Respiratory alkalosis

# Overview
Acid-base status of an organism is determined by the extracellular fluid (ECF) hydrogen ion concentration  since pH is equal to minus log of  i.e. pH = -log. Normal pH of human blood is 7.40 (7.35-7.45). Acidosis raises ECF  thereby lowering pH  whereas alkalosis lowers ECF  thereby raising pH of the ECF. Respiratory alkalosis is an acid-base disorder, primarily a decrease in partial pressure of carbon dioxide in arterial blood means PaCo2  with or without compensatory decrease in serum bicarbonate  (normal bicarbonate is 22-30mEq/L in arterial blood gas analysis) and pH being alkaline (normal pH of blood is 7.35-7.45).

# Pathophysiology
Production of CO2 in body tissues by intracellular metabolic process (from oxidation of fat, carbohydrate and carbon skeleton of amino acids in normal metabolic process produces carbon dioxide and water) and elimination of CO2 through lungs are in equilibrium under normal physiology. CO2 in body tissues from normal metabolic process enters blood in the tissues because its local partial pressure in tissues is greater than the partial pressure in blood flowing through the tissues due to property of gases to diffuse from high pressure to low pressure. Flowing blood transports the CO2 to the lungs, where it diffuses into the alveoli and then to the atmosphere by pulmonary ventilation. The reversible combination of CO2 with water in the red blood cells under the influence of carbonic anhydrase enzyme forms carbonic acid (H2CO3) which dissociates into hydrogen and bicarbonate  ions (H+ and HCO3) ions. HCO3 diffuse from the red blood cells into the plasma, while chloride ions diffuse into the red blood cells to take their place (chloride shift). Hence, most of tissue CO2 is brought to lungs as plasma venous bicarbonate ions that accounts for about 70 percent of the CO2 transported from the tissues to the lungs. Remaining CO2 is transported as carbaminohemoglobin (23%) and as dissolved CO2 in fluids of blood(7%).
Respiratory alkalosis in almost all cases results from increased alveolar respiration (hyperventilation) leading to decrease in blood carbon dioxide concentration measured as PaCO2. This leads to decreased hydrogen ion  and bicarbonate  concentrations. Decreased  leads to increase in pH leading to alkalosis.

## Compensation in respiratory alkalosis
compensation for respiratory alkalosis is mostly mediated through plasma buffers and proteins (eg. hemoglobin in RBC, plasma proteins) in acute stage and by kidneys in chronic compensatory stage.

### Acute compensatory stage
- Starts within minutes to hours and mediated by body's non-bicarbonate buffers (hemoglobin, intracellular proteins and phosphates, plasma proteins) and it consists of cellular uptake of HCO3- and buffered by intracellular phosphates and proteins
- For every PaCO2 decrease of 10 mm Hg, serum bicarbonate decreases by 1-2mEq/L
- Change in pH is unpredictable

### Chronic compensatory stage
- Renal mediated process where reduction in PaCO2 leads to decreased renal tubular H+ secretion. Within the renal tubular cells, CO2, under the influence of carbonic anhydrase enzyme, combines with H2O to form carbonic acid (H2CO3), which then dissociates into HCO3- and H+. Alkalosis inhibits carbonic anhydrase activity, resulting in reduced H+ secretion into the renal tubule. As a result, there is not enough H+ in the renal tubular fluid to react with all the filtered HCO3 from glomerular capillaries of the kidneys. Therefore, the HCO3 that cannot react with H+ is not reabsorbed  and is excreted in the urine. This causes a decrease in urinary net acid excretion(mostly ammonium ions NH4+) and due to increased bicarbonate excretion, body's bicarbonate stores is reduced.
- Starts after 24-36 hours and renal compensation for sustained hypocapnia is complete in 36-72 hours
- For every PaCO2 decrease of 10 mm Hg, serum bicarbonate decreases by 5mEq/L
- pH in chronic compensation is near normal

# Classification
There are two types of respiratory alkalosis: chronic and acute.

## Acute respiratory alkalosis
- Lasting for less than 24-48 hours
- Increased levels of carbon dioxide are "blown off" by the lungs, which are hyperventilating.
- During acute respiratory alkalosis, the person may lose consciousness where the rate of ventilation will resume to normal.

## Chronic respiratory alkalosis
- Lasting for longer than 24-48 hours
- For every 10 mM drop in pCO2 in blood, there is a corresponding 5 mM of bicarbonate ion drop.
- The drop of 5 mM of bicarbonate ion is a compensation effect which reduces the alkalosis effect of the drop in pCO2 in blood. This is termed metabolic compensation.

