Hyperventilation

Dyspnea Microchapters
Overview
Pathophysiology
Causes
Differentiating Hyperventilation from other Diseases

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Jyostna Chouturi, M.B.B.S [2], Amresh Kumar MD [3], Vindhya BellamKonda, M.B.B.S [4], Usama Talib, BSc, MD [5], Iqra Qamar M.D.[6]

Overview

Hyperventilation is the state of rapid breathing which results in the reduction in carbon dioxide levels (below normal) thereby leading to hypocapnia. During rapid breathing, the body loses more carbon dioxide (CO₂) than it can produce resulting in net reduction of CO₂ levels. This state of rapid/faster breathing is most commonly seen in stress and anxiety and termed as hyperventilation syndrome. Kussmaul breathing is also a type of hyperventilation and done to reduce the acidity of body as seen in metabolic acidosis. Hyperventilation may also be voluntarily manifested following episodes of rapid deep breathing. The symptoms of hyperventilation are variable. Some patients are completely asymptomatic while others may present with minimal symptoms such as headache and numbness or tingling in the hands, feet, and lips. More severe symptoms include dizziness, lightheadedness, and fainting. Some patient also report having chest pain and slurred speech particularly when accompanied by the Valsalva maneuver. Voluntary deep breathing and induction of hyperventilation is a common practice among young individuals to attain focus and adrenaline rush. Other similar terms that are completely different from hyperventilation include hyperpnea and tachypnea.

Hyperpnea is commonly seen with exercise or any major physical activity as well as in response to hypoxic states. In these conditions the energy demand of the body either goes up or is not adequately met. To meet this energy deficit, the body increases the depth and rate of breathing which is known as hyperpnea. Other common examples of hyperpneic state include sepsis, anemia, and individuals living at high altitudes. Tachypnea is derived from a Greek word which means "rapid breathing". Tachypnea means rapid and shallow breathing and is also seen with exercise as a compensatory mechanism to increase the oxygen content of the body.

Pathophysiology

Physiology of breathing

The basic physiology of normal breathing is as follows:

• Under normal conditions, breathing is regulated by the central nervous system (CNS).

• The CNS regulates the depth and frequency of each breath to maintain normal levels of carbon dioxide (CO₂) and oxygen (O₂) in the blood and tissues.
• The CNS measures the amount of CO₂ in the body to regulate the breathing process.
• As the CO₂ and O₂ gas exchange mechanism is simultaneous and continuous, any condition resulting in increased high carbon dioxide concentration primarily signals a low oxygen concentration.
• In addition, metabolism in the body uses O₂ and results in the production of CO₂ as a byproduct.

Hyperventilation

Under physiologic conditions, the volume of alveolar gas is in equilibrium with the arterial gas.

• With each breath approximately 10% of the alveolar gas is replaced with atmospheric air.
• The rate and depth of breathing determines the level of CO₂ in the body.
• A rapid and deep breath will lead to a better alveolar - atmospheric gas exchange leading to low CO₂ levels.
• It is to be noted that atmospheric air has 21% O2 content as compared to just 0.03% of CO₂ content.
• This results in low CO₂ content (hypocapnia) with each rapid and deep breath.

Mechanism of Alkalosis

The mechanism of the development of alkalosis following hyperventilation is as follows:

• Majority of the CO₂ in human body is stored as carbonic acid and is a major factor in determining the pH of the body.
• Loss of CO₂ results in blood becoming more alkaline and increase in blood pH.
• In the normal individual, the resultant alkalosis would automatically be countered by reduced breathing except when the neural control is altered or disturbed.

Response of brain vasculature to hyperventilation and hypoventilation

The response of vessels in the brain to hyperventilation and hypoventilation is as follows:

• Conditions causing high CO₂ levels (hypercapnia) results in the body assuming that the O₂ levels are low.
• As a result, to increase the O₂ supply the blood vessels in the brain dilate.

