Respiratory Alkalosis


Definitions

Hyperventilation (see Hyperventilation)

  • Definition
    • Hyperventilation is Defined as an Increase in Respiratory Rate and/or Tidal Volume, Resulting in the Elimination of More Carbon Dioxide than the Body Produces
      • Hyperventilation Results in Hypocapnia (Decreased Arterial pCO2) and Respiratory Alkalosis (at Least Initially, Until Renal Compensation Results in Bicarbonate Excretion with an Eventual Decrease in the pH Back Toward Normal) (see Respiratory Alkalosis)

Hyperpnea (see Hyperpnea)

  • Definition
    • Hyperpnea is Defined as an Increase in Tidal Volume with or without an Increase in Respiratory Rate

Tachypnea (see Tachypnea)

  • Definition
    • Tachypnea is Defined as an Increase in Respiratory Rate

Hypocapnia (see Hypocapnia)

  • Definition
    • Hypocapnia is Defined as Decrease in Arterial pCO2 (i.e. Decreased Arterial Blood Partial Pressure of Carbon Dioxide) to <40 mm Hg

Alkalemia

  • Definition
    • Alkalemia is Defined as Increase in the Arterial pH to >7.40
  • Note that a Patient Can Be Alkalemic without Having a Respiratory Alkalosis
    • Example
      • Metabolic Alkalosis Can Produce Alkalemia without the Presence of a Respiratory Alkalosis

Respiratory Alkalosis (see Respiratory Alkalosis)

  • Definition
    • Respiratory Alkalosis is Defined as an Acid-Base Disorder Characterized by a Decrease in Arterial pCO2 with an Associated Increase in Arterial pH (at Least Initially)
  • Note that a Patient Can Have a Respiratory Alkalosis without Being Alkalemic
    • Example
      • Due to Normal Compensatory Mechanisms, Chronic Respiratory Alkalosis Induces Metabolic (Predominantly Renal) Compensation (with a Progressive Decrease in Serum Bicarbonate Over Time), Culminating in Only Minimal/Absent Alkalemia

Etiology of Hyperventilation/Hypocapnia/Respiratory Alkalosis (see Hyperventilation, Hypocapnia, and Respiratory Alkalosis)

Cardiovascular Disease-Induced Hyperventilation

Congestive Heart Failure (CHF) (see Congestive Heart Failure)

  • Physiology
    • Pulmonary Congestion, Resulting in Stimulation of Pulmonary Vascular and Interstitial Receptors, Increasing Respiratory Drive
    • Low Cardiac Output and Hypotension, Resulting in Stimulation of Arterial Baroreceptors -> Increasing Respiratory Drive
    • “Stagnant Hypoxia” of Carotid Body Chemoreceptors, Resulting in Increased Respiratory Drive

Hypotension (see Hypotension)

  • Physiology
    • Pulmonary Congestion, Resulting in Stimulation of Pulmonary Vascular and Interstitial Receptors, Increasing Respiratory Drive
    • Low Cardiac Output and Hypotension, Resulting in Stimulation of Arterial Baroreceptors -> Increasing Respiratory Drive
    • “Stagnant Hypoxia” of Carotid Body Chemoreceptors, Resulting in Increased Respiratory Drive

Fever/Sepsis-Induced Hyperventilation (see Fever and Sepsis)

Physiology

  • Fever-Related Stimulation of Hypothalamus or Carotid Bodies
    • Occurs Independent of Hypotension and Metabolic Rate

Clinical

  • Respiratory Alkalosis May Occur Early Prior to the Onset of Fever and Hypotension

Hypoxemia-Induced Hyperventilation

High Altitude (see Chronic Mountain Sickness)

  • Physiology
    • Hypoxemia-Induced Stimulation of Peripheral Chemoreceptors in the Carotid Bodies
      • However, the Degree of Hypoxemia-Induced Increase in Minute Ventilation is Modulated by Co-Existing pCO2 and pH, Mechanics of the Lung and Chest Wall, Genetic Factors, and the Overall Duration of Hypoxemia
      • The Increase in Minute Ventilation (VE) in Response to Decrease in pO2 is Non-Linear
        • The Most Pronounced Response is Observed with pO2 <60 mm Hg
      • The Increase in Minute Ventilation (VE) in Response to Decreased SaO2 is Relatively Linear
  • Clinical
    • On Mount Everest (Where pO2 is 27 mm Hg), the pCO2 is Decreased to 7.5 mm Hg (J Appl Physiol Respir Environ Exerc Physiol, 1983) [MEDLINE]