# Risk Factors

## Common Risk Factors
- Common risk factors in the development of respiratory alkalosis include:
Old age
Mechanical ventilation
Lung diseases
Hepatic failure
Infection
High altitude
Anxiety disorder
CNS infection
- Old age
- Mechanical ventilation
- Lung diseases
- Hepatic failure
- Infection
- High altitude
- Anxiety disorder
- CNS infection

## Less Common Risk Factors
- Less common risk factors in the development of respiratory alkalosis include:
Drugs
Poisoning
- Drugs
- Poisoning

# Causes

## Tissue hypoxia (hypoxemia)
- Pneumonia
- Aspiration of foreign body, food or vomitus
- Pulmonary embolism
- Bronchospasm/laryngospasm (eg. in asthma)
- Drowning
- Anemia
- High altitude
- Cyanotic heart disease
- Circulatory failure or hypotension

## Stimulation of chest receptors
- Pneumonia
- Asthma
- Pneumothorax/hemothorax
- Flail chest
- Cardiac failure
- Pulmonary edema (non-cardiogenic)
- Adult/infant respiratory distress syndrome
- Interstitial lung disease

## Stimulators of central respiratory drive
- Pain
- Anxiety
- Fever
- High altitude
- Anemia
- Drugs like doxapram and large doses of aspirin (stimulate the respiratory center), Gallium nitrate, cocaine, catecholamines
- CNS causes, including stroke, subarachnoid haemorrhage, meningitis, encephalitis, CNS tumor
- Caffeine overdose and coffee abuse, methylxanthines (eg. theophyllin, aminophyllin)
- Progesterone

## Systemic diseases
- Sepsis
- Liver failure
- Hyperthyroidism
- Pregnancy
- Iatrogenically during mechanical ventilation of patients
- Carbon monoxide poisoning
- Recovery from metabolic acidosis
- Heat exposure

### Special considerations
- Sepsis or salicylate toxicity are the only single disorders that cause both an elevated anion gap metabolic acidosis and a respiratory alkalosis.
- Ischemia, infection or infarction of the central respiratory centers may result either respiratory acidosis (decreased respiratory drive) or respiratory alkalosis (increased respiratory drive)
- Asthma, and Pneumonia can also present with either repiratory alkalosis or acidosis. Asthma typically presents with a respiratory alkalosis, however as the patient tires, respiratory acidosis may occur.
- Pulmonary embolus can be a life threatening condition and often presents as respiratory alkalosis.
- Progesterone is sometimes used as a respiratory stimulant in obstructive sleep apnea and hypoventilation.
- Respiratory alkalosis is the most common acid base abnormality in critically ill patients.

# Differential Diagnosis
Abbreviations: ABG (arterial blood gas); ACE (angiotensin converting enzyme); BMI (body mass index); CBC (complete blood count); CSF (cerebrospinal fluid); CXR (chest X-ray); DOE (dyspnea on exercise); ECG (electrocardiogram); FEF (forced expiratory flow rate); FEV1 (forced expiratory volume); FVC (forced vital capacity); JVD (jugular vein distention); MCV (mean corpuscular volume); Plt (platelet); RV (residual volume); SIADH (syndrome of inappropriate antidiuretic hormone); TSH (thyroid stimulating hormone); Vt (tidal volume); WBC (white blood cell);

# History and Symptoms
- Symptoms of respiratory alkalosis depends upon duration of disease and underlying diseases. Symptoms of acute respiratory alkalosis are related to decrease blood carbon dioxide levels (PaCO2) that leads to reduced cerebral blood flow resulting from vasoconstriction of cerebral vessels. Most of the symptoms arise when PaCO2 falls below 30 mm Hg.

## History
Patients with respiratory alkalosis may have a positive history of:
- Anxiety disorders or primary neurologic diseases
- Lung or liver diseases
- Critical illness with mechanical ventilation

## Common Symptoms
Common symptoms of acute respiratory alkalosis include:
- Light-headedness
- Syncope
- Confusion
- Seizure
- Peripheral and circumoral paresthesia and cramp
- Chest pain and shortness of breath are seen in patients hyperventilating due to pain or anxiety
- Chronic respiratory alkalosis is generally well tolerated without apparent clinical symptoms
- Signs include:
Carpopedal spasm due to tetany  as a result of decreased levels of ionized calcium in the blood (ionized calcium  are driven inside cells in exchange for hydrogen ion  as compensatory mechanism to correct pH) with no fall in total serum calcium level. Alkalosis also increases protein-bound fraction of calcium reducing free calcium.
- Carpopedal spasm due to tetany  as a result of decreased levels of ionized calcium in the blood (ionized calcium  are driven inside cells in exchange for hydrogen ion  as compensatory mechanism to correct pH) with no fall in total serum calcium level. Alkalosis also increases protein-bound fraction of calcium reducing free calcium.

# Physical Examination
- Physical examination findings of patients with respiratory alkalosis is related to the underlying causes.