• Alternatively, hypocapnia results in constriction of brain's blood vessels causing diminished blood flow leading to lightheadedness.
• Thus, though it seems counterintuitive, breathing too much can result in a decrease in the oxygen supply to the brain.
• Physicians often artificially induce hyperventilation after head injury to reduce the intracranial pressure, although the treatment has potential risks.

Effect of breathing on serum calcium

The effect of breathing on the calcium levels in the serum is given below:

• The level of serum calcium is also regulated by the acid-base balance in the body.
• Ionized calcium is bound by the negatively charged albumin.
• Alkaline promoting conditions (such as hyperventilation), displace ionized calcium from binding sites leading to an increase in the calcium level.
• However, such conditions promoting alkalinity in the blood, lead to reflex respiratory hypoventilation and may lead to decreased serum calcium level.
• Increased CO₂ levels (in hypoventilation) tends to bind more of ionized calcium which ultimately results in low calcium levels.

Causes

Following are the various causes of hyperventilation.

Life-Threatening Causes

• Diabetic ketoacidosis
• Heat stroke
• Pulmonary embolism
• Respiratory alkalosis
• Sepsis

Common Causes

• Acute altitude sickness
• Anxiety
• Ascites
• Asthma
• Chronic obstructive pulmonary disease
• Congestive heart failure
• Drugs such as:
  • Amphetamine
  • Aspirin
• Encephalitis
• Exercise
• Fever
• Graves' disease
• Head injury
• Hyperthyroidism
• Meningitis
• Panic disorder
• Pneumonia
• Pneumothorax
• Pregnancy
• Pulmonary edema
• Pulmonary embolus
• Pulmonary fibrosis
• Stress
• Stroke

Causes by Organ System

Cardiovascular	Cheyne-stokes respirations, congestive cardiac failure, pulmonary embolism, stroke
Chemical/Poisoning	Ammonium chloride, camphor , glycol ether , inhalation of irritants, methanol, salicylate poisoning
Dental	No underlying causes
Dermatologic	No underlying causes
Drug Side Effect	Aminophylline, aspirin, coffee abuse, pralidoxime, tiagabine
Ear Nose Throat	No underlying causes
Endocrine	Diabetic ketoacidosis, renal disease
Environmental	Acute stress disorder
Gastroenterologic	Abdominal surgery, acute liver failure, acute porphyria, end stage liver failure, hepatic cirrhosis, intestinal fistula, pyloric stenosis
Genetic	Acute porphyria, arginosuccinic aciduria, carbamoylphosphate synthetase 1 deficiency disease, carbonic anhydrase va deficiency, hereditary fructose-1,6-bisphosphatase deficiency, Pitt-hopkins syndrome
Hematologic	Acute porphyria
Iatrogenic	No underlying causes
Infectious Disease	CNS infection, fever
Musculoskeletal/Orthopedic	Hip cancer
Neurologic	Altitude sickness, acute brain trauma, central neurogenic hyperventilation, cerebrovascular accident, CNS infection, Cree leukoencephalopathy, damaged respiratory pathways, epilepsy, epileptic encephalopathy, early infantile, 2; head injury, intracranial space-occupying lesion, meningoencephalitis, pain, Pitt-Hopkins syndrome, raised intracranial pressure, stroke, vasovagal attacks
Nutritional/Metabolic	Diabetic ketoacidosis, hereditary fructose-1,6-bisphosphatase deficiency, heat stroke, lactic acidosis
Obstetric/Gynecologic	No underlying causes
Oncologic	Bronchial neoplasm, rib tumor
Ophthalmologic	No underlying causes
Overdose/Toxicity	Biguanide intolerance
Psychiatric	Acute stress disorder, adult panic-anxiety syndrome, agoraphobia, anxiety, Briquet's syndrome, combat stress reaction, Cree leukoencephalopathy,crying or severe distress, Da Costa syndrome, depression, distress, excitement, fear, functional disorders, grief, hypochondriasis, hysteria, malingering, pain, panic attack, phobia, primary habit disorder, Rett's syndrome, schizophrenia, stress, strong emotions
Pulmonary	Acute altitude sickness, apneustic respirations, asthma, ataxic respiration, biot's respiration, central neurogenic hyperventilation, Cheyne-stokes respirations, damaged respiratory pathways, diffuse pulmonary fibrosis, emphysema , hyperventilation syndrome, inhalation of irritants, lung damage, metabolic acidosis, persistent hypoxemia, pleural effusion, pneumonia, pneumothorax, pulmonary embolism, pulmonary oedema
Renal/Electrolyte	Acid-base imbalance, metabolic acidosis, phaeochromocytoma, renal disease
Rheumatology/Immunology/Allergy	Asthma, pseudoallergic reactions
Sexual	No underlying causes
Trauma	Brain trauma, head injury, lung damage, raised intracranial pressure, sponatneous pneumothorax, stroke, surgical relocation of ureters in ileum or colon
Urologic	Surgical relocation of ureters in ileum or colon
Miscellaneous	Abdominal surgery, adulation, childbirth, fever

