Abstract
This chapter provides an overview of respiratory acid-base disorders. Respiratory acid-base disorders are those abnormalities in acid-base equilibrium that are initiated by changes in CO 2 tension (Pco 2 ) of body fluids and whole-body CO 2 stores. There are two respiratory acid-base disorders: respiratory acidosis and respiratory alkalosis. For both respiratory acidosis and respiratory alkalosis, we address the pathophysiology, secondary physiologic response, etiology, clinical manifestations, diagnosis, and therapeutic principles.
Keywords
respiratory acidosis, primary hypercapnia, respiratory alkalosis, primary hypocapnia, pseudorespiratory alkalosis
Respiratory Acidosis
Respiratory acidosis, or primary hypercapnia, is the acid-base disturbance initiated by an increase in the carbon dioxide tension of body fluids and in whole-body CO 2 stores. Hypercapnia acidifies body fluids and elicits an adaptive increment in the plasma bicarbonate concentration [ 
] that should be viewed as an integral part of the respiratory acidosis. Arterial CO 2 tension (P co 2 ), measured at rest and at sea level, is greater than 45 mm Hg in simple respiratory acidosis. Lower values of P co 2 might still signify the presence of primary hypercapnia in the setting of mixed acid-base disorders (e.g., eucapnia, rather than the expected hypocapnia, in the presence of metabolic acidosis). Another special case of respiratory acidosis is the presence of arterial eucapnia, or even hypocapnia, in association with venous hypercapnia in patients who have an acute severe reduction in cardiac output but relative preservation of respiratory function (i.e., pseudorespiratory alkalosis).
Pathophysiology
The ventilatory system is responsible for maintaining P co 2 within normal limits by adjusting minute ventilation (V̇ E ) to match the rate of CO 2 production. V̇ E consists of two components: ventilation distributed in the gas-exchange units of the lungs (alveolar ventilation, V̇ A ) and ventilation wasted in dead space (V̇ D ). Hypercapnia can result from increased CO 2 production, decreased V̇ A , or both. Decreased V̇ A can occur from a reduction in V̇ E , an increase in V̇ D , or a combination of the two.
The main elements of the ventilatory system are the respiratory pump, which generates a pressure gradient responsible for airflow, and the loads that oppose such action. The respiratory pump comprises the cerebrum, brainstem, spinal cord, phrenic and intercostal nerves, and the muscles of respiration. The respiratory loads include the ventilatory requirement (CO 2 production, O 2 consumption), airway resistance, lung elastic recoil, and chest wall/abdominal resistance. Most frequently, primary hypercapnia develops from an imbalance between the strength of the respiratory pump and the weight of the respiratory loads, thereby resulting in a decreased V̇ A . Impairment of the respiratory pump can occur because of depressed central drive, abnormal neuromuscular transmission, or muscle dysfunction. Causes of augmented respiratory loads include ventilation/perfusion mismatch (increased V̇ D ), augmented airway flow resistance, lung/pleural/chest wall stiffness, impaired diaphragmatic function, and increased ventilatory demand. An increased V̇ D occurs in many clinical conditions, including emphysema, cystic fibrosis, asthma, and other intrinsic lung diseases, as well as chest wall disorders. A less frequent cause of primary hypercapnia is failure of CO 2 transport caused by decreases in pulmonary perfusion, a condition that occurs in cardiac arrest, circulatory collapse, and pulmonary embolism (thrombus, fat, air).
Overproduction of CO 2 is usually matched by increased excretion so that hypercapnia is prevented. However, patients with marked limitation in pulmonary reserve and those receiving constant mechanical ventilation might experience respiratory acidosis due to increased CO 2 production caused by increased muscle activity (agitation, myoclonus, shivering, seizures), sepsis, fever, or hyperthyroidism. Increments in CO 2 production might also be imposed by the administration of large carbohydrate loads (>2000 kcal/day) to nutritionally bereft, critically ill patients or during the decomposition of bicarbonate infused in the course of treating metabolic acidosis.
The major threat to life from CO 2 retention in patients who are breathing room air is the associated obligatory hypoxemia (in accordance with the alveolar gas equation). When the arterial oxygen tension (P o 2 ) falls to less than 40 to 50 mm Hg, harmful effects can occur, especially if the fall is rapid. In the absence of supplemental oxygen, patients in respiratory arrest develop critical hypoxemia within a few minutes, long before extreme hypercapnia ensues. Because of the constraints of the alveolar gas equation, it is not possible for P co 2 to reach values much higher than 80 mm Hg while the level of P o 2 is still compatible with life. Extreme hypercapnia with P co 2 values exceeding 100 mm Hg is occasionally seen in patients receiving oxygen therapy, and in fact, it is often the result of uncontrolled oxygen administration.