## Appearance of the Patient
- Patients with acute respiratory alkalosis usually appear anxious in primary hyperventilation syndrome, OR are ill appearing in mechanically ventilation whereas are comfortable in chronic respiratory alkalosis.

## Vital Signs
- High-grade / low-grade fever
- Tachycardia may be present
- Tachypnea or hyperpnea is present with both increase in respiratory rate and tidal volume
- Cheyne-Stokes type of breathing may be seen in upper pontine lesion or heart failure
- Low blood pressure in mechanically ventilated patients with respiratory alkalosis

## Skin
- Cyanosis is present in hypoxic patient
- Jaundice may be present in liver disease

## HEENT
- HEENT examination of patients with respiratory alkalosis is usually normal.

## Neck
- Neck examination of patients with respiratory alkalosis is usually normal

## Lungs
- Lungs are dull to percussion in hemothorax/hyperresonant in pneumothorax
- Fine/coarse crackles upon auscultation of the lung suggest interstitial lung disease/pneumonia as a cause of respiratory alkalosis

## Heart
- Cardiovascular examination of patients with respiratory alkalosis is usually normal except in patients with coronary artery disease

## Abdomen
Hepatomegaly and right upper quadrant tenderness may be seen in cirrhosis

## Back
- Back examination of patients with respiratory alkalosis is usually normal.

## Genitourinary
- Genitourinary examination of patients with respiratory alkalosis is usually normal

## Neuromuscular
- Focal neurologic signs and depressed level of consciousness is seen in respiratory alkalosis of neurologic cause

## Extremities
- Extremities examination of patients with respiratory alkalosis show positive Trousseau sign in acute hypocapnia as a result of tetany.

# Approach to acid-base disorders

# Laboratory Findings
- Arterial blood gas analysis(ABG):
It is the diagnostic test of choice for respiratory alkalosis
primary respiratory alkalosis has pH> 7.45, PaCO2 80mm Hg or 10.7kPa)
- It is the diagnostic test of choice for respiratory alkalosis
- primary respiratory alkalosis has pH> 7.45, PaCO2 80mm Hg or 10.7kPa)
- Serum electrolytes: Decrease in ,,  and ionized  are seen in acute hypocapnia due to intracellular shift whereas decreased  and hyperphosphatemia are seen in sustained hypocapnia.
- Other laboratory test and imaging studies that may be useful in respiratory alkalosis to find out the causes includes:
Urine pH and urinalysis
CBC: elevated WBC in sepsis
Blood/sputum/urine C/S: for sepsis
EKG and ECHO: for congestive heart failure
Drug screening test
Thyroid function test: to rule out hyperthyroidism
Liver function test: abnormal in hepatic causes
pulmonary function test: to rule out chest infections
V/Q scan: to rule out pulmonary embolism
Chest X-ray: for chest infection
CT scan: for pulmonary embolism
MRI brain: to rule out CNS cause of hyperventilation
- Urine pH and urinalysis
- CBC: elevated WBC in sepsis
- Blood/sputum/urine C/S: for sepsis
- EKG and ECHO: for congestive heart failure
- Drug screening test
- Thyroid function test: to rule out hyperthyroidism
- Liver function test: abnormal in hepatic causes
- pulmonary function test: to rule out chest infections
- V/Q scan: to rule out pulmonary embolism
- Chest X-ray: for chest infection
- CT scan: for pulmonary embolism
- MRI brain: to rule out CNS cause of hyperventilation

# Treatment
- Respiratory alkalosis is not a life threatening disorder, so treatment is directed at the underlying causes of the disorder.
patients with hyperventilation disorder (eg. anxiety, conversion disorder) are benefited from rebreathing mask.
High altitude sickness is treated with acetazolamide 250mg 12 hourly, Dexamethasone 4mg 6 hourly, oxygen therapy and descent to lower altitude in severe cases.
For critically ill patients on mechanical ventilation with respiratory alkalosis, tidal volume and respiratory rate needs to be decreased with adequate pain control.
Sedatives and antidepressants should not be used in cases of respiratory alkalosis.
- patients with hyperventilation disorder (eg. anxiety, conversion disorder) are benefited from rebreathing mask.
- High altitude sickness is treated with acetazolamide 250mg 12 hourly, Dexamethasone 4mg 6 hourly, oxygen therapy and descent to lower altitude in severe cases.
- For critically ill patients on mechanical ventilation with respiratory alkalosis, tidal volume and respiratory rate needs to be decreased with adequate pain control.
- Sedatives and antidepressants should not be used in cases of respiratory alkalosis.

# Related Chapters
- Metabolic alkalosis
- Acid-base imbalance
- Metabolic acidosis
- Respiratory acidosis
- Anion gap
- Hypocalcemia
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