Causes in Alphabetical Order

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Differentiating Hyperventilation from other Diseases

Various diseases that can cause hyperventilation may include diseases of respiratory, cardiovascular, endocrine, central nervous system, and musculoskeletal system. Pregnancy, sepsis, and hepatic failure are other conditions that may also result in hyperventilation. Given below is a differential diagnosis of diseases presenting with hyperventilation.

Abbreviations: ABG (arterial blood gas); ACE (angiotensin converting enzyme); βhCG (beta human chorionic gonadotropin); BMP (basic metabolic panel); BNP (brain natriuretic peptide); CBC (complete blood count); COPD (chronic obstructive pulmonary disease); CSF (cerebrospinal fluid); CXR (chest X-ray); CT (computed tomography); DLCO (diffusing capacity of the lung for carbon monoxide); DOE (dyspnea on exercise); ECG (electrocardiogram); FEF (forced expiratory flow rate); FEV1 (forced expiratory volume); FT4 (free T4); FVC (forced vital capacity); HRCT (high resolution computed tomography); JVD (jugular vein distention); LFTs (liver function tests); MCV (mean corpuscular volume); MEN (multiple endocrine neoplasia); MRI (magnetic resonance imaging); P2 (pulmonic heart sound); Plt (platelet); PT (prothrombin time); RBC (red blood cell); RV (residual volume); SIADH (syndrome of inappropriate antidiuretic hormone); S3 ( third heart sound); S4 (fourth heart sound); T3 ((Triiodothyronine); TLC (total lung capacity); TSH (thyroid stimulating hormone); VC (vital capacity); VMA(vanillylmandelic acid); Vt (tidal volume); WBC (white blood cell);