Intracardiac Shunt (see Intracardiac and Extracardiac Shunt)

  • Physiology
    • Hypoxemia-Induced Stimulation of Peripheral Chemoreceptors in the Carotid Bodies
      • However, the Degree of Hypoxemia-Induced Increase in Minute Ventilation is Modulated by Co-Existing pCO2 and pH, Mechanics of the Lung and Chest Wall, Genetic Factors, and the Overall Duration of Hypoxemia
      • The Increase in Minute Ventilation (VE) in Response to Decrease in pO2 is Non-Linear
        • The Most Pronounced Response is Observed with pO2 <60 mm Hg
      • The Increase in Minute Ventilation (VE) in Response to Decreased SaO2 is Relatively Linear

Pulmonary Disease (of Any Etiology Resulting in Hypoxemia)

  • Physiology
    • Hypoxemia-Induced Stimulation of Peripheral Chemoreceptors in the Carotid Bodies
      • However, the Degree of Hypoxemia-Induced Increase in Minute Ventilation is Modulated by Co-Existing pCO2 and pH, Mechanics of the Lung and Chest Wall, Genetic Factors, and the Overall Duration of Hypoxemia
      • The Increase in Minute Ventilation (VE) in Response to Decrease in pO2 is Non-Linear
        • The Most Pronounced Response is Observed with pO2 <60 mm Hg
      • The Increase in Minute Ventilation (VE) in Response to Decreased SaO2 is Relatively Linear

Metabolic Disorder-Induced Hyperventilation

Acidosis (i.e. Acidemia of Any Etiology) (see Metabolic Acidosis-Elevated Anion Gap and Metabolic Acidosis-Normal Anion Gap)

  • Physiology
    • Stimulation of Peripheral and Central Chemoreceptors (and Increased Sensitivity of Peripheral Chemoreceptors to Hypoxia), Resulting in Increased Respiratory Drive

Hyperthyroidism (see Hyperthyroidism)

  • Physiology
    • Due to increased ventilatory chemoreflexes

Liver Disease

  • Etiology
  • Physiology
    • Sympathetic Overactivity, Increased Serum Progesterone and Vasoactive Intestinal Peptide (VIP), Increased Brain Ammonia and Glutamine, and Hypoxemia from the Formation of Small Intrapulmonary Shunts (ie: Hepatopulmonary Syndrome), All Resulting in Increased Respiratory Drive (Int J Cardiol, 2012) [MEDLINE]
  • Clinical
    • Severity of Respiratory Alkalosis Correlates with the Degree of Hepatic Insufficiency

Severe Anemia (see Anemia)

  • Physiology
    • Decreased Oxygen Delivery

Neurologic/Psychogenic Disorder-Induced Hyperventilation

Anxiety/Panic Disorder (see Anxiety)

  • xxx

Brainstem Tumor

  • Physiology
    • Lactic Acidosis by Malignant Cells in Midbrain, Resulting in Increased Respiratory Drive

Central Nervous System Infection

  • Etiology
  • Physiology
    • Involvement of Midbrain or Hypothalamus, Resulting in Increased Respiratory Drive

Intracerebral Hemorrhage (see Intracerebral Hemorrhage)

  • Physiology
    • Red Blood Cell Glycolysis and Acidosis in the Cerebrospinal Fluid, Resulting in Increased Respiratory Drive

Ischemic Cerebrovascular Accident (CVA) (see Ischemic Cerebrovascular Accident)

  • Physiology
    • Impairment of Inhibition of the Cortex on the Brainstem Respiratory Center

Psychogenic Hyperventilation

  • Physiology
    • Anxiety/Stress
      • Supported by the Fact that This Type of Hyperventilation Decreases During Sleep

Traumatic Brain Injury (TBI) (see Traumatic Brain Injury)

  • Physiology
    • Involvement of Midbrain or Hypothalamus, Resulting in Increased Respiratory Drive

Withdrawal

  • Delirium Tremens (DT’s) (see Ethanol)

