 vs Oxygen dissociation curve: SaO2 vs. PaO2 Also shown are CaO2 vs. PaO2 for two different hemoglobin contents: 15 gm% and 10 gm%. CaO2 units are ml O2/dl. P50 is the PaO2 at which SaO2 is 50%.

SaO2 – is it calculated or measured? SaO2 is measured in a ‘co-oximeter’. The traditional ‘blood gas machine’ measures only pH, PaCO2 and PaO2,, whereas the co-oximeter measures SaO2, carboxyhemoglobin, methemoglobin and hemoglobin content. Newer ‘blood gas’ consoles incorporate a co-oximeter, and so offer the latter group of measurements as well as pH, PaCO2 and PaO2. Always make sure the SaO2 is measured, not calculated. If it is calculated from the PaO2 and the O2-dissociation curve, it provides no new information, and could be inaccurate -- especially in states of CO intoxication or excess methemoglobin. CO and metHb do not affect PaO2, but do lower the SaO2.

Carbon monoxide – an important cause of hypoxemia Normal %COHb in the blood is 1-2%, from metabolism and small amount of ambient CO (higher in traffic-congested areas) All smokers have excess CO in their blood. CO binds @ 200x more avidly to hemoglobin than O2, displacing O2 from the heme binding sites. CO : 1) decreases SaO2 by the amount of %COHb present, and 2) shifts the O2-dissociation curve to the left, retarding unloading of oxygen to the tissues. CO does not affect PaO2, only SaO2. To detect CO poisoning, SaO2 and/or COHb must be measured (requires co-oximeter). In the presence of excess CO, SaO2 (when measured) will be lower than expected from the PaO2.

CO does not affect PaO2! A patient presented to the ER with headache and dyspnea. His first blood gases showed PaO2 80 mm Hg, PaCO2 38 mm Hg, pH 7.43. SaO2 on this first set was calculated from the O2-dissociation curve at 97%, and oxygenation was judged normal. He was sent out from the ER and returned a few hours later with mental confusion; this time both SaO2 and COHb were measured (SaO2 shown by ‘X’): PaO2 79 mm Hg, PaCO2 31 mm Hg, pH 7.36, SaO2 53%, carboxyhemoglobin 46%. CO poisoning was missed on the first set of blood gases because SaO2 was not measured!

Causes of Hypoxia 1. Hypoxemia (=low PaO2 and/or low CaO2) a. reduced PaO2 – usually from lung disease (most common physiologic mechanism: V-Q imbalance) b. reduced SaO2 -- most commonly from reduced PaO2; other causes include carbon monoxide poisoning, methemoglobinemia, or rightward shift of the O2-dissociation curve c. reduced hemoglobin content -- anemia 2. Reduced oxygen delivery to the tissues a. reduced cardiac output -- shock, congestive heart failure b. left to right systemic shunt (as may be seen in septic shock) 3. Decreased tissue oxygen uptake a. mitochondrial poisoning (e.g., cyanide poisoning) b. left-shifted hemoglobin dissociation curve (e.g., from acute alkalosis, excess CO, or abnormal hemoglobin structure)

Acid-Base Disorders: A Systematic (step by step) Approach

Terminology Acidemia: blood pH < 7.35 Alkalemia: blood pH > 7.45 Acidosis: a physiologic process that tends to cause acidemia Alkalosis: a physiologic process that tends to cause alkalemia

Step 1: Do the numbers make sense? Check for Internal consistency by using the Henderson-Hasselbach equation: [H+] = 24 X PaCO2 / [ HCO3-]

Step 1: Internal consistency of ABGs PH is inversely related to [H+]; a pH change of 1.00 represents a 10-fold change in [H+] pH [H+] in nanomoles/L 7.00 100 7.10 80 7.30 50 7.40 40 7.52 30 7.70 20 8.00 10

Step 1: Internal consistency of ABGs Examples: Do these numbers have internal consistency? A man with sepsis has the following values: PH 7.5, PaCO2 40, HCO3- 20. A woman with renal failure has the following PH 7.3, PaCO2 40, HCO3- 10. A diabetic child has the following: PH 7.3, PaCO2 21 HCO3- 10.

Step 2: Alkalemia or Acidemia? Determine whether an acidemia (PH < 7.35) or an alkalemia (PH > 7.45) is present. This usually signifies the primary disorder. Keep in mind :The PH may be in normal range but a mixed disorder is present (look at the bicarbonate, PaCO2, anion gap).

Step 3: Is the primary disturbance metabolic or respiratory? Does any change in the PaCO2 account for the direction of the change in PH?

