Respiratory Alkalosis

The respiratory system is responsible for eliminating the volatile acid carbon dioxide (CO2), which is produced via aerobic metabolism. The body produces approximately 15,000 mmol of CO2 daily, which is the majority of daily acid production; the remainder of the daily acid load (only about 70 mmol of nonvolatile acids) is excreted through the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys. When hypoventilation occurs, excess carbon dioxide is blown off and respiratory alkalosis develops. The kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys respond by decreasing serum bicarbonate (HCO3) through increased HCO3 excretion or decreased excretion of H+. Patients present with an increased respiratory rate, dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, light-headedness and potentially psychologic symptoms. Diagnosis involves a thorough history, an exam, and an arterial blood gas measurement. Management focuses on addressing the underlying abnormalities, stabilizing patients in acute distress, and potentially a small dose of short-acting benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines.

 

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Overview

Definition

Respiratory alkalosis refers to the process that results in a decreased level of carbon dioxide (CO2) within the blood.

Epidemiology

  • Gender bias Bias Epidemiological studies are designed to evaluate a hypothesized relationship between an exposure and an outcome; however, the existence and/or magnitude of these relationships may be erroneously affected by the design and execution of the study itself or by conscious or unconscious errors perpetrated by the investigators or the subjects. These systematic errors are called biases. Types of Biases: male = female
  • Incidence: dependent on the etiology
  • Incidence of hyperventilation syndrome: 25%–80% in adults with anxiety

Etiology

Table: Etiologies of respiratory alkalosis
Etiology Examples
Physiologic (not pathologic)
  • Pregnancy Pregnancy Pregnancy is the time period between fertilization of an oocyte and delivery of a fetus approximately 9 months later. The 1st sign of pregnancy is typically a missed menstrual period, after which, pregnancy should be confirmed clinically based on a positive β-hCG test (typically a qualitative urine test) and pelvic ultrasound. Pregnancy: Diagnosis, Maternal Physiology, and Routine Care
  • High altitude
Hypoxia-induced
  • Pulmonary embolism Pulmonary Embolism Pulmonary embolism (PE) is a potentially fatal condition that occurs as a result of intraluminal obstruction of the main pulmonary artery or its branches. The causative factors include thrombi, air, amniotic fluid, and fat. In PE, gas exchange is impaired due to the decreased return of deoxygenated blood to the lungs. Pulmonary Embolism
  • Pulmonary edema Pulmonary edema Pulmonary edema is a condition caused by excess fluid within the lung parenchyma and alveoli as a consequence of a disease process. Based on etiology, pulmonary edema is classified as cardiogenic or noncardiogenic. Patients may present with progressive dyspnea, orthopnea, cough, or respiratory failure. Pulmonary Edema
  • COPD COPD Chronic obstructive pulmonary disease (COPD) is a lung disease characterized by progressive, largely irreversible airflow obstruction. The condition usually presents in middle-aged or elderly persons with a history of cigarette smoking. Signs and symptoms include prolonged expiration, wheezing, diminished breath sounds, progressive dyspnea, and chronic cough. Chronic Obstructive Pulmonary Disease (COPD) or asthma Asthma Asthma is a chronic inflammatory respiratory condition characterized by bronchial hyperresponsiveness and airflow obstruction. The disease is believed to result from the complex interaction of host and environmental factors that increase disease predisposition, with inflammation causing symptoms and structural changes. Patients typically present with wheezing, cough, and dyspnea. Asthma exacerbations
Medications
  • Aspirin overdose
  • Nicotine overdose
  • Progesterone
Intracranial processes
  • Stroke
  • Encephalitis Encephalitis Encephalitis is inflammation of the brain parenchyma caused by an infection, usually viral. Encephalitis may present with mild symptoms such as headache, fever, fatigue, and muscle and joint pain or with severe symptoms such as seizures, altered consciousness, and paralysis. Encephalitis
  • Traumatic brain injury
Psychologic etiologies
  • Anxiety
  • Psychosis
Other processes
  • Pain
  • Fever

Acid–Base Review

Acid–base disorders are classified according to the primary disturbance (respiratory or metabolic) and the presence or absence of compensation.

Identifying the primary disturbance

Look at the pH, PCO2 (partial pressure of CO2), and HCO3 (bicarbonate) to determine the primary disturbance. 