Secondary Physiologic Response
An immediate rise in plasma [ 
] owing to titration of nonbicarbonate body buffers occurs in response to acute hypercapnia. This adaptation is complete within 5 to 10 minutes after the increase in P co 2 . On average, plasma [ 
] increases by about 0.1 mEq/L for each 1 mm Hg acute increment in P co 2 ; as a result, the plasma hydrogen ion concentration [H + ] increases by about 0.75 nEq/L for each 1 mm Hg acute increment in P co 2 . Therefore the overall limit of adaptation of plasma [ 
] in acute respiratory acidosis is quite small; even when P co 2 increases to levels of 80 to 90 mm Hg, the increment in plasma [ 
] does not exceed 3 to 4 mEq/L. Moderate hypoxemia does not alter the adaptive response to acute respiratory acidosis. On the other hand, preexisting hypobicarbonatemia (from metabolic acidosis or chronic respiratory alkalosis) enhances the magnitude of the bicarbonate response to acute hypercapnia, whereas this response is diminished in hyperbicarbonatemic states (from metabolic alkalosis or chronic respiratory acidosis). Other electrolyte changes observed in acute respiratory acidosis include mild increases in plasma sodium (1 to 4 mEq/L), potassium (0.1 mEq/L for each 0.1 unit decrease in pH), and phosphorus, as well as small decreases in plasma chloride and lactate concentrations (the latter effect originating from inhibition of the activity of 6-phosphofructokinase and, consequently, glycolysis by intracellular acidosis).
A small reduction in the plasma anion gap is also observed, reflecting the decline in plasma lactate and the acidic titration of plasma proteins. Acute respiratory acidosis induces glucose intolerance and insulin resistance that are not prevented by adrenergic blockade. These changes are likely mediated by direct effects of the low tissue pH on skeletal muscle.
The adaptive increase in plasma [ 
] observed in the acute phase of hypercapnia is amplified markedly during chronic hypercapnia as a result of the generation of new bicarbonate by the kidneys. Both proximal and distal acidification mechanisms contribute to this adaptation, which requires 3 to 5 days for completion. The renal response to chronic hypercapnia includes chloruresis and the generation of hypochloremia. On average, plasma [ 
] increases by about 0.35 mEq/L for each 1 mm Hg chronic increment in P co 2 ; as a result, the plasma [H + ] increases by about 0.3 nEq/L for each 1 mm Hg chronic increase in P co 2 . More recently, a substantially steeper slope for the change in plasma [ 
] was reported (0.51 mEq/L for each 1 mm Hg chronic increase in P co 2 ), but the small number of blood gas measurements, one for each of 18 patients, calls into question the validity of this conclusion. Empiric observations indicate a limit of adaptation of plasma [ 
] on the order of 45 mEq/L.
The renal response to chronic hypercapnia is not altered appreciably by dietary sodium or chloride restriction, moderate potassium depletion, alkali loading, or moderate hypoxemia. The extent to which chronic kidney disease of variable severity limits the renal response to chronic hypercapnia remains unknown. Obviously patients with end-stage kidney disease cannot mount a renal response to chronic hypercapnia (i.e., generation of new bicarbonate by the kidneys), making them subject to severe acidemia. The degree of acidemia is more pronounced in patients who are receiving hemodialysis rather than peritoneal dialysis because the former treatment maintains, on average, lower plasma [ 
]. Recovery from chronic hypercapnia is crippled by a chloride-deficient diet. In this circumstance, despite correction of the level of P co 2 , plasma [ 
] remains elevated as long as the state of chloride deprivation persists, thus creating the entity of “posthypercapnic metabolic alkalosis.” Chronic hypercapnia is not associated with appreciable changes in the anion gap or in plasma concentrations of sodium, potassium, or phosphorus.