Pain-Induced Hyperventilation

Physiology

  • Adrenergic Stimulation of Peripheral and Central Chemoreceptors

Pregnancy (and Luteal Phase of Menstrual Cycle)-Induced Hyperventilation (see Pregnancy)

Physiology

  • Progesterone and Other Hormone Stimulation of the Medullary Respiratory Center

Pulmonary Disease-Induced Hyperventilation

Asthma (see Asthma)

  • Physiology
    • Stimulation of Mechanical and Chemical Bronchopulmonary Receptors, Resulting in Increased Afferent Vagal Firing, Resulting in Increase in Respiratory Drive (and Cough and/or Bronchoconstriction)
    • Stimulation of Chest Wall Receptors (in Asthma, Pulmonary Fibrosis, and Chest Wall Disease), Resulting in Increased Respiratory Drive (and Dyspnea)

Cardiogenic Pulmonary Edema (see Cardiogenic Pulmonary Edema)

  • Physiology
    • Stimulation of Mechanical and Chemical Bronchopulmonary Receptors, Resulting in Increased Afferent Vagal Firing, Resulting in Increase in Respiratory Drive (and Cough and/or Bronchoconstriction)

Chest Wall Disease

  • Etiology
  • Physiology
    • Stimulation of Mechanical and Chemical Bronchopulmonary Receptors, Resulting in Increased Afferent Vagal Firing, Resulting in Increase in Respiratory Drive (and Cough and/or Bronchoconstriction)
    • Stimulation of Chest Wall Receptors (in Asthma, Pulmonary Fibrosis, and Chest Wall Disease), Resulting in Increased Respiratory Drive (and Dyspnea)

Community-Acquired Pneumonia (CAP)/Hospital-Acquired Pneumonia/Ventilator-Associated Pneumonia (VAP) (see Community-Acquired Pneumonia and Hospital-Acquired Pneumonia and Ventilator-Associated Pneumonia)

  • Physiology
    • Stimulation of Mechanical and Chemical Bronchopulmonary Receptors, Resulting in Increased Afferent Vagal Firing, Resulting in Increase in Respiratory Drive (and Cough and/or Bronchoconstriction)

Interstitial Lung Disease (ILD) (see Interstitial Lung Disease)

  • Epidemiology
    • Respiratory Alkalosis is Common
  • Etiology
    • Idiopathic Pulmonary Fibrosis (IPF) (see Idiopathic Pulmonary Fibrosis)
      • Physiology
        • Stimulation of Mechanical and Chemical Bronchopulmonary Receptors, Resulting in Increased Afferent Vagal Firing, Resulting in Increase in Respiratory Drive (and Cough and/or Bronchoconstriction)
        • Stimulation of Chest Wall Receptors (in Asthma, Pulmonary Fibrosis, and Chest Wall Disease), Resulting in Increased Respiratory Drive (and Dyspnea)

Pneumothorax (see Pneumothorax)

  • Physiology
    • Stimulation of Mechanical and Chemical Bronchopulmonary Receptors, Resulting in Increased Afferent Vagal Firing, Resulting in Increase in Respiratory Drive (and Cough and/or Bronchoconstriction)

Pulmonary Vascular Disease

  • Etiology
    • Acute Pulmonary Embolism (PE) (see Acute Pulmonary Embolism)
      • Physiology
        • Stimulation of Mechanical and Chemical Bronchopulmonary Receptors, Resulting in Increased Afferent Vagal Firing, Resulting in Increase in Respiratory Drive (and Cough and/or Bronchoconstriction)
    • Pulmonary Hypertension (see Pulmonary Hypertension)
      • Physiology
        • Stimulation of Mechanical and Chemical Bronchopulmonary Receptors, Resulting in Increased Afferent Vagal Firing, Resulting in Increase in Respiratory Drive (and Cough and/or Bronchoconstriction)

Drug-Induced Hyperventilation

Beta-2 Adrenergic Receptor Agonists (see β2-Adrenergic Receptor Agonists)

  • Physiology
    • Stimulation of Peripheral and Central Chemoreceptors (or Direct Effect on Brainstem Respiratory Centers), Resulting in Increased Respiratory Drive

Doxapram (Dopram, Stimulex Respiram) (see Doxapram)