  • Normal values:
    • pH: 7.35–7.45
    • PCO2:  35–45 mmHg
    • HCO3: 22–28 mEq/L
  • “-emia” versus “-osis”:
    • “-emia” refers to “in the blood”:
      • Acidemia: more hydrogen ions (H+) in the blood = pH < 7.35
      • Alkalemia: more hydroxide ions (OH) in the blood = pH > 7.45 
    • “-osis” refers to a process:  
      • Acidosis and alkalosis refer the processes that cause acidemia and alkalemia. 
      • pH may be normal in acidosis and alkalosis.
  • Primary (uncompensated) respiratory disorders: 
    • Disorders caused by abnormalities in PCO2
    • Both the pH and PCO2 are abnormal, in opposite directions.
    • Primary respiratory acidosis Respiratory acidosis The respiratory system is responsible for eliminating the volatile acid carbon dioxide (CO2), which is produced via aerobic metabolism. In the setting of hypoventilation, this acid load is not adequately blown off, and respiratory acidosis occurs. Renal compensation occurs after 3-5 days, as the kidneys attempt to increase the serum bicarbonate levels. Respiratory Acidosis:  pH < 7.35 and PCO2 > 45 
    • Primary respiratory alkalosis: pH > 7.45 and PCO2 < 35
  • Primary (uncompensated) metabolic disorders: 
    • Disorders caused by abnormalities in HCO3 
    • Both the pH and PCO2 are abnormal, in the same direction. 
    • Primary uncompensated metabolic acidosis Metabolic acidosis The renal system is responsible for eliminating the daily load of non-volatile acids, which is approximately 70 millimoles per day. Metabolic acidosis occurs when there is an increase in the levels of new non-volatile acids (e.g., lactic acid), renal loss of HCO3-, or ingestion of toxic alcohols. Metabolic Acidosis:  
      • pH < 7.35 and PCO2 < 40 
      • Think: “So the acidosis is not due to ↑ CO2 … it must be due to ↓ serum HCO3 metabolic acidosis Metabolic acidosis The renal system is responsible for eliminating the daily load of non-volatile acids, which is approximately 70 millimoles per day. Metabolic acidosis occurs when there is an increase in the levels of new non-volatile acids (e.g., lactic acid), renal loss of HCO3-, or ingestion of toxic alcohols. Metabolic Acidosis
      • Confirm by looking at HCO3: will be low (< 22 mEq/L)
    • Primary uncompensated metabolic alkalosis Metabolic alkalosis The renal system is responsible for eliminating the daily load of non-volatile acids, which is approximately 70 millimoles per day. Metabolic alkalosis also occurs when there is an increased loss of acid, either renally or through the upper GI tract (e.g., vomiting), increased intake of HCO3-, or a reduced ability to secrete HCO3- when needed. Metabolic Alkalosis
      • pH > 7.45 and PCO2 > 40
      • Think: “So the alkalosis is not due to ↓ CO2… it must be due to ↑ serum HCO3 metabolic alkalosis Metabolic alkalosis The renal system is responsible for eliminating the daily load of non-volatile acids, which is approximately 70 millimoles per day. Metabolic alkalosis also occurs when there is an increased loss of acid, either renally or through the upper GI tract (e.g., vomiting), increased intake of HCO3-, or a reduced ability to secrete HCO3- when needed. Metabolic Alkalosis
      • Confirm by looking at HCO3: will be high (> 28 mEq/L)
  • Simple disorders:
    • The presence of one of the above disorders with appropriate compensation
    • Respiratory disorders are compensated by renal mechanisms.
    • Metabolic disorders are compensated by respiratory mechanisms
  • Mixed disorders: two primary disorders present

Compensation

When acidosis or alkalosis develops, the body will try to compensate. Often, compensation will result in a normal pH.