Etiology
Respiratory acidosis can develop in patients who have normal or abnormal airways and lungs. Tables 15.1 and 15.2 present, respectively, causes of acute and chronic respiratory acidosis. Some conditions can cause both types of the disorder. This classification accounts for the usual mode of onset and duration of the various causes, and it emphasizes the biphasic time course that characterizes the secondary physiologic response to hypercapnia. Primary hypercapnia can result from disease or malfunction within any element of the regulatory system that controls respiration, including the central and peripheral nervous system, respiratory muscles, thoracic cage, pleural space, airways, and lung parenchyma. Not infrequently, more than one cause contributes to the development of respiratory acidosis in a given patient. A vital capacity less than 1 L in patients with myasthenic crisis predicts impending acute respiratory failure with CO 2 retention. Chronic obstructive pulmonary disease (COPD), including emphysema, chronic bronchitis, and small-airway disease, is the most common cause of chronic hypercapnia. Importantly, certain causes of chronic respiratory acidosis (e.g., COPD) can superimpose an element of acute respiratory acidosis during periods of decompensation (e.g., pneumonia, major surgery, heart failure).
| Normal Airways and Lungs | Abnormal Airways and Lungs |
|---|---|
| Central Nervous System Depression | Upper Airway Obstruction |
| General anesthesia | Coma-induced hypopharyngeal obstruction |
| Sedative overdose (opiates, benzodiazepines, tricyclic antidepressants, barbiturates) | Aspiration of foreign body or vomitus |
| Head trauma | Laryngospasm |
| Cerebrovascular accident | Angioedema |
| Central sleep apnea | Epiglottitis |
| Cerebral edema | Obstructive sleep apnea |
| Brain tumor | Inadequate laryngeal intubation |
| Encephalitis | Laryngeal obstruction post intubation |
| Hypothyroidism | Lower Airway Obstruction |
| Hypothermia | Generalized bronchospasm |
| Starvation | Acute severe asthma |
| Neuromuscular Impairment | Bronchiolitis of infancy and adult |
| Cervical spine injury or disease (trauma, syringomyelia) | Disorders involving pulmonary alveoli |
| Transverse myelitis (multiple sclerosis) | Severe bilateral pneumonia |
| Guillain-Barré syndrome | Acute respiratory distress syndrome |
| Acute intermittent porphyria | Severe pulmonary edema |
| Tick paralysis | Pulmonary Perfusion Defect |
| Status epilepticus | Cardiac arrest a |
| Botulism, tetanus | Severe circulatory failure a |
| Crisis in myasthenia gravis | Massive pulmonary thromboembolism |
| Electrolyte abnormalities (hyperkalemia, hypokalemia, hypophosphatemia, hypercalcemia, hypermagnesemia) | Fat or air embolus |
| |
| Drugs or toxic agents (e.g., curare, succinylcholine, aminoglycosides, organophosphates, shellfish poisoning, ciguatera poisoning, procainamide myopathy) | |
| Ventilatory Restriction | |
| Rib fractures with flail chest | |
| Pneumothorax | |
| Hemothorax | |
| Impaired diaphragmatic function (e.g., peritoneal dialysis, ascites) | |
| Iatrogenic Events | |
| Misplacement or displacement of airway cannula during anesthesia or mechanical ventilation | |
| Bronchoscopy-associated hypoventilation or respiratory arrest | |
| Increased CO 2 production with constant mechanical ventilation (e.g., due to high-carbohydrate diet or sorbent-regenerative hemodialysis) |
| Normal Airways and Lungs | Abnormal Airways and Lungs |
|---|---|
| Central Nervous System Depression | Upper Airway Obstruction |
| Sedative overdose (narcotics, benzodiazepines, tricyclic antidepressants) Primary alveolar hypoventilation (Ondine’s curse) Obesity-hypoventilation syndrome (Pickwickian syndrome) Brain tumor Brainstem disease Bulbar poliomyelitis Hypothyroidism Hypothermia Starvation Neuromuscular Impairment Poliomyelitis Multiple sclerosis Muscular dystrophy Amyotrophic lateral sclerosis Diaphragmatic paralysis Myxedema Myopathic disease Hyperthyroidism Eaton-Lambert syndrome Glycogen storage and mitochondrial diseases Ventilatory Restriction Kyphoscoliosis, spinal arthritis Morbid obesity Pectus excavatum Thoracoplasty Ankylosing spondylitis Fibrothorax Hydrothorax Impaired diaphragmatic function |
|
| Paralysis of vocal cords | |
| |
| Airway stenosis after prolonged intubation | |
| Thymoma, aortic aneurysm | |
| Lower Airway Obstruction | |
| Chronic obstructive lung disease (bronchitis, bronchiolitis, bronchiectasis, emphysema) | |
| Disorders Involving Pulmonary Alveoli | |
| Severe chronic pneumonitis | |
| Diffuse infiltrative disease (e.g., alveolar proteinosis) | |
| End-stage interstitial lung disease | |
| Severe pulmonary vascular disease | |
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