  • Physiology
    • Doxapram Stimulates Carotid Body Chemoreceptors (in the Carotid Arteries), Resulting in Stimulation of the Brainstem Respiratory Center
  • Clinical
    • Intravenous Respiratory Stimulant
    • Increases Respiratory Rate and Tidal Volume

Methylxanthines

  • Physiology
    • Stimulation of Peripheral and Central Chemoreceptors (or Direct Effect on Brainstem Respiratory Centers), Resulting in Increased Respiratory Drive
  • Agents

Progesterone (see Progesterone)

  • Physiology
    • Stimulation of Peripheral and Central Chemoreceptors (or Direct Effect on Brainstem Respiratory Centers), Resulting in Increased Respiratory Drive
    • Clinical
    • Progesterone Increases Ventilation and Lowers the Arterial pCO2 by as Much as 5–10 mm Hg

Salicylate Intoxication (see Salicylates)

  • Epidemiology
    • Salicylates are the Most Common Etiology of Drug-Induced Respiratory Alkalosis
  • Physiology
    • Stimulation of Peripheral and Central Chemoreceptors (or Direct Effect on Brainstem Respiratory Centers), Resulting in Increased Respiratory Drive
    • With Salicylates, Secondary Metabolic Acidosis Can Also Drive Respiration

Physiology

Normal Acid-Base Physiology

Renal Compensatory Response to Respiratory Alkalosis


Diagnosis

Arterial Blood Gas (ABG) (see Arterial Blood Gas)


Clinical Manifestations of of Hyperventilation/Hypocapnia/Respiratory Alkalosis (see Hyperventilation, Hypocapnia, and Respiratory Alkalosis)

General Comments

  • Mild Hypocapnia Generally Does Not Have Serious Clinical Effects in Healthy Persons
  • Clinical Manifestations Attributable to Acute Respiratory Alkalosis are More Common Than in Metabolic Alkalosis (see Metabolic Alkalosis)
    • Respiratory Alkalosis Probably Causes a Larger Change in Intracellular and Brain pH than Does Metabolic Alkalosis
      • Acute Respiratory Alkalosis Results in a Rapid Shift in Arterial pCO2, Which is Almost Immediately Transmitted Throughout the Total Body Water (Including the Intracellular Fluid Compartment, the Brain, and the Cerebrospinal Fluid)
        • This Accounts for the Characteristic Symptoms of Paresthesias, Carpopedal Spasm, and Lightheadedness Observed in Acute Respiratory Alkalosis
      • Metabolic Alkalosis-Associated Alterations in Blood bicarbonate Cause slower and Less Marked pH Changes within the Intracellular Fluid Compartment and Across the Blood Brain Barrier

Cardiovascular Manifestations

Arrhythmias

  • Epidemiology
    • Hypocapnia has Been Linked to the Development of Arrhythmias, Both in Critically Ill Patients and in Patients with Panic Disorder
  • Physiology
    • Arrhythmias are Likely Mediated by Alkalosis-Associated Electrophysiologic Effects on the Cardiac Conduction System (J Thorac Cardiovasc Surg, 1966) [MEDLINE]
    • May Also Be Mediated to Myocardial Ischemia (Although Specific Direct Myocardial Effects May Occur)

Chest Pain (see Chest Pain)

  • Epidemiology
    • May Occur in the Setting of Hyperventilation

Myocardial Ischemia (see Coronary Artery Disease)

  • Physiology
    • Decreased Myocardial Oxygen Supply
      • Reduced Coronary Flow and Collateral Flow
      • Increased Coronary Vascular Resistance
      • Increased Risk of Coronary Artery Spasm
      • Increased Coronary Microvascular Leakage
      • Increased Platelet Count and Aggregation
    • Increased Myocardial Oxygen Demand
      • Increased Oxygen Extraction
      • Increased (and Later Decreased) Contractility
      • Increased Intracellular Calcium Concentration
      • Increased Systemic Vascular Resistance (SVR)
    • Myocardial Ischemia
    • Reperfusion Injury

Palpitations (see Palpitations)

  • Epidemiology
    • Palpitations May Occur in the Setting of Hyperventilation/Hypocapnia (Lancet, 1998)[MEDLINE]

Syncope (see Syncope)

  • Epidemiology
    • XXXX

Dermatologic Manifestations

Diaphoresis (see Diaphoresis)