  • In primary respiratory acid–base disorders, the kidney may try to compensate in an attempt to normalize the pH.
    • Kidneys respond to respiratory acidosis Respiratory acidosis The respiratory system is responsible for eliminating the volatile acid carbon dioxide (CO2), which is produced via aerobic metabolism. In the setting of hypoventilation, this acid load is not adequately blown off, and respiratory acidosis occurs. Renal compensation occurs after 3-5 days, as the kidneys attempt to increase the serum bicarbonate levels. Respiratory Acidosis by increasing serum HCO3 through ↑ secretion of H+.
    • Kidneys respond to respiratory alkalosis by decreasing serum HCO3 through:
      • ↓ Secretion of H+
      • Urinary excretion of HCO3 (normally bicarbonate is 100% absorbed)
  • In primary metabolic acid–base disorders, the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs may try to compensate in an attempt to normalize the pH.
    • Lungs respond to metabolic acidosis Metabolic acidosis The renal system is responsible for eliminating the daily load of non-volatile acids, which is approximately 70 millimoles per day. Metabolic acidosis occurs when there is an increase in the levels of new non-volatile acids (e.g., lactic acid), renal loss of HCO3-, or ingestion of toxic alcohols. Metabolic Acidosis by ↑ ventilation.
    • Lungs respond to metabolic alkalosis Metabolic alkalosis The renal system is responsible for eliminating the daily load of non-volatile acids, which is approximately 70 millimoles per day. Metabolic alkalosis also occurs when there is an increased loss of acid, either renally or through the upper GI tract (e.g., vomiting), increased intake of HCO3-, or a reduced ability to secrete HCO3- when needed. Metabolic Alkalosis by ↓ ventilation.
  • Interpreting the serum HCO3:
    • Normal range: 22–28 mEq/L
    • ↑ HCO3 is due to either:
      • Metabolic alkalosis, or
      • Compensated chronic respiratory acidosis Respiratory acidosis The respiratory system is responsible for eliminating the volatile acid carbon dioxide (CO2), which is produced via aerobic metabolism. In the setting of hypoventilation, this acid load is not adequately blown off, and respiratory acidosis occurs. Renal compensation occurs after 3-5 days, as the kidneys attempt to increase the serum bicarbonate levels. Respiratory Acidosis
    • ↓ HCO3 is due to either:
      • Metabolic acidosis, or
      • Compensated chronic respiratory alkalosis

Pathophysiology

Review of relevant pulmonary concepts

  • Tidal volume (TV): volume of air moved into and out of the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs per breath
  • Hypercapnia: elevated levels of CO2 in the blood
  • Dead space: air in the respiratory tree that does not participate in gas exchange Gas exchange Human cells are primarily reliant on aerobic metabolism. The respiratory system is involved in pulmonary ventilation and external respiration, while the circulatory system is responsible for transport and internal respiration. Pulmonary ventilation (breathing) represents movement of air into and out of the lungs. External respiration, or gas exchange, is represented by the O2 and CO2 exchange between the lungs and the blood. Gas Exchange
    • Anatomic dead space:
      • Upper airway down to the terminal bronchioles
      • Fixed volume of air
    • Alveolar dead space:
      • Refers to certain alveoli that are ventilated but not perfused
      • Normally very small total volume, unless there is a pathologic process
    • Physiologic dead space = anatomic dead space + alveolar dead space 
  • Effects of deep versus shallow breaths:
    • Deep breath:  ↑ TV + fixed volume of dead space
      • Dead space is a smaller fraction of total ventilation.
      • Better gas exchange Gas exchange Human cells are primarily reliant on aerobic metabolism. The respiratory system is involved in pulmonary ventilation and external respiration, while the circulatory system is responsible for transport and internal respiration. Pulmonary ventilation (breathing) represents movement of air into and out of the lungs. External respiration, or gas exchange, is represented by the O2 and CO2 exchange between the lungs and the blood. Gas Exchange → no hypercapnia
    • Shallow breath = ↓ TV + fixed volume of dead space
      • Dead space is a higher fraction of total ventilation.
      • Worse gas exchange Gas exchange Human cells are primarily reliant on aerobic metabolism. The respiratory system is involved in pulmonary ventilation and external respiration, while the circulatory system is responsible for transport and internal respiration. Pulmonary ventilation (breathing) represents movement of air into and out of the lungs. External respiration, or gas exchange, is represented by the O2 and CO2 exchange between the lungs and the blood. Gas Exchange → risk for hypercapnia
  • Minute ventilation:
    • Volume of air moved into and out of the lungs Lungs Lungs are the main organs of the respiratory system. Lungs are paired viscera located in the thoracic cavity and are composed of spongy tissue. The primary function of the lungs is to oxygenate blood and eliminate CO2. Lungs per minute
    • Minute ventilation = tidal volume × respiratory rate
  • Alveolar ventilation (VA):
    • The fraction of the minute ventilation that participates in gas exchange Gas exchange Human cells are primarily reliant on aerobic metabolism. The respiratory system is involved in pulmonary ventilation and external respiration, while the circulatory system is responsible for transport and internal respiration. Pulmonary ventilation (breathing) represents movement of air into and out of the lungs. External respiration, or gas exchange, is represented by the O2 and CO2 exchange between the lungs and the blood. Gas Exchange 
    • VA is inversely related to PaCO2 
      • As ventilation ↑ → PaCO2 ↓ 
      • As ventilation ↓ → PaCO2 ↑ 
    • VA = (tidal volume – dead space) × respiratory rate
Alveolar ventilation

Relationship between alveolar ventilation and PCO2

Image by Lecturio.