Organ system	Diseases	Clinical manifestations									Diagnosis					Other features
		Symptoms				Physical exam
		Chest pain	Dyspnea	Fever	Palpitations	Cyanosis	Tachypnea	JVD	Peripheral edema	Auscultation	ABGs	Lab findings	Imaging	PFT	Gold standard
Pulmonary system	Pneumothorax	+	+	+/-	+	+/-	+	-	-	Decreased breath sounds	+/- Hypoxemia	-	X- ray - Mediastinal shift Deep sulcus sign Hydropneumothorax CT-scan - bullae	↓Vt	CT-scan	Hypoxia Hypercapnia Hyperresonance to percussion Vocal resonance Tactile fremitus decreased
	Pulmonary embolism	+/-	+	+/-	+	+/-	+	+/-	-	S3 or S4 gallop	Respiratory alkalosis	↑D-dimer ↑Troponin levels	Duplex Ultrasonography Echocardiography Venography Ventilation-Perfusion Scanning	Normal	CT pulmonary angiography	Hemoptysis History of venous thromboembolismor coagulationabnormalities History of Malignancy
	Pneumonia	+/-	+	+	+	+/-	+	-	-	Bronchial breath sounds Crepitations Bronchophony Egophony Whispering pectoriloquy	+/- Hypoxemia	↑WBC Serology(Mycoplasma, viruses) Sputum Gram stain and culture Blood culture	CXR- Lobar consolidation, Air bronchogram; Atypical pneumonia: Diffuse interstitial infiltrates	Normal	Presence of lung infiltrates on CXR Blood cultures	Altered mental status Tachycardia Rust-colored sputum Green sputum Red currant-jelly sputum Central cyanosis
	Exacerbation of asthma/COPD	+/-	+	+/-	+	+	+	-	-	Decreased breath sounds Wheezing Coarse crackles	+/- Hypoxemia	CBC shows ↑hematocrit Sputum evaluation BNP( to rule out heart failure)	CXR shows Hyperinflated lungs Flattening of the diaphragm Narrow heart shadow Cardiomegaly	↑TLC ↑RV ↓Vital capacity ↓DLco ( Emphysema) Normal DLco ( Chronic bronchitis)	HRCT of the lung	Productive cough Exercise intolerance Altered mental status Cor-pulmonale Hyperresonance on percussion
	Interstitial lung disease	+/-	+	+/-	+	+	+	+/-	-	Fine crackles Loud P2	+/- Hypoxemia	_	CXR- Reticular infiltrates Honey combing	↓FEV1 ↓FVC ↓TLC ↓RV ↓DLco FEV1/FVC normal	HRCT -more accurate than cxr Most accurate test is lung biopsy	Physical examination shows clubbing Decreased pulmonary compliance
	Intrapulmonary shunt	+/-	+	-	-	+	+/-	-	-	Diminished breath sounds	+/- Hypoxemia	CBC shows anemia or polycythemia	CXR and CT shows a smooth nodule with a feeding artery and draining vein	↓Vt, ↑RV (physiological)	Pulmonary CT angiography	Clubbing Chronic hypoxemia
	Upper airway obstruction	-	+	-	-/+	-/+	+	-/+	-	Inspiratory stridor	+/- Hypoxemia	-	Plain radiograph of the neck Steeple sign (Croup in pediatric population) Thumb sign (Epiglottitis) CT MRI	↓VC	HRCT Bronchoscopy	Hoarseness Accessory muscle use during respiration Chest retractions
	High altitude sickness	-	+	+/-	+	+/-	+	-	+	Crackles	Respiratory alkalosis	EKG- Right sided heart strain	CXR- Bilateral patchy infiltrates Brain Ct scan	↓FVC	Test in a hypobaric chamber with and without supplemental O2-breathing	Altered mental status Urinary bladder distention Pulmonary edema Epistaxis Headache Rapid pulse
Cardiovascular system	Acute coronary syndrome	+	+	-	+/-	+/-	+/-	+/-	+/-	S3 Systolic murmur Rales	-	Elevated cardiac enzymes ↑BNP EKG	CXR shows (Cardiomegaly, Pulmonary edema) Echocardiography Myocardial perfusion imaging Cardiac angiography	-	Elevated [[Cardiac enzymes|cardiac biomarkers [Cardiac troponin I, cardiac troponin]] Coronary angiography	[[Nausea and vomiting] Diaphoresis Presyncope Palpitations Lateral displacement of the apical impulse