Step 4: Is there appropriate compensation for the primary disturbance? The body’s homeostatic mechanisms serve to return the ratio of bicarbonate to PaCO2 toward normal and thus normalize the PH. In most cases the compensatory mechanisms fail to fully return the PH to normal.

Step 4: Appropriate compensation in simple Acid-Base disorders Metabolic acidosis PCO2 =(1.5 X HCO3-) +8±2 Metabolic alkalosis PCO2 = 40 + 0.6 X ΔHCO3- Respiratory acidosis Acute: HCO3- = 24 + 0.1 X Δ PCO2 Chronic: HCO3- = 24 + 0.3 X Δ PCO2 Respiratory alkalosis Acute:HCO3- = 24 – 0.2X Δ PCO2 Chronic:HCO3- =24 – 0.4X Δ PCO2

Step 5: Calculate the anion gap The total body concentration of anions= cations. AG = Na+ – (Cl- + HCO3-). The AG accounts for unmeasured anions such as endogenous acids (Phosphates, sulfates, etc) and cations such as albumin. Normally the unmeasured anions exceed the unmeasured kations. Normal value is 12±2. Low anion gap can be caused by low serum albumin.

Step 5: Calculate the anion gap Calculation of the AG is crucial in metabolic acidosis. When the AG is high this signifies a rise in an unmeasured anion such as an endogenous acid (lactate, ketoacids) OR presence of an exogenous acid (methanol, ethylene glucol, salicylates etc). An exogenous compound with osmolar molecules (methanol, ethylene glygol etc) will create an “osmolar gap” = Measured serum osmolality – calculated serum osmolality. Normally < 10 mOsm/l. Calc. Osmol= 2 x Na+ + glucose/18 + BUN/2.8

Step 6: Calculate the Delta AG Compare the change in AG with the change in serum bicarbonate. Useful to identify additional or hidden metabolic disorders. In a simple metabolic acidosis, the change in AG=the decrease in bicarbonate i.e DAG=D HCO3 or measured AG-12 = 24- measured HCO3

Step 6: Calculate the Delta AG If the decrease in bicarbonate is more than the rise in the AG, concurrent with the AG metabolic acidosis there is also a second type of metabolic acidosis present, a non-AG metabolic acidosis. If the decrease in bicarbonate is less than the rise in AG, a metabolic alkalosis is concurrently present with the AG metabolic acidosis.

Respiratory acidosis-Etiology Upper airway obstruction Lower airway obstruction Cardiogenic or non-cardiogenic pulmonary edema Pneumonia Pulmonary emboli Fat emboli Central nervous system depression Neuromascular impairment Ventilatory restriction

Respiratory alkalosis-Etiology Central nervous system stimulation: Fever, pain, fear, cerebrovascular accident, CNS infection, trauma, tumor. Hypoxia: High altitude, profound anemia, pulmonary disease. Stimulation of chest receptors: Pulmonary edema, pulmonary emboli, pneumonia, pneumothorax, pleural effusion. Drugs or hormones : Salicylates, medroxyprogesterone, catecholamines. Miscellaneous: Sepsis, pregnancy, liver disease, hyperthyroidism.

Metabolic Acidosis Elevated AG acidosis Ketoacidosis: Diabetic, starvation, alcoholic. Lactic acidosis. Uremia (phosphates, sulfates, organic anions). Toxins: Ethylene glycol, methanol, salicylate.

Metabolic Acidosis Normal AG acidosis The fall in bicarbonate is matched by a proportional rise in serum chloride (hyperchloremic metabolic acidosis). Most common causes are gastrointestinal and renal loses of bicarbonate. More rarely, it is caused by rapid dilution of the plasma bicarbonate by saline.

Normal AG metabolic acidosis- etiology GI losses Diarrhea Ileostomy, pancreatic or bile drainage Renal losses Renal insufficiency Proximal RTA Distal RTA Type 4 RTA Acetazolamide Rapid saline administration

Normal AG metabolic acidosis: GI or Renal loss of bicarbonate? Calculate the urine anion gap (UAG) It provides information on whether the kidney is able to produce ammonium (NH4+) UAG =UK+ + UNa+ - UCl- A negative UAG suggests that there is NH4+ present in the urine , ie the kidney is able to excrete hydrogen kations and regenerate bicarbonate. Therefore the bicarbonate losses are from the GI tract. The opposite is true with a positive UAG.

Metabolic alkalosis Most common cause is volume depletion, urine Cl- is low and the alkalosis resolves after volume replacement (vompiting, NG suction). Can also occur with bicarbonate administration, mineralcorticoid excess, acetates in TPN, diuretics. Urine Cl- is › 40 mEq/l.

Thank you..