Pathophysiology

Respiratory alkalosis is a process that results in a decreased level of carbon dioxide. 

  • Almost always due to hyperventilation (↑ respiratory rate)
  • The arterial blood gas will show:
    • pH > 7.40 
    • PCO2 < 30 mmHg 
  • The hyperventilation may be caused by:
    • ↑ Drive from the CNS (pathologic or physiologic)
    • Hypoxemia-induced causes → body attempts to correct the hypoxia at the expense of CO2 loss

Renal compensation

  • Kidneys respond to respiratory alkalosis by decreasing serum HCO3:
    • Excretion of HCO3 is increased → threshold for HCO3reabsorption is changed 
    • Decreased secretion of H+ 
  • Process takes 3–5 days to complete:
    • Cells must undergo physical changes.
    • Serum HCO3 and pH decrease slowly during this time.
  • Degree of compensation defines acute versus chronic respiratory alkalosis.
Respiratory alkalosis renal compensation

Renal compensation of respiratory alkalosis:
In respiratory alkalosis, the PCO2 is decreased, shifting the PCO2 curve to the right (1). As HCO3– levels are decreased by the kidneys Kidneys The kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine. Kidneys, the pH improves along the PCO2 line (2)

Image by Lecturio.

Acute versus chronic respiratory alkalosis

Acute versus chronic respiratory alkalosis is defined by the degree of renal compensation.

  • Acute respiratory alkalosis is uncompensated:
    • Not enough time for renal compensation to occur
    • More likely to be symptomatic from hypocapnia
  • Chronic respiratory alkalosis is compensated:
    • Renal compensation is complete.
    • HCO3 decreases by approximately 4 mEq/L per 10-mmHg decrease in PaCO2
    • Usually asymptomatic, despite chronic hypocapnia
    • Hypocapnia is usually mild and pH may be very near normal.

Clinical Presentation, Diagnosis, and Management

Clinical presentation

  • Tachypnea
  • Dyspnea
  • Dizziness/light-headedness
  • Paresthesias (perioral, hands/feet) due to decreased ionized calcium
  • Psychologic symptoms:
    • Anxiety
    • Fear
    • Impending doom
  • Highly variable Variable Variables represent information about something that can change. The design of the measurement scales, or of the methods for obtaining information, will determine the data gathered and the characteristics of that data. As a result, a variable can be qualitative or quantitative, and may be further classified into subgroups. Types of Variables presentation, based on underlying etiology; for example:
    • High-altitude illness: findings consistent with pulmonary and/or cerebral edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema
    • Sepsis Sepsis Organ dysfunction resulting from a dysregulated systemic host response to infection separates sepsis from uncomplicated infection. The etiology is mainly bacterial and pneumonia is the most common known source. Patients commonly present with fever, tachycardia, tachypnea, hypotension, and/or altered mentation. Sepsis and Septic Shock: fever Fever Fever is defined as a measured body temperature of at least 38°C (100.4°F). Fever is caused by circulating endogenous and/or exogenous pyrogens that increase levels of prostaglandin E2 in the hypothalamus. Fever is commonly associated with chills, rigors, sweating, and flushing of the skin. Fever, hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension, findings consistent with originating infection (e.g., cough or dysuria)
    • Pulmonary embolism Pulmonary Embolism Pulmonary embolism (PE) is a potentially fatal condition that occurs as a result of intraluminal obstruction of the main pulmonary artery or its branches. The causative factors include thrombi, air, amniotic fluid, and fat. In PE, gas exchange is impaired due to the decreased return of deoxygenated blood to the lungs. Pulmonary Embolism: calf pain Pain Pain has accompanied humans since they first existed, first lamented as the curse of existence and later understood as an adaptive mechanism that ensures survival. Pain is the most common symptomatic complaint and the main reason why people seek medical care. Physiology of Pain, unilateral lower-extremity edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema

Diagnosis

Diagnosing a respiratory alkalosis typically requires a thorough history and exam and an arterial blood gas measurement.