	Heart failure	+/-	+	-	+/-	+	+/-	+	+	S3	Respiratory alkalosis	Hyponatremia Hypoalbuminemia ↑ (BNP) EKG ( to know underlying cause)	CXR shows ↑Cardiothoracic ratio Pulmonary edema Cardiomegaly Pleural effusion	↓Vt	B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP)	Dyspnea Orthopnea Paroxysmal nocturnal dyspnea Excessive sweating High blood pressure Hepatojugular reflux
	Dysrhythmias	+/-	+	-	+	-	+/-	-	-	High pulse rate	Normal	Abnormal BMP Electrolytes disturbances	Normal	Normal	ECG	Caused by cardiac, psychiatric, medications, thyrotoxicosis and caffeine etc
	Shock	+/-	+/-	+/-	+/-	+/-	+/-	+/-	+/-	Stridor Wheezing	Combined acid-base disorders are frequently encountered in different stages	↑WBC	CXR (for finding the cardiac causes)	↓Vt	Depends on the cause of shock	Pulsus paradoxus Pulsus alternans Altered mental status Decreased skin turgor
Metabolic/Systemic disorders	Diabetic ketoacidosis	-	+	+/-	-	-	-	-	-	Scattered wheeze Kussmaul's respiration	Metabolic acidosis	↑WBC in septic shock Anion gap metabolic acidosis Serum ketones Urinary ketones Hyponatremia Hyperkalemia Hyperosmolality Increased blood glucose	Normal	Normal	Blood test (acidosis, hyperglycemia, ketonemia)	Vomiting Abdominal pain Weakness Confusion Kussumal's breathing Polydipsia Polyuria
	Hypocalcemia	-	+	-	+	-	+/-	-	-	Wheezing	Respiratory alkalosis	↓Serum ionized calcium Abnormal serum Albumin level Electrolytes disturbances Serum 25 -hydroxy Vitamin D Serum PTH ( Parathyroid hormone)	ECG shows prolongation of the QT interval	Normal	Serum Ionized calcium	Tetany Trousseau's sign Chvostek's sign Seizures
	Hypoglycemia	-	+/-	-	+/-	-	-	-	-	Rales, rhonchi or crackles	Normal	Serum insulin levels ↓Serum glucose levels Oral glucose tolerance test	Octreotide scanning localizes insulinomas CT scan	Normal	72-hour supervised fasting test	Neurogenic (autonomic) symptoms Neuroglycopenic symptoms
Endocrine system	Hyperthyroidism	+/-	+	-	+/-	-	+/-	-	-	Systolic hypertension with wide pulse pressure	Variable	↓TSH ↑FT4 and ↑total T3 Autoantibody studies	Diffuse or nodular pattern of uptake on thyroid scanning	Normal	Serum TSH level	Nervousness Anxiety Increased perspiration Heat intolerance
	Pheochromocytoma	-	+	+/-	+	-	+/-	-	-	Asymmetric chest expansion	Normal	Elevated plasma and urinary catecholamines and metanephrines Elevated urinary vanillyl mandelic acid	Radiological evaluation is done to locate site of the tumor	Normal	24-hour urine test for metanephrines, catecholamines and VMA	MEN 1 and MEN 2 syndrome
CNS	Central nervous system tumor	-	+/-	-	-	-	+/-	-	-	Normal	Variable based on tumor location	CSF analysis can show cancerous cell	Magnetic resonance imaging (MRI) with contrast CT scan is done in emergencies	Normal	Contrast-enhanced magnetic resonance imaging (MRI)	Headache Seizures Focal deficits
	Anxiety/panic attacks	+/-	+	-	+/-	-	-	-	-	Normal	Normal	Normal	Normal	Normal	Clinical assessment Psychological interview	Sweating Palpitation Severe anxiety
Others	Pregnancy	+/-	+	-	-	-	-	-	+/-	Normal	Respiratory alkalosis	↑WBC	Normal	↓Vt, ↑RV	βhCG	Missed period Hyperemesis
	Hepatic failure	-	+/-	+/-	+/-	+/-	+	+	+	Right ventricular gallop	+/- Respiratory alkalosis	Abnormal LFTs Abnormal PT time Abnormal serum ammonia	Doppler ultrasonography can show ascites, patency of hepatic artery, hepatic vein and portal vein	Normal	Liver biopsy	Jaundice Encephalopathy
	Sepsis	-	+	+/-	+/-	-	-	-	-	Normal	Variable based on the sepsis phase	↑WBC, neutrophilia	Normal	Normal	SIRS criteria	Chills Confusion

See also

• Hypoventilation, too shallow or too slow breathing
• Control of respiration
• Respiratory alkalosis
• Shallow water blackout, the role of hyperventilation in some drowning incidents