  • Epidemiology
    • May Occur in the Setting of Hyperventilation

Neurologic Manifestations

Carpopedal Spasm (see Carpopedal Spasm)

  • Epidemiology
    • May Occur in the Setting of Hyperventilation/Hypocapnia

Dizziness/lightheadedness (see Dizziness)

  • Epidemiology
    • May Occur in the Setting of Hyperventilation/Hypocapnia

Muscle Cramps (see Muscle Cramps)

  • Physiology
    • Muscle Cramps May Occur in the Setting of Hypocapnia (Lancet, 1998) [MEDLINE]

Neonatal Brain Injury

  • Physiology
    • Cerebral Infarction
    • Cystic Periventricular Leukomalacia
    • Multicystic Encephalomalacia
    • Pontosubicular Necrosis
    • Reactive Hyperemia and Hemorrhage

Paresthesias (see Paresthesias)

  • Physiology
    • Paresthesias May Occur in the Setting of Hypocapnia (Lancet, 1998)[MEDLINE]

Poorer Outcome in Traumatic Brain Injury (TBI) (see Traumatic Brain Injury)

  • Epidemiology
    • In Traumatic Brain Injury, Prophylactic Hyperventilation is Associated with Worse Outcome (and is Therefore, Not Recommended)
  • Physiology
    • Decreased Cerebral Oxygenation
    • Although Hyperventilation May Transiently Decrease Intracranial Pressure, it May Do so at the Expense of Cerebral Perfusion
    • Additionally, Hypocapnia May Exacerbate Secondary Brain Injury, Because Increased Cerebral Vascular Reactivity and Vasoconstriction Can Result in Decreased Regional Cerebral Blood Flow

Poorer Outcome in Acute Ischemic Cerebrovascular Accident (CVA) (see Ischemic Cerebrovascular Accident)

  • Epidemiology
    • In Ischemic Cerebrovascular Accident, Prophylactic Hyperventilation is Associated with Worse Outcome (and is Therefore, Not Recommended)
  • Physiology
    • The Beneficial Effects of Hypocapnia on Intracranial Pressure are Likely Outweighed by the Effects of a Decreased Oxygen Supply (Due to Decreased Cerebral Perfusion)

Postoperative Psychomotor Dysfunction

  • Epidemiology
    • Acute Hypocapnia is Common During General Anesthesia
    • Otherwise Healthy Patients Who are Subjected to Hypocapnia During General Anesthesia Have Been Found to Have Impaired Psychomotor Function for Up to 6 Days
      • Such Effects are Especially Pronounced in Older Patients
  • Clinical
    • Effects are Generally Reversible

Seizures (see Seizures)

  • Epidemiology
    • Seizures May Occur in the Setting of Hypocapnia (Lancet, 1998)[MEDLINE]
  • Physiology
    • Increased Neuronal Excitability, Seizure Activity, and Anaerobic Metabolism
    • Hypocapnic Potentiation of Seizure Activity, in Addition to Increasing Oxygen Demand, Augments Production of the Cytotoxic Excitatory Amino Acids Associated with Seizures
    • Hypocapnia May Also Induce Increased Neuronal Dopamine, which May Increase Risk of Seizures

Tetany (see Tetany)

  • Epidemiology
    • Respiratory Alkalosis Can Cause Tetany Alone or Act Synergistically with Hypocalcemia to Cause Tetany (see Hypocalcemia)

Pulmonary Manifestations

Bronchospasm (see Bronchospasm)

  • Physiology
    • Airway Hypocapnia Increases Airway Resistance by Inducing Bronchospasm and Increasing Airway Microvascular Permeability

Acute Respiratory Distress Syndrome (ARDS) (see Acute Respiratory Distress Syndrome)

  • Physiology
    • Increased Pulmonary Capillary Permeability, Parenchymal Injury, and Depletion of Lamellar Bodies
      • These Effects are All Ameliorated by the Administration of Supplemental Carbon Dioxide
    • Hypocapnia Decreases Lung Compliance in Humans (Possibly Due to Effects on Surfactant Function)
    • Alveolar Hypocapnia Attenuates Hypoxic Pulmonary Vasoconstriction, Worsening Intrapulmonary Shunt and Systemic Oxygenation

Treatment


References