  • Arterial blood gas:
    • Acute respiratory alkalosis (uncompensated): 
      • pH > 7.45
      • PaCO2 < 35 mmHg
      • Normal HCO3
    • Chronic respiratory alkalosis (compensated):
      • pH > 7.4 (slightly high or near-normal)
      • PaCO2 < 35 mmHg
      • HCO3 decreased
  • Electrolytes Electrolytes Electrolytes are mineral salts that dissolve in water and dissociate into charged particles called ions, which can be either be positively (cations) or negatively (anions) charged. Electrolytes are distributed in the extracellular and intracellular compartments in different concentrations. Electrolytes are essential for various basic life-sustaining functions. Electrolytes: Abnormalities are common and may lead to complications.
    • Basic metabolic panel
    • Magnesium
    • Phosphate
  • Chest X-ray: to rule out other causes of tachypnea

Management

  • Assess and address the ABCs (airway, breathing, and circulation) if patient is in acute distress.
  • Attempt to correct the underlying abnormality.
  • Small dose of short-acting benzodiazepine

Clinical Relevance

  • Hyperventilation syndrome: an inappropriate increase in minute ventilation beyond basic needs, typically associated with panic disorder Panic disorder Panic disorder is a condition marked by recurrent and episodic panic attacks that occur abruptly and without a trigger. These episodes are time-limited and present with cardiorespiratory (palpitations, shortness of breath, choking), GI (nausea, abdominal distress), and neurologic (paresthesias, lightheadedness) symptoms. Panic Disorder: Patients will typically present with intermittent episodes of spontaneously resolving hyperventilation, often with mild dyspnea Dyspnea Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea, dizziness, and chest tightness. Metabolic alkalosis may develop. Diagnosis involves excluding physiologic causes of tachypnea. Management involves reassurance and possibly short-acting benzodiazepines Benzodiazepines Benzodiazepines work on the gamma-aminobutyric acid type A (GABAA) receptor to produce inhibitory effects on the CNS. Benzodiazepines do not mimic GABA, the main inhibitory neurotransmitter in humans, but instead potentiate GABA activity. Benzodiazepines.
  • High-altitude illness: a collective term for conditions involving cerebral and pulmonary symptoms that occur initially at high altitude: Hypoxia at higher altitudes stimulates hyperventilation, which can lead to respiratory alkalosis. These conditions are characterized by fluid shifts out of the vessels into the extravascular fluid space, leading to cerebral and pulmonary edema Edema Edema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity). Edema. Management involves descent to a lower elevation and oxygen therapy.
  • Salicylate toxicity: a complex mechanism that results in a mixed acid–base disorder, involving both respiratory alkalosis and metabolic acidosis Metabolic acidosis The renal system is responsible for eliminating the daily load of non-volatile acids, which is approximately 70 millimoles per day. Metabolic acidosis occurs when there is an increase in the levels of new non-volatile acids (e.g., lactic acid), renal loss of HCO3-, or ingestion of toxic alcohols. Metabolic Acidosis: Activation of the respiratory center in the medulla results in hyperventilation, while interference with cellular metabolism can lead to metabolic acidosis Metabolic acidosis The renal system is responsible for eliminating the daily load of non-volatile acids, which is approximately 70 millimoles per day. Metabolic acidosis occurs when there is an increase in the levels of new non-volatile acids (e.g., lactic acid), renal loss of HCO3-, or ingestion of toxic alcohols. Metabolic Acidosis. The patient can also have significant vomiting, and gastric ulcers and platelet dysfunction may develop. After initial stabilization, patients can be treated with activated charcoal to absorb the aspirin.

References

  1. Emmett, M. & Palmer B.F. (2020). Simple and mixed acid-base disorders. UpToDate. Retrieved April 1, 2021, from https://www.uptodate.com/contents/simple-and-mixed-acid-base-disorders 
  2. Feller-Kopman, D.J. & Schwartzstein, R.M. (2021). Mechanisms, causes, and effects of hypercapnia. UpToDate. Retrieved April 1, 2021, from https://www.uptodate.com/contents/mechanisms-causes-and-effects-of-hypercapnia
  3. Theodore, A.C. (2020). Arterial blood gases. UpToDate. Retrieved April 1, 2021, from https://www.uptodate.com/contents/arterial-blood-gases
  4. Feller-Kopman, D.J. & Schwartzstein, R.M. (2021). The evaluation, diagnosis, and treatment of the adult patient with acute hypercapnic respiratory failure Respiratory failure Respiratory failure is a syndrome that develops when the respiratory system is unable to maintain oxygenation and/or ventilation. Respiratory failure may be acute or chronic and is classified as hypoxemic, hypercapnic, or a combination of the two. Respiratory Failure. UpToDate. Retrieved April 8, 2021, from https://www.uptodate.com/contents/the-evaluation-diagnosis-and-treatment-of-the-adult-patient-with-acute-hypercapnic-respiratory-failure

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